EU Research Spring 2020 by Blazon Publishing and Media Ltd

EU Research Spring 2020

COVID 19

Its impact on research and the search for a vaccine New tests under Antarcticaâ&#x20AC;&#x2122;s Doomsday Glacier

EU envisages close research relationship in draft UK BREXIT treaty

The future of Mobility: An in-depth look at Sustainable Transport

Black hole discovery: Astronomers detect biggest bang since big bang

Disseminating the latest research from around Europe and Horizon 2020 Follow EU Research on www.twitter.com/EU_RESEARCH

Editor’s N I

t’s been an eventful beginning to the year. The fight over whether Britain will Brexit is now at an end, and although it’s goodbye from the UK, the negotiations and details are all still yet to be hacked out in the transition period, so not quite ‘done’ as Prime Minister Boris Johnson promised British citizens in his election campaigning. In the mix of those negotiations is of course the next round of funding that will succeed Horizon 2020, the period between 2021-2027, with 100 billion euros up for grabs for worthy projects. Whilst the UK wants a piece of the pie still, it will undoubtedly still need to contribute its fair share for participating and will be excluded in the decision-making about the programme. I’ve long been searching for evidence of any of those elusive Brexit benefits and have yet to come up with anything substantial, but in the UK the search will have to go on. Still, it is with hope from me and many like me, that the UK is able to continue a positive, productive and mutually beneficial relationship with the EU, despite Britain’s determined regression into isolation.

As a seasoned editor and journalist, Richard Forsyth has been reporting on numerous aspects of European scientific research for over 10 years. He has written for many titles including ERCIM’s publication, CSP Today, Sustainable Development magazine, eStrategies magazine and remains a prevalent contributor to the UK business press. He also works in Public Relations for businesses to help them communicate their services effectively to industry and consumers.

In contrast, the deadly Coronavirus has no border issues at all and is at the time of writing, finding its way into various countries, as such outbreaks do. New strains of virus will increasingly become a threat as population goes up, existing medicines become less effective and access to anywhere around the world is so easy. An amazing story around this outbreak is in the response from researchers. Scientists usually take years to develop effective vaccines but in this recent case, Chinese officials made the genetic code of the virus available to anyone who wanted to see it. That information gave research teams from all around the world the means to develop their solutions quicker than ever before, and candidates for vaccines are already developed. In other news, the E-ELT (European Extremely Large Telescope) project continues to make progress – and we interview someone involved with technology in this endeavor, in this very issue. This is a truly amazing project that boggles the mind a little, innovating methods for direct imaging of alien worlds. This is the stuff of science fiction and defines how, with a lot of research and a lot of commitment, human beings are true explorers of this Universe. Planet hunting is not new but as a developing science, the potential for discovery is enormous. It should be humbling for Mankind to understand through observation, it is but the smallest of the Universe’s assets, and is part of the environment, not the lord and master of it.

Hope you enjoy the issue.

Richard Forsyth Editor

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Contents

Research News

EU Research takes a closer look at the latest news and technical breakthroughs from across the European research landscape

INTESTINAL MICROBIOTA Little progress has been made over recent years towards the goal of diagnosing pancreatic cancer at an earlier stage. We spoke to Dr Daniel Globisch about his research into biomarkers associated with pancreatic cancer

DRUG-SEQ The chromatin structure inside a cell plays a major role in determining how cancer patients respond to treatment. We spoke to Dr Raphael Rodriguez about his research into how patients respond to anti-cancer drugs

PhaseAge Defective ribonucleoprotein (RNP) granules are thought to be a major factor in the development of several forms of neurodegenerative disease. Professor Simon Alberti is investigating how these granules form and how they cause disease

InflamCellDeath Pyroptosis causes cells to expand and eventually burst, releasing content that causes inflammation. We spoke to Professor Petr Broz about the work of the InflamCellDeath project in investigating the basis of pyroptotic cell death

20 STUDIES OF THE FUNCTION The High Temperature Requirement A (HtrA) family of proteins plays an important role in protein quality control. We spoke to Dr Björn Burmann about his research into how these proteases work on the molecular level

23 StopLegClots Deep vein thrombosis is a major concern for health authorities. Intermittent pneumatic compression (IPC) therapy could offer an effective, cost-efficient method of prevention, a topic at the heart of Doctor Paul Ackermann’s research

24 EVICARE Researchers in the Evicare project are developing an innovative therapy that could help to stimulate the repair of cardiac tissue and change the course of heart disease, as Professor Joost Sluijter explains

26 iHEAR The iHEAR project brings together researchers in several disciplines to probe deeper into the roots of psychotic experiences in childhood and the longer term outcomes, as Professor Mary Cannon explains

28 The Biological Basis of

Cognitive Impairment due to Suspected Non- Alzheimer’s Pathology (SNAP) Researchers at the University of Geneva are using advanced imaging and analysis techniques to investigate pathways to the development of neurodegenerative disease and its progression, as Dr Valentina Garibotto explains

29 HEALTHSCAPING We spoke to Professor Guy Geltner, Dr Janna Coomans, and Dr Claire Weeda about how the Healthscaping project challenges perceptions of public health provision in earlier eras

30 COVID 19 Pandemic The deadly strain of coronavirus now known as COVID 19 has taken its toll around the world, infecting thousands. In the desperation to undo the pandemic, innovation fights nature in an epic battle of science against disease, all across the globe. Richard Forsyth reports

34 NANOthermMA The NANOthermMA project aims to help researchers identify how materials can be engineered and nanostructured in order to improve thermoelectric performance, as Dr Neophytos Neophytou explains

37 RECEPT Researchers in the Recept project are probing the possibility of new physics beyond the standard model by testing a prediction called lepton universality, as Dr Vladimir Gligorov explains

40 NuclearWaters Nuclear energy is often thought of as a highly modern technology, yet it has much deeper historical roots than commonly imagined, building on the engineering knowledge accumulated by earlier societies, says Professor Per Högselius

42 PHOROSOL We spoke to Dr Conchi Ania about the work of the PHOROSOL project in investigating how metalfree nanoporous carbons can be modified to harvest light, which could open up wider possibilities in various fields

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EU Research Spring 2020

COVID 19

It’s impact on research and the search for a vaccine

44 COVID 19 Update Update regarding the terrifying spread of the COVID 19 Coronavirus pandemic across the globe

46 CHANGE PROCESSES OF

FORESTS AND AGRICULTURE

Forests not only provide ecosystem services, they’re also places where people live and work. Professor Adam Pain and his team are investigating smallholder practices and new forms of land governance

49 BLOODCELLSCROSSTALK Viral diseases threaten the health of fish and cause significant economic losses. We spoke to Dr Maria del Mar Ortega-Villaizan about her research into how rainbow trout respond to viral infections

50 EVOLUTIONARY

PHYSIOLOGY AND GENETICS Environmental changes, like increasing acidity in a pond, can strongly affect the long-term prospects of species. Dr Katja Räsänen aims to understand how natural populations adapt to environmental change

52 CoralAssist Dr James Guest and Dr Adriana Humanes of the CoralAssist project are investigating whether selective breeding and the AGF technique can help some coral reefs survive in the face of climate change

54 Sustainable Transport Targets We ask if the ambitious European Union goals for Sustainable Transport are realistic Richard Forsyth reports

58 LIDD With direct-democratic instruments being used more widely across Europe, it is becoming increasingly important to define their limits and scope, a topic that lies at the heart of Professor Daniel Moeckli’s research

60 NEPOSTRANS The Habsburg Empire collapsed at the end of the First World War, how did society change in this new context? This question is central to Dr Gábor Egry’s work in the Nepostrans project

62 DIVERSE-EXPECON While sometimes discrimination occurs because a decision-maker lacks sufficient information, in other situations it may be taste-based, an issue at the heart of Professor Sigrid Suetens’ research

64 EULER SYSTEMS Euler systems are very hard to construct, but they have very powerful arithmetic applications, such as proving new cases of the Bloch-Kato conjecture as well as the Birch and Swinnerton-Dyer conjecture, as Professor Sarah Zerbes explains

66 IMPACTS OF NEW BASEL III Professor Andreas Dietrich, together with Professor Gabrielle Wanzenried and other researchers, aims to assess the impact of the Basel III framework on the Swiss banking sector

70 SKILLNET Scholars and scientists in the early modern period corresponded extensively. We spoke to Dr Dirk van Miert about his work in reassembling these learned networks through digital analysis of correspondence from the period

72 INCLUSION

THROUGH LEARNING Group work is an important part of education. We spoke to Dr Nina Klang about her research into assessing the effectiveness of group learning in classes where there are students in need of additional support

New tests under Antarctica’s Doomsday Glacier

EU envisages close research relationship in draft UK BREXIT treaty

The future of Mobility: An in depth look at Sustainable Transport

Black hole discovery: Astronomers detect biggest bang since big bang

Disseminating the latest research from around Europe and Horizon 2020 Follow EU Research on www.twitter.com/EU_RESEARCH

EDITORIAL Managing Editor Richard Forsyth info@euresearcher.com Deputy Editor Patrick Truss patrick@euresearcher.com Deputy Editor Richard Davey rich@euresearcher.com Science Writer Holly Cave www.hollycave.co.uk Acquisitions Editor Elizabeth Sparks info@euresearcher.com PRODUCTION Production Manager Jenny O’Neill jenny@euresearcher.com Production Assistant Tim Smith info@euresearcher.com Art Director Daniel Hall design@euresearcher.com Design Manager David Patten design@euresearcher.com Illustrator Martin Carr mary@twocatsintheyard.co.uk PUBLISHING Managing Director Edward Taberner etaberner@euresearcher.com Scientific Director Dr Peter Taberner info@euresearcher.com Office Manager Janis Beazley info@euresearcher.com Finance Manager Adrian Hawthorne info@euresearcher.com Account Manager Jane Tareen jane@euresearcher.com

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RESEARCH

NEWS

The EU Research team take a look at current events in the scientific news

UK and European Universities demand to keep research links University leaders in the UK and Europe have signed a joint statement calling for UK universities to remain part of European research schemes post Brexit. As the UK leaves the European Union, 36 higher education groups have called for a “swift agreement” to allow UK universities to rejoin EU research networks and Erasmus student exchanges. The UK could pay to join these schemes as associate members. The CBI business group backed the statement, as did Universities UK. The statement, issued by representatives of university, research and science groups across Europe, says it would be of “clear mutual benefit” for UK universities to have “full association” with European research projects. In response, the Department for Business, Energy and Industrial Strategy, said it is “open to collaborating” in EU programmes, “if it’s in the UK’s interests”. Universities in the UK have been leading partners - and among the biggest financial beneficiaries - of research funded on a European basis, including major science projects. The next research round, Horizon Europe, will be worth about €100bn (£84bn) - but so far there have been no terms agreed on which UK universities can participate. Countries outside the EU can take part, but the cost and terms of membership have still to be negotiated. The British Universities Minister Chris Skidmore has said in the current round of EU research, UK institutions have taken about £5bn of the funding pot. The universities’ representatives want a deal to be reached by the end of the year on UK participation in research projects. They also want an agreement to allow the Erasmus student exchanges to continue. The statement, from UK and European university leaders, says it would be “good for all of us” if UK universities were able to “continue to work together” with their European counterparts.

Sir David Cannadine, president of the British Academy, has written to national academies across Europe to voice the academy’s support for “continued participation in European research programmes”. “We also know that to tackle the great challenges of the 21st Century, from climate change to the rise of artificial intelligence, academics will need to collaborate across disciplines and across borders,” said Sir David. Prime Minister Boris Johnson has rejected claims that UK students will not be able to take part in Erasmus. “There is no threat to the Erasmus scheme, and we will continue to participate in it. UK students will continue to be able to enjoy the benefits of exchanges with our European friends and partners,” he told the House of Commons last month. A spokesman for the Department for Business, Energy and Industrial Strategy said: “We are open to collaborating with the EU on science and research, including in certain EU programmes, if it’s in the UK’s interests, and consistent with our vision of the future relationship.” New president of the ERC Prof Mauro Ferrari said that science bodies on both sides of the Channel want close existing links to continue. He made his comments at the American Association for the Advancement of Science Meeting in Seattle. “I am very optimistic,” he said. “The stakes are so high. It is in everybody’s interest that a solution that is as good as the current one or better is found.” Although there is near universal agreement that Britain’s current close relationship with the ERC should continue, there is concern that it will become a bargaining chip in the current negotiations on what the UK-EU relationship will look like after the transition period ends on 31 December 2020.

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Astronomers discover ancient black hole blasting radiation toward Earth The universe may have been filled with supermassive black holes at the dawn of time. Nine hundred million years after the Big Bang, in the epoch of our universe’s earliest galaxies, there was already a black hole 1 billion times the size of our sun. That black hole sucked in huge quantities of ionized gas, forming a galactic engine — known as a blazar — that blasted a superhot jet of bright matter into space. On Earth, we can still detect the light from that explosion more than 12 billion years later.

discovering one blazar strongly suggests there were many others, the authors wrote. If only one blazar existed in this early phase of the universe, it would be an extraordinarily lucky break for it to have pointed its narrow, visible beam at Earth. It’s much more likely that there were many such blazars pointing in all sorts of directions, and that one of them happened to throw its light our way.

The University of Insubria used data from the Large Binocular Telescope (LBT) to discover the black hole, which is known as PSO J030947.49+271757.31. Like other supermassive black holes, this one is at the center of a distant galaxy. There are a few labels that can apply to objects like this. It’s an “active galactic nuclei” because the center is very bright across large swaths of the electromagnetic spectrum. This black hole is a specific class of active nuclei called a blazar. That distinction simply means that the beam of radiation pointed in the direction of the observer, which is all of us on Earth. An active galactic nuclei that isn’t aimed at the observer is known as a quasar.

These blazars, the authors wrote, were the seeds of the supermassive black holes that dominate the cores of large galaxies across our universe today — including Sagittarius A*, the relatively quiet supermassive black hole at the center of our Milky Way. “Observing a blazar is extremely important. For every discovered source of this type, we know that there must be 100 similar, but most are oriented differently, and are therefore too weak to be seen directly,” Belladitta said. That information helps astrophysicists reconstruct the story of how and when these monster black holes formed.

The spectrum of PSO J030947 was clearly indicative of a blazar when it appeared in the team’s data. However, the redshift came as a surprise. This object has a redshift value of 6.1, the largest ever observed for a black hole. That tells astronomers that PSO J030947 is about 13 billion light-years away. Therefore, it was out there firing a beam of radiation toward Earth less than a billion years after the big bang.

This black hole could be a boon for scientists interested in studying the early universe. The beams lancing out through space are a result of matter falling into the accretion disc around the black hole. The signals from blazars like PSO J030947 can carry information about the region of space they call home. According to the team, there could 100 other objects like PSO J030947, but they might all be quasars with beams pointed in different directions.

The discovery by Belladitta and her co-authors confirms that blazars existed during an epoch of our universe’s history known as “reionization” — a period after a long, post-Big Bang dark age when the first stars and galaxies began to form. And

The current study focuses on the black hole’s approximate age and location. Additional studies will have to determine how large it is and what the radiation can tell us about the universe 13 billion years ago.

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EU puts €45M into €90M public-private partnership for coronavirus vaccine research The European Commission has pledged €232M in total to help towards containing the coronavirus outbreak, as Italy becomes an infection hotspot. The EU is backing a new €90 million public private partnership to develop a vaccine against the COVID-19 coronavirus, as the epidemic spreads further in Europe. The commission announced the funding shortly after Italy reported a spike in confirmed cases of the infection. The money is on top of €10 million the commission announced at the end of January for research to help stop the spread of the disease. The emergency funding call is open for projects on epidemiology, diagnostics, therapeutics and clinical management of the infection. The €90 million will be channelled through the Innovative Medicines Initiative, a partnership between the EU and the pharmaceutical industry. “This includes €45 million of contribution from pharma companies,” said Janez Lenarčič, EU commissioner for crisis management and European emergency response coordinator. The virus is now quickly spreading through Europe. As of 24 February Italy has confirmed the death of five patients and at least 219 patients have tested positive for the virus. The Italian government has ordered the closure of certain public buildings in the northern region of Lombardia where most cases have been reported. People who may have been exposed to the virus

have been put under surveillance. “Our goal is to contain the outbreak at a global level,” Lenarčič said. The European Centre for Disease Prevention and Control (ECDC) says further global spread is likely. According to data compiled by ECDC, 79,360 cases of infection and 2,619 deaths have been reported around the world since 31 December 2019, most of which were in China. Most cases in Europe have been recorded in Italy. Of particular concern, very few of these cases have any link to travel to China. Patients in Belgium, France, Germany, Spain and the UK have also been infected with the virus, but in all these cases there is a link with China. “As cases continue to rise, public health is the number one priority,” said commission president Ursula von der Leyen. In addition to the research money, the commission is giving €114 million to the World Health Organisation (WHO) to support its global response plan, especially in countries with weak health systems and limited resilience. The commission will also spend €15 million on rapid diagnosis and epidemiological surveillance in Africa, through the Institute Pasteur Dakar in Senegal. An additional €3 million has been allocated for repatriation flights of EU citizens from Wuhan. The commission has sent a joint expert mission of the ECDC and WHO, to support Italian authorities, EU health commissioner Stella Kyriakides stated.

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Scientists discover first ‘animal’ that doesn’t breathe oxygen Israeli research accidentally discover bizarre cousin of jellyfish that has no ability to breathe. Researchers at Tel Aviv University (TAU) have discovered a non-oxygen breathing animal. The unexpected finding changes one of science’s assumptions about the animal world. A study on the finding was published on February 25 in PNAS by TAU researchers led by Prof. Dorothee Huchon of the School of Zoology at TAU’s Faculty of Life Sciences and Steinhardt Museum of Natural History. The tiny, less than 10-celled parasite Henneguya salminicola lives in salmon muscle. As it evolved, the animal, which is a myxozoan relative of jellyfish and corals, gave up breathing and consuming oxygen to produce energy. “Aerobic respiration was thought to be ubiquitous in animals, but now we confirmed that this is not the case,” Prof. Huchon explains. “Our discovery shows that evolution can go in strange directions. Aerobic respiration is a major source of energy, and yet we found an animal that gave up this critical pathway.” Some other organisms like fungi, amoebas or ciliate lineages in anaerobic environments have lost the ability to breathe over time. The new study demonstrates that the same can happen to an animal -- possibly because the parasite happens to live in an anaerobic environment. Its genome was sequenced, along with those of other myxozoan fish parasites, as part of research supported by the U.S.-Israel Binational Science Foundation and conducted with Prof. Paulyn Cartwright of the University of Kansas, and Prof. Jerri Bartholomew and Dr. Stephen Atkinson of Oregon State University. “It’s not yet clear to us how the parasite generates energy,”

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said Huchon. “It may be drawing it from the surrounding fish cells, or it may have a different type of respiration such as oxygen-free breathing, which typically characterizes anaerobic non-animal organisms.” A study on the finding was published February 24 in the journal PNAS. “It is generally thought that during evolution, organisms become more complex,” Huchon concluded. “But here is an animal whose evolutionary process is the opposite. Living in an oxygen-free environment, it has shed unnecessary genes responsible for aerobic respiration and become an even simpler organism.”

Light microscope image of spores of the parasitic cnidarian Henneguya salminicola, from Chinook salmon. Image courtesy of Prof. Stephen D. Atkinson/Oregon State University.

Caveman find could prove Neanderthals more sophisticated than thought The discovery of a 70,000-year-old skeleton has provided fresh evidence Neanderthals buried their dead and conducted funeral rites with flowers. The human ancestor - which died out 40,000 years ago - is thought to be a lot smarter than the world first thought. Archaeologists have unearthed a 70,000-yearold Neanderthal skeleton north of Baghdad, Iraq that they hope will prove that they were sophisticated to perform death rituals. The new specimen was uncovered at Shanidar Cave in Iraq and consists of the upper torso and crushed skull of a middle-aged to older adult. Excavations at Shanidar in the 1950s and 60s unearthed partial remains of 10 Neanderthal men, women and children. During these earlier excavations, archaeologists found that some of the burials were clustered together, with clumps of pollen surrounding one of the skeletons. The researcher who led those original investigations, Ralph Solecki from Columbia University in New York, claimed it was evidence that Neanderthals had buried their dead with flowers. This “flower burial” captured the imagination of the public and kicked off a decades-long controversy. The floral interpretation suggested our evolutionary relatives were capable of cultural sophistication, challenging the view - prevalent at the time - that Neanderthals were unintelligent and animalistic.

Other ongoing research can help determine the gender, but for now, the researchers believe it was a middle-aged adult, possibly older, based on his or her teeth. Shanidar Z’s location in the cave, when regarded along with four of the other Neanderthals found in close juxtaposition, create a “unique assemblage” that caused the researchers to wonder if they routinely returned to this location to bury their dead. A rather large triangular rock was also found prominently placed near the skull of Shanidar Z, likely as a grave marker. “So much research on how Neanderthals treated their dead has to involve returning to finds from 60 or even a 100 years ago, when archaeological techniques were more limited -- and that only ever gets you so far,” said Emma Pomeroy, lead study author at the University of Cambridge’s Department of Archaeology. “To have primary evidence of such quality from this famous Neanderthal site will allow us to use modern technologies to explore everything from ancient DNA to long-held questions about Neanderthal ways of death, and whether they were similar to our own.” A study including details about the Neanderthal, referred to as Shanidar Z, was published in February in the journal Antiquity.

Scientists drill into Antarctic ‘doomsday glacier’ to discover if it will collapse and flood the world ANTARCTICA researchers on the Thwaites Glacier have drilled more than 1,900ft into the frozen landmass to take the world’s first-ever pictures of the glacier’s seabed. Glaciologists have described Thwaites as the “most important” glacier in the world, the “riskiest” glacier, even the “doomsday” glacier. It is roughly the size of Great Britain. It already accounts for 4% of world sea level rise each year - a huge figure for a single glacier - and satellite data show that it is melting increasingly rapidly. There is enough water locked up in it to raise world sea level by more than half a metre. This huge chunk of frozen water was given its ominous apocalyptic nickname because of the risk it will break apart and dump so much freshwater into the ocean that sea levels rise by 65cm – more than two feet. If this disaster came to pass, it could render coastal and low-lying cities totally uninhabitable and cause chaos around the planet.

Keith Nicholls, an oceanographer from the British Antarctic Survey, said: “We know that warmer ocean waters are eroding many of West Antarctica’s glaciers, but we’re particularly concerned about Thwaites. “This new data will provide a new perspective of the processes taking place, so we can predict future change with more certainty.” On top of the seabed study, the Thwaites researchers drilled into the Antarctic glacier to collect ice core samples. The samples were taken from depths between 985ft and 2,300ft (300m and 700m). The researchers also took sediment samples from the seafloor under the glacier and carried out seismic and radar measurements. The results of their surveys are expected to fuel studies and research around the globe in the coming months and years.

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Three billion birds have disappeared from North America since 1970

Photo by Barth Bailey on Unsplash

The declining populations signal the existence of a long-developing yet largely overlooked biodiversity crisis, according to researchers. North America’s skies are lonelier and quieter as nearly three billion fewer wild birds soar in the air than in 1970, a comprehensive study shows. The new study focuses on the drop in sheer numbers of birds, not extinctions. The bird population in the United States and Canada was probably around 10.1 billion nearly half a century ago – and has fallen 29% to about 7.2 billion birds, according to a study in Thursday’s journal Science. “People need to pay attention to the birds around them because they are slowly disappearing,” said study lead author Kenneth Rosenberg, a Cornell University conservation scientist. The team’s calculations were based on bringing together all the bird monitoring in North America for the past 50 years - every major survey carried out across the continent since 1970. “What we saw was this pervasive net loss,” Dr Rosenberg said. “And we were pretty startled to see that the more common birds, the

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everyday backyard birds and generalist species, are suffering some of the biggest losses.” That same pattern, he added, is likely to be mirrored in other parts of the world. And the situation in Asia, as the other study has shown, is a particularly striking case of a human-driven extinction c Some of the most common and recognisable birds are taking the biggest hits, even though they are not near disappearing yet, Mr Rosenberg said. The common house sparrow was at the top of the list for losses, as were many other sparrows. The population of eastern meadowlarks has shrivelled by more than three-quarters with the western meadowlark nearly as hard hit. Bobwhite quail numbers are down 80%, Mr Rosenberg said. Grassland birds in general are less than half what they used to be, he said. Not all bird populations are shrinking. For example, bluebirds are increasing, mostly because people have worked hard to get their numbers up.

Searching for unknown signs of pancreatic cancer Very little progress has been made over the last 40 years in terms of diagnosing pancreatic cancer at an early stage, therefore the prognosis for patients is often poor. We spoke to Dr Daniel Globisch about his research into biomarkers associated with pancreatic cancer, which could eventually lead to earlier diagnosis of the disease. The statistics on

pancreatic cancer survival rates present a stark picture, with only about 30 percent of patients surviving the first year after an initial diagnosis. The limitations of current diagnostic techniques, which often detect pancreatic cancer relatively late, is one of the main reasons for this extremely low survival rate, as Dr Daniel Globisch explains. “There are only very rough diagnosis methods, which are based on assessing blood tests, CT scans, MRI scans or ultrasound scans. But the risk factor associated with this is very imprecise,” he says. “Another diagnostic option is a biopsy, which is highly invasive and is typically only performed at a relatively late stage of the disease, when it’s really clear from the symptoms that a patient is suffering from pancreatic cancer. However, when a patient reaches this stage with symptoms so strong that a biopsy is required, treatment options are limited.”

Diagnosing pancreatic cancer This underlines the importance of finding new biomarkers for pancreatic cancer, a topic that

Figure 1: A procedure using a chemoselective probe immobilized to magnetic beads has been developed to optimize mass spectrometric analysis of metabolites. (Garg et al. Angew. Chem. Int. Ed. 2018, 57, 13805; Conway et al. Chem. Comm. 2019, 55, 9080.)

lies at the heart of Dr Globisch’s research. Very little progress has been made in this area over the last 40 years or so, now Dr Globisch is exploring an approach based on analysis of the microbiome. “The microbiome is heavily

involved in human physiology. Disease development is evident through microbiome dysbiosis,” he explains. The microbiome itself is a topic of great interest to Dr Globisch. “With the microbiome, our bodies are populated by large communities of diverse microorganisms termed microbiota,” he continues. “This leads to the production of many unique molecules that humans cannot produce, which are then absorbed by the body. Some of these molecules have been associated with the development of different kinds of diseases.” The dysbiosis in the microbiome, which can be thought as a sort of imbalance, affects the microbial composition of the gut. A major aim in research is to identify metabolites produced by the microbiome in this context, that could eventually lead to the discovery of biomarkers for pancreatic cancer. “I see a huge potential to identify new biomarkers,” says Dr Globisch. Discovering new biomarkers is a highly complex task, but the metabolite level represents an effective starting point. “It could open up new diagnostic possibilities, with the goal of eventually

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replacing the current highly invasive biopsies,” outlines Dr Globisch. “Recent studies revealed an interaction between the microbiome and disease development. One major question remains if the microbiome dysbiosis drives the host into a disease state or the other way around?” There are many open questions here, and identifying a biomarker will provide a foundation for researchers to investigate them in greater depth. A lot of attention in research is focused on developing new tools to analyse samples, as Dr Globisch says existing techniques have some limitations. “Mass spectrometry is the most common method used in metabolomics research, where we try to identify as many molecules as possible in parallel, but certain factors limit the effectiveness of mass spectrometry,” he explains. New tools are required to obtain more information out of different types of samples (fig. 1). “In my laboratory, we have developed unique new chemical tools and work very closely with local hospitals to collect samples from patients,” says Dr Globisch. “This collaborative project brings together several experts from different areas of medicine, to help us select the samples we require for our analysis.”

will help ensure the project’s findings are highly rigorous, so providing a solid basis for Dr Globisch and his colleagues to assess whether a biomarker would be applicable to a larger population. “There may be differences in the microbiome, for example between individuals in southern and northern Europe as well as other continents,” he says. “So far, I think our results would not only be relevant for Sweden. I expect they would be more general in scope, but further work is required to validate this.”

Treatment effectiveness The primary aim of this project is to enable the earlier diagnosis of pancreatic cancer, however it could also hold wider relevance, for example in monitoring the effectiveness of treatment. Once a biomarker has been identified to help diagnose pancreatic cancer, then it could potentially also be used for prognostic purposes. “It’s important to know what the outcome of treatment is likely to be and if there is any potential for a relapse,” explains Dr Globisch. This could be a future avenue of investigation, but for the moment Dr Globisch says the priority is to find a biomarker that can be used in diagnosis. “This is a matter of

The microbiome is heavily involved in human physiology. Disease development is evident through microbiome dysbiosis. The wider goal here is to identify possible biomarkers of pancreatic cancer from these samples. While a biomarker could be a single molecule, Dr Globisch believes it is more likely to be a combination of different molecules. “A single molecule is very difficult to identify. In the future, diagnosis is more likely to be based on a metabolite pattern,” he says. Pancreatic cancer itself is a very complex disease, and it’s important to select the individual patient and control samples very carefully. “For example, we cannot compare a teenager with an elderly person, as we already know that they have a completely different microbiome. When we recruit control samples, we need to match them by age as well as other factors,” stresses Dr Globisch. “We will also compare early versus late stage to identify changes in metabolite levels.” A number of samples have been gathered so far in Sweden, and this work could eventually form the foundations of a wider study. If the initial results from the project are promising, and the biomarkers are validated, then researchers can look towards investigating a much larger cohort. “We will expand this study to analysis of patient samples from other countries,” outlines Dr Globisch. This

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identifying specific molecules, metabolites upregulated in the disease stage, it’s a bit like searching for a needle in a haystack. It’s very important that those molecules can be used for diagnostic purposes,” he continues. “There are many options here, for example certain antibody or SPR-based tests can be designed for efficient clinical analysis.” Researchers hope to improve the selectivity and analytical capabilities of the tools that have been developed in this project, which could in the future open up new possibilities to diagnose pancreatic cancer. Previously Dr Globisch discovered a biomarker for a disease called onchocerciasis, which has led to the development of a diagnostic test, now he hopes to achieve something similar with pancreatic cancer. “We developed a monoclonal antibody-based urinary lateral flow test, that will soon be tested in the field, with the goal of eventually replacing highly invasive tests,” he outlines. “That’s exactly what I want to achieve with pancreatic cancer, to identify molecules that can be used for precise diagnosis. A diagnostic test will then be developed, which could be based on fecal samples, plasma samples, or urine samples.”

INTESTINAL MICROBIOTA METABOLISM Intestinal microbiota metabolism biomarker discovery for pancreatic cancer Project Objectives

The projects are aiming at the discovery of biomarkers for pancreatic cancer and the link to gut microbiota metabolism. Biomarkers are crucial for the development of non-invasive diagnostics. To overcome limitations in the analysis of metabolites, we have developed methodologies at the interface of Chemistry and Biology for an advanced metabolomics analysis.

Project Funding

Funded by the Swedish Research Council and Science for Life Laboratory.

Project Partners

• Professor Matthias Löhr, Department for Digestive Diseases, Karolinska University Hospital • Professor Lars Engstrand, Center for Translational Microbiome Research (CTMR), Karolinska Institute

Contact Details

Project Coordinator, Dr Daniel Globisch Associate Professor Dept. Medicinal Chemistry Science for Life Laboratory Uppsala University / Sweden T: +46 (0)18-471-4287 E: Daniel.Globisch@scilifelab.uu.se W: http://www.ilk.uu.se/research-groups/ biomarker-discovery/ W: https://www.scilifelab.se/researchers/ daniel-globisch Dr Daniel Globisch

Dr Daniel Globisch received his PhD from Ludwig-Maximilians-University Munich (Germany) with Prof. Thomas Carell. For his postdoctoral studies he joined the laboratory of Prof. Kim D. Janda at The Scripps Research Institute (CA, USA). He started his independent laboratory in 2015 at Uppsala University (Sweden) and was appointed as Associate Professor in 2017.

Targeting iron addiction: Mechanism of action of salinomycin and its synthetic derivative ironomycin against persister cancer cells. This involves lysosomal iron targeting, production of reactive oxygen species (ROS) and cell death by ferroptosis.

A deeper picture of cancer biology Every individual case of cancer is different, and the chromatin structure inside a cell plays a major role in determining how patients respond to treatment. We spoke to Dr Raphael Rodriguez about his research into how patients respond to anti-cancer drugs, which could lay down the foundations for more personalised treatment in future.

The effectiveness of cancer treatment

Gene expression

can vary according to the physiology and genetic background of each individual patient, a topic of great interest to researchers. Based at the Institut Curie in Paris, Dr Raphael Rodriguez is a Research Director at the CNRS, a role in which he is probing deeper into cancer biology. “One of the major aims in our research is to better understand the molecular features of each patient, starting from their genetic and epigenetic features,” he outlines. The structure of chromatin, a component of eukaryotic cells, which is comprised of DNA and proteins, is an important consideration in that respect. “The DNA sequence is a major factor in the structure of chromatin,” explains Dr Rodriguez. “A second point is the histones, proteins around which DNA is wrapped. These histones can be chemically modified, and it is these modifications that essentially determine how the DNA is packed and whether it is accessible to other proteins.”

This helps to determine which genes are expressed or repressed and the defects that may be present in a cell, important considerations in terms of Dr Rodriguez’s wider research agenda. Some existing anticancer drugs target proteins that interact with DNA, or proteins that interact with chromatin, and the effectiveness of these approaches will depend to a degree on how chromatin is structured. “The response of individual patients will be different. This is what we are trying to understand,” says Dr Rodriguez. Cancer is often very heterogeneous in terms of cell types however, which adds another layer of complexity to Dr Rodriguez’s research. “We know that using one drug for a patient doesn’t work, because there are different types of cells and different types of defects,” he continues. “What we can do is try to identify the different types of cells and treat them with a combination of drugs.”

A major challenge here is to understand the heterogeneity of a particular cancer, which could then inform clinical decisionmaking and lead to improved outcomes for patients. Researchers in Dr Rodriguez’s group are using DNA sequencing to identify an individual’s genetic and epigenetic features, which will help clinicians choose the most effective drug for that particular patient. “That’s one aspect of what we are trying to achieve,” he explains. This research also holds relevance to understanding cancer resistance; for many years researchers struggled to identify the different types of cells in cancer, failing to recognise that some of the cells in a tumour do not divide as quickly as others. “That’s quite a natural thing to do in a way. When you use an antiproliferative drug and see that the tumour is shrinking then that’s a positive outcome,” points out Dr Rodriguez. “What you do not know is whether the remaining cells are dividing aggressively, and what’s going to happen when you stop this treatment.”

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Many cancers are or acquired the potential to become resistant, and ‘persister’ cancer cells are thought to be major actors underlying cancer relapse. Cancer stem cells are so named because they have some features and characteristics related to those that can be seen in stem cells, in particular the ability to self-renew and to seed new tumour tissues. “A single cancer stem cell or small group of these cells can generate an entire tumour from these cell, which is not the case with a normal cancer cell,” says Dr Rodriguez. It is thought that around 1-2 percent of the cells inside solid tumours exhibit these stem cell properties, which Dr Rodriguez says gives them the capacity to leave the site of a primary tumour and play a role in the development of a secondary tumour. “They can migrate and contribute to metastasis. This is something that normal cancer cells are not capable of doing,” he explains. “These cancer stem cells also do not typically divide as quickly as we would like them to.” A cancer cell’s identity is not fixed however and it can become a cancer stem cell, another topic of interest to Dr Rodriguez and his colleagues. Researchers are investigating how cells can shift between an epithelial, proliferative state, to a mesenchymal, less proliferative, but more migratory and invasive state. “Most

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of the migratory or invasive capacity of epithelial cells is reduced,” outlines Dr Rodriguez. During the course of their research, Dr Rodriguez and his colleagues have discovered that the transition between the epithelial and mesenchymal states is regulated by the presence of iron. “Iron is required to change the behaviour of cancer cells. We are looking at how metals can basically unlock the expression of certain genes involved in migration,” he continues. “We’re looking at the role of iron inside the nucleus of cells, at how it essentially unlocks the expression of genes involved in the mesenchymal state of cells.”

Iron uptake The next step beyond this could be to block the uptake of iron inside these cells, a possibility that Dr Rodriguez is exploring. When iron is in these cells it is transported via an organelle called the lysosome before eventually reaching the nucleus, a process that researchers are looking to disrupt. “We are developing new molecules that can block iron uptake and trafficking in cells. These molecules can interfere with translocation from the lysosome, such that the iron would no longer go to the nucleus and contributes instead to toxic oxidative stress, killing these cells through a mechanisms reminiscent to ferroptosis,” Cellular detection of lysosomal iron(II) in cancer cells.

Iron Lysosomes Cell Nucleus

Iron

Lysosomes

DRUG-SEQ Unravelling the Genomic Targets of Drugs Using High-Throughput Sequencing

Project Objectives

1. Defining where small molecules bind in genomes. 2. Defining the epigenetic alterations as a results of targeting lysosomal iron. Lysosomal iron targeting in persister cancer cells, regulation of iron endocytosis via CD44 and hyaluronic acids, iron-regulation of epigenome in cancer.

Project Funding

(Total funding over € 4.5M). ERC consolidator, Labellisation Ligue Contre le Cancer, Fondation Charles Defforey, Emergence Ville de Paris, FRM, National Health & Medical Research Council of Australia.

Project Partners

• Kyle Miller • Emmanuelle Charafe-Jauffret • Christophe Ginestier • Mark Dawson

Contact Details

Raphaël Rodriguez, Ph.D., FRSC Research Director at the CNRS Head of Chemical Biology of Cancer CNRS UMR3666 - INSERM U1143 Institut Curie 26 rue d’Ulm Pav. Trouillet 75005 Paris France T: +33 648 482 191 E: raphael.rodriguez@curie.fr W: https://science.institut-curie.org/team-rodriguez CD44 regulates epigenetic plasticity by mediating iron endocytosis. Sebastian Müller, Fabien Sindikubwabo, Tatiana Cañeque, Anne Lafon, Antoine Versini, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Bérangère Lombard, Damarys Loew, Ting-Di Wu, Adeline Durand, Céline Vallot, Sylvain Baulande, Nicolas Servant, Raphaël Rodriguez*. bioRi doi: https://doi.org/10.1101/693424. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. T. T. Mai, A. Hamaï, A. Hienzsch, T. Cañeque, S. Müller, J. Wicinski, O. Cabaud, C. Leroy, A. David, V. Acevedo, A. Ryo, C. Ginestier, D. Birnbaum, E. Charafe-Jauffret, P. Codogno, M. Mehrpour*, R. Rodriguez* Nature Chem. 9, 1025-1033 (2017). Highlighted in CEN.

says Dr Rodriguez. This work builds on the discovery their in-house small molecule called ironomycin alters gene expression profile by targeting lysosomal iron. “When we discovered that ironomycin and the parental natural product salinomycin were selectively killing cancer stem cells by targeting iron, we hypothesised that these cells contained more iron,” explains Dr Rodriguez. “It seemed that these cells, in order to stay in a stem state, needed more iron. We did indeed find that they had an increased iron load.”

epigenetic marks that are affected by iron, valuable information in the context of the search for more personalised forms of cancer treatment. This would be complemented by drugs that are more specific to each patient, recognising that each individual case is different. The development of new drugs and therapies forms a major part of Dr Rodriguez’s research agenda. “We work at the crossroads of chemistry and biology and we are seeking to develop effective drugs. We are in close contact with basic

“We work at the crossroads of chemistry and biology and we are seeking to develop effective drugs. We are in close contact with medical doctors here at Institut Curie. We have developed new drug-like molecules, to target the iron metabolism in cancer.” A major goal here is to understand how these cells use iron in order to maintain their stem cell properties. Researchers used a combination of techniques, including quantitative proteomics, quantitative metabolomics, next generation DNA sequencing, and next generation RNA sequencing to look at these cells in great depth, and Dr Rodriguez says this work has yielded some new insights. “We were able to highlight a few proteins that use iron to produce particular metabolites that lead to the depletion of some histone markers that regulate the shape of chromatin,” he outlines. The aim is to identify the

research scientists and medical doctors here at Institut Curie. We have developed new drug-like molecules, to target iron metabolism in cancer,” he says. A biotech company has been established to look into bringing these new drugs to the clinic, yet Dr Rodriguez is keen to stress that he will continue with more exploratory research into fundamental mechanisms in cancer chemistry and biology in future. “Academic research is very important because we generate knowledge that has intrinsic value in its own sense. Alongside that we are also developing new compounds,” he continues.

Raphaël Rodriguez

Raphaël Rodriguez is the Marie Curie Chair of Chemical Biology at the Institute Curie, where he holds a Senior Principal Investigator Position. He gained his PhD training from the University of Marseille (France) and Oxford (UK), where he completed the total synthesis of complex natural products. He is the first French citizen to receive the prestigious Tetrahedron Young Investigator Award and is the Cofounder of the biotech company SideROS.

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Defective ribonucleoprotein (RNP) granules are thought to be a major factor in the development of amyotrophic lateral sclerosis (ALS) and other forms of neurodegenerative disease, while they are also associated with a number of other conditions. We spoke to Professor Simon Alberti about his work in investigating how these granules form and how they cause disease. Molecular aging of a prion-like RNA-binding protein from a liquid to a solid, aggregated state.

How do RNP granules cause disease? The aggregation of mis-folded proteins in the body is known to be a major factor in the development of certain neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). While younger people are able to essentially clear these mis-folded proteins, this ability declines as we age, which can eventually lead to serious health problems. “The protein quality control (PQC) machinery controls the status of these proteins and keeps them in check. We think that starts to fail as people age,” explains Simon Alberti, Professor of Cellular Biochemistry at TU Dresden. As the Principal Investigator of the PhaseAge project, Professor Alberti is investigating the factors behind this gradual loss of function, looking in particular at the role of ribonucleoprotein (RNP) granules. “These RNP granules are considered to be membraneless organelles as they contain a lot of different factors, such as proteins and RNAs, and they have no membranes around them.” he says.

Many different conditions are associated with defective RNP granules, including not just neurodegenerative diseases, but also a number of other disorders, underlining the wider importance of Professor Alberti’s research. These RNP granules become defective when they undergo a transition from a liquid-like state into an aberrant, more solid state. “The important point with this transition is that the dynamics change. The proteins are essentially trapped inside, and there’s little exchange with the outside,” outlines Professor Alberti. The wider aim of his research is to understand the molecular mechanism behind both the formation of these RNP granules and their transition into an aberrant state. “We want to understand the molecular principles of how these granules form, and how they turn into something that can cause disease. And, most importantly, can we then find factors that can prevent these transitions?” says Professor Alberti.

RNP granules The first step towards this wider goal is to understand how these RNP granules are initially formed inside a cell, with researchers looking at the role of proteins in this process. It is thought that initially RNA-binding proteins and other factors assemble into these membraneless organelles, or RNP granules, within a cell. “At first the properties are maintained, but as we age, we lose the ability to control the material properties of these structures,” says Professor Alberti. By analysing single cells, Professor Alberti and his colleagues hope to gain deeper insights into how these RNP granules are formed, how they age, and how this may affect disease development. “We are looking at healthy cells, while we also mimic ageing in cells. Essentially, we stress the cells, as we know that ageing very often increases stress,” he outlines. “We also purify RNA-binding proteins, then using these proteins we try to put together these structures that normally we only see in cells.”

Liquid-like properties of RNP granules.

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This approach allows researchers to investigate the underlying factors which may affect the formation and overall development of RNP granules. These RNP granules contain information, messenger RNAs that are read in neurons. “Neurons have very complex morphologies. RNP granules are frequently found in neurons, so neurons are very vulnerable to the problems that can arise with these RNP granules,” explains Professor Alberti. Researchers now have the ability to build RNP granules in a test tube, based on the principle of phase separation, a recently described process which is thought to play a major role in the formation of membraneless organelles. “Phase separation is really a new phenomenon that was only described a couple of years ago,” continues Professor Alberti. “Previously we didn’t really understand how large membraneless organelles formed, we didn’t have a concept of how this could work.” A membraneless organelle is thought to be formed through a physical process that can be loosely compared to mixing oil and vinegar. When mixed, oil and vinegar will separate, and Professor Alberti believes that biomolecules work in a similar way in the formation of a membraneless organelle. “That’s how a membraneless organelle is formed. Phase separation is an increasingly important concept in cell biology, and it’s the focus of a lot of attention in research,” he

says. It is now possible to build RNP granules in the test tube, based on this principle of phase separation, from which researchers hope to gain deeper insights which could open up further avenues of investigation. “We’re pretty good at forming these RNP granules. The next step is to look at the transition from these liquid-like, physiological states, to these aberrant, more solid-like states, and

Cajal Bodies

Stress Granules

results have been gained. “We have found a few proteins that completely prevent these modifications when you add them to a liquid reconstituted system. So they keep these granules in a liquid state,” outlines Professor Alberti. “It could be interesting to target these with a drug and maybe up-regulate them, as they seem to prevent the transition into an aberrant state.”

We want to understand the molecular principles of how these granules form, and how they turn into something that can cause disease. Can we then find factors that can prevent these transitions? we’ve achieved this already to some degree,” explains Professor Alberti Researchers have identified several important protein components during the course of this work, and are also looking at the possibility of preventing the formation of these aberrant, solid-like states. One part of this work involves looking for drugs that would dissolve these membraneless organelles, and Professor Alberti says there have been some promising results in this area. “We have found a few interesting drug candidates,” he says. Another part of the project’s research centres on investigating candidate proteins and the PQC machinery, and again some interesting

PCQ machinery The aim with a drug would be to essentially enhance the PQC machinery and strengthen it in some way, so as to prevent the formation of defective RNP granules. It is therefore important to identify the components of the PQC machinery, which is a major priority in Professor Alberti’s research. “The PQC machinery is a large system, it has many components. We’re trying to figure out which of those components are important for the control of RNP granules, then in future we can look to strengthen them,” he explains. While this is an exciting prospect, opening up the possibility of improved treatment of neurodegenerative

P Bodies

EU Research

PhaseAge The chemistry and physics of RNP granules: how they form, age and cause disease

Project Objectives

Many debilitating age-related diseases affect the nervous system but the molecular causes of these diseases have remained largely unknown. In recent years, deficiencies in RNA metabolism mediated by RNA-binding proteins (RBPs) have come into the focus. In PhaseAge, researchers; • Investigate the molecular mechanisms of RNP granule formation • Study the molecular events that lead to aberrant RNPs, focusing on disease-associated mutations, changes in environmental conditions, post-translational modifications and molecules with fluidizing or solidifying effects • Define the mechanisms of RNP granule quality control, which prevent aberrant phase transitions or reverse RNP granule aggregates to their normal state

disease, the focus in research at this stage is more on understanding the basic mechanisms involved in the formation of defective RNP granules. “The molecular mechanisms behind the formation of these structures and how they become defective has not yet been described,” says Professor Alberti. This remains the focus of attention in research, yet Professor Alberti is also aware of the wider picture beyond the project’s immediate agenda. Defective RNP granules are associated with a wide variety of conditions, including schizophrenia, autism and many other examples. “Many different brain and developmental diseases are associated with defective RNP granules,” stresses Professor Alberti. Evidence from the brains of patients with ALS shows that changes in RNP granule properties are an important consideration in terms of the development and progression of these diseases. “We often see these RNAcontaining aggregates in stressed neurons, or clumps of protein and RNAs. We also find a certain set of proteins clumped in diseased cells,” continues Professor Alberti. “These proteins stick together and adopt abnormal structures. These structures are very difficult to dispose of – they could be toxic and eventually kill the cell.” With evidence mounting of the involvement of RNP granules in different types of disease, Professor Alberti is keen to continue his

work in this direction. “I’m in touch with many other researchers, as I think there is a lot of potential to look at other diseases, to investigate what’s happening there and what’s going on,” he says. “Can we then again identify the key factors? Will it be possible to identify targets for therapeutics later on?”

PML Bodies

Nucleoli

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Project Funding

Funded by an ERC Consolidator Grant (PhaseAge) and JPND (CureALS)

Project Partners

• Anthony Hyman MPI-CBG Dresden • Jared Sterneckert CRTD Dresden • Rohit Pappu and Alex Holehouse Washington University, USA) • Serena Carra, University of Modena

Contact Details

Simon Alberti Professor of Cellular Biochemistry Technische Universität Dresden Center for Molecular and Cellular Bioengineering (CMCB) Biotechnology Center (BIOTEC) Tatzberg 47/49, 01307 Dresden, Germany T: +49 351 46340236 E: Simon.Alberti@tu-dresden.de W: http://www.biotec.tu-dresden.de/ research/alberti.html Alberti S, Dormann D (2019). Liquid-liquid phase separation in disease (2019). Annual Reviews in Genetics, doi: 10.1146/annurev-genet-112618-043527. Alberti S, Gladfelter A, Mittag T (2019). Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates. Cell, 176(3):419-434. doi: 10.1016/j.cell.2018.12.035.

Professor Simon Alberti

Simon Alberti is a Professor of Cellular Biochemistry at BIOTEC, Technische Universität Dresden in Germany. He received his PhD in Cell Biology from the University of Bonn in 2004 and has since held research positions in Europe and America. His recent work shows that cells form many membraneless compartments via a biophysical process known as phase separation.

Behind pyroptotic cell death A pro-inflammatory form of programmed cell death, pyroptosis causes cells to expand and eventually burst, releasing content that then causes inflammation. We spoke to Professor Petr Broz about the work of the InflamCellDeath project in investigating the basis of pyroptotic cell death and its wider impact. A form of

programmed cell death first reported around 20 years ago, pyroptosis differs significantly from the more wellknown process of apoptosis. While apoptosis is a non-inflammatory, immunologically silent form of cell death, pyroptosis is proinflammatory. “A pyroptotic cell enlarges and balloons until it explodes. This releases cytokines and so-called danger signals that cause inflammation in the tissue,” explains Professor Petr Broz. As the Principal Investigator of the InflamCellDeath project, Professor Broz is analysing the underlying basis of pyroptotic cell death. “We know that pyroptosis is caused by a type of protein called gasdermin D, which is a pore-forming protein,” he outlines. “This protein is activated by proteolytic cleavage, by proteases. It’s believed that the N terminal part of the protein is cleaved from the C-terminal part, which is the regulatory, inhibitory domain.”

Membrane pores The N-terminus then targets the plasma membrane, where it forms huge pores. These pores allow the uncontrolled influx of water into the cell, which eventually leads to the death of the cell. “This influx of water results in the swelling and rupture of the cell, and eventually the release of inflammatory content,” says Professor Broz.

This form of programmed cell death normally occurs during infection. “Pyroptosis is the outcome of a signalling cascade known as the inflammasome pathway. A pattern recognition receptor recognises pathogenderived molecules, and assembles a signalling platform known as the inflammasome,” explains Professor Broz. “A protein called caspase 1 activates gasdermin D to kill off the cell, so that the pathogen can’t replicate anymore. It will also cause inflammation, so that other immune cells converge on the site of infection.”

says there is a lot of interest in the idea from the pharmaceutical sector. “Could we develop an inhibitor that would prevent the pore from forming and prevent the inflammation?” he asks. “This is a very interesting area for pharmaceutical companies.” There is a lot of interest in particular in the NLRP3 inflammasome, which is an important component of the innate immune system. Activation of the NLRP3 inflammasome is associated with several inflammatory disorders, and gasdermin D has been identified as an important target for therapeutic

A pyroptotic cell enlarges and balloons until it explodes. This releases cytokines that cause inflammation in the tissue. This can be very beneficial in terms of clearing a pathogen, yet an excessive inflammatory response in itself can damage healthy tissue. In some cases the inflammasome complex assembles even without an infection, due for example to a certain mutation, which may then be a factor in the development of auto-inflammatory disease. “Where the inflammasome pathway activates, you get caspase 1 activation and inflammation,” outlines Professor Broz. Blocking the gasdermin D protein could be an effective therapeutic strategy in this respect, and Professor Broz

development. “By better understanding the gasdermin D protein, we hope to eventually help develop inhibitors and assess whether, by blocking the gasdermin D protein, we can prevent inflammation in those types of diseases,” says Professor Broz. The project is largely exploratory at this stage however, with researchers aiming to define, in vivo, the role of gasdermin D in the inflammasomedependent bacterial host defence. “We hope to provide more insights into the gasdermin D protein, and to pinpoint where it is important,” continues Professor Broz.

Pyroptosis

Apoptosis

Time-lapse microscopy images showing a cell dying by apoptosis (upper row) and pyroptosis (lower row).

EU Research

InflamCellDeath Mechanism and function of gasdermininduced inflammatory cell death Project Objectives

The objectives of InflamCellDeath is to characterize pyroptosis, a regulated form of necrotic and highly pro-inflammatory cell death that is induced in response to infections or cell stress. The aim is to understand how gasdermin family members, the executors of pyroptosis, are activated and regulated, and how pyroptotic cell death contributes to pathogen clearance and immune defense

Project Funding

Funded by an European Research Council Consolidator Grant.

Contact Details

Atomic force microscopy (AFM) images of Gasdermin D pores.

Gasdermin D pore formation A further strand of the project’s research centres around investigating how the gasdermin D protein is regulated and activated. This work is central to understanding how pores are formed in a cell membrane during pyroptosis. “We have found that there are two phases of gasdermin pore formation. There is an initial phase where the gasdermin pores are formed in the plasma membrane, but the cell doesn’t die. Still, the gasdermin proteins function to release cytokines through the pores – so the pores themselves serve as a release mechanism of cytokines. It is only later on, once too many pores have accumulated around the plasma membrane, that the cell eventually dies,” says Professor Broz. “Not all cells die after the activation of caspase 1.” The gasdermin D protein is the focus of a lot of attention in research, yet it is just one of a family of six, and Professor Broz is keen to learn more about the other members as well. These proteins are among the most cytotoxic substances that cells are known to make, yet relatively little is known about their function and how they are regulated. “We don’t really know much about the conditions under which these highly efficient cell killers are activated. What’s their function? In which diseases would we need to inhibit them?” says Professor Broz. These types of questions will form an important part of Professor Broz’s research agenda in future. “We are trying to identify the function of the other gasdermin family members,” he continues. “We know that

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all of these gasdermins have the ability to cause pyroptotic cell death.” Research suggests that gasdermin E plays an important role in the innate immune defence against cancer, as a proinflammatory form of cell death could result in an immune reaction against the disease. However, less is currently known about the other family members. “We don’t know whether they function in infection, or what their biological function is,” says Professor Broz. It has been established that these proteins are specifically expressed in the skin and the gut, but there is much that remains unclear. “It’s known that if these proteins get activated they can cause very strong inflammation, but currently we don’t know the signal,” explains Professor Broz. “Mutations have been identified that cause the activation of these proteins, so they can get activated without a signal. This causes very strong inflammation in the skin, leading to alopecia.” This research into other members of the wider gasdermin family will be combined with continued investigation into gasdermin D. With the project set to enter the third year of its funding term, Professor Broz and his colleagues are working towards some ambitious objectives. “By the end of the project we hope to have identified how the gasdermin D protein is regulated on a posttranslational level, and how pore formation is regulated,” he outlines. “We also aim to identify novel functions for gasdermin D in inflammatory diseases in general, and to identify an inhibitor of the protein.”

Project Coordinator, Petr Broz, Ph.D., Associate Professor Department of Biochemistry University of Lausanne Chemin des Boveresses 155 CH-1066 Epalinges Switzerland T: +41 (0)21 692 5656 E: petr.broz@unil.ch W: https://cordis.europa.eu/project/ id/770988 Rühl S., Shkarina K., Demarco B., Heilig R., Santos J.C. and Broz P. ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation. Science, 362 (6417) pp. 956-960 (2018) Santos J.C., Dick M.S., Lagrange B., Degrandi D., Pfeffer K., Yamamoto M., Meunier E., Pelczar P., Henry T. and Broz P. LPS targets host guanylate-binding proteins to the bacterial outer membrane for non-canonical inflammasome activation. The EMBO journal, 37 (6) pp. 1-19 (2018) Chen K.W., Demarco B., Heilig R., Shkarina K., Boettcher A., Farady C.J., Pelczar P. and Broz P. Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly. The EMBO Journal, 38 (10) (2019). Broz P., Pelegrín P. and Shao F. The gasdermins, a protein family executing cell death and inflammation. Nature Reviews Immunology 2019 Nov 5.

Professor Petr Broz

Professor Petr Broz is an Associate Professor in the Department of Biochemistry at the University of Lausanne, Switzerland. He has previously worked in Europe and the United States, including post-doctoral training at Stanford University. His current research focuses on host defense mechanisms, inflammasomes and the induction of pyroptosis, a lytic inflammatory cell death.

Diving deeper into protein function The High Temperature Requirement A (HtrA) family of proteins plays an important role in protein quality control, and loss of function is directly associated with several serious diseases. We spoke to Dr Björn Burmann about his research into how these proteases work on the molecular level, which could lay the foundations for further exploitations of these proteases in the future. The HtrA family of proteins are thought

HtrA proteases

to play a significant role in the development and progression of several different diseases. Experimental evidence suggests that loss of proteolytic activity is a key factor in certain types of cancer, as well as some neurodegenerative conditions. As an Assistant Professor at the Wallenberg Centre for Molecular and Translational Medicine, Dr Björn Burmann aims to dive deeper into the structure and function of these proteins. “In my lab we are looking in detail into how they actually work on the molecular level,” he outlines. There are four of these proteins in humans within the HtrA (high temperature requirement A) family, and they function as proteases, helping to break down or cleave proteins and aggregates. “One of the main functions of proteases is to kind of chop down proteins, to degrade them,” explains Dr Burmann.

There is still much to learn about these HtrA proteases however, in particular how their function is modulated by interactions with aggregated proteins, a topic central to Dr Burmann’s research. One part of this work involves using nuclear magnetic resonance (NMR) spectroscopy in solution to gain deeper insights into these proteases. “We do a lot of biochemistry and use other biophysical analysis techniques to study protein interactions and their consequences. In order to get information on the atomic level about these proteins as well as structural and dynamical changes, we need to use NMR,” outlines Dr Burmann. This is a structural biology technique allowing Dr Burmann and his colleagues to analyse proteases in great depth. “We can look at the proximity of amino-acids in a 3-dimensional structure for example. With NMR we get a picture of how a protein behaves in solution,” he says.

A number of other techniques are also being utilised in research, including X-ray crystallography and cryo-electron microscopy. These techniques are highly complementary to NMR spectroscopy, says Dr Burmann. “We’re making use of these different techniques, combining them in the most convenient way possible to answer biological questions,” he outlines. A lot of attention in Dr Burmann’s group is focused on the HtrA2 protease in particular, which is involved in triggering apoptosis, the controlled cell death program. “HtrA2 resides in the membrane of mitochondria. The signal which leads to the initial cleavage and which effectively activates this protein is unknown,” he explains. “On a cartoon level, it is known that HtrA2 has to be effectively detached from this membrane through protein cleavage.” Preparing E. coli cultures to express recombinant HtrA2.

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STUDIES OF THE FUNCTION Putting an HtrA2-sample into an NMR spectrometer.

Studies of the function of HtrA protease at atomic level by NMR spectroscope Project Objectives

The overall aim of the study is the determination of the structural and dynamical properties of the oligomeric human mitochondrial HtrA2–protease, its structural adaptions upon maturation, the structural basis of substrate recognition, and elucidating its role in apoptosis and neurodegenerative diseases.

Project Funding

This project is funded by the Swedish Research Council (Vetenskaprådet 2016-04721).

Contact Details This apoptosis function needs to be tightly regulated, as dysfunction can eventually lead to serious health problems. However, the underlying mechanisms behind how HtrA2 is regulated in the body are not yet well understood. “First there is protein cleavage, then HtrA2 is further activated by phosphorylation. But we’re missing a lot of details about how this activation actually happens and the individual steps involved,” says Dr Burmann. One possibility is that there is a kind of stress signal in mitochondria, which then triggers further events. “It looks like it’s a multi-step process, but our knowledge is fairly limited at this point. There might also be alternative activation mechanisms,” continues Dr Burmann.

Researchers are also looking at how the HtrA2 protein interacts with several known partners, including the α-synuclein protein, which is associated with Parkinson’s disease. A deeper understanding of the structure and function of these proteins could help lay the foundations for future drug development, believes Dr Burmann. “We hope to contribute important new information, which down the road might lead to the identification of small molecule effectors,” he explains. However, the main focus in research at this stage is on understanding the fundamental behaviour of these proteins. “We are now starting to look into how it recognises its substrates, and how it does the job of proteolytic cleavage,” continues Dr Burmann.

NMR we get a detailed picture of how the protein behaves in solution. We are now starting to look into how it recognises its substrates, and how it does the job of proteolytic cleavage.

Project Coordinator, Dr. Björn Burmann, Assistant Professor Department of Chemistry and Molecular Biology Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg P.O. Box 462 SE-405 30 Gothenburg T: +46 31 786 3937 E: bjorn.marcus.burmann@gu.se W: www.wcmtm.gu.se/research-groups/burmann

The Swedish NMR Centre of the University of Gothenburg is acknowledged for spectrometer time.

With solution

By using solution NMR and other structural biology techniques to study proteases, together with biophysical methods, Dr Burmann and his colleagues hope to shed new light in this area. NMR provides very rich information about structure and dynamical changes in solutions, from which researchers can then look to gain deeper functional insights. “We can put the protein in a test tube and study it in a timedependent manner, over different timescales. Then we can look at things like how does phosphorylation occur? Over what time period does phosphorylation occur in vitro?” he outlines. Phosphorylation is a form of chemical modification of the protein, where a phosphor group is added to the protein. “We are trying to understand what phosphorylation does to the behaviour or functionality of HtrA,” explains Dr Burmann.

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The next step beyond this point will be to develop an experimentally-driven model of how the protein works on the atomic level. This would potentially enable researchers to predict how the protein would react to the presence of different substrates, invaluable information in terms of future drug development. “We could offer suggestions, so that we understand what that protein does upon recognising the substrate, and how it then goes on to cleave it. What parts of the protein are important for this?” outlines Dr Burmann. Once researchers understand how these proteins work, they can then look towards manipulating them in certain ways to improve therapeutic outcomes. “The longterm goal would be to understand how these proteins work and what goes wrong when they don’t function properly,” says Dr Burmann.

Dr Björn Burmann

Dr Björn Burmann is Associate Senior Lecturer in Chemistry at the Wallenberg Centre for Molecular and Translational Medicine, part of the University of Gothenburg. He investigates macromolecular protein machines which underly essential cellular functions using high resolution NMR. He aims to elucidate the function of these machines at the atomic level, in order to understand their dysfunction in certain diseases.

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Putting a stop to leg clots Deep vein thrombosis is a major concern for health authorities, and a lot of attention is focused on prevention in patients at risk of developing blood clots in the leg. Intermittent pneumatic compression (IPC) therapy could offer an effective, cost-efficient method of prevention, a topic at the heart of Doctor Paul Ackermann’s research. Many

patients have their legs immobilized after surgery, which affects blood circulation and increases the risk of a blood clot in the limb, known as venous thromboembolism or deep vein thrombosis (DVT). While low molecular weight heparins are available to minimize the risk of DVT, they are not always effective in patients whose lower limbs have been immobilized. “Low molecular weight heparins are often given as a subcutaneous injection in the stomach, then distributed throughout the body via the blood circulation. However, when the blood circulation in the lower limbs is limited, for example during immobilization, patients don’t receive the optimal prophylactic effect from the treatment” explains Doctor Paul Ackermann, a Lecturer and Senior Physician at the Karolinska Institute and Karolinska University Hospital, Stockholm. Preventing leg blood clots is a major health priority; Dr Ackermann and his colleagues are now assessing the effectiveness of an alternative approach called intermittent pneumatic compression (IPC) therapy, based on a device

Mechanisms of action of IPC applied to the calf. Increased venous return Increased arterial circulation Improved oedema reduction Increased chemical bloodcloth prophylaxis

has to be persistent in using the treatment during that time. This is one of the main challenges in this study, to get the patients to use the device consistently” says Dr Ackermann. Beyond preventing blood clots in people recovering after surgery or injury, this treatment could also be used to improve health; “The treatment could be beneficial for people who live a sedentary lifestyle which includes prolonged sitting. It’s logical to think that these individuals might have low blood

The IPC treatment could be beneficial for people who live a sedentary lifestyle which includes prolonged sitting. It’s logical to think that these individuals might have low blood circulation in their limbs. which squeezes the calf muscles to increase the blood flow. “IPC is a mechanical therapy designed to address the blood stasis problem, when blood flow in the limb is low, such as during leg immobilization” he outlines. This treatment is commonly used today in hospitals immediately after surgery in patients who are at high risk of forming blood clots in the leg. Dr Ackermann aims to study its effectiveness as a home-based therapy in a group of 1,400 patients in a clinical, randomized trial of orthopaedic patients with lower limb injuries requiring leg immobilization. The IPC treatment, which is performed when the patient is in a sedentary position - i.e. sitting or lying down - has to be continued during the whole time that a patient’s leg is immobilized, which could be up to 8 weeks in some cases. “The patient

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circulation in their limbs, and that more profound circulation would be beneficial” Dr Ackermann points out. “The treatment could also be used for other patient groups. We have in this study chosen to investigate patients which we know are at high risk of developing a blood clot.” The cost-efficiency of the IPC approach is another important consideration in Dr Ackermann’s research. With budgets under strain, health authorities are keen to use resources efficiently, a context in which the IPC treatment takes on clear importance. “Patients borrow the machine which produces the intermittent compression. It is very costefficient in comparison to pharmacological prophylaxis,” explains Dr Ackermann. Researchers are currently studying the effectiveness of the treatment on a large

cohort of patients, which will provide the foundations for a more detailed cost-efficiency analysis in future. “We’ve looked at around 100-150 patients so far in this study, and we’re planning to include around 1,400 patients overall,” continues Dr Ackermann. “We are looking to heighten awareness among people. When people are more aware of the problem of blood clots in the leg, we can start to include more patients to assist with this very big and important project.”

StopLegClots Swedish multicenter Trial of Outpatient Prevention of Leg Clots The study is funded by the Swedish Research Council nr: 2017-00202. Supported by the Swedish Orthopedic Traumatology Society (SOTS). Associate Professor Paul Ackermann M.D, Ph.D. Specialist in Orthopaedic Surgery Orthopaedic Department Karolinska University Hospital SE-17176 Stockholm SWEDEN T: +46 8 517 700 00 E: paul.ackermann@ki.se W: https://ki.se/mmk/stopleg-clots Dr. P.W. Ackermann is the Head of the Integrative Orthopedic Research Group, focusing his research on neuro-vascular regulation of venous thromboembolism, pain and musculoskeletal tissue repair in collaboration with a global network of researchers.

Extracellular vesicle production Microvesicles 100-1000nm

Exosomes 40-100nm

Extracellular vesicle subpopulation separation Organelles

Early endosome Secretion vesicles

Golgi Stress signals thrombin DNA damage intracellular calcium extracellular ATP LPS hypoxia

Apoptic bodies 1-5μm

Uptake pathways

Extracellular vesicle engineering

Reporter systems

A kick-start for the damaged heart Over 3.5 million people are diagnosed with heart failure in Europe every year, and their long-term prognosis is poor. Researchers in the Evicare project are developing an innovative therapy that could help to stimulate the repair of cardiac tissue and change the course of heart disease, as Professor Joost Sluijter explains. A number of

measures are commonly used to treat heart disease, such as lifestyle changes and certain medications like betablockers and ACE inhibitors, yet these typically only slow the progression of the disease. With heart failure the most common cause of death across the world, there is a clear need for effective new therapies, a topic at the heart of the Evicare project’s work. “We are looking into manipulating the response of the heart to injury, helping it to repair itself, so that we can essentially prevent heart failure,” outlines Professor Sluijter, the project’s Principal Investigator. This work centres on using stem-cell derived extracellular vesicles, containing nature’s own biological materials, to help repair the damaged organ. “One part of our research involves looking at the mechanisms of how this works. If you add the vesicles into the damaged organ, how does it help the repair mechanisms? Which cell types are targeted and which processes are affected?” explains Professor Sluijter.

Extracellular vesicles The aim here is to stimulate endogenous mechanisms in the heart using extracellular vesicles, which typically contain a mixture

of proteins and different RNA species. These vesicles, which are derived from stem cells or made of synthetic materials, or a hybrid of the two, are being studied within the project on essentially three levels. “One part involves looking at the vesicle itself. We are looking to characterise the vesicles on the RNA and protein level, and we’re also investigating items like their density and size,” says Professor Sluijter. Researchers are also investigating the impact of these

A lot of attention within the project is focused on the question of how to deliver these extracellular vesicles to the location where they are required to help stimulate cardiac repair. These extracellular vesicles are so small that they could be moved away from the heart relatively easily, so Professor Sluijter says it’s important that they are delivered as accurately as possible to damaged parts of the organ. “We’re investigating how we can produce enough vesicles and how we can get them to the right location,” he says.

If you want to kick-start

a chronically ill heart and repair it effectively, then a single injection is unlikely to be enough. That’s why we think that local, slow-release systems are essential.

vesicles on certain cell culture systems. “We do in vitro studies where we put those vesicles on different cardiac cells in a culture model, and then we assess how they behave. The third level is where we go to in vivo studies – where we use pre-clinical animal models, mainly in rodents. There, we treat diseased hearts with the vesicles,” explains Professor Sluijter.

While it is possible to inject vesicles into the bloodstream, Professor Sluijter believes that a more localised approach is necessary in terms of the project’s wider objectives. “If you want to kick-start a chronically ill heart and repair it effectively, then a single injection is unlikely to be enough,” he continues. “That’s why we think that local, slow-release systems are essential. For a patient, it will mean a single operation.”

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CPC-EVs

EVICARE Protein miRNA

Project Objectives RNA

Cardiac Progenitor Cell (CPC)

CPC-EV treatment

Increased vessel density Slow release

Treatment and prevention This approach could potentially be used both in treating people who have experienced serious cardiac problems, and also in prevention. While Professor Sluijter does not envisage using the extracellular vesicles on healthy individuals, he believes they could help change the course of heart disease in some patients. “It may be that we can start treating a certain population earlier, for example people who have an injured heart due to a myocardial infarction. It might be possible to treat people with diabetes, or other people at high risk of developing heart failure,” he outlines. The vesicles could also be used to bring other drugs into the heart, another issue that Professor Sluijter and his colleagues in the project are exploring. “We see the vesicles as

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Heart failure is a growing chronic disease with a 50% mortality within 4 years. There is a major need for more innovative, regenerative therapies that have the potential to change the course of disease. We aim to recondition heart failure by stimulating cardiac repair with extracellular vesicles that are derived from progenitor cells.

Project Funding

This work was supported by the Project EVICARE (No. 725229) of the European Research Council (ERC) and PPS grant (No. 2018B014) of the Dutch Heart Foundation.

Contact Details

Inhibition of cardiomyocyte death

The vesicles will be encapsulated in materials that facilitate the slow release of biomaterials over an extended period, rather than a single exposure. These vesicles are designed to ensure that they cannot be flushed out easily, but instead slowly get into the organ and then affect the cells that they need to affect, with the ultimate goal of restoring an individual’s heart function. “It’s about restoring the natural blood supply and the contractility of the heart,” says Professor Sluijter. The dosage of extracellular vesicles required to achieve this may vary according to the extent and location of damage in the heart; for now however, Professor Sluijter says the priority is to improve blood flow in the diseased organ. “We’re aiming to help certain cell types survive in the diseased heart, and to achieve better perfusion,” he explains.

Extracellular Vesicle-Inspired CArdiac Repair

a natural way of getting into a target cell and affecting that cell type,” he explains. The next step beyond this could be to load different biological species or other drugs into these vesicles, which opens up the possibility of using them to treat a variety of other conditions. A key challenge here remains delivering the vesicles to the ideal location, which will remain the focus of a lot of attention in research. “That’s one of the key issues in the project,” stresses Professor Sluijter. Researchers have learned a great deal about how to isolate and characterise these vesicles over the course of the project, and Professor Sluijter is keen to make further progress in the years ahead. “In the future we will aim to move forward towards local applications,” he continues. “Further ahead, we will look towards designing these vesicles. A hybrid of synthetic and natural materials is likely to be more effective than natural materials on their own.” The ultimate long-term goal is to use this approach to help regenerate the heart and limit the impact of heart disease, which is a major priority for health authorities across the world. This is not an immediate prospect however, and at this stage researchers aim more to demonstrate the feasibility of using extracellular vesicles to repair the heart, laying the foundations for further development in the future. “With this project, we want to show that we can manipulate vesicles around the heart, to demonstrate that it can be done,” says Professor Sluijter. “We aim to show that this approach works in a natural way, and that we can make these hybrid extracellular vesicles for a clinical phase trial.”

Project Coordinator, Professor Joost Sluijter UMC UTRECHT Heidelberglaan 100 3584 CX Utrecht E: J.Sluijter@umcutrecht.nl W: sluijterlab.com · Mol EA, Lei Z, Roefs MT, Bakker MH, Goumans MJ, Doevendans PA, Dankers PYW, Vader P, Sluijter JPG. Injectable Supramolecular Ureidopyrimidinone Hydrogels Provide Sustained Release of Extracellular Vesicle Therapeutics. Adv Healthc Mater. 2019 Oct;8(20):e1900847. · Maring JA, Lodder K, Mol E, Verhage V, Wiesmeijer KC, Dingenouts CKE, Moerkamp AT, Deddens JC, Vader P, Smits AM, Sluijter JPG, Goumans MJ. Cardiac Progenitor Cell-Derived Extracellular Vesicles Reduce Infarct Size and Associate with Increased Cardiovascular Cell Proliferation. J Cardiovasc Transl Res. 2019 Feb;12(1):5-17. · Sluijter JPG, Davidson SM, Boulanger CM, Buzás EI, de Kleijn DPV, Engel FB, Giricz Z, Hausenloy DJ, Kishore R, Lecour S, Leor J, Madonna R, Perrino C, Prunier F, Sahoo S, Schiffelers RM, Schulz R, Van Laake LW, Ytrehus K, Ferdinandy P. Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2018 Jan 1;114(1):19-34.

Professor Joost Sluijter

Professor Joost Sluijter is a Medical Biologist and heading the Experimental Cardiology Laboratory in which he is focussed on stimulating cardiac regeneration, thereby using advanced technologies of cardiac tissue engineering and the use of secreted progenitor cell vesicles to induce cardiac repair. He is awardee of an ERC consolidator grant.

Probing the roots of psychotic symptoms A significant proportion of young people experience psychotic symptoms in childhood, which leaves them at higher risk of developing mental ill-health later in life. The iHEAR project brings together researchers in several disciplines to probe deeper into the roots of psychotic experiences in childhood and the longer term outcomes, as Professor Mary Cannon explains. A number of

different symptoms are associated with psychotic disorders, including hearing voices and delusional beliefs. These types of experiences are more common than might be expected, with emerging evidence that a significant proportion of young people have experienced them at some point in their lives. “In my study I distributed questionnaires to 11-13 year old children in schools. Around 20 percent of students ticked a box saying that they had experienced one of a list of seven symptoms associated with psychotic disorders. When we interviewed them we found that they were indeed suffering these symptoms,” says Mary Cannon, Professor of Psychiatric Epidemiology and Youth Mental Health at the Royal College of Surgeons in Ireland (RCSI). As the Principal Investigator of the iHEAR project, Professor Cannon aims to help build a fuller understanding of the young people who experience these symptoms. “We are trying to increase our knowledge about the young people who describe these symptoms, why they experience these symptoms and their outcomes,” she outlines.

iHEAR project This work is multi-disciplinary in scope, bringing together researchers in epidemiology, social science and neuroscience to develop a broad perspective on psychotic symptoms in young people. Researchers have data on a large cohort of young people, from which Professor Cannon hopes to gain some deeper insights. “We have information on whether these children have experienced these symptoms by the age of 13. That will allow us to look at risk factors in a large population,” she explains. Another strand of her research involves brain imaging and detailed psychological testing. A further strand involves conducting in-depth interviews with a smaller group of young people who experienced psychotic symptoms at an earlier point in their lives. “We want to find out what’s been going on in their lives. What may have triggered these symptoms? What stresses were they undergoing?” says Professor Cannon. “I’m interested in whether an accumulation of trauma or adversity in childhood could lead to an increased risk of psychotic symptoms.”

Above: The iHEAR team: from left to right – Helen Coughlan, Colm Healy, Prof Mary Cannon, Dr Aisling O’Neill, Eleanor Carey. Right: iHEAR team members Colm Healy and Aisling O’Neill at the College of Psychiatrists of Ireland Spring Meeting, March 2019. Below: iHEAR team member Eleanor Carey presenting her work at the RCSI Research Day 2019.

Adversity in this context does not necessarily mean serious cases of abuse and neglect, but rather relatively common experiences that can nevertheless leave a significant mark on young people. Childhood adversities could involve going through parental conflict, bullying, or the loss of a grandparent for example. “These things all cause difficulties for young children,” stresses Professor Cannon. Some children may be able to overcome these difficulties, while others struggle. “Bullying can be incredibly painful for some young people for example, while others are very resilient. We’ve seen some young people who’ve come through horrendous bullying and done very well,” says Professor Cannon. “They’ve been able to overcome difficulties by volunteering for instance, or helping other people – that seems to be very important.”

There are others who are less resilient however, and their experiences during their youth may leave them at higher risk of developing a disorder later in life. While some

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individuals may be pre-disposed to developing a disorder, in others it may be that a particular risk factor led to them developing a condition when they wouldn’t have otherwise. “One thing I’m very interested in is cannabis use. Can that trigger a psychotic disorder later in life in a young person who may not otherwise have

the ones we don’t have to worry about?” she asks. “That’s very important for designing an intervention, as you don’t want to be subjecting a child to treatment when they don’t need it.” Results emerging already from Professor Cannon’s team suggest that self-esteem is very important in modifying the risk of

Around 20 percent of 11 to 13 year olds ticked a box saying that they had experienced one of a list of seven symptoms associated with psychotic disorders. When we interviewed them we found that they were

iHEAR Investigating the meanings and mechanisms of psychotic experiences in young people: a novel, mixed-methods approach Project Objectives

The objectives of the iHEAR project are to investigate the meanings and mechanisms of psychotic experiences in young people and to advance understanding of why some young people who report psychotic symptoms are at greater risk of poorer outcomes later in life.

Project Funding

The project is funded by European Research Council. Funding amount: €1.78 million.

indeed experiencing these symptoms.

Project Partners

developed it?” says Professor Cannon. “This is something that we will be able to explore in greater depth as the cohort grows older.” A firmer evidence base in this area could lead to the development of interventions designed to prevent mental illness in at-risk groups. Quite a number of adverse outcomes are associated with psychotic symptoms in young people, with evidence suggesting that they are more likely to experience anxiety and depression. “This doesn’t mean that all young people who experience psychotic symptoms will go on to develop mental illness, but some of them may be affected,” continues Professor Cannon. Some young people report these symptoms in early adolescence but then don’t report them again, another area of interest to Professor Cannon. “Is there any way we can predict which young people will go on experiencing these symptoms, and which are

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developing a mental illness. Young people with high self-esteem seem to be better equipped to overcome adversities in life, which could represent a potential avenue for intervention,Professor Cannon says there are also other possibilities. “The issue of parentchild attachment is an area where it could be possible to intervene and help reduce the risk of experiencing these symptoms,” she outlines. The wider aim with this research is to help identify those young people who may be at risk of developing serious mental health difficulties later in life, and potentially develop effective interventions. “We could perhaps develop interventions tailored to individual needs, or maybe groups of young people within the population who report these symptoms and experiences,” says Professor Cannon. “We may be able to identify sub-groups who would benefit from specific types of treatments.”

• Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland Project Coordinator, Professor Mary Cannon MB BCh BAO, FRCPsych, MSc, PhD RCSI Psychiatry Royal College of Surgeons in Ireland RCSI Education & Research Centre, Beaumont Hospital, Beaumont Dublin 9 Ireland T: +35 3 1-809 3855 E: marycannon@rcsi.com W: www.rcsi.com

Transforming Healthcare Education, Research and Service: RCSI Strategic Plan 2018-2022 Professor Mary Cannon

Mary Cannon is Professor of Psychiatric Epidemiology and Youth Mental Health in the Department of Psychiatry, Royal College of Surgeons in Ireland. She also works as a consultant psychiatrist in Beaumont Hospital Dublin. Her longstanding research interest is in the area of childhood and adolescent risk and protective factors for adult mental.

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The biological basis of cognitive impairment Deposits of tau and amyloid in the brain are the two main hallmarks of the pathology of Alzheimer’s disease, the most common cause of dementia. Researchers at the University of Geneva are using advanced imaging and analysis techniques to investigate pathways to the development of neurodegenerative disease and its progression, as Dr Valentina Garibotto explains. The onset of

dementia is marked by a decline in brain functioning, causing then a progressive cognitive deterioration which affects memory, language and attention, and subsequently leads to reduced autonomy in daily activities. Cognitive impairment is defined in terms of certain age-related norms, to differentiate a ‘pathological’ decline from the decline which occurs normally as we age. “Patients are diagnosed as having cognitive impairment or dementia when they have impairments in memory or other domains that are more marked than expected for their age,” explains Dr Valentina Garibotto, head of the Laboratory of Neuroimaging and Innovative Molecular Tracers at the University of Geneva. In her research Dr Garibotto is investigating the biological basis of cognitive impairment, looking at people over the age of 50 and comparing those patients who have mild The Biological Basis of Cognitive Impairment due to Suspected NonAlzheimer’s Pathology (SNAP): Studying the interplay between amyloidosis and tau-related neurodegeneration Valentina Garibotto Department of Radiology and Medical Informatics, HUG 4 rue Gabrielle-Perret-Gentil CH-1211 Genève 14 T: +41 22 372 72 52 E: Valentina.Garibotto@unige.ch W: https://www.unige.ch/ medecine/radio/en/researchgroups/984garibotto/

Valentina Garibotto is a Group Leader in the Department of Radiology and Medical Informatics at the University of Geneva. She uses molecular neuroimaging to evaluate neurological and psychiatric diseases.

An example of a subject showing the PET signal of tau pathology in the temporal cortex, indicating an early stage of Alzheimer’s Disease.

cognitive impairment with those who do not. Among the subjects who have mild cognitive impairment, researchers are also investigating those who are stable and those who worsen over time. “We are also interested in individuals who have a cognitive complaint, the perception that something is not going well. Even if it is not always a sign that there is a ‘real’, objective cognitive impairment, this could possibly be a preclinical index of subtle cognitive and brain alterations” says Dr Garibotto.

and amyloid in different regions of the brain. “We’ve observed that the areas in which tau is deposited are linked to a specific individual’s clinical expression. For example, a subject with marked memory problems will have a higher level of tau deposition in those brain regions linked to memory,” she continues. A clearer picture of where tau and amyloid have been deposited in the brain could lead to a deeper understanding of each individual case, which is a major motivating factor behind Dr Garibotto’s research. A lot of attention in the project is currently focused on developing and improving imaging tools, with a view to potentially using them in diagnosis. “We want to understand the factors that influence the results, in order to then use them subject-bysubject to provide diagnostic information. Where does the subject have the pathology? How is the disease likely to evolve over the following years?” asks Dr Garibotto. This latter point is an issue of great interest to Dr Garibotto, with plans for a follow-up project.

We’ve observed that the areas in which tau is deposited are linked to a specific individual’s clinical expression. For example, a subject with marked memory problems will have a higher level of tau deposition in those

brain regions linked to memory.

Imaging and analysis This research involves the use of sophisticated imaging and analytical techniques, including positron emission tomography (PET), to observe neurological differences between different groups of subjects. Techniques like PET tracers allow researchers to monitor the presence and distribution of specific substances in the brain, among which are tau and amyloid, the two main hallmarks of the pathology of Alzheimer’s disease, the most common cause of dementia. “With PET tracers, we essentially inject a radioactive dye that is as specific as possible for amyloid or tau. We effectively end up with a map that quantifies the amount of tau or amyloid overall in the brain,” says Dr Garibotto. From this point, Dr Garibotto and her colleagues in the project can then look to study levels of tau

“The participants in our current project will be re-contacted to enter into a longitudinal study in which we aim to repeat the procedures, in order to see how and where tau and amyloid deposition has changed,” she explains. This research could also lead to new insights into the cognitive reserve, essentially the capacity of the brain to tolerate the pathology without it causing damage. Taking regular physical exercise, doing mental puzzles and in general remaining active are thought to protect people against dementia, but the precise mechanisms are not fully understood. “It’s not clear if these types of activities provide some sort of resistance to the pathology, or if the pathology is ultimately there anyway, but the extent of their cognitive reserve means an individual is able to cope with it better. This is something that we’re going to look at,” continues Dr Garibotto.

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Mapping health in the Middle Ages Public health is often thought of as a by-product of modernity, yet historical evidence shows that numerous stakeholders in Medieval Europe took steps to reduce risks and improve health outcomes. We spoke to Professor Guy Geltner, Dr Janna Coomans, and Dr Claire Weeda about how the Healthscaping project challenges perceptions of public health provision in earlier eras. The Middle Ages are commonly viewed as a time when healthcare was fairly limited in scope, in both preventative and curative terms. As the Principal Investigator of the Healthscaping project, Professor Guy Geltner challenges this perception. “We aim to reevaluate the terms by which we discuss prophylactics in earlier societies,” he explains. The project brings together researchers from several different disciplines, including archaeology, cultural history and urban history, to identify preventative measures in Italy and the Low Countries over the period between 1200-1500. “We chose this chronology partly because the Black Death falls in the middle (1347-51). That way we can evaluate whether the outbreak led to a shift in approaches to prophylactic care,” says Professor Geltner.

Roman physician Galenus. This knowledge underpinned prophylactic measures designed to protect public health, which was a major concern for residents, guilds and public officials. “Policy-makers were thinking about how to make sure that population numbers were high enough to ensure their community was economically successful,” explains Dr Claire Weeda, another postdoctoral researcher in the project. This was a particularly prominent concern in the aftermath of the Black Death, and to some extent public health was an economic issue. “Population health affects productivity, so there were clear policies to try and increase the number of residents,” says Dr Weeda. “One way to do that was by allowing migration into the city, but they could also look at measures to improve public health.”

We’re looking at sources describing what’s happening on the ground. This could be people getting fines for polluting certain spaces, or officials addressing the presence hazardous materials in the poorer parts of a city. Routine hazards A pandemic on the scale of the Black Death may be expected to have prompted a recalibration of public health programmes, yet prophylactic measures were in fact already in place, in part because cities had been rapidly growing for centuries. Accordingly, they developed policies and practices of waste disposal and sanitation management, major topics of interest in the project. “We trace the routine hazards and risks that communities recognized, and how those influenced general policies,” outlines Professor Geltner. By analysing several different types of sources, researchers aim to build a fuller picture. “We’re looking at sources describing what’s happening on the ground. This could be people getting fines for polluting certain spaces, or officials addressing the presence of hazardous materials in the poorer parts of a city,” says Dr Janna Coomans, a post-doctoral researcher in the project. This period also saw the spread of medical and scientific knowledge in Europe, for example the teachings of the Greco-

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The team is identifying different stakeholders who were active in this respect, including religious and charitable organisations. Some historians have emphasised the role of the modern state in the development of healthcare programmes, a viewpoint that Professor Geltner is keen to qualify. “We don’t want to diminish the role of central bureaucracy, but we don’t think that it’s a sine qua non for developing and enforcing public health programmes,” he says. While governments did play a major role in establishing healthcare programmes in some

countries, preventative interventions far pre-date them. “It’s worth looking at different cultures and collaborate with scholars working in other regions. Waiting for benchmarks like the growth of bureaucracies and the emergence of modern medicine is tantamount to saying that groups knowingly neglected their health before the 19th century,” continues Professor Geltner. “That’s a rather harsh judgement on past civilizations.” The team now plans to bring together the data they’ve gathered into dynamic urban health maps, working with GIS. These spatial reconstructions will help them and other researchers see new connections between processes and gain a deeper understanding of how earlier societies understood and dealt with health challenges. “The maps will be openly accessible, so others will be able to use our data and add their own layers, as there are similar mapping projects in different cities around the world,” says Professor Geltner.

HEALTHSCAPING Healthscaping Urban Europe: Bio-Power, Space and Society, 1200-1500 G. Geltner | Professor of History University of Amsterdam Oost Indisch Huis kamer D1.04C Kloveniersburgwal 48 1012 CX Amsterdam T: +31 (0)20 525 4662 E: g.geltner@uva.nl W: https://premodernhealthscaping.hcommons.org/

Bologna’s fango official en route. Archivio di Stato di Bologna, Curia del podestà, Ufficio delle acque, strade, ponti, calanchi, seliciate e fango 21, reg. 4 (1355–1356), front cover. Photograph by Guy Geltner.

Guy Geltner (top left), Claire Weeda (top centre), Janna Coomans (top right) Lola Digard (bottom left), Léa Hermenault (bottom centre), Taylor Zaneri (bottom right)

By kind permission of the Ministero dei beni e delle attività culturali e del turismo-Archivio di Stato di Bologna.

Scientists vs COVID 19

The deadly strain of COVID 19 has taken its toll around the world, killing over 15,000 at the time of writing, with a mortality rate of around 2 percent. In the desperation to undo the pandemic, innovation fights nature in an epic battle of science against disease, all across the globe. Right now, there is real terror in the world as the virus spreads like a fire through every population on Earth. It’s mutating, it’s escalating and no one really knows how or when this will end. By Richard Forsyth

very so often, nature ambushes us and for all our knowledge, we are at its mercy. A lot of people knew this was going to happen one day and now it has. In December 2019, somewhere in the busy, primal Huanan Seafood Wholesales Market in Wuhan, China, the deadly strain of the Coronavirus now known as COVID 19 took hold of one of the caged animals there, like an unexploded viral bomb, ticking away. There were over 100 animals, many wild and illegally trafficked, listed in the market for sale, kept in small cages in unsanitary conditions. The list included bats, beavers, pangolins, peacocks, snakes and wolf cubs, all destined for dinner plates. Such markets are not uncommon in China and in response, since the disaster escalated, the consumption and trade of wild animals has been banned in China. It was here that researchers now believe a bat or pangolin became the link to the human pandemic. COVID 19 leapt from an animal to a human. Human bodies have never seen this virus before and so have no immunity to it. Since that fateful moment in Wuhan, we all know what has happened.

Viral grip The coronavirus adopted its name from the word ‘corona’ meaning halo or crown – attributed to its appearance when viewed through an electron microscope as it has protrusions which it uses to attach to host cells. It has seven types and it causes different symptoms in different mammals. For example, cows and pigs can get diarrhea but in humans, it causes respiratory infections. Some strains do no more

harm than a common cold but the latest strain, discovered late last year, now known as COVID 19, is different. As well as fever, coughing and breathing difficulty it can cause pneumonia, kidney failure or multiple organ failure and it can kill you, particularly if you are old, frail or have healthcare issues and preconditions. The true horror of this strain, just like previous virulent, serious strains such as SARS and MERS, is that of course, it is contagious and exponentially spreads (the WHO believe it has the RO around 2.5 – this is the average number of people infected by one person) and in addition, there are no known vaccines or antiviral drugs. It can attach to surfaces, making it easy to pick up, living on surfaces from two hours to nine days depending on material and conditions. If you catch it, you have to accept there is not much you can do, except hope and wait. It incubates, it travels across borders, it flies with people across oceans and it is now evidenced in 183 countries around the world. Cruise ships with outbreaks have been kept at sea, stadium games and events have been cancelled, hotels have been cordoned off, cities and now countries have been locked down and several transport routes are off limits. It has, at the time of writing, infected more than 350,000 people it is estimated, and claimed the lives of over 15,200 but the true figures are not known as not all cases are recorded. By the time this is published, the figures will have risen. We are living through an historic and terrible pandemic. These evolving strains are a cycle of nature today and many regard them as inevitable in current human culture. What’s different about this viral outbreak, is the way in which scientists have responded. Normally,

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This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. A novel coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019. The illness caused by this virus has been named coronavirus disease 2019 (COVID-19).

vaccines for outbreaks like this can take several years to develop. Because Chinese officials released the genetic code of the strain relatively quickly, governments and research teams around the world responded quicker and with better technology than with previous outbreaks, to work out how it might mutate, and how they can protect people from it. A quick call for collaboration worldwide is speeding up the pace to the response dramatically. Although this has radically sped up the processes for a vaccine – trials may even start in weeks for candidates – it’s likely a vaccine will not be population-ready for a year, which is still an age, when the virus is spreading so aggressively around the world.

Europe’s response The EU has joined the fight against this virus which the World Health Organization (WHO) called ‘a grave threat to the world’. Largescale investment has been secured and is being distributed as a matter of emergency. The European Commission has made a financially backed commitment to tackling COVID 19, funding urgent research relevant to

diagnostics, therapeutics and prevention, and every country affected has made it the priority above all else. There seems no upper limits to how much each country is prepared to put into this, with billions of investment pumped into helping people reorganising infrastructure and fighting the disease, set against ever more endangered economies, now in tatters from lockdowns and ceased trading. There are several EU Projects that have been relevant in the collaborative response, including The Prepare Project, EVA-GLOBAL, ZAPI and COMBACTE-NET. Some are focused on readiness. For example, The Prepare Project is constantly working out the dynamics of the outbreak, making sure European hospitals are as ready as feasible to respond to mushrooming outbreaks and public health information is ready to go. It is essentially a European-wide network intent on harmonising large-scale clinical research studies on infectious disease. It establishes a common research structure in hundreds of hospitals across the EU and clinical investigators are deployed in 48 hours of an outbreak. The approach

COVID 19 shows us that today, disease is harder to contain because of our global access and large interacting populations, but at the same time our advances are such that we learn and adapt and counter-attack, just as the virus has. www.euresearcher.com

seeks to improve response effectiveness, not missing opportunities to prevent outbreaks spreading, learning from the disease and saving lives. The Prepare Project was quick to respond to the outbreak in Italy, getting on site and dealing with the challenges as best they could. There is also ZAPI, The Zoonotic Anticipation and Preparedness Initiative. This project creates new platforms and technologies to facilitate a fast, coordinated response to new infectious diseases. This looks at designing new manufacturing processes to deliver antibodies and vaccines to battle emerging diseases in a matter of months from the outbreak. COMBACTE-NET (Combatting bacterial resistance in Europe) has a mandate to build clinical, laboratory and research networks across Europe, testing novel treatment strategies. There is also pooling of existing knowledge for fast access seen in European Virus Archive – GLOBAL (EVA-GLOBAL or EVag). This provides a virtual collection of human, animal and plant viruses and has to date responded to hundreds of requests from dozens of countries to provide access to the necessary material for diagnosing coronavirus infection. Building knowledge databases and making the relevant organisations aware of them, is a vital part of the coordination against diseases that spread fast. These projects are now actively involved in dealing with the COVID 19 threat. China and Italy have taken the biggest battering from the virus, with COVID 19 reaching its deadly ‘tendrils’ deep and wide into Europe, now the epicenter of the outbreak. Italy especially experienced a shock, with over 5,000 deaths at the time of writing. Initially across Europe, most of these cases were imported but where the numbers shot up, as they did early on in Italy, it was clear that it did not take long for the virus to be locally acquired. The disease also evolves, which adds to the challenge. Children seemed to sustain a lesser version of the disease whilst the elderly, especially men, and those with underlying health issues, were more seriously affected. One problem with COVID 19 is that

it presents similar symptoms to having a bad cold or the flu, including fever and a persistent dry cough. It can also be in someone for two weeks without their knowledge and spread. This makes a huge proportion of people potential victims of the virus as well as aiding its distribution. One of the best pieces of common sense advice has been to wash hands with soap for 20 seconds, as soap breaks down the fatty membrane around the virus, so it falls apart.

Innovation on the frontline Innovations have been helping around the world to tackle the spread of this disease. In China, eCommerce company, Alibaba has gotten together with Beijing-based Global Health Drug Discovery Institute, developing an open source coronavirus data platform. It’s also lent its cloud-based AI powered computing platform to institutions around the world to accelerate gene sequencing, protein screening and research on the deadly strain. AI is good at forecasting and predicting which is also a useful skill for second guessing outbreaks. More accessible, is the WeChat instant messaging app that 1 billion users have, now has an outpatient clinical map so WeChat users can locate nearby clinics. Then there is the amazing ‘sci-fi’-like contribution from TmiRob, a company that has now sent dozens of their medical robots to hospitals in Wuhan and Shanghai. The robots check patients’ temperatures, deliver medication and sterilise areas. In the hope of preventing its spread across borders and seas, airports have been scanning passengers to take their temperature. Thermal imaging cameras at Sultan Iskandar Muda International airport in Indonesia, for instance, has been taking temperatures of people passing by the camera. Anyone with a high temperature or fever had been stopped and checked. Now, of course many transport routes, including air travel have simply been shutdown to avoid any possibility of spreading transmission. For some Chinese workers, disinfectant spraying tunnels were

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Macau Photo Agency

deployed where the workers pass through them to get to work. A mist of disinfectant coats each individual, before accessing safe zones.

Keeping calm whilst carrying on It is worth stepping back a little at the end of this article, to take stock when all the alarms are setting off in the media. The truth is that new viruses like this sound horrendous, scare officials and generally make people anxious and panicky. However, most people who catch this virus experience mild symptoms and fully recover. It’s not a foregone death sentence by any means, and in fact many may have not even realised they had caught it, mistaking it for a more common illness. The advice for this kind of problem is simply tell your nearest healthcare provider and ensure you isolate yourself, stay indoors, stay rested, keep hydrated. If you are a reasonably fit person – this ordeal is maybe simply a story you’ll tell people in years to come. For the unlucky two percent, however, the body’s immunity fights back too hard and causes severe illness and it can be fatal. COVID 19 shows us that today, disease is harder to contain because of our global access and large interacting populations, but at the same time our advances are such that we learn and adapt and counterattack, just as the virus has. Despite all the coordinated global efforts to thwart it and best it, COVID 19 does show robust determination to thrive. The horror of such outbreaks is going to recur in the future, with new strains and evolutions, so understanding the best strategies for COVID 19 will create vital lessons for future pandemics. The best way to prevent it before a vaccine is synthesised, does seem to be simply, isolation and quarantine. Whilst several cities have had to endure this torturous isolation on a mass scale, with citizens staying inside their homes and away from the street, the shops and work, this crude solution works better than any other. Diseases need hosts, deprive a virus of hosts and it’s like robbing a fire of its fuel.

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DIFFERENT APPROACHES Herd immunity with phased measures in the UK The UK bucked the trend of hardline isolation as the virus erupted within its counties, opting for the natural herd-immunity approach. This is when the population carries on as normal to a degree, with the acceptance of infection, so the majority of people develop natural immunity faster in theory and break the chain of infection. The herd immunity approach was criticised by the WHO, as too little was known about the virus to say if this would work. It also means an initial spread of the disease is faster. In fact, the UK all but abandoned testing protocols, opting initially for soft measures like advising on self-isolation and washing hands as the main population protections. Social distancing measures are introduced in steps as the virus spreads.

Building of mega hospitals in China China built mega hospitals at an unprecedented pace in response to the aggression of the virus, and the demands it would place on existing healthcare facilities. China is tackling the virus with a temperature checks at every point of potential contact they can think of, such as transport and buildings. Anyone with a high temperature is then taken away to the special fever clinics to be tested and potentially isolated.

Testing everyone in South Korea South Korea has gone for an aggressive ‘trace, test and treat’ methodology, tackling the disease head on by ramping up health care efforts, testing as many people as possible on a large scale. In stark contrast to the UK approach for example, 20,000 people are being tested a day in this country, where people are swabbed in car parks and tests are carried out around the clock in labs.

Lockdown in Italy Italy has gone for a simple and brutal approach of locking down populations, keeping everyone as separate as possible so the disease can not spread person to person.

The heat goes up on thermoelectric materials There are huge sources of heat in the environment, which can be converted into electricity by thermoelectric materials. The NANOthermMA project aims to help researchers identify how materials can be engineered and nanostructured in order to improve thermoelectric performance, as Dr Neophytos Neophytou explains. The development of thermoelectric materials opens up the possibility of generating electricity from temperature differences, an exciting prospect in the context of energy sustainability concerns. However, thermoelectric materials have traditionally been quite inefficient, and even current nanostructured materials - which provide a boost in performance - are not yet efficient enough for wider implementation, a topic Dr Neophytos Neophytou and his colleagues are addressing in the NANOthermMA project. “The goal in the project is to create a new class of more efficient nanostructured materials, building on theory, simulations and experiments,” he outlines. The thermoelectric performance of a material is quantified by the ZT figureof-merit. “The numerator in the ZT includes the electrical conductivity multiplied by the square of the Seebeck coefficient. This is what we call the power factor,” explains Dr Neophytou. “The denominator is the thermal conductivity, which determines the heat flow, resembling the losses in the process.” A lot of attention has previously been focused on putting nanostructured features into a material to reduce thermal conductivity, so essentially reducing the denominator in the ZT figure-of-merit. While this has proved effective up to a point, there is only limited potential for further reductions, so Dr Neophytou and his colleagues are now taking a different approach. “The way to further improve

Nanostructured material geometry. Grain boundaries, nanoinclusions, and atomistic defects present obstacles for phonon transport (heat) as it propagates from the hot to the cold sides of a thermoelectric material.

efficiency is to work with the numerator, the power factor,” he outlines. There are some significant technical hurdles to overcome in this work however. “Nanostructuring reduces the electrical conductivity. We want to develop a nanostructure that doesn’t reduce the conductivity too much,” says Dr Neophytou. “There’s also an inherent relationship between the conductivity and the Seebeck coefficient – they are inversely proportional to each other.”

NANOthermMA project A material with a very high electrical conductivity will have a low Seebeck coefficient and vice-versa, and any effort to increase one

multi-scale geometries

mesoscale 34

will reduce the other. The aim of the project is to investigate how to effectively decouple this interdependence, which could eventually lead to the development of more efficient thermoelectric materials. “The inverse relation between conductivity and the Seebeck coefficient is strong, but there are ways that you can tweak that,” explains Dr Neophytou. This research is built on a deep understanding of material structure and how electrons and phonons flow through it. “If you zoom into a 3-d bulk material you will often find that it has a lot of grain boundaries, dislocations and defects. It’s a bulk material, but if you zoom in there internally, you find that it’s not a perfect crystal, it has a lot of defects,”

Zooming in a nanostructured thermoelectric material, where the matrix material is described in a continuum way, but the smaller defects are treated in an atomistic manner.

atomistic scale EU Research

simple energy surface:

real energy surfaces:

says Dr Neophytou. “Materials scientists also know how to create materials with a lot of nanostructured features.” This opens up the possibility of modifying the material in certain ways to improve thermoelectric efficiency. If there are a lot of these grains and defects in a material then they slow down the flow of phonons, which describe thermal conductivity. “Phonons are vibrations of atoms in the material, and can be thought of as waves, or particles, that flow through a material,” outlines Dr Neophytou. Grains and defects also reduce the flow of electrons through a material

The complex-shaped energy surfaces of typical thermoelectric materials look nothing like the uniform, spherically described ideal surfaces.

and current. Doping a material – essentially introducing a different atomic element in the material and more mobile charges – enables researchers to minimise current reductions while also maintaining a high Seebeck co-efficient. “When you dope a material, these dopants act as additional scattering centres. If you can redistribute them so that they are concentrated in some regions of the material and not others then you have clean regions for electrons to flow,” explains Dr Neophytou. This is called modulation doping. The wider aim here is to direct the flow of electrons in the nanostructure

Nanostructuring has led to important improvements, but reduces the electrical conductivity. We want to develop nanostructures that don’t reduce the conductivity too much. There’s an inherent relationship between the conductivity and the Seebeck coefficient that we also want to break. however, an issue Dr Neophytou and his colleagues are investigating in the project. “One idea we’re exploring to decouple electrical conductivity and the Seebeck coefficient is by effectively building barriers in the material,” he says. “A barrier is like a wall in the material that electrons have to jump over. Only the high-energy electrons will make it over – the low-energy ones will not. This is called energy filtering.” The energy filtering approach leads to an increase in the Seebeck coefficient, yet it also leads to reduced electronic conductivity

and relate the intrinsic properties of the material to the nanostructure geometry. “There is a link between how you design the nanostructure – such as the size of grains, the thickness of the grain boundaries, the height of the barrier walls – with the actual physical properties of the material, such as how the electrons interact with phonons,” says Dr Neophytou. Materials scientists have recently developed the ability to create these features in nanostructures for a large number of materials, most of them consisting of

heat flow at the atomistic scale

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complex characteristics and properties. Now the aim is to understand how they can be used to decouple the Seebeck coefficient and electrical conductivity. This research is largely theoretical in nature, and Dr Neophytou and his colleagues in the project are working with simulations. “We use multi-scale physics and multi-scale geometries. We start with fairly simple models, then we go to more accurate and elaborate semi-classical models to look at particle transport,” he outlines. “Then we go to much more sophisticated quantum transport models, looking at the behaviour of electrons in a quantum mechanical sense. Then we do the same thing for the heat, looking at phonons as particles and as waves. This is the simulation aspect of the work.” This research could open up new insights into how to decouple the Seebeck coefficient and electrical conductivity in a material, while the project also has an experimental dimension. The aim with the experimental work is to create structures through which specific effects can be validated, so demonstrating the potential of nanostructured thermoelectric materials. “We have now identified three or four different things that have to be combined for this concept to work, and each provides its own performance boost in the power factor,” says Dr Neophytou. “We are trying to validate these different concepts through experiments. Our colleagues in the project are building ultra-thin structures, and then looking to verify whether they lead to a power factor improvement under certain conditions that we have proposed in the project.” Snapshot of wave effects in heat flow as phonons encounter pore defects in a nanostructured thermoelectric material.

NANOthermMA Advanced Simulation Design of Nanostructured Thermoelectric Materials with Enhanced Power Factors

Project Objectives

The main objective is to resolve the on-going problem that limits the efficiency performance of thermoelectric materials, which is the inverse interdependence of the Seebeck coefficient and the electrical conductivity. The project establishes a theoretical strategy that relaxes the interdependence and achieves 5x efficiency improvements compared to state of the art, experimentally validates the theoretical propositions, and develops a large state-ofthe-art electrothermal simulator, open to the community, in order to guide the design of the novel nanostructured materials proposed.

Project Funding

ERC Starting Grant. Total funding: 1.5M Euro

Project Partners

My group is a theory and simulation group, and the project has experimental partners: • Professor Dario Narducci, University of Milano-Bicocca • P rofessor Giovanni Pennelli, University of Pisa

Contact Details

Project Coordinator, Dr Neophytos Neophytou School of Engineering University of Warwick T: +44 24 7652 3123 E: N.Neophytou@warwick.ac.uk W: https://warwick.ac.uk/fac/sci/eng/ research/grouplist/sensorsanddevices/ computational_nanotechnology_lab/ erc_nanothermma Vassilios Vargiamidis and Neophytos Neophytou, ‘Hierarchical nanostructuring approaches for thermoelectric materials with high power factors’, Phys. Rev. B 99, 045405, (2019). Laura de Sousa Oliveira and Neophytos Neophytou, ‘Large-scale molecular dynamics investigation of geometrical features in nanoporous Si,’ Phys. Rev. B 100, 035409 (2019).

Dr Neophytos Neophytou

Dr Neophytos Neophytou is currently an Associate Professor at the School of Engineering, University of Warwick UK, where he runs the Computational Nanotechnology Lab. His area of specialization is theory, computational modelling and simulation of electronic and thermal transport in complex bandstructure materials, nanomaterials, nanodevices, and thermoelectric materials for energy conversion and generation.

n a n o s t r u c t u r i n g

electron transport

multi-physics particles & classical

waves & quantum

(a) From the electrons’ point of view, nanostructuring builds potential energy barriers (‘walls’) that obstruct their flow. Only electrons with energies higher than the ‘wall’ can pass through. (b) Electrons as particles flowing in a superlattice material with potential barriers (red-right, blue-left). (c) Electrons as waves in the superlattice material.

Simulator

Applications for thermoelectrics

The aim now is to build on the findings so far, and one part of the project involves developing a simulator which the research community can use to guide the design of the nanostructuring for their own materials, with a view to improving thermoelectric efficiency. This will allow researchers to identify the effects of nanostructuring on performance and assess how they correlate to a pristine material. “We aim to provide the community with a sort of nanostructure recipe that can decouple the conductivity and the Seebeck coefficient, so that you can increase both of them simultaneously. That will provide a huge boost in both the power factor and the figure of merit,” outlines Dr Neophytou. “A second major output will be to bring together all the computational tools that have been developed during the project and put them under a unified umbrella of a multi-physics, multi-scale, high-performance framework.” This framework will have a very accessible interface with the user, allowing them to choose which simulation they want to run. A user will be able to choose the geometry, tools and physics relevant to their specific simulation, from which they can assess the performance of the structure. “It will be generic in the sense that we will put all these different tools there, but the user has to know what can be done in relation to the particular problem that they want to address. For example, if you want to simulate how the wave nature of electrons or phonons interacts with defects in a material, then you are bound to simulate quite small structures, but you can simulate larger structures with semi-classical tools,” says Dr Neophytou. “The tools that you can use are restricted by the nature of what you want to simulate. There is also scope to add more tools to the framework in the future.”

The wider context here is the goal of improving the performance of thermoelectric materials, which hold a lot of potential in terms of addressing concerns around energy sustainability. There are many sources of heat in the environment, and Dr Neophytou says thermoelectric materials could be used to convert this heat into electricity. “There are many potential applications, such as microscavenging. For example flexible thermoelectrics are worn on clothes or skin, and they create electricity from the heat difference between your body and the surrounding environment to power small sensors. The materials can allow self-powered electronics in general without the need for a battery,” he explains. Thermoelectric materials could also be used on larger energy scales. “Some car companies are working on creating a thermoelectric generator around the exhaust of the car. A third of the gas that is used in the car goes into motion, while the remainder is waste heat,” says Dr Neophytou. Extracting some of this waste heat from a car’s exhaust and reusing it could greatly improve efficiency, while thermoelectric materials could also be used as heaters or coolers, or in car seats to improve comfort. There are also many other potential applications in industrial processes, such as in the steel industry, which produces enormous quantities of waste heat. Cost is of course an important issue in terms of applying thermoelectric materials more widely. “It depends on the efficiency and price of the material,” acknowledges Dr Neophytou. Thermoelectric materials are already applied in certain areas, notably space missions, now by helping to improve the efficiency of cheaper materials Dr Neophytou hopes to encourage their use in a wider range of areas. “If the efficiency of cheap materials goes up, then there is the potential of scaling this to a wide range of technologies,” he says.

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A window into

new physics

The standard model of particle physics is extremely successful in describing nature on microscopic scales, yet it is not completely compatible with theories of the macroscopic universe. Researchers in the Recept project are probing the possibility of new physics beyond the standard model by testing a prediction called lepton universality, as Dr Vladimir Gligorov explains. The standard model of particle physics

RECEPT project

is extremely successful at describing nature on microscopic scales, in the sense that it predicts the properties of a wide range of particles. A contradiction emerges when researchers attempt to reconcile the behaviour of these particles as described by the standard model with theories of the macroscopic universe, such as the Big Bang. “There are numerous difficulties, one of which is the problem of dark matter and dark energy. Essentially, on macroscopic cosmological scales, there is a mis-match between the quantity of visible matter and the mass of matter that you would infer from how the galaxies move around. This is why people hypothesise the existence of dark matter, that could exist outside the standard model,” says Dr Vladimir Gligorov. Based at Cern in Geneva, where the Large Hadron Collider (LHC) is located, Dr Gligorov is the Principal Investigator of the Recept project, a collaborative international initiative aiming to test the predictions of the standard model, which could lead to new insights into fundamental physics questions. “Are there particles or forces beyond the standard model which resolves the early universe?” he asks.

This research involves monitoring the behaviour of particles, using data from the LHCb experiment at Cern, and then looking for evidence of new physics. Despite being based at Cern, LHCb is very much a collaborative initiative, bringing together researchers from 16 countries. The data is generated at the

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that have been described, and while it can be difficult to produce these particles in the laboratory, Dr Gligorov says it is still possible to investigate them indirectly. “Even if new particles and forces are too heavy to be produced directly in the laboratory, they could interact virtually with the existing particles that you do produce,” he explains.

“The more you can automate, the more you save your energy for the things that matter. LHCb’s real-time algorithms allow us to infer not only whether an LHC collision looked interesting but also which parts of this collision are most relevant for further analysis.” LHC then distributed across the globe via the worldwide computing grid, essentially a network of data centres in different countries, giving researchers across the world access to important data. “It’s very democractic everybody involved in the collaboration has equal access to all this data,” says Dr Gligorov. A number of new particles and forces have been postulated to explain the inconsistencies

Researchers in the project are using this kind of approach to test a specific prediction of the standard model called lepton universality. “This is very interesting because it’s something that the standard model predicts very precisely,” says Dr Gligorov. “The standard model states that there are six leptons, three of which are charged leptons – the electron, the muon and the tau. There are also three

associated neutral leptons, or neutrinos, one for each type of charged lepton.” The standard model predicts that beauty mesons should couple in the same way to electrons, muons and taus, yet some of the evidence gathered from the LHCb experiment has hinted at a different picture. By probing these differences, researchers hope to gain deeper insights into the possibility of new physics beyond the standard model. “If you observe non-standard behaviour then there might be some new particle which is causing this deviation. From the size of this deviation, we can then try to learn something about what kind of new particle is causing it,” explains Dr Gligorov. Researchers in the project are analysing the decay processes of certain particles and looking for evidence of new physics, for example if beauty mesons couple preferentially to an electron, muon or tau. “When we measure lepton universality we rely on collecting huge numbers of abundantly produced particles, and observing their rare leptonic decays which might reveal this universality breaking at high levels of precision.” explains Dr Gligorov. A large volume of data has been generated at the LHCb experiment, representing a vast source of information for Dr Gligorov and his colleagues to analyse. While some

observers had expected that the LHC would reveal the existence of entirely new particles when it was first turned on in 2010, this has in fact not been the case, which Dr Gligorov says illustrates the importance of indirect searches in the investigation of new physics. “If these particles are too heavy to be produced directly in the LHC, then maybe we can indirectly seek evidence of their existence,” he says. This work also holds

Data processing This could help researchers to probe a number of major open questions in physics in even greater detail, including those around testing lepton universality. A very wide range of measurements can be made to probe lepton universality, and Dr Gligorov says there is scope to improve the way these measurements are gathered and stored. “For that, we need to upgrade

The standard model states that there are six leptons, three of which are charged leptons – the electron, the muon and the tau. There are also three associated neutral leptons, or neutrinos, one for each type of charged lepton. relevance in terms of the design of the next generation of particle colliders, which is an important aspect of the project’s research. “Cern has recently proposed building a new collider called the future circular collider,” outlines Dr Gligorov. “The existing LHC has a circumference of 27 kilometres. The future circular collider would be 100 kilometres in circumference and operate at far higher energy levels.”

the experiments, to collect a lot more data. In order to collect more data, we have to upgrade our data processing capabilities,” he says. Dr Gligorov and his colleagues are heavily involved in this work. “The aim is to achieve the capability to process 40 terabits of data each second. The LHC collides for approximately 6 x 10 6 seconds per year, so this data must be reduced to around 80 gigabits per second in order to fit

Expected rate of different signal particles produced in a future upgrade of the LHCb detector, plotted against the transverse momentum of the particle.

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within the available storage resources. For that, you essentially have to build a custom data centre, on a relatively small budget,” he continues. This has been the focus of a lot of attention in the Recept project. “We’ve been working to develop new algorithms, including on some new architectures. Until now LHCb has used CPUs for its real-time processing, but we’ve also developed a way that allows part of this work to be performed on GPU processors – which are potentially more cost-effective,” outlines Dr Gligorov. This ‘Allen’ framework developed by the Recept team is able to process around 80 gigabits of data per second on a single GPU, and make decisions which parts of that data should be kept. Identifying the important information more rapidly means Dr Gligorov and his colleagues can then devote more of their attention to the most interesting data. “The more you can automate, the more you save your energy for the things that matter,” he stresses. “LHCb’s real-time algorithms allow us to infer not only whether an LHC collision looked interesting but also which parts of this collision are most relevant for further analysis.” The Recept team is currently waiting to learn if the LHCb collaboration will decide

to use Allen for its data processing, but Dr Gligorov stresses that whichever option is chosen the lessons learned from developing a GPU solution will benefit the team and collaboration in the long term. A successful real-time analysis provides the foundation on which researchers can look to test lepton universality. Researchers are currently in the process of finalising two pieces of analysis on lepton universality, one on rare decay and another on semileptonic decay. “They will help to increase the precision with which we are able to look at lepton universality in different channels,” says Dr Gligorov. Alongside research on lepton universality, Dr Gligorov and his colleagues are also looking forward towards future further upgrades of the LHCb detector. “Looking further ahead, we still plan to gather much more data and to probe lepton universality at higher levels of precision,” he says. “These kinds of experiments run over long timescales, and future upgrades of the detector are already being planned. They will have even bigger data volumes and we are investing a lot of effort in developing our skills in real-time processing on different architectures so we can best tackle those challenges.”

RECEPT Real-timE preCision tEsts of lePton universaliTy

Project Objectives

The Standard Model (SM) of particle physics is a remarkably successful description of microscopic nature. Nevertheless, it is in contradiction with successful theories of the macroscopic universe. The RECEPT project uses the LHCb experiment to search for traces of particles or forces from a more fundamental theory beyond the SM which reconciles these. In the process, RECEPT researchers are developing new methods of processing data in real-time which allows these searches to achieve their maximum potential.

Project Funding

Funded by the European Research Council (ERC) € 1,986,000 total funding.

Contact Details

Project Coordinator, Dr Vladimir Gligorov Laboratoire de Physique Nucléaire et de Hautes Energies Sorbonne Université, Campus Pierre et Marie Curie Tour 22 - 1er étage 4 Place Jussieu 75252 PARIS CEDEX 05 T: +33 1 44 27 43 34 E: Vladimir.Gligorov@cern.ch W: http://teamlhcb-lpnhe.in2p3.fr/ rubriqueRecept.html W: http://www.cnrs.fr W: https://lpnhe.in2p3.fr

Dr Vladimir Gligorov

Dr Vladimir Gligorov is a research scientist at CNRS in Paris. He gained his undergraduate and doctoral degrees in physics from the University of Oxford, and completed his post-doc in Glasgow, before spending six and a half years working at CERN as a research scientist. As an experimental physicist, he specializes in the analysis of beauty hadron decay processes and real-time data processing.

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Back to the past of nuclear energy Nuclear energy is often thought of as a highly modern technology, yet it has much deeper historical roots than commonly imagined, building on the engineering knowledge accumulated by earlier societies. The NuclearWaters project aims to explore these parallels and integrate nuclear energy into a much deeper history of engineering, as Professor Per Högselius explains. The nuclear energy industry

is often thought of as being built on modern science, in particular the discovery of how to split the atom and harness the resulting release of energy. However, while modern physics and chemistry research has undoubtedly been central to the development of nuclear power, the industry is actually part of a much longer history, believes Professor Per Högselius. “Nuclear engineers and industry advocates tend to talk about new reactors as essentially another way of generating steam. So nuclear reactors actually have a place in a longer history of steam engines,” he says. Based at the KTH Royal Institute of Technology in Stockholm, Professor Högselius is the Principal Investigator of the NuclearWaters project, an initiative which aims to analyse the history of the nuclear energy industry from a water-based perspective. “We want to look at the history of nuclear energy from a water-based perspective, so we are looking not at nations, but rather bodies of water,” explains Professor Högselius.

NuclearWaters project This research centres around six case studies, in which Professor Högselius and his colleagues aim to probe deeper into the history of nuclear energy. While modern nuclear reactors are highly complex, Professor Högselius says that a nuclear power plant shares some features with other forms of power generation. “With nuclear power, essentially nuclear fission is used to boil water. There are many components

which are more or less the same as in conventional thermal power plants,” he outlines. Nuclear power was nevertheless seen as an exciting, innovative source of energy when it was first developed, and many countries invested a lot of resources in it, particularly in the post-war era. “Nuclear energy entered the stage at a time when demand for energy was growing rapidly. During the post-war period, especially from the ‘50s onwards, electricity consumption grew across the Western world,” says Professor Högselius. “This new source of energy was seen as somehow different, and there were highly ambitious visions about what it could do.”

all built nuclear power plants in the Rhine river basin, so they depend on water from the basin and its major tributaries,” says Professor Högselius. The question of how different countries interacted to address public concerns and coordinate their work is of great interest for Professor Högselius and his colleagues. “For example, peasants and farmers were worried about what would happen if these nuclear power plants were built. How would that affect the local climate?” he outlines. A nuclear power plant is highly disruptive to the local ecology, while vast amounts of water are required to cool a reactor, another topic of interest in the project.

Engineers in China, Mesopotamia, Egypt and other ancient societies struggled with precisely the same issues that nuclear hydraulic engineers struggle with today. They were trying to

manage floods, to keep water flowing. These visions were based to some extent on the idea that nuclear energy represented a radical break from what had gone before, now researchers in the project aim to explore a different perspective. One case study looks at the history of the nuclear industry in the area around the Baltic Sea, while another focuses on the Rhine river in western Europe, both of which are transnational bodies of water. “The Rhine passes through a number of western European countries, including France, Switzerland, the Netherlands and Germany. They have

Marine pollution may affect the quality of cooling water, for example if an oil spill occurred close to a nuclear power plant. “In that type of situation water at the required quality might not be available any longer, and the safe operation of the nuclear power plant might be at stake,” explains Professor Högselius. Safety is a paramount concern in the nuclear industry; it’s important to note here that many accidents were not caused by the nuclear fission process, or even the reactor itself. “Nuclear accidents are often related to failures in much more mundane

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technical components. For example, the Three Mile Island accident was essentially caused by a valve that happened to be closed when it should have been left open,” outlines Professor Högselius. “ There have also been several incidents where flooding has compromised the safe operation of nuclear power plants.” The serious accident at the Fukushima power plant in 2011 is a notable example, where a tsunami led to flooding of the site, while there have also been several other less dramatic incidents. As nuclear power plants need to be located close to natural, largescale bodies of water, they are vulnerable to flooding. “Many are located more or less directly on the beach, while others are positioned by major rivers, lakes or water courses,” says Professor Högselius. Guaranteeing that cooling water will keep on flowing is the major priority for today’s nuclear engineers; Professor Högselius says that engineers in earlier historical periods grappled with broadly the same problem. “Engineers in China, Mesopotamia, Egypt and other ancient societies struggled with precisely the same issues that nuclear hydraulic engineers struggle with today. They were trying to manage floods, to keep water flowing,” he explains. “This is one way in which we can relate nuclear history to a much longer history of humanity.” Many of the early advocates of nuclear power saw it as an exciting new source of

energy that marked a clean break with the past, yet it has become apparent that it is in fact much more similar to conventional, thermal energy than people had understood at the time. Nuclear energy involves a combination of different technologies, many of which are part of a much longer tradition, and this creates risks. “This interaction between old and new gives rise to the risks that we have seen in the nuclear sector,” says Professor Högselius. These risks have led many to question whether nuclear power should be part of future energy provision, while Professor Högselius says the wider trend towards liberalised energy markets is another important consideration. “In a liberalised market you cannot really plan future energy prices, they are decided through market transactions,” he points out. “Nuclear energy doesn’t really fit very well into that kind of thinking, about electricity being bought and sold on a market. A much more long-term strategy is required.” The NuclearWaters project will make an important contribution to the debate about the future of nuclear energy by integrating its history into a much deeper picture of human civilisation. If it is acknowledged that nuclear energy is in essence a hydraulic technology, then it can be thought of as part of a longer process. “It’s the latest stage in a long historical process, in a series of hydraulic civilisations,” explains Professor Högselius.

NUCLEARWATERS Putting Water at the Centre of Nuclear Energy History Project Objectives

NUCLEARWATERS develops a groundbreaking new approach to studying the history of nuclear energy. Rather than interpreting nuclear energy history as a history of nuclear physics and radiochemistry, it analyses it as a history of water. The project shows that nuclear energy is in essence a hydraulic form of technology, and that, as such, it builds on millennia of earlier hydraulic engineering efforts worldwide.

Project Funding

Funded by the European Research Council (ERC), the project is led by Prof. Per Högselius at the Division of History of Science, Technology and Environment, KTH Royal Institute of Technology, Stockholm. It was started up in May 2018 and will be completed in April 2023. Including co-funding from KTH, it has a total budget of €2.5 million.

Contact Details

Project Coordinator, Professor Per Högselius KTH Royal Institute of Technology SE-100 44 Stockholm Sweden T: +46 70 2130944 E: per.hogselius@abe.kth.se W: https://nuclearwaters.eu/

Professor Per Högselius The Loviisa nuclear power plant in Finland.

Per Högselius is Professor of History of Technology at KTH Royal Institute of Technology, Stockholm. His teaching and research centres on energy, infrastructures and natural resources in historical and transnational perspective. In Sweden he is also active as an author of popular history books and essays.

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Exploring the potential of nanoporous carbons Nanoporous carbons are capable of efficiently absorbing photons, which can then be converted into photochemical reactions in confined nanopore spaces. We spoke to Dr Conchi Ania about the work of the PHOROSOL project in investigating how metal-free nanoporous carbons can be modified to harvest light, which could open up wider possibilities in various fields. Since the ability

of some metallic oxides to absorb light and decompose water was first demonstrated, a lot of attention in research has been focused on modifying and tailoring the characteristics of different materials to improve their light absorption features. In particular, scientists are exploring how to achieve higher efficiencies and improve the stability of materials through tuning their composition, size, or structure. Based at the French National Centre for Scientific Research (CNRS), Dr Conchi Ania is Principal Investigator of the PHOROSOL project, an ERC-backed initiative investigating the potential use of light responsive nanoporous carbons. “We want to explore the ability of these materials to absorb light and to integrate them in various applications,” she outlines. The disruptive approach of the project is based on exploiting the potentialities of earth-abundant and metal-free carbons with well-defined nanopores for photochemical applications. “We have to address two main challenges; the first is that most of the photochemistry is based on non-porous materials, whereas we investigate the fate of the light/solid interactions upon nanoconfinement. The second is that carbon materials are strong absorbers themselves, thus it is a challenge to reach efficiencies comparable to those of common materials,” says Dr Ania. The ambition of PHOROSOL is to develop more efficient materials to boost technologies for light energy utilization, profiting from the dual nature of nanopore carbons as strong light absorbing materials with unique electronic features and nanoporosity. They are also commercially available at a relatively low cost in comparison to most competitors.

PHOROSOL project Porous carbons are some of the oldest materials known to human beings with a long history of applications going back to BC times (inks in cave paintings, Chinese ink, water purification, medicine). Their fabrication has ancient origins, and current manufacturing processes are well known and based on work carried out more than a century ago. However, these conventional methods do not allow perfect control of the pores in the full nanometric scale; this has triggered intensive research efforts, with the aim of developing new methods to obtain porous

carbons with perfectly defined pore architectures. “Designing the perfect material for a given application is complex, as the properties must be tuned/tailored to a certain extent to fulfill the requirements of the specific application; and for this, understanding of the fundamentals of the technological process itself becomes crucial,” explains Dr Ania. Researchers are investigating novel approaches to control and tune carbon materials with ad-hoc nanopore voids (nanopores are very small in size, below 100 nanometres in length), while adjusting other properties, such as structure, chemical composition and morphology, that are essential to improving photochemical performance. An abundantly available set of materials is being considered, which includes gels and grapheneoxide frameworks.

when photochemical reactions occur in the confined space of the nanopores,” says Dr Ania. “We are not only handling these pores, we are also handling the materials. A large amount of light is absorbed directly by the matrix itself, and is not directly used in the photochemical reaction.” Another difficulty is the lack of consensus and collective understanding of how to evaluate photonic efficiencies in all type of materials. This is a central part of the project’s research agenda, along with modifying these materials and tailoring their properties. “In order to understand the interactions of light in the confined space, we have to modify the average nanopore size in these materials,” continues Dr Ania. Understanding the properties of these nanoporous carbons and how their characteristics can be modified is an important step towards the objective of

We have seen that we can tune the amount of light absorbed and the type (in terms of energy or wavelength) by modifying the composition. This is important to control the amount of energy that can be harvested and that will define the photochemical reaction where the material can be applied. It is the porosity at the nanoscale level that confers extremely interesting properties to porous carbons, as it is their photochemical activity that is being explored in this project. Such photochemical features have been reported for graphene, whereas the behaviour of nanoporous carbons (which are disordered and defective graphene layers) has not been studied. Dr Ania’s work has shown that it is possible to harvest light in these materials and to promote photoinduced reactions inside the pores. This has opened up new perspectives for the old, black nanoporous carbons (very often considered the ‘ugly duckling’ of the carbon family). Evaluating the performance of these materials using standard methods is complex. “The difficult part is determining and quantifying how light interacts in the confined space of the nanopores,” explains Dr Ania. This is mainly due to the difficulties associated with measuring the photons that have been absorbed and discriminating the fraction of light reaching the carbon surface and the pores, from that absorbed by the carbon matrix itself. “One of the big goals in the project is to understand what happens

bringing them to wider application. “In some contexts there are a few mechanisms that are well understood, but the overall picture is highly complex,” explains Dr Ania. By building a deeper understanding of the effect of pore size and chemical composition on photoactivity, researchers hope to lay the foundations for a more structured approach in future. “We hope to develop a portfolio of carbon materials with known photoactivity, defining as many physico-chemical features as possible,” says Dr Ania. While a great deal of progress has been made in this respect over the course of the project so far, there is still significant scope to further improve efficiency, which will remain an important topic in Dr Ania’s research. The composition of these materials is another major factor in terms of how effectively and efficiently the carbon nanopores absorb light. “We have seen that we can tune both the amount of light absorbed and the type (in terms of energy or wavelength) by modifying the composition,” outlines Dr Ania. This is important in terms of controlling the amount of energy that can be harvested, which will define the photochemical

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PHOROSOL Integrating photochemistry in nanoconfined carbon-based porous materials in technological processes Project Objectives

The main goal of the research project is to exploit the potentialities of coupling the nanoconfinement and photochemical ability of metal-free carbon materials reach important breakthrough in interdisciplinary fields of applied photochemistry for gas sensing, energy conversion and environmental protection. The challenge stands from the understanding of the fundamentals of the role of confinement in the light/solid/molecule interactions. An example would be the design of spatially organized carbons with high electron mobility and multimodal pore systems. These systems are expected to show enhanced diffusion and photoactivity, with a great potential in applications where a fast, sensitivity and selective response is needed.

Reprinted from Adv. Sci. 2018, 180029

reaction (the application) where the material can be applied. “We want to understand which surface groups are more effective in increasing the overall efficiency of converting light into chemical reactions,” says Dr Ania. The first step here is to functionalise the materials. “We are working with the O-, N-, and Ssurface groups,” outlines Dr Ania. The significance of the various physical and chemical defects and the role of the moieties that are incorporated has become the focus of intense research.

Applications Part of the project team is working on investigating the origin of the interactions of light within nanopores, and studying the nature of the ensuing reactions, while researchers are also looking towards the possible applications of these materials. “One part of the team is looking towards integrating the materials in certain reactions, to see if they can work effectively with - or in competition - currently available materials for these applications,” continues Dr Ania. “They could potentially work in combination with other materials, but it’s not yet clear how versatile they will prove to be.” A number of possible applications, coupling their photochemical performance with nanoconfinement effects, have been put forward, including the removal of pollutants in certain environments, synthesis of fuels and chemicals with added value, nanoenergetic materials and organic synthesis, among others. An exciting potential application of photoresponsive nanoporous carbons is in transforming CO2 and H2O into sustainable fuels, which is a major global research priority. “In a world that urgently needs to redress the balance of energy derived from fossil fuels, efficient conversion of sunlight into energy is key to producing carbon-neutral fuels,” points out Dr Ania.

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This challenge calls for the development of more efficient materials, a deep understanding of the nano-microscale phenomena, and a clear approach to the design of devices to integrate such materials. “Carbon catalysts have been shown to be among the most interesting candidates to replace metallic catalysts in the production of CO2-derived solar fuels,” says Dr Ania. The potential of noble metal-free carbon catalysts has attracted a lot of attention across the wider scientific community, and Dr Ania plans to continue her research in this area in the future. “We have gained some promising results, combining functionality and porosity; we are now looking at how this can be optimized to synthesize long fuel molecules”, she continues. The team has recently been able to measure light emission features in some of these porous carbons, which could have a significant impact on the development of sensors with improved sensitivity and selectivity. The team is now working to control the emission/absorption wavelength, and the stability in different environments, as these may be the key to broadening the portfolio of applications beyond those initially forecast in the project. As an example, a tight nanopore confinement of oxidizers in porous carbons has been revealed to be critical to the performance of the composite in terms of releasing thermal energy; some mixtures are capable of competing with the best performing nanoenergetic materials in the market for civil and military applications, with better safety performance. While a great deal of progress has been made in this respect over the course of the project so far, there is still significant scope to further improve efficiency, which will remain an important topic in Dr Ania’s research.

Project Funding

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 648161, PHOROSOL).

Contact Details

Dr Conchi Ania Conditions Extremes Materiaux: Haute Temperature et Irradiation (CEMHTI) CNRS (UPR 3079), Site Haute Température 1D Av. de la Recherche Scientifique CS 90055 45071 - Orléans Cedex 2, France T: +33 (0) 238 25 55 13 E: conchi.ania@cnrs-orleans.fr W: https://www.cemhti.cnrs-orleans.fr

Dr Conchi Ania

Dr Conchi Ania is the head of POR2E group at CEMHTI-CNRS (Orléans, France). She has a long-standing interest on developing nanoporous materials with tailored surface chemistry and architectures as structural and functional solids for high-tech applications, covering energy storage and conversion and environmental protection. Current research interests focus on water treatment, photocatalysis, electrocatalysis, gas adsorption and separation, and solar energy conversion.

Situation update worldwide, as of 23 March 2020 Epidemiological update The data presented on these pages has been collected between 6:00 and 10:00 CET Since 31 December 2019 and as of 23 March 2020, 338 307 cases of COVID-19 (in accordance with the applied case definitions and testing strategies in the affected countries) have been reported, including 14 602 deaths. The deaths have been reported from Italy (5 476), China (3 276), Spain (1 720), Iran (1 685), France (674), United States (471), United Kingdom (281), Netherlands (179), South Korea (113), Germany (94), Belgium (75), Switzerland (60), Indonesia (48), Japan (41), Turkey (30), Brazil (25), Philippines (25), Sweden (21), Iraq (20), San Marino (20), Canada (18), Austria (16), Algeria (15), Greece (15), Ecuador (14), Portugal (14), Denmark (13), Egypt (10), Malaysia (10), Luxembourg (8), Australia (7), Hungary (7), India (7), International conveyance in Japan (7), Norway (7), Poland (7), Pakistan (5), Peru (5), Argentina (4), Ireland (4), Lebanon (4), Morocco (4), Bangladesh (3), Bulgaria (3), Burkina Faso (3), Dominican Republic (3), Panama (3), Tunisia (3), Ukraine (3), Albania (2), Bahrain (2), Colombia (2), Costa Rica (2), Democratic Republic of the Congo (2), Mauritius (2), Mexico (2), Romania (2), Singapore (2), Taiwan (2), United Arab Emirates (2), Azerbaijan (1), Bosnia and Herzegovina (1), Cayman Islands (1), Chile (1), Croatia (1), Cuba (1), Czech Republic (1), Finland (1), Gabon (1), Ghana (1), Guam (1), Guatemala (1), Guyana (1), Iceland (1), Israel (1), Kosovo** (1), Lithuania (1), Moldova (1), North Macedonia (1), Paraguay (1), Serbia (1), Slovenia (1), Sudan (1) and Thailand (1).

Geographic distribution of COVID-19 cases worldwide, as of 23 March 2020

Cases have been reported on the following continents: Africa: Egypt (294), South Africa (274), Morocco (115), Algeria (102), Tunisia (75), Senegal (67), Burkina Faso (64), Democratic Republic of the Congo (30), Nigeria (30), Cameroon (27), CĂ´te dâ&#x20AC;&#x2122;Ivoire (25), Ghana (24), Rwanda (19), Kenya (15), Togo (15), United Republic of Tanzania (12), Ethiopia (11), Seychelles (7), Equatorial Guinea (6), Gabon (6), Central African Republic (4), Congo (4), Eswatini (4), Cape Verde (3), Liberia (3), Madagascar (3), Namibia (3), Zambia (3), Angola (2), Benin (2), Chad (2), Guinea (2), Mauritania (2), Sudan (2), Zimbabwe (2), Djibouti (1), Eritrea (1), Gambia (1), Mozambique (1), Niger (1), Somalia (1) and Uganda (1). Asia: China (81 649), Iran (21 638), South Korea (8 961), Malaysia (1 306), Japan (1 089), Israel (1 071), Pakistan (784), Thailand (721),

Indonesia (514), Saudi Arabia (511), Qatar (494), Singapore (455), India (439), Philippines (380), Bahrain (334), Lebanon (248), Iraq (233), Kuwait (188), Taiwan (165), United Arab Emirates (153), Vietnam (118), Jordan (99), Brunei Darussalam (88), Sri Lanka (87), Cambodia (86), Kazakhstan (60), Palestine* (59), Oman (55), Uzbekistan (46), Afghanistan (34), Mauritius (28), Bangladesh (27), Kyrgyzstan (14), Maldives (13), Mongolia (10), Bhutan (2), Nepal (1), Syria (1), TimorLeste (1) and Myanmar (0). America: United States (35 206), Brazil (1 546), Canada (1 430), Ecuador (789), Chile (632), Peru (363), Mexico (316), Panama (313), Argentina (266), Colombia (235), Dominican Republic (202), Uruguay (158), Costa Rica (134), Trinidad and Tobago (50), Venezuela (36),

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Distribution of COVID-19 cases by continent (except China), as of 23 March 2020 (according to the applied case definition and testing strategies in the affected countries)

Cuba (35), Bolivia (27), Honduras (27), Paraguay (22), Guatemala (19), Jamaica (19), Barbados (17), Netherlands Antilles (13), Bermuda (6), Guyana (5), Suriname (5), Bahamas (4), Cayman Islands (3), El Salvador (3), Greenland (2), Haiti (2), Nicaragua (2), Saint Lucia (2), Antigua and Barbuda (1), Dominica (1), Grenada (1), Montserrat (1) and Saint Vincent and the Grenadines (1). Europe: Italy (59 138), Spain (28 572), Germany (24 774), France (16 018), Switzerland (6 971), United Kingdom (5 683), Netherlands (4 204), Austria (3 631), Belgium (3 401), Norway (2 132), Sweden (1 906), Portugal (1 600), Denmark (1 395), Turkey (1 236), Czech Republic (1 165), Ireland (906), Luxembourg (798), Poland (634), Finland (626), Greece (624), Iceland (568), Russia (438), Romania (433), Slovenia (414), Estonia (326), Croatia (235), Armenia (190), Serbia (188), Bulgaria (185), Slovakia (185), Hungary (167), San Marino (151), Lithuania (143), Latvia (139), Bosnia and Herzegovina (125), Faroe Islands (115), North

Macedonia (114), Andorra (113), Cyprus (95), Moldova (94), Malta (90), Albania (89), Belarus (76), Azerbaijan (65), Georgia (54), Ukraine (47), Liechtenstein (46), Kosovo** (31), Monaco (23), Montenegro (21), Guernsey (17), Gibraltar (15), Jersey (15), Isle of Man (2) and Holy See (1). Oceania: Australia (1 709), New Zealand (102), Guam (27), French Polynesia (18), New Caledonia (5), Fiji (3) and Papua New Guinea (1). Other: International conveyance in Japan (696). * This designation shall not be construed as recognition of a State of Palestine and is without prejudice to the individual positions of the Member States on this issue. ** This designation is without prejudice to positions on status, and is in line with UN Security Council Resolution 1244/1999 and the International Court of Justice Opinion on the Kosovo Declaration of Independence.

https://www.ecdc.europa.eu/en Distribution of COVID-19 cases worldwide, as of 23 March 2020

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Forestry management through another lens Forests play a vital role in the provision of ecosystem services, but they’re also places where people live and work. We spoke to Professor Adam Pain about his team’s work investigating smallholder practices and new forms of land governance in Brazil, Nepal and Peru, and the wider importance of building research networks to encourage collaboration and knowledge-sharing. Many people across Brazil, Nepal and

Forest transitions

Peru live and work around forests, where they often cultivate and manage relatively small areas of land. The interests of these smallholders are not always compatible with the wider agenda of using forests as a carbon sink to mitigate the impact of climate change, while commercial interests are also keen to exploit natural resources like timber. “You’ve got the global interests of the climate change agenda, commercial markets in timber, and also smallholders. These are essentially the main stakeholders in forest management,” explains Adam. While smallholders clearly have a strong interest in maintaining and managing forests, the practices they use are often not widely appreciated. “A lot of what smallholders do is actually not recognised as forestry. It’s seen as something else that lies outside it,” he outlines.

A lot of the debate in this area has centered on the idea of forest transitions, which is related to the wider goal of reversing the decline in forest cover. However, this idea carries with it an enormous set of assumptions about the conditions under which forest areas increase. “Nepal has gone through a forest transition, in the sense that the overall forest area is increasing. However, it has happened under very different circumstances than in the West,” says Adam. While in the West the increase in forest size was driven in large part by economic shifts and the diminishing role of agriculture in the economy, Adam says this was not the main factor in Nepal. “Nepal is still a subsistence economy. The forest transition in Nepal has come about largely because of community forestry,” he explains.

the interests of the people who live and work there. As forests in Nepal have recovered, this has been accompanied by an agrarian crisis in the mid-hills, where many people have not been able to make ends meet. “Their access to forests has been restricted and there has been a process of labour out-migration due to a failing agrarian economy,” outlines Adam. This loss of labour has led to a retreat of the agricultural boundary, which has had wider consequences. “Trees have actually crept out of the formal forest boundary, down into agricultural land,” he continues. “That’s one important dynamic in Nepal. The situation is different in Peru, where agriculture is still expanding.”

There is abundant

evidence that the Amazon has been managed for hundreds of years through selective planting, enrichment, and intensive agricultural practices. The way in which forests are viewed by bureaucracies has been shaped more by international agencies and forestry departments rather than the people who actually live and work there, believes Adam. The interdisciplinary research team which Adam leads is investigating issues around smallholder practices, land governance and agricultural changes in Brazil, Nepal and Peru, with the aim of helping build a wider perspective on forest management. “The project is partly about using different lenses to look at what goes on,” he says. Forestry departments and bureaucracies have proved to be relatively poor managers of forests. “Often they don’t understand the complexity of landscapes and the specific context, whereas the people who live there do understand, because they live there and manage it,” says Adam.

The ‘90s saw the emergence of democratic and social forestry movements in Nepal, as control of the forests came back into the hands of the people that traditionally used them. This has helped forests recover from the position in the ‘70s, when there was deep concern about the extent of deforestation. “Democratic de-centralisation has helped forests recover, particularly in the mid-hills,” says Adam. However, as forests have become more valuable, the forestry department has become increasingly interested in taking a greater degree of control. “There’s an ongoing debate between the forestry department and smallholders about their rights, as to who can manage the forests,” he says. The emerging market around carbon capture and sequestration opens up the possibility of using forests as a means to generate revenue, yet this is not necessarily in

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This blurring of the boundary between agricultural and forest land raises questions around the approach to land governance. In Nepal, agriculturalists don’t like having trees in the agricultural landscape, because they see it as an unproductive use of land, while the flip-side of this can be seen in Peru, where the practice of swidden farming has been blamed for deforestation. “Swidden farming is a shifting system. It’s a fallowing system of land management that allows regeneration, selective burning and recovery,”

explains Adam. While this approach is low energy input and helps to maintain a diverse mix of crops and trees in forest areas, this is not encouraged by the Peruvian authorities. “The forestry department in Peru dislikes people practicing swidden systems in forest management,” he says. The Peruvian government has argued that swidden farming is one of the primary causes of deforestation, yet Adam and his colleagues in the project believe this doesn’t reflect the complexity of the overall picture. In Peru,

migration patterns have been a major factor in driving changing patterns of land use. “The indigenous kechwa-lamas people in Peru have historically mixed hunting with subsistence practices. Now migrants are moving down from the Andes into Amazonian areas where land is available. They are clearing it and establishing crops, particularly cocoa and coffee,” he explains. “This is partly driven by the commercialisation agenda of the provincial authorities, which are very interested in developing a sort of agroCrossing the upper reaches of the Amazon in San Martin, Peru, January 2019.

Discussions with a community forest group in Dolokha, Nepal, November 2019.

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CHANGE PROCESSES OF FORESTS AND AGRICULTURE Change processes of forests and agriculture, small-scale farmers’ practices and new forms of land management

Project Objectives

The project aims to strengthen an existing collaboration on forests and people with research partners in Sweden, Nepal, Peru and Brazil and develop new ideas for future research. This will be undertaken through joint fieldtrips, analytical workshops, collaborative writing and new communication activities.

Project Funding

The project is funded by the Swedish Research Council, network grant 2017-5444 for approximately Euros 108,000.

Project Partners

• Brazilian Agricultural Research Cooperation, Embrapa, Belem, Brazil • Southasia Institute of Advance Studies (SIAS), Nepal • Waman Wasi, Lamas, San Martin, Peru

Contact Details

Project Coordinator, Professor Adam Pain, Swedish University of Agricultural Sciences (SLU) P.O. Box 7012, SE-750 07 Uppsala SWEDEN T: +46 79 697 44 73 E: adamnpain@gmail.com W: https://www.slu.se/en/departments/ urban-rural-development/research/ruraldevelopment/peca/ Professor Adam Pain

Adam Pain has since 2006 been a Visiting Professor in Rural Development at SLU, Uppsala, Sweden. Over the last fifteen years he has undertaken research on environmental service provision, on Climate Change and rural institutions in Nepal, Peru and Brazil, common property management in Nepal and on biodiversity management in India. He is the co-author with Kjell Hansen of ‘Rural Development’ (2019, Routledge).

The research team from Nepal, Sweden and Peru on fieldwork in Nepal, November 2019.

industrial economy in the region. That’s what has attracted people.” A high level of in-migration by Andean people to cultivate commercial crops is leading to extensive forest clearance that is challenging to the forestry departments and their conservation agenda, This agenda is based to an extent on a perception of forests like the Amazon as pristine environments, untouched by man, which does not match the reality. “There is abundant evidence that the Amazon has been managed for hundreds of years through selective planting, enrichment, and intensive agricultural practices,” Adam says. This is related to the wider debate about primary and secondary forests, which Adam believes is deeply problematic. “It is based on models of ecological succession that simply don’t hold up. Most forests globally, whether they’re primary or secondary, have seen forms of intervention,” he stresses.

Forest management The practices used to manage these forests have evolved over time in response to changing conditions, yet in many cases they are not recognised by formal forestry science. By extending networking opportunities to international researchers, the project aims to help encourage knowledge-sharing. “We’re trying to stimulate debate and compare ideas,”

Adam says. The project will also make an important contribution to the ongoing debate around land management. “We work with a rights-based group in Peru which focuses on the rights of the kechwa-lamas people. Those rights have been systematically denied, particularly around issues of land and land tenure,” continues Adam. “We also have a strong engagement with a forest action group in Nepal, which is very actively engaged in policy debates.” Research into smallholder practices on the ground provides the basis on which these kinds of groups can challenge forestry departments where necessary and ensure that their voices are heard. A network meeting will be held in Nepal and November, which will provide valuable opportunities for researchers to exchange ideas and explore alternative theories about forest management. “A lot of national organisations are quite isolated. It’s important to bring in opportunities for critical debate about theory and evidence in relation to forest issues,” says Adam. This is not limited to members of the project network but also extends to other partners, which will help open up new avenues of investigation and opportunities for collaboration. “We want to use these forms of collaboration to leverage new research grants,” he continues. “It’s part of a collaborative and deliberative process. We aim to help our partners to develop their research capacities.”

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Fish red blood cells aid the fight against viral infections Viral diseases are a major concern to the aquaculture sector, as they threaten the health of fish and cause significant economic losses. We spoke to Dr Maria del Mar Ortega-Villaizan about her research into how rainbow trout, and specifically its red blood cells (RBCs), respond to viral infections, work which holds important implications for the aquaculture sector. A number of

recent research papers by Dr Maria del Mar Ortega-Villaizan’s group at Miguel Hernández University have suggested that nucleated RBCs play a wider role in the immune system of fish than previously thought. As the Principal Investigator of the BloodCellsCrosstalk project (funded with an ERC Starting Grant), Dr OrtegaVillaizan’s research sheds new light on how RBCs (or erythrocytes) contribute to fighting viral infections. “We are looking at viral haemorrhagic septicaemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV) in particular. VHSV and IPNV are important

has been combined with in vivo research on fish from the aquaculture sector. “We are working with fish from a company that grows rainbow trout,” explains Dr Ortega-Villaizan. Researchers have used a variety of techniques, including transcriptomic and proteomic analyses, to look at the involvement of RBCs in the antiviral response. “We have identified mechanisms involving RBCs that could halt the viral infection. We have identified proteins that are involved in these mechanisms,” says Dr Ortega-Villaizan. “We have found targets within the project and have selected several antiviral proteins. We are investigating how

We are looking at viral

infections because they cause high economic losses in aquaculture, as there are no effective therapeutics or prophylactics against them. pathogens, because they cause high economic losses in aquaculture,” she outlines. VHSV and IPNV have been used as a working model in Dr Ortega-Villaizan’s lab for several years, now she and her colleagues are using it to explore how rainbow trout RBCs respond to viral infection. “After infection the RBCs produce cytokines that stimulate other blood immune cells to respond against the virus, as well as produce antiviral molecules,” she says. The aim in the project has been to investigate the role of RBCs and the communication between RBCs and other immune cells during infection, using co-cultures developed in Dr Ortega-Villaizan’s lab. This in vitro work

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they can be used in treatment, for example by increasing production of these antiviral proteins to help improve protection.” This research holds important implications for the aquaculture sector, which is heavily affected by diseases like VHSV and IPNV. By finding novel immunomodulants and antiviral targets, Dr Ortega-Villaizan and her colleagues hope to help reduce the economic losses caused by viral infections in the aquaculture sector and to lay the foundations for a more sustainable and profitable future. “The idea is to strengthen the internal mechanisms within rainbow trout and prevent the development of the infection,”

she outlines. The main focus of interest in the project at this stage is rainbow trout, but viral infections are a major concern across the aquaculture sector, so there is a lot of interest in strengthening the immune system in fish more widely. “Researchers in other labs are also studying the immune system of different fish species” says Dr Ortega-Villaizan.

BLOODCELLSCROSSTALK The Crosstalk Between Red And White Blood Cells: The Case Of Fish

Funded by the European Research Council ERC Maria del Mar Ortega-Villaizan Institute of Research, Development, and Innovation in Healthcare Biotechnology in Elche (IDiBE) Avinguda de la Universitat d’Elx, s/n, 03202 Elche, T: +34 9 6665 8431 E: mortega-villaizan@umh.es W: https://idibe.es/research/ red-blood-cells-antiviralimmunology/ Dr Maria del Mar Ortega-Villaizan is an Assistant Professor in the department of Biochemistry and Cell Biology at the University Miguel Hernandez.

Evolutionary physiology and adaptation in the moor frog Natural environments vary in space and time and are now drastically changing due to human activities. Environmental changes, like increasing acidity in a pond, can strongly affect the long-term prospects of species. We spoke to Dr Katja Räsänen from Eawag about her work on the moor frog (Rana arvalis), in which she aims to understand how natural populations adapt to environmental change. Organisms exposed to

challenging environments face evolutionary pressure to adapt, which could lead to modifications in a variety of traits, such as morphology, physiology and behaviour. Based at Eawag, the Swiss Federal Institute of Aquatic Science and Technology, Dr Katja Räsänen holds a deep interest in mechanisms of adaptation in natural populations. She studies the moor frog, Rana arvalis, a species which is found in parts of Europe and Western Siberia. “We’re using the moor frog as our main model system to look at the broader question of how natural populations adapt to environmental change,” she outlines. This species is important in pond ecosystems, where they play a number of ecologically significant roles. “In addition to consuming resources, they are also a food for predators and a host for parasites. They also play an important role in transmitting nutrients between aquatic and terrestrial environments,” says Dr Räsänen. As the Principal Investigator of a long running research project looking at the moor frog, Dr Räsänen aims to probe deeper into the underlying factors behind how this species adapts to environmental acidification. To do so, her team studies several different populations of the moor frog along an acidification gradient in Sweden, with pond pH levels ranging from 4 to 7.3. “Amphibians – including the moor frog – are studied because of their ecological importance and sensitivity to environmental change. We want to look

Assistant Frida Sjösted setting up a laboratory experiment.

at the bigger picture,” says Dr Räsänen. One aspect of this research involves looking at the impact of both natural and human induced acidification, which leads to natural selection in many traits across the whole lifecycle of the moor frog, right from the early stages.

Acidified environments Acidification can cause mortality and affect development of amphibians, while also leading to changes in the distribution of predators. “Embryonic stages are very heavily affected by acidity. A range of studies over decades have demonstrated that amphibian embryos in acidified waters often fail to hatch,” explains Dr Räsänen. The evidence suggests that changes in the coats which surround embryos (i.e. egg coats) prevent them from hatching. This is thought to be due to a maternal effect, a topic that Dr Räsänen has studied extensively over the course

of her career. “Interestingly, moor frog mothers from acidified environments produce egg coats with an altered molecular composition, which increases embryonic survival in acidified water,” she says. In tadpoles, both acidity and predators cause natural selection. “The classic defence traits in tadpoles are related to behaviour and morphology. In some environments, for example, it may be beneficial for a tadpole to grow rapidly as it reduces the risk of predation from predators that cannot eat larger tadpoles,” explains Dr Räsänen. By studying different populations of the moor frog along the acidification gradient, where the abundance of invertebrate predators increases as the acid concentration rises (whereas fish and newt predators can disappear), the team hopes to build a deeper picture of how different stressors influence adaptation. A tadpole’s tail morphology is a classic defence

Stora Tottatjärn, Sweden. A study site where Rana arvalis has adapted to acidity.

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EVOLUTIONARY PHYSIOLOGY AND GENETICS Evolutionary physiology and genetics of adaptation along multifarious stress gradient: insight from Rana arvalis Project Objectives

Schematic presentation of effects of environmental acidification on Rana arvalis, with comparison of an acidic and a neutral pH pond.

trait; a deeper tail may affect the tadpole’s swimming behaviour and improve its defences against predators. “Invertebrate predators, like dragonfly larvae, may be more likely to grab the tail, rather than the vital main body, when the tail is relatively large,” explains Dr Räsänen. The higher abundance of invertebrate predators in acidified ponds can lead to selection for deeper tails. “Our previous research showed that tadpoles from populations from acidic environments have deeper tails and higher survival rates when encountering predators than those from neutral pH environments. Based on laboratory experiments, there is likely a genetic basis to this morphological divergence,” continues Dr Räsänen.

forecast whether or not there is the potential for certain responses in the moor frog. The specific effects that these changes will then have is more difficult to forecast – it’s also important here to consider other simultaneously changing factors and the natural history of these populations,” she continues. While much of the team’s work has centred on the moor frog itself, the species is also an effective model for understanding general adaptation mechanisms, so the project’s work holds wider relevance. “It does tell us about the general processes that might be taking place in response to changing environments and different environmental stressors,” outlines Dr Räsänen. A deeper understanding

In addition to consuming resources, Rana arvalis are also a food for predators and a host for parasites. They also play an important role in transmitting nutrients between aquatic and terrestrial environments. The current aim of Eawag and the Uppsala University team is to probe deeper into the underlying factors behind morphological and behavioural divergence in tadpoles. “We are trying to understand the extent to which stress hormones, such as corticosterone, allow species to adapt relatively rapidly to acidification and correlated environmental changes – which can then lead to multidimensional change,” says Dr Räsänen. This work holds wider importance for understanding how organisms are likely to adapt to environmental change in future. “Understanding how the moor frog adapts to environmental stress is essential if we are to forecast what might happen in the future,” stresses Dr Räsänen. Predicting what may happen in future is a challenging task, and there are many uncertainties, yet Dr Räsänen believes it is possible to make certain forecasts. “We can

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of these evolutionary processes could prove important also in the management of natural populations. “We do different laboratory experiments to causally link different driving factors,” says Dr Räsänen. “In terms of management, it’s important to recognise that the populations that we see of any given species are not actually identical.” These differences among populations need to be taken account in the development of management strategies, while it’s also important to consider the wider objectives. If the goal is to restore specific populations of a particular species for example, then it’s important to know what type of selection pressures they have historically been exposed to. “Understanding the evolutionary history of any specific population in a species matters for their ability to cope with different changes” explains Dr Räsänen.

This SNF funded project aims to understand the role of corticosterone (CORT) stress hormones in rapid multi-trait adaptation to environmental stress. The project represents a long line of research illustrating whole-life cycle adaptation of amphibians to environmental acidification. This project sheds new light on how genotype, environment and phenotype jointly (i.e. the G-E-P map) affects fitness, the currency of natural selection.

Project Funding

The project research is funded by the Swiss National Science Foundation (SNSF). SNF grant number 31003A_166201

Project Partners

My main project partner (in addition to own students) is Professor Anssi Laurila from Uppsala University, Sweden.

Contact Details

Project Coordinator, Dr Katja Räsänen Department of Aquatic Ecology Eawag: Swiss Federal Institute of Aquatic Science and Technology T: +41 58 765 5186 E: katja.rasanen@eawag.ch W: www.eawag.ch/~rasaka

Dr Katja Räsänen

Dr Katja Räsänen is a senior scientist at the Swiss Federal Institute of Aquatic Science and Technology (Eawag) and teaches at ETH-Zurich. Her research focuses on understanding the dynamic interactions between environmental change and eco-evolutionary processes of natural populations. She integrates lab experiments and molecular tools with field surveys, with focus on freshwater organisms.

A helping hand for coral reefs With the temperature of the world’s oceans rising, concern is growing about the ability of coral reefs to adapt to climate change. We spoke to Dr James Guest and Dr Adriana Humanes about the work of the CoralAssist project in investigating whether selective breeding and the assisted gene flow (AGF) technique can help some coral reefs survive in the face of climate change. The world’s coral reefs

have been degraded by human activities, such as overfishing, over a long period, but this has accelerated over recent decades and rates of coral mortality have increased significantly over the last three decades. The largestscale coral mortalities that have occurred in recent years have been caused by rising sea surface temperatures, as Doctor James Guest explains. “If the sea temperature rises above what corals normally experience, and that temperature remains high for even just a week or two, then the corals will start to appear very pale. That’s because they’ve lost the symbiotic algae that occur inside their tissues. Those algae are part of a symbiotic partnership with the coral animal host, which is critical to the coral’s health,” he outlines. Some corals are better able to withstand heat stress than others, a topic of great interest to Dr Guest. “We have seen that if we put corals from a genetically diverse population under heat stress, we find some individuals which are more resistant than others,” he says. “What interests me is whether the attributes that make some corals more resistant can be passed on to their offspring.”

CoralAssist project This is a central part of the research agenda in the CoralAssist project, an ERC-funded initiative which brings together scientists from several different disciplines to investigate whether the Assisted Gene Flow (AGF) technique could be used in coral reef conservation. AGF involves the deliberate movement of individuals within or between habitats for the express purpose of increasing the frequency of better

adapted individuals to a desired condition in a population. A key step here is to identify the corals that are more resistant to heat stress. “We have tagged around 400 coral colonies on the reef, which we’ve been following for two years,” explains Dr Adriana Humanes, a post-doctoral researcher in the project. The aim is to identify which coral colonies have the highest tolerance to heat stress. “We take small fragments from these corals and bring them to the laboratory. Then we put them in tanks where we increase the temperature over a period similar to what they have experienced on reefs where there have been bleaching events,”

combining a range of different techniques, including physiology and proteomic analysis of the different corals, Dr Humanes and her colleagues aim to build a deeper understanding of the factors that affect heat-tolerance. “We’re looking at different characteristics of these coral colonies, to try and understand what gives them this higher heat-tolerance,” she explains. While a lot of research in this area has previously centered on the genes that these corals express, the project is looking at the proteins they produce rather than the genes. “These proteins actually control the traits that are expressed,” says

We have seen that if we put corals from a genetically diverse population under heat stress, we find some individuals which are much more resistant than others. What interests me is whether the attributes that make some corals more resistant than others can be passed on to their offspring. continues Dr Humanes. “So, we perform heat stress in a similar way to that seen in the natural environment, then record which fragments bleach and die and which ones survive.” Once it has been established which corals have a higher tolerance to heat stress, they can be bred together to find out if these traits are passed on to their offspring. Baby corals from these selected crosses are reared until they are adults to see if this heat tolerance persists through time - it may even be possible to see if it passes on to second or third generations. The underlying mechanisms behind these differing levels of heat-tolerance among corals are not fully understood, but this is a major topic of interest for CoralAssist. By

Dr Guest. “We’re working with proteomics specialists and protein chemists who have a lot of expertise in using mass spectrometers. That’s quite a novel part of our research.” This is a complex area, and there are many considerations to take into account when investigating coral health responses to heat stress. Alongside the coral animal itself, algae on the coral, the microbiome, and various other factors may affect heat-tolerance. “There are many areas of interest at the same time. Previous studies have suggested that in some cases, characteristics of the host coral are involved in heat-tolerance, but in other cases components of the microbiome, or the type of symbiotic algae inside the tissue may be more

Two-year old selectively bred corals being reared within an ocean nursery in Palau. Photograph by Till Roethig.

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CoralAssist Assisting Coral Reef Survival in the Face of Climate Change Project Objectives

Coralassist spans multiple disciplines and aims to answer four broad questions: 1) do trade-offs exist between heat tolerance and other fitness traits? 2) Which physiological and proteomic traits correlate with heat tolerance? 3) Is heat tolerance heritable? 4) Can AGF and selective breeding lead to shifts in heat tolerance in coral populations?

Project Funding A typical healthy, vibrant coral reef in Palau. Photograph by James Guest.

important,” outlines Dr Humanes. However, while heat-tolerance may seem like an entirely positive trait in terms of ensuring the survival of corals, there may also be costs in other areas. “If the coral is allocating more energy to heat-tolerance, it could be that other traits are compromised, such as its capacity for growth,” acknowledges Dr Humanes. “There could be trade-offs, and we still don’t know how they work and how they are related to each other. That’s something we are investigating – we aim to build more knowledge of heat-tolerance and the implications.”

Climate change The project’s work is part of the wider agenda of protecting coral reefs in the face of ongoing concern about the impact of climate change. Researchers also aim to develop a cost-effective methodology to restore coral reefs after they have been damaged, using sexual reproduction. This has advantages over commonly used asexual techniques as it increases the diversity of the gene pool of restored reefs. “Genetically diverse populations have a much better chance of surviving disturbances,” points out Dr Guest. By using selective breeding scientists have the added advantage of being able to decide which corals to breed together. Corals with high heat-tolerance reproduce normally in nature; however, Dr Guest says that it’s possible to greatly increase the fertilisation and survival rates through laboratory propagation. “It may be that the eggs and sperm of resistant corals will meet in nature and they will reproduce, but many of those will die naturally before they become adults, so there may be only one or two individuals that actually continue to the next generation,” he explains. “By bringing them into the laboratory, we can ensure that almost all of the eggs are fertilised and survive. We’re essentially increasing the proportion of what we think will be more resistant individuals.”

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A lot of attention is currently focused on the possibility of outplanting these types of corals onto reefs as a way of enhancing resilience. However, Dr Guest says that there are also other factors to consider beyond the heat-tolerance of the coral itself. “It’s not enough to produce a coral that has a higher heat-tolerance than if we just allowed those corals to reproduce randomly. We’ve got to be able to put that coral out onto the reef and to show that it has, on average, equal or better survival prospects than corals on the reef, which recruit naturally,” he stresses. It’s also important to develop a method of cost-effectively outplanting corals in large numbers, without having adverse consequences. “If there are trade-offs, if an outplanted coral grows more slowly for example, then potentially it may cause more problems than it solves,” points out Dr Guest. “It’s a complex area. The problems are very significant however, so we really need to do the research now to understand what will work well.” This holds clear importance in the context of concern about the impact of climate change on coral reefs and their ability to provide ecosystem services like coastal protection, food security and job opportunities. Coral reefs are home to a quarter of all marine species and support more than 500 million people worldwide, so Dr Guest says it’s important to consider their long-term future. “It may well be worth investing in efforts to get reefs to recover quickly from heat stress and boost their resistance to future climate change,” he says. The project will make an important contribution in this respect by building a science-evidence base to inform future decision-making. “By understanding the trade-offs and benefits, we can advise the authorities on what techniques would be the most appropriate in terms of giving us the best chance of having reefs that will survive for the next few decades,” continues Dr Guest.

Coralassist is funded by a 5-year European Research Council Consolidator Grant awarded to James Guest.

Project Partners

Coralassist works closely with the Palau International Coral Reef Centre, The University of Derby, The Horniman Museum and Gardens, the Australian Institute of Marine Sciences, The University of Sydney and Secore International.

Contact Details

Principle Investigator, Dr James R. Guest, PhD, ERC Research Fellow School of Natural and Environmental Sciences 4th floor, Ridley Building 2 Newcastle University Newcastle upon Tyne NE1 7RU United Kingdom T: +44 (0)191 208 3619 E: jrguest@gmail.com W: https://www.coralassistlab.org/

Dr James Guest

Dr Adriana Humanes

Dr James Guest (Principle Investigator) is a coral reef ecologist based at Newcastle University in the United Kingdom examining the feasibility of assisting coral reef adaptation via assisted gene flow and selective breeding. His current research goals are to assess the role that these interventions can play in maintaining ecosystem services in the face of climate change. Dr Adriana Humanes (Postdoctoral Research Associate) is a marine ecologist interested in the impacts of climate change on coral reef ecosystems, with special emphasis on corals and their reproductive biology.

Sustainable Transport targets: Electrifying or a shock to the system? We ask if the ambitious European Union goals for Sustainable Transport are realistic. By Richard Forsyth

o mitigate climate impacts, a sizable ‘elephant in the room’ is transport. Making transport sustainable is a mighty challenge, in terms of infrastructure, practicality, economics, investment and innovation. Given that we are unlikely to stop using transport for travel, shipping goods, business and pleasure, how is the EU looking to reshape the transport industry to swap out combustible fuel for electric power? The objective of the European Green Deal aims to reach net-zero greenhouse gas emissions by 2050. A major sector to overhaul to achieve this is the transport sector. The transport sector uses more than half of the global oil demand and creates a quarter of global CO2 emissions from fuel combustion. Transport contributes to 30% of the total CO2 emissions in the EU. Within the European transportation sector, road transport contributes 73% of EU CO2 emissions, followed by aviation at 13% and maritime, 11%. Rail has already championed electrification significantly, which means only 1.6%. Indeed, electric is hailed as the champion for an alternative source of sustainable energy for this sector. To accomplish the ‘holy grail’ of net zero emissions, we need to stop burning diesel and petrol and swap over to transport powered by electric batteries. It’s a huge undertaking and one that needs a coordinated and committed approach across European nations. Here we look at how Europe is preparing, planning and innovating to go electric across all our modes of transport.

Charging Ahead Whilst they are increasingly more common on our roads (385,000 sold through Europe in 2018), electric vehicles are currently still perceived as a niche product, and you could argue this is in part is due to the sporadic supporting infrastructure. Current policy aims indicate that 33 million electric cars will be on the roads by 2030 and for a truly climate neutral scenario that rises to 44 million electric cars. That would require a huge rise in electric charging points. An EU policy framework for alternative fuels infrastructure seeks to address this need. At the end of 2019 there were 185,000 public charging points in the EU, which in terms of ratio, serves the current electric car market adequately (7 cars per charging point). With the ambitions for e-mobility high, this will need to rise. By 2030 there will be 3 million charging points needed, requiring and investment of 1.8 billion Euros in the year 2025, which equates to 3% of EUs annual investment in road transport infrastructure. As for the vehicles, car manufacturers have great motivation to develop electric car models as each country sets targets for zero emissions. Car manufacturers are now engaged in electric car innovations and developing new models, which is deemed necessary to remain competitive. The EU is set on stiff regulations, high taxes and even bans on fossil fuels in relatively tight timelines, so it is now a race to be ‘future-proof’ for car manufacturers. With the EU spelling out that electric is the future – and to compound this, they will be penalised

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if continuing with petrol and diesel â&#x20AC;&#x201C; the choice of electric cars in the marketplace is going to increase. Manufacturers like Volkswagon, Volvo, Nissan, General Motors, Mercedes and Toyota are committed to producing electric car models. The projection is that almost half of all vehicles sold in 2030 in Europe will be EVs whilst it is desired by the EU that by 2035, all new car sales will be electric in Europe. Some say that this is not nearly enough to combat climate mitigation but re-booting established economies poses a staggeringly large undertaking on a Europe-wide scale.

passenger and freight activity will have doubled by 2050. Some EU countries are way ahead in terms of adoption, such as Switzerland, the Swizz Federal Railways rail network is 100% electrified, for example. The EU regulation of the railway sector will mean a technical standardisation in line with sustainable goals. By moving more road freight to rail, which is the plan, impacts will be significant for sustainable aims.

Trucks and Buses In May 2018, the European Commission put forward legislation for the first mandatory reductions for CO2 emissions for trucks, coaches and buses. It required a reduction of 15% by 2025 and 30% by 2030. The regulations will initially apply to 16 tons and above but from 2022 this will extend to lighter trucks, buses and coaches. Manufacturers will be incentivised to achieve zero tail pipe emissions, meaning going electric. As with cars, if the manufacturers fail to meet the emissions targets, they will face substantial fines, so investments in research and development is paramount. The stark reality at present is that, progress is relatively limited.Â In 2018, electric vehicles associated with freight were mostly light-commercial vehicles (LCVs), accounting for around 250,000 units in 2018, while medium electric truck sales were in the range of 1,000 - 2,000 in 2018. Whilst a climate emergency requires action, some manufacturers, already burdened with other market pressures, will face enormous strain from the demands for radical and effective innovation.

Trains Time for a success story. Trains are already hailed as a good choice for sustainable transport because compared to cars and planes they emit up to 80% less carbon and in some countries less that 3% of all transport emissions come from trains. Walking and cycling are said to be the only methods more environmentally friendly. Three quarters of passenger rail activity takes place on electric trains today, which is good news. Trains are the most reliant vehicles in the transport sector on electricity. Whatâ&#x20AC;&#x2122;s more, all around Europe there are plans to increase reliance on electric railways further, which is promising when according to a report by the IEA in 2019,

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Electricity in the Air

E-ships

The EU technical environmental goals of the European Commission’s Flightpath 2050 Vision for Aviation is the reduction of CO2 by 75%, reduction of NOx by 90% and noise reduction by 65%. So how realistic are these goals? Disappointingly, at the present time, not very. New technology is urgently needed and innovation is the only way to keep these lofty targets from being ‘pie in the sky’. The European Aviation Environmental Report (EAER) was pretty clear in the most recent assessment published in 2020, that aviation activities were increasing impacts to climate change, as well as ‘affecting the health and quality of the life of European citizens’. In Aviation, CO2 emissions are rising. Aviation is responsible for 3.6% of the total EU28 greenhouse gas emissions. There is a forecast growth of 42% in the number of flights between 2017 and 2040, which would mean a 21% increase in CO2 emissions. Pretty grim statistics when contrasted with the noble aims of climate impact mitigation adopted by European countries. Aviation is a thorn in the side of climate mitigation hopes. Whilst electric cars may seem a feasible future for the roads, the air travel is not ‘so simple’, relatively speaking, with technologies available.

An oft ignored diesel polluter in the sustainable transport debate is shipping, yet greenhouse gas emissions from shipping are the same as the carbon footprint of a quarter of passenger cars in Europe. The Yara Birkeland from Norway, is hailed to be the first electric powered autonomous container ship with zero emissions. It can carry 120 containers over 30 nautical miles. Although it represents breakthrough technology, there are diesel container ships around that carry 150 times as many containers over 400 times the distance, and four times faster. The problem, as always, is the economics around the logistics. To scale up an electric powered ship to make it compete means the batteries would take up 40% of the cargo capacity. Anyone can see the issue here. In the past 70 years the energy density of commercial batteries has only marginally shifted. Despite the difficulties, there are calls for the EU to impose a CO2 levy on EU shipping and create a European maritime climate fund to reinvest in the sector to help mitigate its carbon footprint.

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An oft ignored diesel polluter in the sustainable transport debate is shipping, yet greenhouse gas emissions from shipping are the same as the carbon footprint of a quarter of passenger cars in Europe. However, there is always hope for change. In 2019 at the Paris air show, an Israeli aircraft manufacturer unveiled Alice – a 9 seater electric plane powered by lithium-ion battery – capable of 650 miles at 10,000 ft on a single charge - expected in service by 2022. There is real motivation demonstrated from many countries to get ahead of the curve on electric powered flights. Take Norway as a leader in adoption of electric planes. Norway intends to make sure all short haul flights under an hour and a half are via electric planes by the year 2040. Avinor, Norway’s public operator of Norwegian airports, is planning to test commercial routes flown by small electric planes with 19 seats, from 2025. It will have some advantages economically as well as environmentally, with lower operational costs. Before we get there though, hybrid planes and biofuels will be initial steps to this goal. Hybrids are a little more palatable for some in this sector when talking about short haul commercial flights. If the planes can get off the ground with help from conventional engines, then once airborne the hope is they can fly with more reliance on electric motors. Airbus for example, are partnering with Rolls Royce and Siemens to develop a hybrid solution, the E-Fan X with its maiden voyage as a demonstrator as soon as in 2021. This aircraft seeks to be key in advancing aircraft design and determine requirements for future certification of electric aircraft. There is a sense of great innovation and continued tweaking in this sector, but the major impacts will

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be in making large commercial planes electric whilst being safe and reliable. When, how and even ‘if’ this will happen is yet not possible to say. Like all transport, the innovations need to step change to make it feasible. Considering that in 2018, 1,106 million people in the EU travelled by air, the challenge that is ahead in this sector alone, is obviously enormous. Leaving on a positive note, whilst electric commercial planes are ‘eeking’ slowly forward, aviation technologies in general are constantly aspiring to transform to be more lightweight, more efficient and less polluting – as it just makes commercial sense to improve efficiencies.

Electric dreams Summarising the plans and checking against realities, the future decades will no doubt see great changes, however, pressuring industry to such extremes in tight deadlines will no doubt mean casualties in business. There will be winners, losers and ambitious targets can sometimes fail. What’s proposed is a transformation of a transport infrastructure to a scale we have not witnessed before and it’s clear, the EU is determined to instigate an enforced widescale industrial change. Incentives, high level support, customer buy-in and investments into science will be the combined catalyst necessary to make change work. Electric is coming, the real problem is, of course, we need the change instantaneously if we are to make meaningful headway in climate mitigation.

Defining the limits of direct-democractic instruments A number of referendums have been held across different European states in recent years on various contentious topics, including immigration law, same-sex marriage and membership of the EU. With direct-democratic instruments being used more widely, it is becoming increasingly important to define their limits and scope, a topic that lies at the heart of Professor Daniel Moeckli’s research. A

referendum gives people the opportunity to directly influence government policy, as it provides a clear picture of public opinion on a particular issue. However, more and more often, citizens across Europe have been called to vote on proposals that are problematic from the perspective of the rule of law, such as immigration restrictions or prohibition of same-sex marriage. It is this tension between popular sovereignty and the rule of law that the LIDD project seeks to address. “We ask what types of limits are, and should be, imposed on direct-democratic instruments,” explains Professor Daniel Moeckli, the project’s Principal Investigator. Direct-democratic instruments have mushroomed over recent years, now Professor Moeckli and his colleagues in the project are investigating how exactly they are used. “What kinds of issues are excluded from the scope of those instruments? Is it possible to hold a referendum on something that violates international law, or human rights? Are certain policy issues, such as budgets and finances, excluded from the scope of these instruments? Should they be? And who decides whether a referendum may or may not go ahead?” he outlines. 58

LIDD project The LIDD researchers draw a distinction between substantive limits on the one hand and formal limits on the other. Substantive limits preclude referendums and initiatives on certain types of subject matter. “One topic that has been voted on in quite a number of European states is same-sex marriage, yet prohibiting it could

issue in this regard is whether the clarity requirement implies that voters must also be able to foresee the legal consequences of voting yes or no – which might have been questionable in the case of the Brexit referendum.” One of the aims of the project is to identify whether there is a core of issues that is regarded as being beyond the reach

issues are excluded from the scope of direct-democratic instruments? Is it possible to hold a referendum on something that violates international law, or human rights? What kinds of

be regarded as a violation of human rights. Referendums on immigration restrictions that, in all probability, violate international treaties have recently been held in Hungary and Switzerland,” says Professor Moeckli. The proposal or question that is to be voted on also needs to meet certain formal limits. “It must be possible for voters to freely form an opinion. Thus, the referendum question must be clear, precise and intelligible – and it must not include two different topics,” continues Professor Moeckli. “One key

of direct democracy. When Turkish president Recep Tayyip Erdoğan suggested that he might decide to hold a referendum on whether to reintroduce the death penalty for example, European states were clear that this would not be permissible. “We want to investigate whether there are some issues, such as the death penalty, where there is agreement between European states that holding such a referendum would be in violation of international law,” outlines Daniel Moeckli. Researchers will look at how

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direct-democratic instruments are handled by all 47 member states of the Council of Europe. “We want to find out whether, in terms of the practice, there is agreement on certain minimum standards,” explains Professor Moeckli. This research involves analysing the legal regulations of these 47 states. Professor Moeckli and his colleagues have created a database bringing together these regulations, from which they hope to gain deeper insights. “What does the law in a specific state say with regard to these questions? What types of issues are excluded from popular votes? What does the law say with regard to formal limits, to the formulation of a referendum question? What institutions and procedures are involved in making these decisions?” he asks. The information in the database is in the process of being verified by constitutional law experts from all over Europe and will then be made publicly available through an online tool that will also provide various ways of analysing the data. The first part of the project centres around investigating how direct-democratic instruments are handled, which provides the foundations for further research and analysis. A second database is also being developed that brings together information on all the referendums held over the last 30 years or so in Europe, enabling the LIDD researchers to investigate which proposals have proved particularly problematic. Some of these proposals have been subject to legal challenge, another topic of interest in the project. “We want to look at how this is done

in practice. For example, what does a court understand as a clear or unclear form of a question?” says Daniel Moeckli.

European Citizens’ Initiative Another part of the project concerns the European Citizens’ Initiative (ECI), a type of agenda initiative. This is a direct-democratic instrument that allows EU citizens to put forward proposals that are then considered by the European Commission. The ECI was based to a degree on the direct-democratic instruments that had been introduced at the national level. The experiences at the national level can thus help to inform the development of the ECI, which is an important aspect of Professor Moeckli’s research. “One of the core ideas of the project is to draw on the knowledge and experience of different European states with direct-democratic instruments,” he explains. The LIDD project will, first, identify a core of issues that is regarded as being beyond the reach of direct democracy across all European states and elaborate best practices that will help states define and apply the limits of direct democracy in a sensible way. Second, the project will identify common European minimum standards that institutional and procedural systems for reviewing compliance with these limits must satisfy and make suggestions for improving these systems: What would be the ideal body for making decisions on the admissibility of referendums? This research holds important implications for how direct-democratic instruments are used in future.

LIDD Popular Sovereignty vs. the Rule of Law? Defining the Limits of Direct Democracy Project Objectives

With the mushrooming of referendums and other direct-democratic instruments throughout Europe, the relationship between popular sovereignty and the rule of law is set to become one of the defining political issues of our time. Where should the legal limits of direct democracy be drawn? Who should review compliance with these limits? It is the objective of LIDD to provide the scientific basis for answering these questions.

Project Funding

The project is funded by a Consolidator Grant from the European Research Council (ERC) (Grant agreement 772160).

Contact Details

Project Coordinator, Professor Daniel Moeckli University of Zurich Institute for International and Foreign Constitutional Law Rämistrasse 74/50 CH-8001 Zürich Switzerland T: +41 44 634 58 81 E: daniel.moeckli@uzh.ch W: https://www.ivr.uzh.ch/en/ institutsmitglieder/moeckli/Researchproject-LIDD.html

Professor Daniel Moeckli

Daniel Moeckli is Professor of Public International Law and Constitutional Law at the University of Zurich. He studied law at the University of Bern before obtaining an LLM from the LSE and a PhD from the University of Nottingham. He has held visiting positions at University of Cambridge, Hebrew University of Jerusalem, the EUI and NYU. His research focuses on questions related to human rights and democracy.

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From Empire to nation state The Habsburg Empire collapsed at the end of the First World War, to be replaced by separate nation states across central and eastern Europe. How did society change in this new context? What norms and practices from the Habsburg era were carried over into the post-1918 era? These questions are central to the work of the Nepostrans project, as Dr Gábor Egry explains. The collapse of

the Habsburg Empire in 1918 following defeat in the First World War led to a dramatic shift in the social and political landscape across Central and Eastern Europe, as the previous imperial structure was replaced by nation states. As the Principal Investigator of the Nepostrans project, Dr Gábor Egry aims to investigate the nature of this transition from Empire to nation state. “In the project we are looking for both signs of continuity and also signs of rupture in institutional and cultural practice,” he outlines. While the primary focus in the project is on the post-imperial transition, researchers are also using material dating back to before 1918, in order to build a deeper picture of the practices and habits of both people and states. “We’re looking at how these local societies and administrations operated, what kind of individual relations mattered in that context? What were the important local institutions and what were of secondary importance?” explains Dr Egry.

Nepostrans project This research involves extensive analysis of material and documents available from local and national archives in nine regions and the different national capitals, from which Dr Egry and his colleagues hope to gain new insights into how society and institutions changed following the end of the Habsburg Empire. The Empire itself originated in the 13th century, and while its borders shifted over time, it still covered vast expanses of territory across central and eastern Europe at the start of the First World War in 1914. “The Habsburg Empire was very heterogenous in terms of people, culture and language,” says Dr Egry. The Empire functioned as a dual monarchy from the latter part of the 19th century, with some areas administered from Vienna, and others from Budapest. “There was a dual centre. Different areas were often treated differently by the centre in terms of the application of certain legal frameworks and political relations,” continues Dr Egry. “Which social groups were integrated into the Imperial framework and which were excluded? This question is partly related to the political and cultural background.”

From Karlovy Vary to Kotor, From Bregenz to Brașov and Trieste to Lviv.

Researchers aim to investigate these types of questions through analysis of archival material, then look to identify continuities in the post-1918 era, as well as any ruptures. The institutional position, and the development of new modes of governance, is one topic Dr

Plans for the statue of King Ferdinand in Caransebeș, Romania to be erected on the pedestal of the former Francis Joseph statue. Photo made by Gabor Egry

Egry and his colleagues are addressing in the project. “Who were the faces of the state? Who represented the state? Who tried to shape the state?” he outlines. The way in which a state was built helped to shape perceptions of the authorities and their wider role. “If there is a friendly face behind a desk in a state office, then that’s very different to meeting somebody who adopts a very dismissive attitude towards you from the moment they meet you. It gives people a very different impression of the state,” points out Dr Egry. “As an individual you may encounter people who are more or less efficient, but the inner workings of the state can still be similarly revealing. We’re interested not just in individual attitudes, but also certain ideas about how the state should operate when it encounters the people and faces society.” The attitude of state officials towards the wider population helped to shape public attitudes and perceptions of its legitimacy, another topic of interest in the project. Researchers are looking at the legitimising aspects of statehood, how the state perceived itself and how it actually functioned. “What kind of influence did

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historical events and individuals exert on these dual aspects of state formation?” asks Dr Egry. This process of state-building took place against a backdrop of major changes to national borders following the Treaty of Trianon in 1920, which left many people who felt themselves to be culturally and linguistically Hungarian outside the new national borders, while Dr Egry says that people in other areas of the former Habsburg Empire experienced a similar dislocation.

the project’s research, with the first couple currently in the process of being prepared. “We want to conclude the whole project with a collective monograph that touches on issues of statehood, continuity and rupture,” continues Dr Egry. “We will deal with certain themes (state, elites, ethnicity, discourses) on the basis of our research related to these broader discourses around nationhood. We will also produce some more traditionally comparative work.”

We’re looking at how these local societies and administrations operated, what kind of individual relations mattered in that specific context? What were the important local institutions and what were of secondary importance? “It’s also true for parts of the newly-created country of Czechoslovakia, where many people felt culturally German, while millions of Ukrainians lived in Poland. This was a general feature of the area of the former Habsburg Empire,” he explains. There were however also some commonalities, in terms of culture, social practices, like cuisine or coffeehouse culture and a whole host of other social norms, a shared legacy of being part of the Habsburg Empire for so long. Through focused analysis of the available data, Dr Egry hopes to identify the areas of continuity and the areas of rupture following the end of the Imperial era. “We want to focus on the local level, to look at the common people’s experience of transition from empire to nation state,” he stresses. The plan is to publish a number of papers on the basis of

This year is an opportune time to reflect on these issues of statehood, as the centenary of the Treaty of Trianon will be marked in June. The centenary will give Dr Egry and his colleagues an opportunity to present their research and challenge conventional thinking on the history of central and eastern Europe. “We want to challenge some of the dominant ideas and to explore the politics of memory, as well as to contribute to a new history of Eastern Europe,” he says. “At some point we want to bring together secondary school students from different states to discuss these issues and publish our results. We want to influence how society thinks about the past, and also about how this relates to the present. How do individuals relate to the state? How do they view and handle diversity within society?” Polish customs guard controlling a carriage on the border between Bukovina an Galica, early 1920s. National Digital Archive of Poland, public domain.

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NEPOSTRANS Negotiating post-imperial transitions: from remobilization to nation-state consolidation. A comparative study of local and regional transitions in post-Habsburg East and Central Europe Project Objectives

The main objective is to shed light on state and society relations and interactions through the experiences of and throughout a profound change of statehood. The local focus offers access to a history that challenges the narrative of overall nationalization still prevalent regarding the former Habsburg Monarch and the comparative method enables a generalization that would enrich the theories of statehood too.

Project Funding

The project is funded by the ERC CoG 2017 772264 agreement.

Project Partners

Project patners are University of Strasbourg, University of Ljubljana, Trianon100 Momentum Research Group of the Hungarian Academy of Sciences, The Transition of Croatian Elites from the Habsburg Monarchy to the Yugoslav State (Croelites) research project at the University of Zagreb.

Contact Details

Gabor Egry, MTA doktora/DSc történész/historian Principal Investigator/Vezető kutató ERC CoG-2017 NEPOSTRANS főigazgató/director-general Politikatörténeti Intézet/Institute of Political History 1054, Alkotmány u. 2, Budapest T: +36 30 821 4667 E: info@phistory.hu E: egrygabor@phistory.hu W: www.nepostrans.eu W: www.1918local.eu Dr Gábor Egry

Gábor Egry is Doctor of the Hungarian Academy of Sciences (2018) and directorgeneral of the Institute of Political History, Budapest. His research topics are ethnicity, nationalism, politics of memory and identity in modern East Central Europe. He held fellowships at the New Europe College, Bucharest, Stanford University, Imre Kertész Kolleg Jena, IOS Regensburg.

The figure shows the rate at which native Dutch citizens opt for an equal split of 160 Euro (indicated as sharing) versus keeping 85 Euro for oneself and giving 20 Euro to a partner. Included are the overall rate of sharing, the rate of sharing of citizens who are rather intolerant to ethnic diversity, and that of citizens who are tolerant to ethnic diversity.

Tastes in discrimination research Evidence suggests that people from ethnic minority backgrounds face discrimination in everyday life, for example in the employment market, or in the ability to rent a car. While sometimes discrimination occurs because a decision-maker lacks sufficient information, in other situations it may be taste-based, an issue at the heart of Professor Sigrid Suetens’ research. Many

European countries are characterised by high levels of ethnic diversity, with people from all over the world living and working together, particularly in major cities. However, people from ethnic minority backgrounds may still face discrimination in the employment market, according to Sigrid Suetens, Professor of Economics at Tilburg University in the Netherlands. “People from an ethnic minority background often have a hard time in finding a job. Studies have shown that job applicants with a minority background are less frequently invited for a job interview than applicants from the majority, even if their qualifications are the same,” she says. Discrimination is also still evident in other areas of everyday life, despite efforts to tackle it. “For example, in a study on ebay sports cards held by a white-skinned hand were sold for lower prices than the same cards held by a black-skinned hand,” explains Professor Suetens. “It’s also been shown that it’s much harder for people from minority backgrounds to rent a house.” 62

Diverse-Expecon project As the Principal Investigator of the DiverseExpecon project, Professor Suetens aims to investigate the role of so-called tastes in discrimination. To study discrimination, a distinction is often drawn between tastebased discrimination (TBD) and statistical discrimination, the latter of which is closely related to the idea of stereotyping. “Discrimination can be thought of in a way as a very rational behaviour, in the sense that if you do not have a lot of information about a specific group in society, then as an employer you might use the general information available to make a decision,” outlines Professor Suetens. TBD is different to statistical discrimination; in a way it has deeper roots. “The easiest way to understand TBD is to consider an example where an employer wants to hire someone, knows perfectly that the future productivity of all applicants will be the same, and still discriminates on the basis of ethnicity,” explains Professor Suetens. The aim in the project is to study whether tastes are important to understand discrimination,

and if so how they are important, which could in future help inform policy development. One part of the work involved giving people the opportunity to make choices that have reallife financial consequences, then assessing their responses. “We ran an experiment in the Netherlands on a large sample of Dutch people. We confronted them with a case where there wasn’t really any statistical uncertainty involved for the decision-maker,” says Professor Suetens. This allowed researchers to investigate whether respondents treated people from an ethnic minority background any differently. “In this experiment, people had to decide who got what in terms of money,” continues Professor Suetens. “The trade-off was basically a choice between two parties getting an equal amount, which would still be reasonably high, or the decision-maker getting a higher amount.” Researchers varied the first name of the other person involved in this experiment, aiming to uncover any differences in how people from ethnic minority backgrounds are treated. In one treatment, all the first names were related to

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DIVERSE-EXPECON Discriminative preferences and fairness ideals in diverse societies: An ‘experimental economics’ approach Project Objectives

people from a Dutch majority background, and in the other the name was associated with people from an ethnic minority background. “The name was a very clear signal of that particular person’s background. We also made sure that the names corresponded to real people,” outlines Professor Suetens. Respondent shared substantially less with partners from an ethnic minoirity group; in particular those who are relatively intolerant to ethnic diversity in society (see figure). Another strand of Professor Suetens’ research agenda involves studying people’s underlying ideas on fairness. “I’m extremely curious about how an external observer, a spectator who has nothing at stake him- or her-self, would decide about how to redistribute money between two people,” she continues. “Are the spectator’s ideals about redistribution going to be different depending on who the two people are? And is it going to matter whether the money has been earned in a productive task?”

This research holds wider importance in the context of the refugee crisis of 2015 and the ensuing influx of migrants into Europe. Researchers have access to reports on people from the ethnic majority’s views on diversity in society, which is an invaluable source of data for Professor Suetens. “We have followed these people over time. We know that some of them were exposed to new groups during a particular period of the study – often people from the Middle East, sometimes from North Africa – while other people were not exposed,” she outlines. This gave researchers the opportunity to investigate the impact of exposure to ethnic minorities on people’s attitudes towards them, so whether meeting Syrian refugees led to increased sympathy for ethnic minorities for example. “We have investigated whether people’s attitudes towards ethnic minorities in general change over time, because of the increased exposure,” explains Professor Suetens.

I’m extremely curious about how an external observer, a spectator who has nothing at stake him- or her-self, would decide about how to redistribute money between two people. Are ideals about redistribution going to be different depending on who the two people are? An individual’s propensity to discriminate may be associated with a number of factors, including their age, the area in which they live, and their educational background. Analysis of the available data reveals some important insights in this respect. “What we have found is that older people, above median age, are more likely to discriminate than younger people. We have also found that more educated people are less likely to discriminate,” says Professor Suetens. Correlation is not causation however, so Professor Suetens and her colleagues plan to dig deeper. “We’ve seen that amongst people who have a lot of daily contact with ethnic minorities, there tends to be less discrimination, but it’s really hard to know whether there is a causal relationship. It may be that people with that attitude are more likely to live in an ethnically diverse area,” she explains. “In an ongoing study we study whether exposure to ethnic minorities has a causal effect on attitudes towards them.”

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The Diverse-Expecon project aims to systematically study taste-based discrimination (TBD) in ethnically diverse societies. Identifying TBD is tricky however, as it is impossible to identify using uncontrolled empirical data, because these data are characterised by strategic uncertainty.

Project Funding

Funded by the European Research Council.

Project Partners

NHH, Norwegian School of Economics (Alexander Cappelen and Bertil Tungodden). Post-doc researchers: Pascal Achard, Paul van Bruggen PhD students (non-funded): Phuc Phung and Yi Sheng Collaborators: Elena Cettolin (Tilburg University). Sabina Albrecht (Queensland University of Technology). Riccardo Ghidoni (University of Milano-Bicocca)

Contact Details

Project Coordinator, Professor Sigrid Suetens Department of Economics Tilburg University Postbus 90153 5000 LE Netherlands T: +31 13 466 8790 E: S.Suetens@uvt.nl W: http://sigridsuetens.weebly.com Academic publications Cettolin E. and Suetens S. (2019), Return on trust is lower for immigrants, Economic Journal, vol. 129, pages 1992-2009

Professor Sigrid Suetens

Policy development A deeper understanding of the nature of the nature of discrimination observed in society can then inform policy designed to prevent it. If it is assumed that all the discrimination observed in daily life is statistical, then this implies that providing more information would help to prevent it, yet this would not necessarily be effective where discrimination is taste-based. “It’s really important to have information about the nature of discrimination. That can have significant policy implications,” stresses Professor Suetens. Many questions remain unanswered however, and Professor Suetens plans to devote a lot of her attention in future to questions around fairness and redistribution, and how they are affected by the ethnicity of the recipient. “We plan to design a really big experiment, to get at the heart of redistribution ideals,” she continues. “As an outsider, you might see that person A is rich and person B is poor. How much are you going to redistribute from A to B?”

Sigrid Suetens is a Professor of Economics at Tilburg University in the Netherlands. She holds a PhD in applied economics from the University of Antwerp, from where she also gained her degree . Her main research interests are ethnic discrimination and the strategic and non-strategic incentives that can encourage cooperation between actors.

Euler systems and arithmetic applications Euler systems can be thought of as a collection of points or cohomology classes attached to an algebraic object, which satisfy some very precise compatibility relations. These systems are very hard to construct, but they have very powerful arithmetic applications, such as proving new cases of the Bloch-Kato conjecture as well as the Birch and Swinnerton-Dyer conjecture, as Professor Sarah Zerbes explains. A collection of cohomology classes for a given algebraic object, the first example of an Euler system was constructed by the Russian mathematician Victor Kolyvagin. While these systems are named after the highly influential 18th century Swiss mathematician Leonhard Euler, they were only introduced relatively recently. “In the case of Kolyvagin’s work, an Euler system is a collection of points on modular elliptic curves,” explains Sarah Zerbes, Professor of Maths at University College London. Euler systems, once constructed, have very powerful applications to some of the central open conjectures in number theory. “Kolyvagin recognised that his Euler system could be used to prove new cases of the conjecture of Birch and Swinnerton-Dyer.” says Professor Zerbes. These Euler systems are extremely difficult to construct however, and until relatively recently only four were known to exist. Professor Zerbes and her collaborators have since developed a new approach to constructing them. “It started with the Euler system of Beilinson-Flach elements. We found that the method with which we had constructed this system could be applied in great generality, so now we have greatly increased the number of known Euler systems,” she says. As the Principal Investigator of an ERC-funded research project based at UCL, Professor Zerbes is now investigating the arithmetic applications of these systems. “Euler systems are fundamentally geometric constructions. The underlying objects are socalled Shimura varieties, which are algebraic varieties arising in the representation theory of matrix groups,” she outlines.

Euler systems The construction of these systems is based on the use of geometric methods, as well as methods from representation theory and number theory. While researchers were able to construct new examples of Euler systems, it was not initially possible to use them for arithmetic applications. “We constructed these geometric objects, but it was difficult to establish that they were non-zero. We were in the frustrating situation where we

Graphs of the L-functions attached to elliptic curves of ranks 0,1 and 2, respectively.

had many new Euler systems, but we didn’t know that they were non-zero,” explains Professor Zerbes. New results have since emerged which formed the missing piece of the puzzle, enabling Professor Zerbes and her colleagues to give a criterion for the nonvanishing of the Euler systems, and to study the various arithmetical applications. “The way to prove the non-vanishing of an Euler system is by relating it to the value of an L-function. Such a relation is called an explicit reciprocity law.” This opens up many new exciting avenues of research, with Professor Zerbes particularly interested in proving new cases of the BlochKato conjecture, which predicts that certain values of the L-function govern the size of a Selmer group, attached to the underlying

Shimura variety. An Euler system is extremely useful in terms of proving new cases of the conjecture. “Two things can be attached to an Euler system. Firstly, we can attach to it a Selmer group, which is a certain cohomology group. We can also attach to it an L-function, which is a complex analytic function,” outlines Professor Zerbes. This provides the basis for researchers to investigate possible new cases of the Bloch-Kato conjecture. “If the L-function at a certain point does not vanish, then this Selmer group should be zero. This is the case that an Euler system will prove,” continues Professor Zerbes. “We are also interested in the Birch and SwinnertonDyer conjecture. One can think of the BlochKato conjecture as a vast generalisation of the Birch and Swinnerton-Dyer conjecture.”

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EULER SYSTEMS Euler systems and the Birch-Swinnerton-Dyer conjecture Project Objectives

To prove new cases of the Bloch—Kato conjecture on special values of L-functions, via a systematic construction and study of so-called Euler systems. In particular, to prove the Birch—Swinnerton-Dyer conjecture for elliptic curves over imaginary quadratic fields in analytic rank 0.

Project Funding

Funded by the European Research Council total funding € 1,070,473.

Project Partners

The research programme has been developed jointly with Professor David Loeffler (University of Warwick), who is funded by a Royal Society URF.

The Birch and Swinnerton-Dyer conjecture is one of the Clay Millennium Prize Problems; it is concerned with the rational solutions on a so-called elliptic curve, which is an equation in two variables of the form y2 = f (x) where f is a cubic polynomial with distinct roots. The set of rational points on the curve (together with the point at ∞) forms an abelian group, which is known to be finitely generated; the rank of this group measures the “density” of rational points on the curve – in particular, the rank is 0 if - and only if - the set of rational points is finite.

is currently focused on a case where the underlying Shimura variety is a Siegel modular variety. “This is a certain Shimura variety which is attached to the symplectic group GSp (4). We constructed the Euler system, and we are currently proving the explicit reciprocity law,” explains Professor Zerbes. “We are in the process of writing that up, and hopefully it will be available in the next few months. That would have applications to the Birch and SwinnertonDyer conjecture for abelian surfaces.”

We constructed these geometric objects, but it was difficult to establish that they were non-zero. We were in a position where we had lots of new Euler systems, but we didn’t know that any of them were non-trivial. The Birch-Swinnerton-Dyer conjecture, which was formulated in the 1960s based on extensive numerical computations, relates this quantity to another, very different aspect of the elliptic curve: its L-function. This is a complex-analytic function of a variable s, defined as an infinite product over primes in which the factor for a prime p is determined by counting points on the reduction of the curve modulo p. The conjecture predicts that although this L-function is built up from local data, it encodes global information: the rank of the elliptic curve should be equal to the order of vanishing of the L-function at the point s = 1 (the “analytic rank”). One specific goal for Professor Zerbes and her colleagues is to prove new cases of a generalisation of the Birch and SwinnertonDyer conjecture for Abelian surfaces. “To do that, we need the Euler system and we need the explicit reciprocity law, which relates the Euler system to the value of the L-function,” she says. A lot of attention

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Researchers are also continuing to look at other Euler systems, which can be constructed in vastly greater generality than previously possible. Over the next few years the aim is to prove explicit reciprocity laws in all of the cases where Euler systems can be constructed, which can then be used to prove many new cases of the Bloch-Kato conjecture and enable researchers to look towards more ambitious objectives. “The long-term goal would be to prove the Bloch-Kato conjecture in general, or at least for certain Shimura varieties,” says Professor Zerbes. This is a complex and as yet not fully-defined task, however it is a topic that Professor Zerbes is keen to address in her research in future. “The Euler systems give results when the L-function does not vanish at certain points. If it does vanish then everything becomes much more complicated, and at present a strategy for dealing with these cases is not known,” she outlines. “That’s something that my collaborators and I are certainly planning on thinking about in the future.”

Contact Details

Project Coordinator Professor Sarah Livia Zerbes Department of Mathematics University College London Gower Street London WC1E 6BT United Kingdom E: s.zerbes@ucl.ac.uk W: http://www.homepages.ucl. ac.uk/~ucahsze/

Professor Sarah Livia Zerbes

Professor Sarah Zerbes, a German mathematician, completed her undergraduate education at the University of Cambridge in 2002. She then went on to do her doctoral studies under the supervision of Professor John Coates, FRS, receiving her PhD in 2005. She is interested in special values of L-functions and Iwasawa theory, which she investigates together with her husband and close collaborator David Loeffler.

Assessing the impact of Basel III The Basel III framework was developed in response to the issues revealed by the 2008 financial crisis, now Professor Andreas Dietrich together with Professor Gabrielle Wanzenried and other researchers at the Lucerne University of Applied Sciences and Arts aim to assess the impact of these new rules and guidelines on the Swiss banking sector. The crisis of 2008 revealed significant deficiencies in the way the financial sector was regulated as banks across the world experienced severe liquidity problems, to which many governments responded by bailing out major institutions. New rules around liquidity and funding structures have since been agreed in the Basel III regulatory framework, now Professor Andreas Dietrich and his research team aim to assess their impact on Swiss retail banks in a new research project. “Our belief is that these liquidity rules are the ones that really matter for banks. We want to assess the impact of these new liquidity rules on the banks, on their overall profitability and performance. How have they reacted to these new rules and guidelines?” he outlines. Prior to 2008, liquidity rules often weren’t discussed at a strategic level, but the impact of the crisis prompted a major re-think. “After the financial crisis, it was realised that liquidity risk is actually very important,” says Professor Dietrich.

Market liquidity This relates both to a bank’s ability to raise capital from selling assets, and also the extent of its cash reserves. Professor Dietrich and his colleagues are essentially

addressing two aspects of liquidity in their research. “One is short-term liquidity, which can be thought of as a fairly basic form of liquidity. So if liquidity flows out during a stress scenario, then the banks still need to have enough liquidity to cover short-term demands from customers,” he outlines. Many banks found themselves unable to do this in 2008, as they were over-leveraged and had extended excessive amounts of

example provides mortgages that are funded by deposits over a more extended period. The Basel III framework set out the liquidity coverage ratio (LCR) and the net stable funding ratio (NSFR) to promote more sustainable funding structures. “These funding ratios are the focus of our project,” says Professor Dietrich. These ratios set out the amount a bank should hold in cash and assets in relation to its cash outflows

We want to assess

the impact of these new liquidity rules on the banks, on their overall profitability and performance. How have they reacted to these new rules and guidelines? credit, leaving them badly exposed when the crisis hit. “Liquidity risk can be thought of as the danger that a bank will not be able to fulfill all its liquidity requirements. So people remove money from their accounts, because they are afraid that the bank might not have sufficient liquidity any more,” explains Professor Dietrich. A second part of the project’s research centres on long-term liquidity, which relates to a bank’s ability to maintain liquidity in the long run, where an institution for

under certain scenarios, with the ultimate goal for regulators of helping the market run effectively, while still giving banks scope to lend money and take on risk at an appropriate level. “These two new ratios were included in the Basel framework and as a result I believe the liquidity risk is now lower than it was before the financial crisis,” continues Professor Dietrich. As head of the institute of financial services at Lucerne University of Applied Sciences and Arts in Switzerland, Professor

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Dietrich has written a number of papers exploring the impact of these ratios on the banking sector. One part of his research involved looking at data from a sample of over 900 banks over the period between 1996-2010, with researchers using a regression framework to analyse the effects of these liquidity rules. “We can get pretty close to the NSFR by looking at historical data from banks’ balance sheets. How would it have looked if banks had already had to implement these ratios previously?” asks Professor Dietrich. Research shows that those banks which expanded rapidly have generally maintained lower NSFRs. “A lot of banks were trying to essentially optimise their return on equity, that was the main target,” explains Professor Dietrich. It is more difficult to establish a longterm perspective on the LCR, as there is a lack of consistent data on the same kind of level as the NSFR. However, since 2015 banks have been required to report it, while researchers also have access to data from

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a representative set of Swiss retail banks, which provides a basis for Professor Dietrich and his colleagues to investigate it in greater depth. “How will banks operate in future? What will happen if the interest rate goes up in Switzerland? What will that mean for the LCR?” he continues.

Market entrants The impact of the LCR will vary to a degree according to the size of the bank and the nature of its operations, so Professor Dietrich and his colleagues are looking at data on a wide range of institutions in their research, from small banks to large institutions. While many major institutions are able to ensure that they comply with the ratios, it can be more of a problem for smaller banks, who may not be able to commit the same level of resources.“Fulfilling regulatory requirements is often a major task for smaller banks, as they may not have a separate team for the job,” explains Professor Dietrich. This is a prominent concern for regulators, who may want to

ensure a degree of diversity and ensure that the market is open to potential new entrants. “We can see that new banks coming into the market face a lot of challenges. In Switzerland and the UK for example, there are different kinds of regulations for these challenger banks,” says Professor Dietrich. A number of new banks have entered the UK market over recent years, in part because of relatively enlightened regulation from the authorities which has encouraged new entrants. The Financial Conduct Authority (FCA) in the UK adjusted its regulations for new banks, which Professor Dietrich says has helped introduce more diversity into the market. “There is space to allow these new kinds of challengers,” he outlines. The Swiss financial regulator, FINMA, also has a rigorous regulatory framework, where larger banks are subject to a more intense degree of scrutiny, with the wider aim of maintaining stability in the final system. “FINMA has five categories of banks, where the largest banks are in category 1, while the smallest

ones are in category 5,” continues Professor Dietrich. “We saw that introducing LCR was more expensive in overall cash terms for the larger banks.” The smaller banks were nevertheless hit harder by these new regulations, as the costs of introduction were significantly higher in relation to their overall profits. For a large bank, introductory costs of a billion Swiss francs may be relatively negligible in terms of their overall profits, whereas a smaller bank would be hit much harder. “Introductory costs of 500,000 Swiss francs in relation to the profits of a smaller bank could be a higher burden than a billion for the larger banks, who often make enormous profits,” points out Professor Dietrich. This may raise concern for regulators in terms of market competition, so Professor Dietrich’s research holds wider relevance for the authorities. “I was recently invited to FINMA to talk about our results,” he says. “During the course of our research, we realised that there are some elements of our work that can be fed back to regulators, to help them optimise some aspects of the regulatory regime.” A relatively small bank that lends primarily to companies and businesses in its local area is of course very different to a

major international institution with a global reach and an investment portfolio that spans the world. However, regulations are often developed with the bigger institutions in mind, which can create problems for smaller banks. “A smaller bank may argue that it would cost a lot of money to comply with a specific regulation, and the problem it seeks to address isn’t relevant to them,” explains Professor Dietrich. This is an issue that FINMA is addressing through the small banks regime. “The regulator is looking at how it can kind of make changes for smaller banks, so that they have to deal with less regulation than larger banks,” continues Professor Dietrich. “A one-size-fits all approach is not the best way to regulate the banking sector.” The major banks operate internationally, so it could be argued that a global regulatory framework is required to provide a level playing field and ensure fair competition. However, smaller banks don’t operate on the same kind of scale, and Professor Dietrich says regulations under the small banks regime have been modified to reflect this, subject to the bank meeting certain criteria in terms of liquidity and capitalisation. “Under the small banks regime, banks don’t need to report as regularly, and they also have some other

freedoms,” he outlines. One major area of divergence is that these smaller banks do not need to calculate and comply with the NSFR. “This is one way in which small banks are released from this big regulatory burden that was constructed more for the bigger banks,” explains Professor Dietrich. Researchers at Professor Dietrich’s institute are working to assess the impact of these new rules on the Swiss retail banking sector, work which holds important implications for the banks themselves and their evolution. Banks are of course keen to maximise profits while also preparing for the future and considering how the market will evolve; Professor Dietrich’s research could lead to some important insights in this respect. “We are very close to industry and a common question from bankers is, how should we plan for the future?” he outlines. Regulatory frameworks can in a sense be seen as quite reactive, as they are often developed in response to the issues that led to an earlier crisis, so it is difficult to forecast how the banking sector will evolve. However, Professor Dietrich maintains close contacts with industry, and says the project has generated some interesting results. “I have been advising banks on what they might do in some areas in future,” he outlines.

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The specific economic context in which banks are currently operating is an important consideration in this respect. At the moment interest rates remain extremely low, and they have even strayed into negative territory at some points over the last few years, yet this cannot persist indefinitely, and when rates do rise the impact is likely to be significant. “I think we can only say whether liquidity rules work and assess their impact on the

Evidence suggest that the Basel III rules are proving effective in terms of helping banks maintain adequate liquidity, but are also affecting the efficiency of their operations. At the moment there is enough liquidity in the Swiss market, as many people are putting their money into savings accounts rather than investing in shares, yet circumstances may change in future. “A bank looking to invest in high-quality liquid assets would normally invest in assets like bonds for

We can get pretty

close to the NSFR by looking at historical data from banks’ balance sheets. How would it have looked if banks had already had to implement these ratios previously? economy when interest rates go back to normal levels,” says Professor Dietrich. When interest rates do go back to a more historically normal level, of say 2-3 percent, then banks will need to invest more in highquality liquid assets like bonds, which can be converted quickly into cash without losing their value. “This will be much more expensive for banks than what they are doing now,” continues Professor Dietrich.

example. However, bonds aren’t a particularly attractive asset class at the moment. So, what banks can do is put money in a certain type of account, where the costs are lower than if they were to spend that money investing in high-quality liquid assets,” outlines Professor Dietrich. “We don’t know how people will react if interest rates rise in future, but the cost of fulfilling the LCR will be much more expensive for banks than it is today.

Impacts of new Basel III Impacts of new Basel III liquidity rules on retail banks in Switzerland Project Objectives

As a reaction to the latest financial crisis, the Swiss banking sector is confronted with a large variety of new rules and guidelines. The research project investigated the impacts of the new Basel III liquidity rules on retail banks in Switzerland, i.e. it analyzed the determinants of the liquidity coverage ratio (LCR)1 and the net stable funding ratio (NSFR) and their impacts on Swiss retail banks’ performance as well as range of products.

Project Funding

The project was funded by the Swiss National Science Foundation SNF

Contact Details

Professor Andreas Dietrich Institute of Financial Services Zug IFZ , School of Business Lucerne University of Applied Sciences and Arts T: +41 41 757 67 46 E: andreas.dietrich@hslu.ch

Professor Gabrielle Wanzenried Professor Andreas Dietrich

Professor Gabrielle Wanzenried is professor of finance at the School of Management and Engineering in Yverdon, part of the University of Applied Sciences and Arts of Western Switzerland, a position she has held since September 2019. Prior to joining (HEIG-VD) she was professor of corporate finance at the Institute of Financial Services Institute of the Lucerne Unviersity of Applied Sciences and Art. Her research and teaching topics are Corporate Finance, Banking Corporate Governance, Diversity and Real Estate. Professor Andreas Dietrich heads the Institute of Financial Services Zug IFZ, where he has worked since 2008. He obtained his doctorate at the University of St. Gallen (HSG), where he also worked as a research associate. He also sits on the board of directors of the Lucerne Cantonal Bank.

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Putting back the pieces of scholarly social networks

User statistics of CEMROL. In the month of November 2019, 666 unique users marked or transcribed letters. Since the launch of CEMROL in December 2018 more than 128.000 classifications were completed (with one classification being equal to one item marked or the transcription of one particular feature).

The ideal of open science has a long history, with evidence that scholars and scientists in the early modern period corresponded extensively with each other, often to share ideas and knowledge. We spoke to Dr Dirk van Miert about his work in reassembling these learned networks through digital analysis of correspondence from the period. A high degree of collaboration is a central feature of academic research, with scientists and scholars often sharing knowledge with colleagues to gain deeper insights across both the humanities and sciences. Scholars also shared ideas with their peers during the period of the Republic of Letters, a term which dates back to 1417, although it did not become more commonly used until the 16th century. “The phrase ‘Republic of Letters’ or respublica literaria, was a term frequently used by scholars in their letters to each other between 1500-1800,” explains Dr Dirk van Miert. As the leader of the SKILLNET project, Dr van Miert aims to effectively reassemble these social networks through analysis of letters and text mining techniques, focusing primarily on the period between 1500-1800. “We focus on printed letter collections. Many of these letters were sent by scholars across European states to colleagues in different countries,” he says. “They were also often assembled and then published later on, as sources about who was communicating with who.”

Public engagement Printed letter collections from the period are widely available in digitized form on the internet and researchers are encouraging the public to get involved in gathering data about these letters through the CEMROL crowdsourcing project. With the SKILLNET project funded by the taxpayer, Dr van Miert is keenly aware of the need to engage the public and demonstrate the wider relevance of their research. “People with an interest in history can get involved

CEMROL crowdsourcing project screenshot.

by gathering data,” he continues. The correspondence itself relates to a wide range of scholars; one figure of interest is the Dutch scholar Aernout van Buchel, or Buchelius. “He was raised as a Catholic scholar, then when the reformation came to Holland he converted to Protestantism and became an influential

the Republic of Letters coincided with major social and religious change, in particular the Reformation, which effectively split the intellectual world. “The Republic of Letters can be thought of as a scholarly or scientific community which evolved alongside the great crises or revolutions in learning in Europe,” says Dr van Miert. “It survived the Reformation, the Scientific Revolution and came into its own during the Enlightenment, when scholars and scientists communicated not only through letters and books, but also through scientific journals.” The focus of the project is the social fabric of the Republic of Letters. “We’re particularly interested in the networks these people created,”

We’re looking at the Republic of Letters from a social perspective. We’re particularly interested in

the networks these people created. Protestant,” explains Dr van Miert. “He was very interested in antiquity, in buildings and archaeology. He kept on collecting that kind of material, writing about it and making drawings of buildings and sharing that knowledge through his letters. He was based in Utrecht, but he maintained correspondence with friends of his, in Rome for example.” A further prominent example is the philosopher and scholar Desiderius Erasmus, who helped popularise the concept of a Republic of Letters through his correspondence and writings. The rise of

Dr van Miert explains. The relationships between scientists were established in different ways – they may have been friends, fellow students, or neighbours – but it is their correspondence with each other that is of interest in the project. “A letter ties one person to another at a particular time or date, across a particular space,” points out Dr van Miert. “So, if somebody in London wrote to somebody in Amsterdam on a specific date then there’s a link between them. If you have many of these links then you can start reassembling these correspondence networks and model them as a social network.”

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SKILLNET Sharing Knowledge in Learned and Literary Networks Project Objectives

The SKILLNET project aims to unravel the social fabric of the early modern world of learning, known as the ‘Republic of Letters’. It seeks to map the popularity of this term and to analyze how the collective identity of this transnational community was based on the ideal of sharing knowledge.

Project Funding Volunteers of crowdsourcing project CEMROL at a presentation of preliminary results of their work.

The correspondence might relate to new scientific ideas or religious teachings, yet equally it might be about something else entirely. It’s not realistic to read through all of the hundreds of thousands of these letters which are still kept in manuscript form or in printed editions in European libraries, so researchers are instead looking at the meta-data “Who wrote to whom? When and where? We’re looking to reconstruct the overall picture here, to see who was central in a particular network,” explains Dr van Miert. “We are using social network techniques and distance reading techniques to sift through these thousands and thousands of letters, without necessarily studying every single page,” he says. “We’re really looking at structures in the meta-data to find out how solid this community really was.” There are many databases around which list metadata from these letters, yet it’s not always in an easily accessible format, so Dr van Miert says the public can play an important role in the project by gathering more data on correspondence in the Republic of Letters. People from in- and outside the project have contributed blogs to the skillnet.nl website, with dynamic visualisations of networks. “This is part of what we call citizen science, which is about engaging citizens with what we

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do at the university. This is also very helpful for us as researchers,” he says. “The sources are in many different languages – often Latin, but also English, Italian and German.” There is vast scope to gather further data, which will help researchers build a deeper picture of scholarly networks in the Republic of Letters, so Dr van Miert is keen to encourage further collaboration. This could involve students, retired people, hobbyists, or other interested parties who are ready to spend time gathering data and preparing it for further analysis by researchers. Everybody can contribute at https://cemrol.hum. uu.nl, you don’t even have to create a login. “One major challenge in the project is to standardise this data and feed it into a system where we can analyse it. We can then use this data to perform analyses and visualise learned networks,” outlines Dr van Miert. Engaging the public in this way then enables the SKILLNET research team to devote more of their time and energy to analysing the available data, which often involves the use of innovative digital techniques. From 4-6 November 2020, SKILLNET organises its second international conference in Utrecht, under the heading “Leaving the Ivory Tower: the social lives of early modern intellectuals”.

CEMROL volunteers at a city walk about the learned citizens of both Utrecht and the Republic of Letters, standing in front of the house of top author and correspondent Isabelle de Charrière-van Zuylen (1740-1805).

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 724972).

Project Partners

Project partners are Utrecht University’s Digital Humanities Lab (https://dig.hum.uu.nl/) and Oxford University’s Early Modern Letters Online (http://emlo.bodleian.ox.ac.uk/). SKILLNET is fully financed through the ERC Consolidator grant scheme (project nr. 724972).

Contact Details

Project Coordinator, Dr Dirk van Miert Early Modern Cultural History Utrecht University | Department of History and Art History Drift 6, 3512 BS, Utrecht, The Netherlands | room 0.25 T: +31 (0)30 - 253 2166 E: D.K.W.vanMiert@uu.nl W: www.skillnet.nl

Dr Dirk van Miert

Dr Dirk van Miert is an associate professor of Early Modern Cultural History at Utrecht University. His research focuses on the early modern world of learning: the people, the networks they formed, the letters they exchanged, the institutes where they worked, and the books they published.

Group learning - keeping children on track? Group work is an important part of education, giving students the opportunity to collaborate with their peers and share ideas to get a deeper understanding of academic content in a lesson. We spoke to Dr Nina Klang about her research into assessing the effectiveness of group learning in classes where there are students in need of additional support. The majority of

Swedish children go into mainstream schools when they enter formal education, including those with special educational needs. In many cases these children learn alongside their peers in the same class, an area of great interest to Dr Nina Klang, a senior lecturer in the Department of Education at Uppsala University in Sweden. “The participants in our study are children in mainstream educational settings, but we have data on the number of children with special needs in each class,” she outlines. As the Principal Investigator of a project based at the University, Dr Klang aims to gain deeper insights into how children with different educational abilities learn together, looking specifically at data on a group of 11-year olds. “Our primary aim in the project is to evaluate the effectiveness of cooperative learning, an inclusive group learning method, and to see how it works in classes where there are children in need of special support,” she explains. This method involves groupwork, structured to promote interdependence among group members, as each member has a degree of responsibility for the group’s work. By comparing outcomes for students Inclusion through learning in group - a study with mixed method design Funded by the Swedish Research Council (SRC). Dr Nina Klang, Project Coordinator Uppsala University Department of Education von Kraemers allé 1 A 752 37 Uppsala T: +46 18-471 1674 E: nina.klang@edu.uu.se W: https://www.edu.uu.se/ forskning/pedagogik/ps/ kooperativt_larande/

Dr Nina Klang is a researcher at the department of education at Uppsala university. She conducts research in the field of special educational needs. Her main research areas are social inclusion and instruction for children with intellectual disabilities.

Cooperative learning class at one of the schools in the project.

A child may need someone to help them think things through. This is what happens in those small groups. who experienced this type of teaching with a control group, researchers aim to build a stronger evidence base on its effectiveness. “In the intervention group the students participated in groupwork, structured according to the principles of cooperative learning instruction,” says Dr Klang. In the study, which includes 958 students and 55 teachers, the research team are looking at outcomes in reading comprehension and mathematical problem solving, alongside investigating peer relations and perceptions of support from peers. “We used questionnaires where children had to name the classmates that they wanted to work with and who they wanted to be friends with,” outlines Dr Klang. “We also recorded how children actually worked in groups”. A further dimension of the project’s work involves analysing video recordings of groupwork in which children are engaged in collaborative tasks. The research team have made about 50 hours video footage of group work. “In one in-depth study of four children’s learning trajectories in mathematical problemsolving in groups, we could see that the children

gained knowledge as they got explanations from each other and used these in trying to solve problems,” continues Dr Klang. A child may be reluctant to ask a question of a teacher in front of the class when a new concept is unclear to them, or they may not have identified what they want to ask, but group work gives them the opportunity to learn from their peers. “A child may need someone to help them think things through. This is what happens in those small groups,” points out Dr Klang. Another important part of the project concerns how teachers in the study implemented the instructional method of cooperative learning. Although there are a lot of well-researched instructional methods, the challenge is to get them implemented in the classrooms. “We have interviewed 22 teachers in the intervention group about their experiences of implementing cooperative learning,” says Dr. Klang. The hope of Dr Klang and her colleagues is that the project may give a deeper understanding of how the cooperative learning method can be implemented to create inclusive classroom environments, where no child is left behind.

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EU Research Spring 2020

Articles inside

INCLUSION THROUGH LEARNING

SKILLNET

IMPACTS OF NEW BASEL III

EULER SYSTEMS

DIVERSE-EXPECON

NEPOSTRANS

Sustainable Transport Targets

LIDD

CoralAssist

EVOLUTIONARY PHYSIOLOGY AND GENETICS

BLOODCELLSCROSSTALK

CHANGE PROCESSES OF FORESTS AND AGRICULTURE

COVID 19 Update

NANOthermMA

RECEPT

PHOROSOL

COVID 19 Pandemic

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HEALTHSCAPING

The Biological Basis of Cognitive Impairment due to Suspected Non- Alzheimer’s Pathology (SNAP

EVICARE

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STUDIES OF THE FUNCTION

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INTESTINAL MICROBIOTA

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