JOURNYS Issue 9.1

Art by Connie Chen and Alexander Hong 1 | JOURNYS | FALL 2017

San Diego Local Section 2 | JOURNYS | FALL 2017

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Website: www.journys.org // Email: eic@journys.org Journal of Youths in Science Attn: Brinn Belyea 3710 Del Mar Heights Road San Diego, CA 92130

“

Jonathan Kuo

Organic chemistry has many possible areas of study for the future, such as the expansion of molecular machine applications, the synthesis of complex compounds, and perhaps even the creation of an artificial cell.

Arpad Kovesdy Minha Kim

Muscular Dystrophy

Isa Stelter

Alina Luk Karishma Shah Melba Nuzen Sanil Gandhi Natalia Rojas Allison Jung

“ “

Kevin Ren

Markov chains allow us to compute probabilities for entities we have no control over—until they happen.

Poorvi Datta

Each second may or may not seem to last as long as the previous, proving psychological time to be highly subjective and malleable.

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Organic Chemistry. Just the name of this sophomorelevel university course is enough to curl students’ lips down with disgust, as they recall memories of hurriedly memorizing reaction mechanisms, and scribbling and erasing molecular structures in futile attempts to understand how chemistry works. As the famous chemist Friedrich Wöhler said, “Organic chemistry is enough to drive one mad… [it is] a monstrous and boundless thicket, with no way of escape, into which one may well dread to enter.” [1] But what is organic chemistry, and what do organic chemists do?

Organic chemistry is the study of carbon compounds.

It encapsulates a wide variety of modern fields, ranging from pharmaceuticals to explosives. In today’s world, organic chemists are mainly concerned with synthesizing new compounds; chemists spend weeks in labs performing reaction after reaction trying to make a new compound that might be useful in medicine, or might simply allow an existing compound to be formulated more easily. This experimentation usually involves two possible types of molecular manipulation: changing the stereochemistry – the spatial arrangement of atoms in a compound – and/or changing the composition primarily through the modification of functional groups – small chains of atoms which are connected at different points to the rest of the compound. A compound spatially arranged in one way may have different chemical properties than that same compound arranged in another way, as seen in the chemical thalidomide. Thalidomide is unique since it can have two spatial arrangements that are mirror images of one another yet are not the same, in the same way that a person’s left hand and right hand are mirror images, but perform different tasks. In the 1950s, a form of thalidomide called S-thalidomide was prescribed to pregnant women as a sedative to help them sleep. However, it was not yet known that R-thalidomide, another form of thalidomide included in the medication, had a more damaging effect on the body that resulted in fetuses with abnormal or missing limbs [2].

Likewise, small changes in the composition of molecules can have drastic effects. Ethanol (CH3CH2OH) is the main component of any alcohol-based drink and is known to be a nervous system depressant; although methanol (CH3OH) has only one less carbon than ethanol, it can cause blindness and motor impairments when consumed even in small amounts [3]. Organic chemists have to consider many factors like these 4 | JOURNYS | FALL 2017

when synthesizing new compounds.

Recently, some organic chemists have gone beyond changing molecular stereochemistry and have begun examining the spatial arrangements of multiple molecules interacting with each other. In this new field, called topological chemistry, chemists attempt to link molecules together, resulting in mechanically-interlocked molecular architectures (MIMAs) such as catenanes (interlocking rings), knotanes (interwoven compounds) and rotaxanes (compounds that can rotate about each other). When these molecules were first discovered, synthesis was mostly a guessing game: researchers created straight molecules with reactive groups on the end and hoped these groups would react with each other, forming rings. A catenane could then only be formed if another straight molecule in the solution happened to poke through a ring and make another ring.

However, further research eventually resulted in a better solution and made catenane synthesis easier. Basically, instead of making rings and hoping that another ring would link with it, scientists bound molecules to a copper atom ligand that gave them a “drive” to form rings, instead of relying upon luck [4].

Last year’s Nobel Prize for Chemistry was awarded to JeanPierre Sauvage, Sir J. Fraser Stoddart, and Bernard L. Feringa for the synthesis of tiny molecular machines a thousand times smaller than a human hair. These molecular machines take advantage of MIMAs in order to produce molecules that can move around each other and perform work.

Sauvage’s research group, which discovered the previously mentioned method of producing catenanes more efficiently, also designed special catenanes that could be controlled to rotate around each other. When Sauvage’s catenanes are given a specific amount of heat, one ring of the catenane will rotate around the other a certain amount of times [5]. Sauvage’s group has also experimented with rotaxanes, producing a rotaxane that acts like a muscle filament. When a muscle filament is given ATP, myosin heads grabs and pulls on actin chains, inducing muscle contraction. Similarly, when Sauvage’s rotaxanes are exposed to heat, the molecular loops will pull on each other, contracting the entire structure.

Stoddart’s research group has also come up with a variety of applications for MIMAs. The most basic structure they have synthesized is a molecular shuttle, which consists of an electron-poor ring surrounding a chain with electron-rich regions. Since electrons are electrically charged, the shuttle is attracted to one of the electron rich regions on the chain.

When the shuttle is exposed to heat, the thermal energy

causes the ring to move, eventually hitting another electron-rich region on the chain and attaching to it. This sort of structure has also been used in constructing a molecular lift that can raise the electron ring 0.7 nm above a surface. Additionally, Stoddart’s group has constructed a nanovalve: a 400 nm thick glass sphere with a rotaxane opening that could be used to deliver drugs to specific cells in the body [6]. Currently, Stoddart’s group continues to pursue applying MIMAs to nanotechnologies related to electronic circuitry and health.

Feringa’s research group has experimented with molecular motors—molecules that move in only one direction. The molecule they have constructed consists of two overlapping rotor blades connected with a double bond. When the molecule is exposed to UV light, one blade spins 180 degrees and then “snaps” over the other blade, preventing backward rotation.

This rotation can be continued with more exposure to UV light, and has been optimized to reach speeds of 12 million revolutions per second. Feringa’s group has used these motors to move other molecules, creating a molecular car with four motors as wheels and transporting a glass cylinder over 10,000 times bigger than the motors.

So, what is the point of all these molecular machines? Although the answer may not be apparent, molecular machines have the potential to revolutionize the scientific world in the same way steam engines revolutionized the industrial world in the 1700s. Because of their small size, molecular machines have a variety of applications for medical research, ranging from new surgical techniques to improved drug delivery. Molecular machines could make computer transistors even smaller, resulting in even more powerful computers. Organic chemistry has many possible areas of study for the future, such as the expansion of molecular machine applications, the synthesis of complex compounds, and perhaps even the creation of an artificial cell. Although organic chemistry is viewed with fear by many undergraduate students, it has established its role in the scientific world for decades to come.

[1] Science Quotes by Friedrich Wöhler. Today in Science History. https:// todayinsci.com/W/Wohler_Friedrich/WohlerFriedrich-Quotations.htm.

Accessed June 13, 2017.

[2] Teaching Chemistry Through The Jigsaw Strategy. Chinese University of Hong Kong. http://www3.fed.cuhk.edu.hk/chemistry/files/chiraldrug. pdf. Accessed June 13, 2017.

[3] Methanol Toxicity. Medscape. http://emedicine.medscape.com/ article/1174890-overview. Published January 31, 2017. Accessed June 13, 2017.

[4] PV. Olympicene.

YouTube. https://www.youtube.com/ watch?v=k2tkfbc18Vw. Published July 27, 2012. Accessed June 13, 2017.

[5] Brunning A. The 2016 Nobel Prize in Chemistry: Molecular Machines. Compound Interest. http://www.compoundchem. com/2016/10/05/nobel16chem/. Published October 5, 2016.

Accessed June 13, 2017.

[6] Rice J. Nanovalves for Drug Delivery. MIT Technology Review. https://www. technologyreview.com/s/409737/ nanovalves-for-drug-delivery/.

Published March 13, 2008.

Accessed June 13, 2017.

[7] Gerwick WH. Plant Sources of Drugs and Chemicals.

ScienceDirect. http://www.sciencedirect. com/science/ar ticle/pii/ B9780123847195001118.

Published February 5, 2013.

Accessed June 13, 2017.

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ABSTRACT Terraformation, or the act of creating an Earthlike environment on another planet, has been considered an impossible and impractical task since the start of the Space Age. However, the terraformation of Mars is indeed technologically possible, and can potentially assist colonization efforts to protect the human race.

As private companies begin to lead a new era of space exploration, humanity will soon set foot on planets like Mars, where terraformation will be possible by heating up the atmosphere to create livable conditions with a sufficient supply of water and a substantial ozone layer.

To accomplish this goal, large amounts of greenhouse gas like sulfur hexafluoride (SF6) can be pumped into the Martian atmosphere, heating up the surface over time and releasing trapped carbon dioxide in the Martian soil to create a stronger greenhouse effect. In as little as fifteen years, one hundred portable generators can produce enough greenhouse gas to begin a carbon dioxide release cycle. On a carbon dioxide-rich Mars, water will be released purely from carbon dioxide’s heating effect while Earth-like temperatures can be induced with artificial heating, creating a warmer environment more suitable for human life. Together, these stepping stones can lead to simple, ground-level habitation and rapid colony growth while creating the necessary foundation for an oxygenated atmosphere populated with plants and animals from Earth.

A SCIENTIFIC AND TECHNOLOGICAL VIEW ON THE PRACTICALITY OF A MARTIAN PLANET On July 20th, 1969, a new age of space exploration began when astronauts Neil Armstrong, Buzz Aldrin, and Michael Collins landed on the moon during the Apollo 11 mission, the first to walk on another world [14]. Suddenly, a manned Mars mission seemed more possible than ever. As research and technology progresses, a future with humans on the red planet seems inevitable. Perhaps we could one day establish a permanent colony on the Red Planet and search for unique life. Further into the future, we may also consider modifying the planet into a hospitable environment for humans, pushing society toward an important milestone of human existence: multi-planetary human life.

Terraformation, the term used for the creation of an Earthlike planet via planetary engineering, is necessary for the existence and preservation of the human race and its cultures [1, 12]. The first important component to terraformation is ecopoiesis, or the creation of conditions that allow the development of a hospitable ecosystem

[1]. The hostile conditions of Mars such as the thin atmosphere and dangerous radiation from space impede humanity’s multi-planetary existence and prevent the adoption of Mars as a home for humans. Out of terrestrial organisms, only extremophile microorganisms would be able to survive in Mars’ current conditions [15].

With recent technological developments, Mars can be terraformed into a habitable planet with a suitable atmosphere, sufficient water, and a protective ozone layer. Realistically, terraformation will not result in a duplicated Earth, but instead it will remove many of Mars’s harsh conditions and allow a diverse ecosystem to expand over several millennia. After settling on Mars, infrastructure could be set up to create industrial capacity for mineral extraction and production of greenhouse gases. Water will be released from the ice caps and soil while the ozone layer will be strengthened over time by pressure and carbon dioxide in the atmosphere.

BY APRAD G. KOVESDY ART BY SKYLAR JUNG JOURNYS || FALL FALL 2017 2017 66 || JOURNYS

GETTING TO MARS AND ESTABLISHING INFRASTRUCTURE Although robots such as rovers have already begun to analyze the environment that Mars provides, a human colony is necessary since firsthand analysis is required for the complete picture. First, the exact composition and properties of the soil, ice caps, and atmosphere must be analyzed to determine the levels of available carbon dioxide, water, nitrogen, and oxygen. Expeditions to locate fluorine and sulfur deposits required for sulfur hexafluoride production should be conducted along with other geographical and biological surveys before terraformation is initiated.

In order to start the heating process on Mars, factories must produce the required greenhouse gases. These factories must be shipped from Earth via rocket, since the complex engineering required to build them would be beyond the scope of existing infrastructure on Mars. Because the largest concentration of greenhouse gases exists at the polar ice caps, factories would be placed near the ice caps. Additionally, the factories would have to be close to large sulfur and fluoride deposits to minimize transport distances between mines and factories. Once factories have been established, time can be spent mining the required resources, transporting them, refining them, and operating these facilities.

“Together, these stepping stones can lead to simple, groundlevel habitation and rapid colony growth while creating the necessary foundation for an oxygenated atmosphere populated with plants and animals from Earth .”

Producing Large Amounts of Greenhouse Gases Sulfur hexafluoride has numerous traits that would make it an advantageous greenhouse gas for Mars (Table 1).

First, it is a “colorless, odorless gas that is completely inert,” which means it will not interact with or disrupt any other chemicals during the terraformation process [6]. According to the European Fluorocarbon Technical Committee, this gas will not eat away at the ozone layer or become toxic in any amount to humans or other organisms [2]. Additionally, it will not escape into space because of its weight. The gas is a potent greenhouse gas that does not dissociate in the atmosphere for an extremely long time, creating an intense heating effect.

TABLE ONE: SULFUR HEXAFLUORIDE PROPERTIES PROPERTIES

GREENHOUSE EFFECT

-Colorless, Odorless, Completely Inert, Will not react with water, five times heavier than air* -Lifespan: 3,200 years in the upper atmosphere**

20 year scale: 16,300 times stronger than CO2** 100 year scale: 22,800 times stronger than CO2**

* According to The National Center for Biotechnology Information (2014) and The European FluoroCarbons Technical Committee (2005) ** According to the IPCC (2007) study

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The gas is made up of two elements that are readily available on Mars; compounds such as fluorite and sulfur dioxide have been detected at both the Rocknest Deposit and John Klein Rock by instruments on the Curiosity Rover [3, 10, 13]. These compounds can easily create the necessary fluorine gas and pure sulfur, so virtually no reactants need to be imported for the production of sulfur hexafluoride [6].

The process of releasing sulfur hexafluoride will create a greenhouse effect that will heat the planet. According to an analysis written in 1993 by aerospace engineer Robert Zubrin and NASA researcher Christopher McKay, this process will start a positive feedback loop of carbon dioxide release from the ice cap and the soil [18].

A model by science writer Barton Paul Levenson was utilized to find the amount of sulfur hexafluoride needed in the atmosphere to produce the desired heating effect of 4 K [8]. The 4 K rise in temperature is the most realistic goal to start with, since afterwards the greenhouse effect can be achieved even without gas production. Figures 1 and 2 estimate the effects of the number of generators and the amount of sulfur hexafluoride on the Martian temperature.

FIGURE ONE*

FIGURE TWO

6

Note: The effectiveness of SF6 as a greenhouse gas is only known for a 20 and 100 year period. The other decadal marks are estimations.

As shown in Figures 1 and 2, a very large heating effect can be created with a hundred small generators in just over fifteen years.

This 4 K increase of global temperature can also be concentrated at the poles, leading to even less gas required for a greenhouse effect -15 -2 to begin the carbon dioxide evaporation process. As Zubrin and McKay state, a Mars with only between 400-500 millibar (mb) of carbon dioxide available will have a maximum tropical temperature of around 260 K [18]. Over time, the artificially produced greenhouse effect can place the maximum tropical temperature well over 273 K. On a hypothetical Mars with plentiful carbon dioxide reserves, an increase to a maximum tropical temperature of 273 K can be achieved, while artificial greenhouse gases easily put both the pressure and temperature to levels very similar to Earth [18].

The ozone layer is a protective shield of gas in the upper atmosphere that is necessary for filtering out ultraviolet (UV) radiation; a thicker ozone layer will decrease UV radiation exposure and protect cells from DNA damage [9]. In 1997, researchers estimated that tripling the thickness of Mars’s current ozone layer will allow organisms to survive without protection [5]. The creation of a more significant ozone layer on Mars will happen automatically with three major components: carbon dioxide, oxygen, and pressure in the atmosphere [5]. When carbon dioxide is released from the ice cap and the soil, it will react and form ozone. Additionally, the atmospheric pressure will increase as more gas is released from the soil. In the upper atmosphere, some of the carbon dioxide will dissociate due to photolysis (UV radiation breaking down molecules) and split into CO and O [4]. Small amounts of existing oxygen gas (0.13% of atmosphere by volume) and O gas from photolysis will combine under pressure to form O3, or ozone [16]. The atmosphere will pressurize during the greenhouse period, allowing the ozone layer to grow with little hindrance without the degrading effects from water vapor. A small increase in temperature will start an automatic process to strengthen the ozone layer and consequently shield humans, plants, and other life from UV light.

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ACCLIMATION TO THE NEW PLANET AND TERRAFORMATION A new environment will begin to form after ecopoiesis has been reached: the once-dried riverbeds and lakes will fill with liquid water, plants will spread along the red rock, and the atmosphere will become suitable for life. As the carbon dioxide concentration rises above about 250 mbar, the gas pressure will be sufficient to discard pressure suits [11]. Instead, only a breathing apparatus would be required, and humans could “travel freely in the open wearing ordinary clothes and a simple SCUBA type breathing gear” [18]. Since the pressure differential between the Martian atmosphere and habitable atmosphere would be negligible, human habitation will no longer require heavy fortification [18]. At temperatures above 273 K, melting ice would fill the empty oceans, allowing large-scale plant life to grow [15]. However, it would take “centuries to melt Mars’ ice and deeply buried permafrost” in order to completely activate the hydrosphere and complete the weather cycle [18].

The next significant challenge would be creating atmospheric conditions suitable for life from Earth. A large amount of oxygen and an inert buffer gas like nitrogen will be needed to support cellular respiration and photosynthesis [11]. The production of oxygen would be the most challenging aspect of terraformation, since oxygen generation is a slow process. Without more efficient lifeforms to convert carbon dioxide to oxygen, conventional photosynthesis would take over 100,000 years to produce an oxygenated atmosphere for humans [11]. Zubrin and McKay estimate that with up to 2200 terawatt-years of energy, enough oxygen to support plant-life (1 mbar) could be produced by breaking up chemicals in soil [18]. They also estimate that certain photosynthetically-efficient terrestrial plants could produce enough oxygen for human life (120 mbar) in approximately 1350 years [18]. To produce a buffer gas, the nitrogen in soil nitrates must be unlocked, or another buffer gas must be imported from elsewhere in the solar system. The former option is more feasible, since large amounts of nitrogen are present in the soil. Using today’s plants and technology to achieve a fully terraformed planet may take 1,000 to 100,000 years, but the task will only be accelerated as modern technology develops [17].

CONCLUSION A giant calculator the size of a room seemed unwieldy and impractical upon its invention; however, it was a stepping stone for our commonplace, modern computers, which are only a fraction of the original’s size. Much like the rapid advancement of computers, the technology necessary to create an habitable atmosphere on Mars can be developed within a matter of decades. With the technology outlined in this paper, the vision o f Mars terraformation is not as far-fetched as it initially seems. And since large technological advancements will undoubtedly occur by the time ecopoesis is achieved, this vision may be even closer than we realize. To accomplish this goal, steps must be taken to prepare and progress, continuing the mission that three courageous explorers started on July 20th, 1969.

REFERENCES [1] Ahrens, P. (2003, December). The Terraformation of Worlds. Retrieved from Nexial Quest: http://www.nexialquest.com/The%20Terraformation%20of%20Worlds.pdf [2] European FluoroCarbons Technical Committee. (2005, October). Frequently asked Questions (FAQ) and Answers on SF6. Retrieved from Fluorocarbons.org: http:// www.fluorocarbons.org/wp-content/uploads/2005/10/capie-sf6-faq-oct-2005.pdf [3] Forni, O., et. al. (2014). First Fluorine Detection on Mars with ChemCam On-Board MSL. 45th Lunar and Planetary Science Conference (p. 1328). Houston: USRA. [4] Gerstell, M. F., Francisco, J. S., Yung, Y. L., Boxe, C., & Aaltonee, E. T. (2001, February 27). Keeping Mars warm with new super greenhouse gases. Proceedings of the National Academy of Sciences of the United States of America, 98, pp. 2154-2157.

[5] Hiscox, J., & Lindner, B. (1997). Ozone and the Habitability of Mars. (R. Zubrin, Ed.) From Imagination to Reality: Mars Exploration Studies of the Journal of the British Interplanetary Society Part II: Base Building, Colonization, and Terraformation, 327-328.

[6] The National Center for Biotechnology Information (2004, September 16). Sulfur Hexafluoride. Retrieved from PubChem: pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?from=compound&cid=17358 [7] Intergovernmental Panel on Climate Change. (2007). Direct Global Warming Potentials. Retrieved from IPCC Fourth Assessment Report: Climate Change 2007: www.ipcc.ch/publications_and_data/ar4/wg1/en/ch2s2-10-2.html [8] Levenson, B. P. (2008, 4 4). How to Estimate Planetary Temperature. Retrieved from bartonpaullevenson.com: bartonpaullevenson.com/NewPlanetTemps. html [9] Lindberg, C. and Horneck, G. 1991. Action spectra for survival and spore photoproduct formation in Bacillus subtilis irradiated with short wavelength (200-300 nm) UV at atmospheric pressure and in vivo. Journal of Photochemistry and Photobiology 11: 69-80.

[10] McAdam, C. A. (2014, February). Sulfur-bearing phases detected by evolved gas analysis of the Rocknest aeolian deposit, Gale Crater, Mars. doi:10.1002/ 2013JE004518 [11] McKay, C. P., Toon, O. B., & Kasting, J. F. (1991, August 8). Making Mars habitable. Nature, 352, pp. 489-496.

[12] Musk, E. (2014, September 30). Exodus. (R. Anderson, Interviewer) [13] NASA. (2013, 3 12). Major Gases Released from Drilled Samples of the “John Klein” Rock. Retrieved from Nasa.gov: mars.jpl.nasa.gov/msl/multimedia/ images/?ImageID=5125 [14] NASA. (2014, July 14). July 20, 1969: One Giant Leap For Mankind. Retrieved from Nasa.gov: https://www.nasa.gov/mission_pages/apollo/apollo11.html [15] Todd, P. (2006). Planetary Biology and Terraforming. In P. Todd, Gravitational and Space Biology (p. 79+). General Science Collection.

[16] Williams, R. D. (2016, December 23). Mars Fact Sheet. Retrieved from NASA: https://nssdc.gsfc.nasa.gov/planetary/factsheet/marsfact.html [17] Zubrin, R. (2004, July 12). Zubrin on Terraforming Mars. (F. Cain, Interviewer) [18] Zubrin, R. M., & McKay, C. P. (1993, July). Technological requirements for terraforming Mars. Retrieved from www.users.globalnet.co.uk/~mfogg/zubrin.htm

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HIGH FRUCTOSE CORN SYRUP AND THE BRAIN Most of us are familiar with high fructose corn syrup, the ubiquitous, inexpensive, and oft-criticized sweetener found in a multitude of American foods from soft drinks to cereal. Fructose, or fruit sugar, is a natural simple sugar found in fruits, honey and some vegetables. It is an isomer to glucose; in other words, it has the same molecular formula as glucose (C6H12O6) but a different arrangement of atoms, forming an aldehyde group in glucose and a ketone group in fructose. As a result, fructose appears more frequently in the active open-chain configuration. This may seem like a minor difference, but in the brain this molecular configuration causes greater reactivity with amines as described in the Maillard reaction (2). This increased reactivity ultimately leads to more advanced glycation end products (AGEs), that are associated with diabetic complications and neurodegeneration [3,4]. However, all the negative impacts of fructose, most often in the form of high fructose corn syrup, are far more expansive than this. Thus, it is worth examining the detrimental long-term effects of excessive fructose consumption.

As mentioned above, not all monosaccharides are created equal,

The USDA estimates an American eats

131 grams per day

High fructose corn syrup consumption increased between 1970 -1990

1,000% amount of high fructose corn syrup the average American consumed in 2009

grams

of American adults consume 1-6 beverages high in high fuctose corn syrup per week.

BY MINHA KIM // ART BY WILLIAM LA 10 | JOURNYS | FALL 2017

and the brain responds differently to glucose and fructose. of others, Yang said.” (1) For one, fructose amplifies the reward circuits in the Finally, individuals with high fructose levels have more nucleus accumbens of the brain, whereas glucose does not. difficulty recovering from traumatic brain injury compared This amplification causes a desire to eat in response to a to those who do not consume as much fructose. In another food cue, such as images or videos of food and eating. This study on mice at UCLA, neuroscientists first gave laboratory effect was tested by Dr. Kathleen Page at the Keck School mice standard rat food and trained them to escape a maze of Medicine and her colleagues at USC by fMRI scanning for five days. After that, mice were randomly split to two subjects upon drinking either fructose or glucose and groups, one of which was fed with plain water and other then viewing images of food. This scanning indicated that one of which was fed with fructose-infused water, at a fructose indeed similar fructose affects the concentration reward circuit of Our findings suggest that fructose disrupts to that of soda, the brain, while plasticity — the creation of fresh pathways for six weeks. glucose does not. all the mice between brain cells that occurs when we Then Further more, intentionally fructose and learn or experience something new ... That’s u n d e r w e n t glucose are a huge obstacle for anyone to overcome ...” anesthesia and m e t a b o l i z e d Gomez-Pinilla had a brief differently; glucose injection of fluid is metabolized throughout the entire body, while fructose to the head to simulate traumatic brain injury in humans. is metabolized almost primarily in the liver. The brain, After another six weeks, the scientists tested all the mice which demands more than 20 percent of our daily energy again to determine how well they were able to recall the intake, requires glucose as a primary source of energy. (5) route and escape the maze. The researchers found that the Another way by which fructose causes extensive damage mice who were fed with fructose took 30 percent longer to the brain is through the alteration of genes. In 2016, than the mice fed plain water to escape the maze. The a life sciences research team at UCLA studied “more fructose interfered with the neuronal communication, than 20,000 genes in the rats’ brains, and identified more post-injury plasticity, and memory retention of the mice. than 700 genes in the hypothalamus (the brain’s major “Our findings suggest that fructose disrupts plasticity — metabolic control center) and more than 200 genes in the the creation of fresh pathways between brain cells that hippocampus (which helps regulate learning and memory) occurs when we learn or experience something new,” says that were altered by the fructose. The altered genes they Gomez-Pinilla, who is a member of the UCLA Brain identified, the vast majority of which are comparable to Injury Research Center. “That’s a huge obstacle for anyone genes in humans, are among those that interact to regulate to overcome — but especially for a TBI [traumatic brain metabolism, cell communication and inflammation. Among injury] patient, who is often struggling to relearn daily the conditions that can be caused by alterations to those routines and how to care for himself or herself.” genes are Parkinson’s disease, depression, bipolar disorder, Fructose, especially in the form of the ever-present high and other brain diseases, said Yang, who also is a member fructose corn syrup, has been proven to have a detrimental of UCLA’s Institute for Quantitative and Computational effect on the brain. Unfortunately, it is still common in Biosciences. Of the 900 genes they identified, the many sugary and savory foods. It is difficult to entirely researchers found that two in particular, called BGN and avoid the consumption of foods that contain high fructose FMOD, appear to be among the first genes in the brain that corn syrup, but we should take steps to consume such are affected by fructose. Once those genes are altered, they foods only sparingly and raise awareness about the issue can set off a cascade effect that eventually alters hundreds for others.

References [1] Meng Q, Ying Z, Noble E, et al. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders. PubMed. https://www.ncbi.nlm.nih.gov/ pubmed/27322469. Published May 2016. Accessed June 16, 2017.

[2] Dills Jr. Protein Fructosylation: Fructose and the Maillard reaction. PubMed. https://www.ncbi.nlm.nih.gov/pubmed/8213610. Published November 1993. Accessed June 16, 2017.

[3] Maillard L-C. Action des acides aminés sur les sucres; formation des mélanoïdines par voie méthodique. University of Lorraine. http://ticri.univ-lorraine.fr/wicri-lor.fr/index. php/C._r._hebd._s%C3%A9ances_Acad._sci._(1912)_Gautier. Published 1912. Accessed June 16, 2017.

[4] Semchyshyn HM, Miedzobrodzki J, Bayliak MM, Lozinska LM, Homza BV. Fructose compared with glucose is more a potent glycoxidation agent in vitro, but not under carbohydrate-induced stress in vivo: potential role of antioxidant and antiglycation enzymes. PubMed. https://www.ncbi.nlm.nih.gov/pubmed/24361593. Published January 30, 2014. Accessed June 16, 2017.

[5] Gomez-Pinilla F. How Does the Brain Use Food as Energy? BrainFacts.org.

[6] 19 Notable High Fructose Corn Syrup Statistics. HealthResearchFunding.org. http://healthresearchfunding.org/19-notable-high-fructose-corn-syrup-statistics/. Published December 21, 2014. Accessed June 16, 2017.

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By Isa Stelter // Art by Alexander Hong Muscular dystrophy, a neurodegenerative disease, affects about one in seven thousand males aged five to twenty-four years old worldwide by severely shortening an affected person’s life span and producing uncomfortable symptoms [7]. Muscular dystrophy is a sex-linked genetic disease passed down from generation to generation, so female carriers do not experience symptoms, but the prevalence of muscular dystrophy patients suggests a need for further research and understanding of the disease.

Muscwular dystrophy is caused by a mutation in the dystrophin gene, which codes for proteins that aid in muscle structure and support [1]. As an X-linked disease, the gene is carried on the X-chromosome, and males’ singular X-chromosomes make them much more susceptible to this condition; inheriting one allele would automatically translate into the disease [5]. If a female were to inherit one mutant allele, the other X-chromosome could contain the the wild-type allele which would code for a functioning dystrophin protein.

There are many types of muscular dystrophy, but the main types are Becker and Duchenne. Duchenne muscular dystrophy is more severe since it is caused by a frameshift mutation; in frameshift mutations, one nucleotide is deleted from the reading frame, henceforth causing a shift in each codon (a group of three nucleotides that are translated into a specific amino acid) [1]. This may result in a non-functioning protein or even complete termination of the protein’s production, leading to serious effects on the muscles throughout the body [2]. However, Becker muscular dystrophy occurs when an entire codon is deleted, while the rest of the translation process remains unfazed, resulting in a milder symptoms and a longer lifespan than Duchenne [6].

The lack of functional dystrophin proteins leads to gradual muscle loss and weakness, until the symptoms spread to essential muscles such as

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the heart or diaphragm and inhibit their ability to operate properly [2]. This physical deterioration is also accompanied by numerous painful symptoms, which ultimately result in death.

Duchenne muscular dystrophy is characterized by progressive muscle weakness, difficulty getting up, constant falling, shortness of breath, and tight leg muscles from early childhood [1].

Comparatively, Becker is typically a late-onset condition, with symptoms appearing during a patient’s adolescent years. Like Duchenne, Becker is marked by muscle weakness, and also includes a tendency to walk on the toes, a wobbly gait, and severe muscle cramps [6].

While there is no established cure for muscular dystrophy, there are treatments to help make symptoms more bearable. For example, physical therapy aids patients in maintaining muscle function for as long as possible with exercises and stretching routines [3]. There are also certain medications that may provide temporary relief, such as corticosteroids, which slow down disease progression and promote muscle regeneration, and beta blockers, which help maintain heart function [5].

Meanwhile, medical breakthroughs in muscular dystrophy treatment are being made in new clinical trials. One company, Sarepta Therapeutics, is testing a drug called eteplirsen, which aims to eliminate the mutation that causes muscular dystrophy by replacing the missing nucleotides in the DNA sequence. Subjects treated with the drug experienced an increase in dystrophin protein levels and a six-minute improvement in the “walking test,” where affected patients are timed as they walk a set distance to measure disease progression [5]. Another major clinical trial is ongoing at UCLA, where researchers are studying the effects of muscular dystrophy on the heart. Through genetic engineering, an alternative method has succeeded in isolating the dystrophin gene and creating a synthetic version to replace the damaged gene [4]. Recent advancements in modern technology and creative biomedical approaches have led scientists closer than ever to discovering a cure. With promising results from clinical studies, it seems that the prevalence of muscular dystrophy patients may decrease in coming years.

References

[1] About Neuromuscular Diseases. Muscular Dystrophy Association. https://www.mda.org/ disease. Published June 8, 2017. Accessed June 13, 2017.

[2] Distal Muscular Dystrophy (DD). Muscular Dystrophy Association. https:// www.mda.org/disease/distal-muscular-dystrophy/signs-and-symptoms. Published January 1, 2016. Accessed June 13, 2017.

[3] Muscular Dystrophy.

MedlinePlus. https://medlineplus.gov/ musculardystrophy.html. Published February 1, 2017. Accessed June 13, 2017.

[4] Muscular Dystrophy. Medscape. http://emedicine.medscape.com/ article/1259041-overview. Published January 6, 2017. Accessed June 13, 2017.

[5] Gupta RC, ed. Muscular Dystrophywww. KidsHealth. http://kidshealth. org/en/teens/muscular-dystrophy.html?WT.ac=ctg. Published July 2014.

Accessed June 13, 2017.

[6] Roddick J. Becker Muscular Dystrophy. Healthline. http://www. healthline.com/health/beckers-muscular-dystrophy#symptoms2. Published January 12, 2016. Accessed June 13, 2017.

[7] Muscular Dystrophy. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/musculardystrophy/facts.html. Published April 7, 2016. Accessed June 13, 2017.

Effects of Varying Methacrylated Hyaluronic Acid Gel Stiffness on Cardiac Progenitor Cell Phenotype Cardiac tissue engineering is currently a very relevant topic because of its application in in vitro studies of cardiac diseases and cell therapy. One technique used in this field is seeding cardiac cells onto engineered scaffolds made of biomaterials, such as hydrogels that can simulate a 3D environment. It is known that different environmental factors can influence the mechanical properties of these cells; however, it is unknown how changing the stiffness of the gels of the cell plates can affect cardiac progenitor cells (CPCs). By varying the amount of UV light exposure to gels made of methacrylated hyaluronic acid (Me-HA), these hydrogel scaffolds can be modified to different stiffnesses, which can simulate tissues in a fetal heart, healthy adult heart, or infarcted (unhealthy or damaged) heart. It was hypothesized that the CPCs situated in the fetal heart stiffness gels would result in the highest functionality and proliferation compared to the other gels. After exposing the gels to UV rays, the CPCs were plated and tested for proliferation and functionality by performing multiple assays [1]. The results revealed that differing the stiffnesses of the gels impacted cell proliferation more than differentiation in the 2D culture hydrogel. These results can further display that the best conditions for cardiac related experimentation involving CPCs are those that allow for the best cell proliferation in healthy adult heart-like gel stiffness.

Cardiac progenitor cells are found in the adult heart and have regenerative capabilities. They can differentiate into cardiomyocytes, cardiac muscle cells, and other specific cells [2]. Hydrogels are hydrophilic polymer gels that are often used to create a 3D environment for cells to grow and interact with each other.

Methacrylated hyaluronic acid is used to create the hydrogels due to crosslinking properties when exposed to UV rays. When the gel groups are exposed to UV light, a double bond attracts electrons from the irgacure compound that is involved in the photoinitiation process of UV crosslinking, and is split into two single bonds [3].

This process repeats until the light is turned off, resulting in the varying stiffnesses (the longer the exposure, the stifferl). The hydrogels simulating a fetal heart, healthy adult heart, and infarcted heart provide varying 2D environments for the CPCs. The goal of the experiment is to discover which stiffness of the Me-HA gels will be best for supporting cardiac progenitor cell proliferation and function.

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First, an atomic microscope was used to determine the amount of UV exposure that correlates with the desired stiffness. In a UV box, the gels were each stiffened according to the set level of light. Next, the cardiac cells were suspended into the gels and incubated.

Having plated the gels, the first assay, or analyzation technique, was performed: a live/dead assay. The purpose of this assay was to determine how the cells were surviving in the different gel environments by applying two different dyes, calcein and ethidium homodimer-1, to distinguish between live cells and dead cells. In this case, higher absorption of Alamar Blue Dye demonstrated greater cell proliferation. Alamar Blue was also employed to estimate the magnitude of cell proliferation and viability by quantitatively measuring the fluorescence signal that was produced in a diluted Alamar Blue/media mixture against negative and positive controls.

The media color turned from blue to pink, indicating proliferation, and some of the solution was inspected by spectrophotometer to view the results of the proliferation. qPCR, an analytical technique that amplifies RNA transcripts using reverse transcriptase, was used to analyze gene expression by creating a solution of gene markers and quantifying RNA. The components of the solution included GATA-4 , a transcription factor found in cardiac stem cells, cACTIN, cDNA, and RNA. A thermocytometer was used to measure the qPCR fluorescence produced. Our final assay was indirect immunofluorescence, in which a fluorescent secondary antibody binds to a primary antibody that is specifically attached to a target of interest. The functionality of the CPCs was determined by fixing, permeabilizing, blocking, and staining the antibodies Rabbit anti-Ki-67, Mouse anti-Beta-Integrin, and Mouse antiCardiac-Actin, that were attached to the cells. These antibodies were stained with fluorescence for a clearer view of the cells under a immunofluorescence microscope [4].

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On Day 1, the cells in the fetal heart gel (3.87 kPa) were round and clumped, indicating little adherence to the gel surfaces. After observing the cells on Day 4, however, they had a higher confluency, or adherence ability, and were elongated, indicating greater proliferation. The cell morphology in the healthy adult heart gels (12.59 kPa) on Day 1 was more elongated, indicating better adherence. A few were rounded, signifying that some of the cells were left out for too long on Day 1. On Day 4, blank spots developed where no cells grew and round spheroid cells, surrounded the “blank” areas instead. The cell morphology of the infarcted heart gels (48.79 kPa) on Day 1 was even more elongated than the other two conditions, but on Day 4, it experienced the same process of developing “blank” spaces. This development indicated better proliferation and confluency in the adult heart simulated gels.

The live/dead assay revealed that there was an abundance of live cells in the 3.87 kPa gel, a greater amount of dead cells but a higher live-to-death ratio in the 12.59 kPa gel, and a high abundance of live cells and the greatest amount of dead cells in the 48.79 kPa gel. The results for Alamar Blue are shown below:

Figure two shows results of Alamar Blue proliferation assay. All of numbers were determined by taking each individual well and substracting the negative control from the fluorescence units of the well, and then averaging that number with the other two wells that had the same gel stiffness.

The qPCR assays revealed that 48.79 kPa expressed less genes than the other gels, also indicated in this graph (CTR/CT value represents the cycle threshold):

The indirect immunofluorescence assay revealed that all the gels contained expression of Ki-67 and Beta-Integrin antibodies; however, there was no visible expression of cACTIN.

3.87 kPa

12.59 kPa

48.79 kPa

Based on our Alamar Blue assay results, we discovered that the fold increase, or the amount of change, for the cells on the fetal heart gels and adult heart gels proliferated at a similar rate. The cells were very confluent, and that caused them to create blank spaces. Unlike our hypothesis that the CPCs in the simulated fetal heart stiffness gel would proliferate more, our observations revealed that the cells growing on the simulated adult heart gel had a greater tendency to proliferate. The qPCR and indirect immunofluorescence assay both revealed that none of the three conditions showed any cardiac actin expression, suggesting that the environment did not have any impact on cell differentiation. qPCR indicated that the CPCs are more likely to differentiate in an infarcted heart than the others, because it showed minimal expression of the cardiac genes.

Our results suggest that cell proliferation and not differentiation is impacted by varying the stiffness of methacrylated-hyaluronic acid gel. This research can be used for further in vitro studies of cardiac disease and as a baseline for test cell therapies.

[1] Ondeck, Matthew G., and Adam J. Engler. Mechanical Characterization of a Dynamic and Tunable Methacrylated Hyaluronic Acid Hydrogel. Journal of Biomechanical Engineering. The American Society of Mechanical Engineers, 8 Nov. 2015. Web. 29 July 2016.

[2] Lv, Hongwei, Lisha Li, Meiyu Sun, Yin Zhang, Li Chen, Yue Rong, and Yulin Li. Mechanism of Regulation of Stem Cell Differentiation by Matrix Stiffness. Stem Cell Research & Therapy. BioMed Central, 27 May 2015. Web. 30 July 2016.

[3] Park, Si-Nae, Jong-Chul Park, Hea Ok Kim, Min Jung Song, and Hwal Suh. Characterization of Porous Collagen/hyaluronic Acid Scaffold Modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Cross-linking. Characterization of Porous Collagen/hyaluronic Acid Scaffold Modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Cross-linking. ScienceDirect, 15 Feb. 2002. Web. 26 July 2016.

[4] “Immunofluorescence Sample Preparation.” Duke University Light Microscopy Core Facility. N.p., n.d. Web. 11 Aug. 2016. <http://microscopy.duke.edu/sampleprep/if.html>.

[5] EVERGREEN INC. “Tissue Culture Plates: 6-well, 12-well, 24-well & 96-well.” EVERGREEN. EVERGREEN, 2000-2016. Web. 26th July 2016.

[6] Fabrication of Collagen I Gels. IBIDI - Cells in Focus, 10 Dec. 2014. Web. 28 July 2016.

[7] Gaetani, Roberto, Dries A.m. Feyen, Vera Verhage, Rolf Slaats, Elisa Messina, Karen L. Christman, Alessandro Giacomello, Pieter A.f.m. Doevendans, and Joost P.g. Sluijter. “Epicardial Application of Cardiac Progenitor Cells in a 3D-printed Gelatin/hyaluronic Acid Patch Preserves Cardiac Function after Myocardial Infarction.” Biomaterials 61 (2015): 339-48. Web. 26 July 2016 [8] Gaetani, Roberto, Christopher Yin, Neha Srikumar, Rebecca Braden, Pieter A. Doevendans, Joost B.J. Sluijter, and Karen L. Christman. Cardiac Derived Extracellular Matrix Enhances Cardiogenic Properties of Human Cardiac Progenitor Cells. Ingenta Connect. Ingenta, 16 Nov. 2015. Web. 26th July 2016.

[9] Guvendiren, Murat, and Jason A. Burdick. “Stiffening Hydrogels to Probe Short- and Long-term Cellular Responses to Dynamic Mechanics.” Nature.com. Nature Publishing Group, 24 Apr. 2012.

Web. 30 July 2016.

[10] Happe, Cassandra L., and Adam J. Engler. “Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis.” Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis. American Heart Association, 10 Nov. 2015. Web. 29 July 2016.

[11] Discher, Dennis E., Paul Janmey, and Yu-li Wang. Tissue Cells Feel and Respond to the Stiffness of Teir Substrate. Science. AAAS, 18 Nov. 2005. Web. 26th Nov. 2016.

[12] Levett, Peter A., Dietmar W. Hutmacher, Jos Malda, and Travis J. Klein. Hyaluronic Acid Enhances the Mechanical Properties of Tissue-Engineered Cartilage Constructs. PLOS ONE. PLOS ONE, 1 Dec. 2014. Web. 26 July 2016.

[13] Discher, Dennis E., David J. Mooney, and Peter W. Zandstra. Growth Factors, Matrices, and Forces Combine and Control Stem Cells. Science. AAAS, 26 Jan. 2009. Web. 27 July 2016.

[14] Caliari, Steven R., Maryna Perepelyuk, Brian D. Cosgrove, Shannon J. Tsai, Gi Yun Lee, Robert L. Mauck, Rebecca G. Wells, and Jason A. Burdick. Stiffening Hydrogels for Investigating the Dynamics of Hepatic Stellate Cell Mechanotransduction during Myofibroblast Activation. Nature. Nature: Scientific Reports, 24 Feb. 2016. Web. 26 July 2016.

[15] Lee, C.R., A.J. Grodzinsky, and M. Spector. “The Effects of Cross-linking of Collagen-glycosaminoglycan Scaffolds on Compressive Stiffness, Chondrocyte-mediated Contraction, Proliferation and Biosynthesis.” The Effects of Cross-linking of Collagen-glycosaminoglycan Scaffolds on Compressive Stiffness, Chondrocyte-mediated Contraction, Proliferation and Biosynthesis. ScienceDirect, Dec. 2001. Web. 26 July 2016.

[16] Shapira-Schweitzer, Keren, and Dror Seliktar. Matrix Stiffness Affects Spontaneous Contraction of Cardiomyocytes Cultured within a PEGylated Fibrinogen Biomaterial. Matrix Stiffness Affects Spontaneous Contraction of Cardiomyocytes Cultured within a PEGylated Fibrinogen Biomaterial. ScienceDirect, Jan. 2007. Web. 29 July 2016.

[17] Sullivan, K. E., K. P. Quinn, K. M. Tang, I. Georgakoudi, and L. D. Black, 3rd. “Extracellular Matrix Remodeling following Myocardial Infarction Influences the Therapeutic Potential of Mesenchymal Stem Cells.” National Center for Biotechnology Information. U.S. National Library of Medicine, 24 Jan. 2014. Web. 30 July 2016.

[18] “Useful Numbers for Cell Culture.” Thermo Fisher Scientific. Thermo Fisher Scientific, 2016. Web. 30 July 2016.

[19] Young, J. L., K. Kretchmer, M. G. Ondeck, A. C. Zambon, and A. J. Engler. Mechanosensitive Kinases Regulate Stiffness-induced Cardiomyocyte Maturation. National Center for Biotechnology Information. U.S. National Library of Medicine, 19 Sept. 2014. Web. 30 July 2016.

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By Karishma Shah // Art by William La

What Will the Future of Medicine Look Like with the Rise of Superbugs?

It sounds like a science fiction story—Superbugs, resistant to all forms of medicine known to mankind, take over the world. However outlandish this may sound, it isn’t far from reality. ‘Superbugs’ is a term used to describe strains of bacteria that are resistant to the majority of antibiotics commonly used today [1]. Antibiotic resistance is a naturally occurring phenomenon that cannot be stopped and has become a serious issue over the past several years due to the overprescription and the resultant overuse of antibiotics [1]. According to the Centers for Disease Control and Prevention, two million people become infected with bacterias that are resistant to antibiotics each year and at least 23,000 people die as a direct result of these infections [2]. This number is bound to increase with each coming year unless a panacea is found soon, something that is beginning to seem impossible as major drug companies are giving up on finding new antibiotics [3]. There have been many magazine covers about “the end of antibiotics.”

But Dr. Srinivasan, an associate director at the CDC’s National Center for Emerging Zoonotic and Infectious Diseases, says that he “would change the title to ‘the end of antibiotics,’ period” [3].

Bacteria carry most of their genes in what is known as the bacterial

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chromosome. Bacteria have only one circular chromosome, but can have multiple accessory rings of self-replicating DNA called plasmids. It is on these plasmids (specifically R plasmids) that antibiotic resistance genes are found. Antibiotic resistance genes code for enzymes that specifically destroy certain antibiotics. R plasmids also contain genes that encode sex pili and enable plasmid transfer from one bacterial cell to another. They may carry as many as ten genes for resistance to that many antibiotics. More often than not, R plasmids are responsible for the epidemic spread of multiple drug-resistance throughout an entire bacterial population.

One of the most infamous Superbugs is the Methicillin-resistant Staphylococcus aureus, otherwise known as MRSA. Since it was first identified fifty years ago, MRSA infections have spread worldwide.

In the U.S. alone, 11,285 deaths per year are attributed to MRSA [5].

In the beginning, MRSA was able to be treated by certain antibiotics but the deadly ability of MRSA to adapt and spread to any condition or location has proven to be a challenge for doctors, scientists, and patients. MRSA is part of the Staphylococcus (staph) family of bacteria, which is often found on the skin and nose of many healthy people [6]. However, staph can be a problem once it manages to get inside the body, often through a cut. Some strains of staph like MRSA have now become resistant to methicillin, amoxicillin, penicillin, oxacillin, and other antibiotics [6]. MRSA infections were first seen in hospitals, but since then have appeared in communities with healthy people; this type of MRSA is called community-associated MRSA (CA-MRSA) [7]. CA-MRSA is more likely to affect young people; the average age of a person with CA-MRSA is only twenty three [6]. It has also been documented that CA-MRSA is seen more in populations that have close skin-to-skin contact such as team athletes and children in daycare [6].

Outbreaks of antibiotic resistance bacteria can occur anywhere and at anytime. During the latter half of 2011, the prestigious National Institute of Health’s Clinical Center experienced a deadly outbreak. Nationally, most hospitals aren’t required to report outbreaks to the government.

However, Frontline, PBS’s investigative journalism television show, was able to find out more about the Klebsiella pneumoniae carbapenemase (KPC) outbreak at the NIH in 2011. It all started when a woman carrying this disease was transferred from a hospital in New York City to the NIH Clinical Center in Bethesda, Maryland. Soon

after she was treated, KPC bacteria turned up in the respiratory culture of a patient in a different part of the hospital. An infectious disease specialist, Dr. Tara Palmore, realized that the KPC bacteria had spread to other patients. The routine antibiotics weren’t working and Dr. Palmore even unsuccessfully combined five or six antibiotics in an attempt to treat the outbreak [3]. The clinical center diagnosed a new case almost every week, and unprecedented preventative measures were taken to try and stop it from spreading further. These measures failed and the outbreak continued to spread throughout the hospital. After isolating all cases of KPC, the outbreak was contained [3]. Six months after patient one had arrived, eighteen had become infected and six had died. A new multi-drug resistant bacteria had taken its toll.

Although the obvious solution to these deadly superbugs is to fund new antibiotic research, several problems remain. The first major problem is the fact that antibiotics are based on chemicals that exist in nature, produced by organisms like soil bacteria and fungi—for instance, penicillin is derived from fungi [7]. It is difficult for researchers to find entirely new chemicals that will work, and only a few new antibiotics have been discovered in the past few decades. Another contributing factor is the low profitability for pharmaceutical companies. Creating a new drug and putting it on the market requires, on average, an investment of $800 million and a time span of ten years or longer [8]. Furthermore, bacteria evolve very rapidly and, according to Dr. Jean Patel, deputy director of the office of antimicrobial resistance at the Center for Disease Control and Prevention, “one thing we’ve learned about them

2 million

is that anytime an antibiotic is introduced, resistance follows very quickly” [7]. Thus, an decade-long investment of around $800 million may yield a product that that is useful for only one to two years—an unappealing prospect for many companies. In addition, more and more doctors are beginning to use antibiotics sparingly, thereby lowering pharmaceutical companies’ profits for this category of drugs. Companies are focusing their efforts on creating new medicines to treat chronic illnesses such as high cholesterol, high blood pressure, arthritis, and dementia. These illnesses never change and typically require ongoing medication therapy, maximizing profits for companies in the drug industry.

The best solution we have for minimizing the number of superbugs is intensely controlling our use of existing antibiotics. Antibiotics are often prescribed for nonbacterial infections, providing no benefits to the patients and leading to the emergence of superbugs [9]. CDC data show that at least 30% of antibiotics prescribed in the United States are unnecessary [10]. In 2015, as part of the effort to stop the inappropriate prescription of drugs and thus curb antibiotic resistance, the White House released The National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) [10]. Dr Cars, a professor of infectious disease, stated that “ultimately, we need to avoid all unnecessary use of antibiotics [7].” With the rise of superbugs, we have arrived at a future that was predicted many years ago by Alexander Fleming when he said that “the thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism” [11].

$80 million

investment required to to produce people are infected with bacterias that and sell a new drug are reistant to antibiotics each year.

30% = 100,000 individuals

of prescribed drugs in the United States are deemed unnecessary.

References

[1] Tosh P. What are Superbugs and How Can I Protect Myself from Infection? www.mayoclinic.org. http://1.http://www.mayoclinic.org/diseases-conditions/infectious-diseases/expert-answers/ superbugs/faq-20129283. Accessed February 2, 2017.

[2] CDC. Antibiotic / Antimicrobial resistance. www.cdc.gov. https://www.cdc.gov/drugresistance/. Accessed February 2, 2017 [3] PBS-FRONTLINE. Hunting the nightmare bacteria. www.pbs.org. http://www.pbs.org/wgbh/frontline/film/hunting-the-nightmare-bacteria/. Accessed February 3, 2017.

[4] Ventola LC. The antibiotic resistance crisis. 2015;40(4). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/. Accessed February 3, 2017.

[5] Unknown. Understanding MRSA infection. WebMD. http://www.webmd.com/skin-problems-and-treatments/understanding-mrsa#1. Accessed February 3, 2017.

[6] Mosbergen D. The age of the Superbug is already here, scientists warn. Huffington Post. September 20, 2016. http://www.huffingtonpost.com/entry/antibiotic-resistance-crisis-un_us_57d8ea87e4b0fbd4b7bc66c4. Accessed February 3, 2017.

[7] Conly J, Johnston B. Where are all the new antibiotics? The new antibiotic paradox. 2005;16(3). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095020/#B3. Accessed February 3, 2017.

[8] Fox CR, Linder JA, Doctor JN. How to stop Overprescribing antibiotics. Sunday Review. April 1, 2016. https://www.nytimes.com/2016/03/27/opinion/sunday/how-to-stop-overprescribing-antibiotics.html?_r=0. Accessed February 2, 2017.

[9] CDC. CDC: 1 in 3 antibiotic prescriptions unnecessary new CDC data show large percentage of antibiotics misused in outpatient settings. www.cdc.gov. https://www.cdc.gov/media/releases/2016/p0503-unnecessary-prescriptions.html. Accessed February 3, 2017.

[10] Calderone J. Penicillin’s discoverer predicted our coming post-antibiotic era 70 years ago. Business Insider. http://www.businessinsider.com/alexander-fleming-predicted-post-antibiotic-era-70-years-ago-2015-7. Accessed February 3, 2017.

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In the late 19th century, Friedrich Miescher isolated an unknown substance, something that was neither a protein nor a lipid. Since it was found in a cell nucleus, Mischer first named it a nuclein and later renamed it deoxyribonucleic acid, or DNA for short [1]. However, it wasn’t until the mid-1900s that DNA—not protein—was proven through several experiments involving bacteriophages to be the macromolecule that carry genetic material. After that, researchers Watson and Crick published a succinct paper detailing the doublehelix structure of DNA, another milestone in the study of science and biology, and in 2003, the entirety of the human genome was sequenced a n d mapped [2].

It seems as though there are new discoveries every day in the field of science, especially in the studies of DNA and genetics. Since the discovery of DNA, there have been an increasing number of people and experiments invested in learning more about the so-called “blueprint of life.” But even in the rapidly developing area of genome engineering and editing, there are discoveries that stand out.

A particularly outstanding recent development is CRISPR-Cas9.

Today, there are thousands of known human genetic disorders, such as hemophilia, Huntington’s disease, Parkinson’s disease, and sickle cell disease, to name a few [3]. Now, to cure these genetic diseases, imagine using a new type of gene editing technology that could go into any human genome and cut out specific abnormal or disease-carrying segments of DNA, replacing them with different, more desirable strands of DNA [4].

Imagine using the same technology to purposefully engineer specific 18 | JOURNYS | FALL 2017

traits into or out of animal or human DNA: this is the ultimate goal of CRISPR-Cas9. Although the technology is not yet sophisticated enough to accomplish such specific engineering, CRISPR-Cas9 certainly opens up many intriguing opportunities in the world of genetic engineering.

The history of CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, begins a little further in the past than one might expect. In the decade leading up to the 21st century, scientists began identifying unusual repeating sequences of DNA in bacterial genomes. These short, repeating bacterial sequences of DNA were CRISPR. However, in the same way that the discovery of DNA proved to be underwhelming until DNA was proven to be genetic material, the discovery of CRISPR was of little importance until 2007, about thirty years after CRISPR were first identified. In a study led by Rodolphe Barrangou and Philippe Horvath, two researchers working at the company DuPont, scientists discovered that CRISPR were actually a type of defense mechanism used by bacteria against their assailants: viruses, phages, and plasmids [5].

The bacterial immune system breaks down the intrusive virus DNA, cutting the pathogenic DNA into unusable segments, which are then saved and inserted into the bacteria’s DNA, stored in the CRISPR spaces with the enzyme Cas9 that has the ability to cut across DNA. The segments of virus DNA are then transcribed into RNA strands called guide RNA (gRNA) which function

as tags, duplicated from and designed to stick to viral DNA. Thus, if the bacteria is attacked by the same virus, gRNA identifies and tags the virus. Then Cas9 can cut up the intruder virus’s DNA, completely eliminating the virus. Essentially, bacteria can use old virus DNA they saved to identify new intruding viruses, and then Cas9 cuts up the intruding viral genome, protecting bacteria from harm [6, 7].

Scientists were quick to see how the CRISPR-Cas9 technique could be applied to human genetics. In 2013, researchers were able to use a version of the CRISPR-Cas9 system to cut DNA in both mouse cells and human cells using RNA guide sequences [8]. CRISPR-Cas9 cut the mouse and human DNA precisely where the scientists wanted it to, which showed the CRISPR-Cas9 system’s first real potential for

While the broader idea of geneediting is no longer revolutionary, the CRISPR-Cas9 system is easy to manipulate and targets only specific DNA segments, making the CRISPR-Cas9 technique more effective and accurate than other genome editing techniques. becoming a precise gene-editing technique—not only for bacteria, but mammals and humans as well. Now, using any strand of selected DNA, CRISPR-Cas9 can potentially identify and edit desirable genes into or out of any human genome.

While the broader field of gene-editing is not a revolutionary idea, with the CRISPR-Cas9 technique, gRNA tags and neutralizes only dangerous viral DNA, making the CRISPR-Cas9 technique more effective and accurate than other genome editing techniques.

The CRISPR-Cas9 technique’s precision, accuracy and affordability have made it one of the most popular techniques for gene-editing in 2016 [6, 9]. For example, a group of Chinese scientists have planned on using the CRISPR technique on a human patient to test engineered cells in treating lung cancer [10]. Though the treatment is still recruiting participants, the experiments plans on inserting a programmed cell death gene into blood cells with CRISPR, and then

reintroducing those edited blood cells back into the patient. In cancer cells, cell death signals are ignored, resulting in the uncontrollable division of these cells. The introduced death gene is meant to prevent the metastasis and continued proliferation of these cancer cells. Numerous other experiments—from growing longer cashmere goat hair to engineering tougher crops to developing immune cells to attack cancer—involve CRISPR, which continues to be a diverse technique applicable to many fields [11, 12]. In the case of the cashmere goats, the researchers, using CRISPR, edited a specific follicle gene that resulted in longer and more cashmere [11]. For crops, CRISPR has been also used to successfully create strains of grain that are genetically engineered to be more disease-resistant and drought-resistant [12]. The success of these experiments show how many possibilities CRISPR can offer science and the world.

However, as with any new technology, there are arguments against the use and the effectiveness of CRISPR-Cas9. Ethical arguments against CRISPR and gene-editing include the fear that the ability to manipulate DNA may result in abnormal and unnatural animals or even humans. Selective control over undesirable or desirable traits may lead to eugenics [13, 14]. Ethics aside, many consider CRISPRCas9 to be too novel and untested to be a viable option for geneediting. Only in its early stages of development, CRISPR-Cas9 still requires refinement to answer criticism. How can CRISPR-Cas9 treat humans if no two human genomes are identical? Why would CRISPR be used when there are safer, more tested options on the market? What if removing a gene containing a disease makes the disease worse? Furthermore, the large size of the human genome, in comparison to bacterial DNA, often has identical sequences of DNA, which CRISPR-Cas9 could cut accidentally [14]. Nevertheless, since its early results with mammal DNA and plant DNA are promising, with further testing and more time, CRISPR-Cas9 may prove these critics wrong and become the next genetic breakthrough in modern science.

Although CRISPR-Cas9 currently remains in its developmental stage, with research focused solely on isolated human cells and animal subjects, it’s evident that the technology is quickly developing. Like the rest of the research dedicated to DNA and genetics, CRISPRCas9 has gained popularity with time. From 2011 to 2016 alone, there was a 1,453% increase in number of published scientific papers about CRISPR and for good reason [15]. The potential of CRISPR is limitless: whether it be creating more prosperous crops, curing cancer or altering human embryos, CRISPR-Cas9 is able to to impact all aspects of human life and is a scientific development that deserves attention in the future.

[1] Dahm, Ralf. “Discovering DNA: Friedrich Miescher and the early years of nucleic acid research.” Human Genetics Jan. 2008: 565-81. Print.

[2] “The Francis Crick Papers: The Discovery of the Double Helix, 1951-1953.” U.S. National Library of Medicine. National Institutes of Health. Web. 18 Jan. 2017.

[3] “Specific Genetic Disorders.” National Human Genome Research Institute (NHGRI). 18 Jan. 2017. Web. 19 Jan. 2017.

[4] “CRISPR/Cas9 GENE EDITING.” CRISPR Therapeutics. Web. 17 Jan. 2017.

[5] Barrangou, Rodolphe, and Philippe Horvath. “The CRISPR System Protects Microbes against Phages, Plasmids.” Microbe 2009: 224-30. Print.

[6] “Research Highlights: CRISPR.” Broad Institute. Broad Institute, 2016. Web. 19 Jan. 2017.

[7] Pak, Ekaterina. “CRISPR: A game-changing genetic engineering technique.” Science in the News. Harvard University: The Graduate School of Arts and Sciences, 31 July 2014. Web. 19 Jan. 2017.

[8] Cong, L., F. A. Ran, D. Cox, R. Barretto, N. Habib, P. D. Hsu, et. al. “Multiplex genome engineering using CRISPR/Cas systems.” National Center for Biotechnology Information. U.S. National Library of Medicine, 15 Feb. 2013. Web. 19 Jan. 2017.

[9] “What is CRISPR-Cas9?” Your Genome. Wellcome Genome Campus, 19 Dec. 2016. Web. 19 Jan. 2017.

[10] “PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer.” ClinicalTrials.gov. U.S. National Institutes of Health, Nov. 2016. Web. 19 Jan. 2017.

[11] Wang, Xiaolong, Bei Cai, Jiankui Zhou, et. al. “Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers.” PLOS Journals. PLOS ONE, 22 Nov. 2016. Web. 19 Jan. 2017.

[12] Talbot, David. “10 Breakthrough Technologies 2016: Precise Gene Editing in Plants.” MIT Technology Review. MIT Technology Review, 21 Feb. 2017. Web. 16 Apr. 2017.

[13] Andrew, Elise. “Genome Editing Poses Ethical Problems That We Cannot Ignore.” IFLScience. IFLScience, 15 Aug. 2016. Web. 16 Apr. 2017.

[14] Rodriguez, E. “Ethical Issues in Genome Editing Using Crispr/Cas9 System.” OMICS International. OMICS International, 24 Mar. 2016. Web. 16 Apr. 2017.

[15] “STAT’s stats of the year: 2016 by the numbers.” STATnews.com. STAT, 28 Dec. 2016. Web. 19 Jan. 2017.

19 | JOURNYS | FALL 2017

overview: seizures

th

s y s s n t r e m e

Epilepsy is the fourth most common neurological disorder in the world, behind only migraines, stroke, and Alzheimerâ&#x20AC;&#x2122;s disease.

Predictions reveal that 1 in every 26 people will develop epilepsy at some point in their life [3].

While the words seizure and epilepsy are used interchangeably, they are actually different in meaning. A seizure refers to a single incident in which there is unusual brain cell activity. This internal chaos is accompanied by a variety of physical symptoms, including fatigue, muscle spasms, pins and needles, jerky movements, and loss of consciousness [2]. Epilepsy, on the other hand, is a disorder in which a person experiences two or more of these episodes [3].

the rns system The Responsive Neurostimulation (RNS) system developed by NeuroPace is considered by leading neurology experts to be the most innovative and effective treatment for patients who have epilepsy. Similar to a pacemaker which monitors and responds to heart rhythms, the RNS system is designed to monitor and respond to brain activity. The RNS system involves a surgery which allows for the implant of a neurostimulator inside the skull of the patient. This neurostimulator is connected to leads which are placed on the area of the brain associated with seizures. The system is then able to monitors brainwaves during the day and even when the person is sleeping, looking for signs of unusual brainwave activity that would correlate with the onset of a seizure. When abnormal activity is detected, the neurostimulator sends brief pulses which interrupt the unusual activity and normalize the waves emitted by brain cells. Overall, the RNS system is very effective because it almost always recognizes and counteracts abnormal brain activity even before the patient realizes something is wrong [1].

In order to track their patientsâ&#x20AC;&#x2122; brain activity on a regular basis, patients scan the neurostimulator using a remote mon-

by sanil gandhi art by william la 20 | JOURNYS | FALL 2017

itor which automatically uploads the information stored on the neurostimulator to the Patient Data Management System.

This system stores all the information recorded by the neurostimulator, both normal and abnormal brain activity. Thus, doctors can gain insight as to what exactly the activity looks like just before the neurostimulator interrupts and normalizes brain cell activity [1].

why the rns system?

When determining what route to take in their seizure treatment, patients are given two options: traditional anticonvulsants or the new RNS system. Due to the nature of intervention that the RNS system uses, there are possible complications associated with the surgery and other effects that surgery may cause, such as infection and bleeding, both of which may dissuade people from trying the RNS system. However, one of the biggest reasons why patients choose the implant is it does not cause any of the side effects that result from anticonvulsants, such as dizziness, confusion, drowsiness, and depression [4]. Furthermore, the RNS system is a reversible therapy, which means that the neurostimulator implanted can be removed at any time. Statistics show that patients who have had the implant for 3 or more years have a 60% decreased incidence of seizures, and continued improvement of technology will only allow this efficacy to increase [1].

long-term implications The RNS system is revolutionary as it is the first system that can track and automatically respond to brainwaves that correlate with seizures[1]. However, it holds even more promise in that the technology that is currently used to treat seizures can eventually be applied to treating other neurological disorders.

references [1] The RNS System. NeuroPace. http://www.neuropace.com/the-rns-system/. Accessed February 20, 2017.

[2] Schachter SC, Shafer PO, Sirven JI. What is a Seizure? Epilepsy Foundation. http:// www.epilepsy.com/learn/epilepsy-101/what-seizure. Accessed February 20, 2017.

[3] Sirven JI, Shafer PO, eds. What Is Epilepsy? Epilepsy Foundation. http://www. epilepsy.com/learn/epilepsy-101/what-epilepsy. Accessed February 20, 2017.

[4] Schachter SC, Shafer PO, Sirven JI. Side Effects. Epilepsy Foundation. http://www. epilepsy.com/learn/treating-seizures-and-epilepsy/seizure-and-epilepsy-medicines/ side-effects. Accessed February 20, 2017.

The Effect of Rh Factor on Pregnancy

By Natialia Rojas Many people know if their blood type is A-positive or O-negative, but few people know what this “-positive” or “-negative” really means. These attachments signify the presence of the Rhesus (Rh) factor, so named because it was first discovered in 1937 on the red blood cells of the rhesus monkey [2]. Testing positive for the Rh factor indicates its presence on a person’s red blood cells; testing negative for it indicates its absence [1], [2], [3]. Most people in the United States test positive for Rh factor. It is found in 85% of Caucasians in the United States and 95% of African Americans [2]. Despite its prevalence, Rh factor can have negative side effects and can cause complications, notably during pregnancy. Problems arise when a mother is Rh-negative (Rh-) and a father is Rh-positive (Rh+), meaning a fetus may potentially be Rh+ if they inherit their father’s Rh+ allele. If the mother’s Rh- allele and the fetus’s Rh+ allele come into contact, the mother’s immune system (which lacks the Rh factor) may treat the fetus’s Rh+ red blood cells as foreign threats [4]. This in turn can lead to Rh disease - or erythroblastosis fetalis - which occurs when the mother’s immune system develops antibodies against the fetus’s Rh+ blood [1], [2], [4], [5]. Once anti-Rh antibodies have been created, the woman is said to be Rh sensitized [4]. These antibodies can be created through childbirth, miscarriage, amniocentesis, chorionic villus sampling, a C-section, abortion, ectopic pregnancy, or any other circumstance where the Rh+ blood and the Rh- blood come into contact [1], [2], [3], [4].

If the woman creates anti-Rh antibodies, these antibodies pose problems for any future pregnancy with an Rh+ fetus. The antibodies will attack the red blood cells of the fetus [2], and as a result, the fetus may develop conditions such as hemolytic anemia, which is caused by a lack of red blood cells in the body [3], [4]. Anemia in the fetus can have dangerous repercussions, such as an increase in bilirubin, which puts the fetus at risk of brain damage [2].

In extreme cases, an anemic fetus can also fall victim to heart failure and death.

Fortunately, an Rh- mother with an Rh+ fetus can take preventative measures to ensure a healthy and successful pregnancy [1]. For example, an Rh- mother can be given an Rh immune globulin vaccine (also referred to as RhoGAM or Rhlg) in order to prevent the development of anti-Rh antibodies [1], [2], [3], [4]. However, this treatment can only be used during a woman’s first pregnancy

Art by Yerin You before she has developed antibodies. Because the blood type of the fetus is not known before a mother’s antibodies develop, Rhlg is used primarily as a precautionary measure [1], [2]. During the first trimester, an Rh- woman is tested for antibodies; if none are found, the vaccine can be freely administered. This procedure is repeated in the 28th week of pregnancy to ensure that antibodies have still not been created. [5]. This treatment continues after childbirth, after the baby’s blood type has been tested. An Rh- baby with an Rh- mother, will pose no issues , but with a Rh+ baby the entire procedure will need to be repeated [1], [5]. In spite of these inconveniences, Rhlg is still extremely useful because it can be delivered to the mother even if any of the previously mentioned afflictions —such as miscarriage and amniocentesis—take place. [2], [3], [4], [5].

However, if a woman has already created anti-Rh antibodies and is already sensitized, Rhlg loses its effectiveness. [3], [4]. At that point, the pregnancy must be closely observed to ensure the amount of antibodies present in the mother’s Rh- blood will not harm the baby [2], [4]. If the amount of antibodies begins to endanger the health of the fetus, the fetus must undergo a blood transfusion [2], [3], [4], [5].

Despite their limitations, Rh immune globulin vaccine administration and fetal blood transfusions are still established operations for dealing with complications that arise from Rh factor and its relationship to pregnancy. Most citizens of the United States and the world have a blood type that is either “-positive” or “-negative”, but few fully understand the ramifications of those supplements. Something as simple as an antigen attached to a red blood cell can have a huge impact on the health and development of a child, and can lead to life-altering consequences.

References: [1] Sundstrom, K. “What Being Rh Negative Means For Your Pregnancy”. Parenting.

2017. Web. 10 Mar. 2017.

[2] Marshall L. Rh Factor.

The Gale Encyclopedia of Science. 2014. Available at: http://link. galegroup.com/apps/ doc/CV2644031915/ SCIC?u=alex41841_e&xid=a17a9cfe.

Accessed March 10, 2017.

[3] Rh Factor. American Pregnancy Association.

Available at: http://americanpregnancy.org/pregnancy-complications/rh-factor/. Accessed March 10, 2017.

[4] The Rh Factor: How It Can Affect Your Pregnancy. ACOG. 2013. Available at: http://www.acog.org/ patients/faqs/the-rh-factor-how-it-can-affect-your-pregnancy. Accessed March 10, 2017.

[5] Mayo Clinic Staff. Why it’s done. Mayo Clinic. 2015.

Available at: http://www.mayoclinic.org/tests-procedures/ rh-factor/basics/why-its-done/prc-20013476.

Accessed March 10, 2017.

[6] Campbell NA, Reece JB. Biology. 7th ed. San Francisco: Pearson, Benjamin Cummings; 2005.

[7] Basu S, Kaur R, Kaur G. Hemolytic disease of the fetus and newborn: Current trends and perspectives. Asian Journal of Transfusion Science. 2011;5(1):3-7. doi:10.4103/0973-6247.75963.

21 | JOURNYS | FALL 2017

Calculating the Distance of Stars To the ancient Greeks, stars acted as the founding pillars Hipparcos and Gaia satellites have measured the parallaxes for of imagination, depicting heroes and animals that led to the millions of stars with an accuracy of 2-4 milliarcseconds, and creation of myths. To explorers, the North Star served as a have broadened our view of space [3]. convenient navigation tool. Nowadays, stars are in nursery Another way scientists can calculate the distance of a star rhymes, movies, and the greatest hits in music. Though the is by comparing the absolute magnitudes of different stars. way stars have been Absolute magnitude is the intrinsic incorporated into brightness of an object, which is how cultures is very different, bright a star would be if it were ten one thing that we can all parsecs away. In the night sky, a star agree on is that stars are that appears brighter may not actually far away. Light travels be brighter; this is because closer stars at 186,000 miles per appear brighter than those that are second, and a light year, far away. A law that portrays this is which has a distance of the Inverse Square Law, which states almost 6 trillion miles, is that intensity is inversely proportional p=parallax angle in arcseconds the distance light travels to the square of the distance. For d=distance in parsecs annually. Even the closest example, if you are twice as far star to Earth, Alpha from a light, it will appear four times *once the parallax angle in arcseconds is determined Centauri, lies over four dimmer, and if you are three times light years away, so that as far from a light, it will appear nine brings up the question: times dimmer [4]. how do astronomers predict the distances Objects with of these stars [1]? approximately The most accurate method utilized by the same absolute astronomers is parallax—the effect where magnitude are if an observer moves, objects will change called standard position compared to the distant objects candles. Cepheid m-M+5 behind it. To observe this, stick out your Variables and Type 5 thumb at an arm’s length in front of you 1a Supernovae d=distance in parsecs and cover one eye. Then cover the other eye are commonly and note the shift that occurs [2]. In stellar used standard m=apparent magnitude parallax, scientists observe the star from candles that help M=absolute magnitude opposite sides of Earth’s orbit around the determine the sun. One angle is taken when Earth is on distance of stars one side of its orbit, and another angle is over 100 parsecs measured six months later. While an object away [5]. closer to Earth will shift more, an object at a greater distance Cepheid Variables, which are stars that brighten and dim will shift less. at certain intervals, can help calculate the distance of farther Once the parallax angle in arcseconds or 1/3600th of a stars. A Cepheid is a unique kind of variable star because its degree is determined, the distance of a star in parsecs can be period, or the time it takes to brighten and dim, is directly found using the simple formula d=1/p where p=parallax angle related to its absolute magnitude. The longer a Cepheid’s in arcseconds and d=distance in parsecs. For example, a star period, the brighter the star is. Given the period of a Cepheid, with a parallax of one arcsecond has a distance of one parsec. we can determine its absolute magnitude as well as its apparent Parallax is the most reliable way to determine distance, but magnitude, the brightness seen from Earth. As long as the because more distant stars have a smaller parallax, it is more apparent and absolute magnitude of an object is known, the accurate for stars that are closer. Only a few hundred stars are distance modulus equation can be used to find distance using near enough, so scientists have released satellites into space in the equation d =10m-M+55parsecs, where d=distance in order to accurately record distances of stars farther away. The parsecs, m=apparent magnitude, and M=absolute magnitude.

Distance of Stars in Parsecs*

d=1/p

Distance Modulus Equation

d=10

22 || JOURNYS JOURNYS || FALL FALL 2017 2017 22

A star with a distance modulus of zero is ten parsecs away [6].

Scientists also monitor Type 1a supernovae for even farther stars. A Type 1a supernovae results from a white dwarf accreting mass from its companion star until it reaches the Chandrasekhar limit, which is 1.4 times the mass of the sun. Once it reaches this limit, the white dwarf explodes.

Type 1a Supernovae usually reach the same absolute magnitude—about -19.3—so scientists can determine the apparent magnitude and use the distance modulus formula to calculate the distance of the stars [6].

Astronomy continues to advance as new discoveries and technologies are made. We are able to view stars farther away in the universe than ever before. Recently, a team of astronomers discovered a galaxy that formed just

400 million years after the Big Bang. Using the Hubble’s Wide Field Camera 3 (WFC3), its distance from Earth was calculated by measuring the galaxy’s red shift: a phenomenon where light is stretched towards the red wavelength of the color spectrum. This galaxy, named GNz11 and found in the constellation Ursa Major, is 32.2 billion light years away, making it the farthest galaxy ever measured [7].

The discovery of GN-z11 is just one of the ways in which the calculation of stellar distance has allowed scientists to make substantial breakthroughs in astronomy.

Through the use of parallax, comparisons of absolute magnitude, Cepheid variables, and Type 1a Supernovae, scientists are able to calculate the distance to stars near and far. As new technology broadens our horizons, we continually extend the limits of our own knowledge.

Even the closest star to Earth, Alpha Centauri, lies over four light years away, so that brings up the question: how do astronomers predict the distances of these stars?

[1] McClure, Bruce. “How Far Is a Light-year?” EarthSky. EarthSky Communications Inc., 11 July 2016. Web. Feb. 2017. <http://earthsky.org/astronomy-essentials/howfar-is-a-light-year>.

[2] “How Do Astronomers Measure Distances to Stars and Galaxies?” StarDate. StarDate, n.d. Web. Feb. 2017. <https://stardate.org/astro-guide/faqs/how-do-astronomers-measure-distances-stars-and-galaxies>.

[3] Lucas, Jim. “What Is Parallax?” Space.com. Punch, 29 Aug. 2015. Web. Feb. 2017. <http://www.space.com/30417-parallax.html>.

“Methods of Measuring Stellar Distances.” Stellar Distances. Hands on Universe, n.d. Web. Feb. 2017. <http://www.ast.cam.ac.uk/~mjp/index.html>.

[4] “Cepheid Variable Stars & Distance.” Australia Telescope National Facility. CSIRO, 07 July 2016. Web. Feb. 2017. <http://www.atnf.csiro.au/outreach/education/ senior/astrophysics/variable_cepheids.html>.

[5] “Cepheid Variable Stars, Supernovae and Distance Measurement.” Las Cumbres Observatory. Las Cumbres Observatory, n.d. Web. Feb. 2017. <https://lco.global/ spacebook/cepheid-variable-stars-supernovae-and-distance-measurement/>.

[6] “Hubble Breaks Cosmic Distance Record.” Hubble Space Telescope. Esa, 3 Mar. 2016. Web. Feb. 2017. <https://www.spacetelescope.org/news/heic1604/>.

by Allison Jung 23 || JOURNYS JOURNYS || FALL FALL 2017 2017 23

MARKOV

CHAINS

Suppose two people, Alice and Bob, play a game. Alice goes first, and the players each take turns flipping a coin. The first person to flip heads wins the game. What is the probability that Alice wins?

Intuitively, Alice should have a better chance of winning.

Indeed, this is the case. Let p be the probability that Alice wins.

Consider Alice’s turn. If she flips heads (with probability 12), then she wins. Otherwise, if Alice flips tails, it is Bob’s turn. Because Alice wins with probability p on her turn, that is also Bob’s probability of winning on his turn, so the probability of Alice winning on flipping tails is 1-p. Thus, we have:

p=1/2+1/2(1-p) 3/2p=1 p=2/3 Notice that even if the process may go on for many moves (if Alice and Bob both are very unlucky and both flip tails lots of times), we can still compute the probability of Alice winning. This is the essence of states, which describe the intermediate stages of an event. [1] States can vary from “10 seconds away from nuclear war” to a “match point in tennis.” The only condition is that later states depend solely on previous states (and not on other meta-information). For instance, in our game, the states are “Alice’s turn” and “Bob’s turn.” On each turn, we have the choice to either jump to the opposite state in the case of tails or terminate in the case of heads. No other information is encoded in the state, which makes it so versatile.

MARKOV MARKOV By Kevin Ren

By Kevin Ren

Art by Alexander Hong Art by Alexander Hong 24 | JOURNYS | FALL 2017

States

are useful because they allow the decomposition of complicated events into smaller, more manageable events. Consider the last problem from the 2014 AMC 10B:

In a small pond, there are eleven lily pads in a row labeled 0 through 10. A frog is sitting on pad 1. When the frog is on pad N, 0<N<10, it will jump to pad N-1 with probability N10 and to pad N+1 with probability 1-N10. Each jump is independent of the previous jumps. If the frog reaches pad 0 it will be eaten by a patiently waiting snake. If the frog reaches pad 10 it will exit the pond, never to return. What is the probability that the frog will escape being eaten by the snake? [2] The first step is to identify the states. We only care about the frog, so we let the states be the lily pad the frog is on. Let pn be the probability that the frog will escape if it is on pad n. Then by the condition, we have this system of equations:

p1=1/10*0 + 9/10p2 p2=2/10p1+8/10p3 p3=3/10p2+7/10p4 … p9=9/10p8+1/10p10 p10=1

This can be solved using a computer, but a clever trick is worth more than a thousand computers. The crucial idea is that pi+p10-i=1 for each 0<i<10, because by symmetry the probability the frog goes from i to 10 is equal to the probability of going (in the reverse direction) from (10-i) to 0. In particular, we get p5+p5=1→p5=12. Now we know p2=109p1, so 109p1=210p1+810p3 →8290p1=810p3→p3=4136p1. Continuing, we get 4136p1=13p1+710p4→p4=145126p1 and finally 145126p1=410*4136p1+610 *12→p1=63146≈0.431507.

More generally, a Markov Chain is a collection of states and rules governing the probabilities of going from one state to another.

Like states, Markov chains have the property that the future is independent of the past. [3] Suppose we have states {S1,S2,S3,…, Sn}.

Then we can construct an n × n transition matrix {aij} such that aij is the probability of going, or transitioning, from state j to state i.

The matrix has the following properties.

The sum of the entries in any column must be 1, because the probability of leaving a state, and going to some other state, is 1.

The entries are between 0 and 1 inclusive, because they represent probabilities.

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The transition matrix gives a way to move between states, but we need a way to keep track of probabilities of being in a certain state at a certain time. This function is served by the state matrix, which is a column matrix whose i’th entry represents the probability of being in state Si. The crucial fact is that given a state matrix X and a transition matrix P, the next state matrix will be PX. This can be shown by matrix multiplication. By repeating the process, the state after n iterations will be PnX. [4] {Picture of Markov chain OR collection of states} We are interested in long-term trends, so it is desirable to compute the limit of Pn as n→∞. For example, let us return to our AMC problem. By filling in the entry in the i’th row and j’th column with the probability of going from state j to state i, we determine that the state matrix is:

1 0 0 0 0 0 0 0 0 0 0

0.1

0

0

0 0.9

0.2 0

0 0.3

0 0 0 0

0 0 0 0

0.7 0 0 0

0 0

0 0

0

0 0 0

0.8

0

0

0

0 0

0 0

0 0

0 0

0

0.4

0

0

0

0

0

0

0

0 0.6 0 0

0.5 0 0.5 0

0 0.6 0 0.4

0 0

0 0

0 0

0

0

0

0

0 0

0 0 0.7 0

0 0 0 0.8

0

0.2

0.3 0

0 0

0 0

0 0

0

0

0 0 0 0 0

0.9 0 0.1

0 0 0 0 0 0 0 1

When you get to state 10, you cannot go to another state (because the frog has already “won” by escaping the pond); hence the probability of state 10 going to itself is 1, so state 10 is an absorbing state. [4] Similarly, state 0 is also absorbing. A Mathematica calculation raising the transition matrix to the 1,000,000th power gives:

1 0 0 0 0 0 0 0 0 0 0

0.568493 0.520548 0.508562 0.503425 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0

0 0 0 0 0

0 0 0 0 0 0

0 0 0 0 0 0 0 0.431507 0.479452 0.491438 0.496575

26 | JOURNYS | FALL 2017

0.5 0.496575 0.491438 0.479452 0.431507 0 0

0 0 0 0 0

0 0 0.5

0 0 0 0 0 0 0

0 0 0 0 0 0 0

0 0 0 0 0 0 0

0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0.503425 0.508562 0.520548 0.568493

0 0 0 0 0 0 0 0 0 0 1

Multiplying this matrix by the column state matrix X=[0 1 0 0…0]T, which represents the initial state (the frog starts at pad 1), we get its second column. Thus, after 1,000,000 jumps, the frog will be on pad 0 with probability 0.568493 and on pad 10 with probability 0.431507 (and approximately probability 0 for each of the other pads). The probability that the frog escapes is thus approximately 0.431507, which matches our answer from before. Notice that we can easily find the probability of escaping from starting from another state using the above matrix, by multiplying by a different starting X. For instance, we can verify the probability of escape from pond 5 is 0.5.

In fact, if we take large enough n, Pn eventually converges to a stable matrix. This is true for any absorbing matrix. Indeed, we can express the state matrix in standard form, in which all the absorbing states are listed first, resulting in a matrix of the form

I S O R where I is an identity and O is the zero matrix. It turns out that the stable matrix is just

If we convert the matrices in the example to standard form, we can verify that this result holds. [4] The above example demonstrates an absorbing Markov chain, which has the following two properties: It has at least one absorbing state.

For each other state, there exists a way (with nonzero probability) to get to an absorbing state via state transitions. [4] Absorbing Markov chains are often times used to solve problems like the AMC one, in which there can potentially be infinitely many moves. One example that uses an absorbing Markov Chain is the classic gambler’s ruin problem. In a casino, a person must play games with win probability p, such that he wins $m on winning and loses $n otherwise. The person wins if he makes $X in net profit and loses if he goes broke, at any point in the scenario.

The player must eventually win or lose, and hence the problem can be modelled by an absorbing Markov Chain. Other examples include the spreading of disease in a population (in which death is the absorbing state) and random walks on a number line (in which reaching a certain number or numbers ends the walk) [3]. The disease model is quite interesting when applied to epidemiology, as In a casino, a person must play games with it can lead to prescribing the optimal strategy to control epidemics win probability p, such that he wins $m on in a population and estimate the costs and severity of the epidemic winning and loses $n otherwise. The person using only empirical information, such as the rate of disease transmission and the survival rate. wins if he makes $X in net profit and loses if he Markov chains are an intriguing concept in mathematics. goes broke, at any point in the scenario. The They allow for the analysis of random, possibly infinite events in an player must eventually win or lose, and hence orderly manner, using techniques from linear algebra and a model the problem can be modelled by an absorbing of the states. Markov chains allow us to compute probabilities for Markov Chain. entities we have no control over—until they happen.

Gambler’s Ruin

References [1] Patrick D. Intermediate Counting and Probability. United States: Alpine, California, U.S.A.: AoPS; 2007.

[2] 2014 AMC 10B Problems/Problem 25. Art of Problem Solving. https://www.artofproblemsolving.com/wiki/index.php/2014_AMC_10B_Problems/Problem_25. Accessed February 10, 2017.

[3] Weisstein EW. Markov chain. Wolfram MathWorld. http://mathworld.wolfram.com/MarkovChain.html. Accessed February 10, 2017 [4] Larson RE, Edwards BH, Heyd DE. Finite mathematics. MA, United States: Houghton Mifflin; February 1, 1990.

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Tick Tock: Time Differs FROM A B P D CLOCK A B W L y oorvi atta rt y illiam a

Many can relate to the movie trope of the bored student counting down the seconds until school ends. To the student, each second stretches into infinity and time slows to a snail-like pace. This is one of the many phenomena that appear with human temporal perception. The way humans perceive time diverges greatly from what appears on a clock. Each second may or may not seem to last as long as the previous, proving psychological time to be highly subjective and malleable [1].

This malleability arises from the fact that psychological time is regulated by the cerebral cortex in the brain, which is prone to change. However, it is unlike circadian clocks, the internal biological clocks which regulate actions like sleeping and hormone production on a roughly 24-hour cycle. Psychological time is more closely related to faculties like attention. The amount of attention to detail greatly impacts how long humans think an event lasted. New events receive more attention, more detail, and are thus perceived to have a longer duration. Memory plays a key part in time perception as well.

Humans infer the duration of an event from the memories they have of it. Although unrelated to the internal biological clocks, metabolic rate also affects psychological time. Time passes quickly for large animals with slower metabolic rates and slowly for small animals with faster ones. When tested, small animals were able to differentiate small, quick-changing events easily, which is why a fly can avoid a fly swatter with ease [2].

Much of this reasoning arose from experiments testing possible explanations for observed temporal, or time-related, phenomena. The problem with experiments involving temporal perception is that if the participants are told before the experiment that they will be requested to make duration 28 28 || JOURNYS JOURNYS || FALL FALL 2017 2017

estimates, then they may think about time, thus using more of the cerebral cortex than they would have if they were uninformed. Scientists have solved this problem by dividing participants into two groups: prospective and retrospective. Prospective participants are told before an experiment that they will be asked to estimate time duration, while retrospective participants are not given this information. This enables researchers to observe whether there is a difference between the two groups [3].

Experiments involving temporal perception have helped develop ideas on phenomena known as temporal illusions, or distortions of time due to psychological or natural causes [2]. One of the most common temporal illusions manifests in the common phrase, “Time flies when you’re having fun!” The first Friedman phenomena, outlined by William Friedman who published a review of seventy time experiments in 1990, observed that people underestimated duration when completing a difficult task. One possible explanation is that attention is moved from timekeeping in the cerebral cortex to the challenging activities, so the time estimate is less accurate as less attention is being paid to it. Participants overestimate time durations during periods of fear, anticipation, or high expectation—when maximum attention is being directed to timing. Therefore, when attention is being directed somewhere other than timekeeping, it would logically produce the opposite effect. This theory was confirmed in a recent study at the University of Alberta, where scientists Anthony Chaston and Alan Kingstone proved that time passes more quickly for participants whose attentions are engaged. In the experiment, groups of participants worked on a puzzle similar to “Where’s Waldo,” which involves the cerebral cortex; in both retrospective and prospective measurements, as the activity grew more difficult, participants increasingly underestimated the amount of time elapsed [3].

Time not only seems to pass quickly when occupied, but also as humans get older; this is another temporal illusion. Evidence supporting this idea can be observed in an informal experiment by National Public Radio, where an interviewer stopped pedestrians who were either very young or very old. They were asked to close their eyes and tell the interviewer when they felt that one minute had passed. The younger participants were very close to a stopwatch-minute whereas the older people tended to overshoot drastically, averaging around ninety seconds. While there is no definitive reason to this illusion, there are three proposals: the physiological explanation, the proportional explanation, and the neurological explanation. The physiological explanation argues that the neural con-

duction velocity, or the speed at which brain cells pulse, slows down as humans age, causing time to flow differently when they are older.

As the brain slows down with age, perception of time slows down for aging people, so everything around them appears to go faster. Since objective time itself is the same, more seems to occur, which is shown as the elder subjects believe that 90 seconds of events happened within 60 seconds of real time, and time appears to go faster. The proportional explanation states that when a human is, for example, six years old, two years represent one-third of their life. When the same person is sixty-three years old, two years represents only 1/32 of their life so, proportionally, time means less and goes faster. The neurological explanation links back to the idea that new events receive more attention and detail, and are thus perceived to have a longer duration; the brain uses more energy to remember these details. Since there is much more to remember, the event seems to be longer, because humans subconsciously tend to assume that a set series of events takes a certain set amount of time.

That’s why a forty-fifth birthday seems shorter than a sixth birthday—it is not new to the viewer and has less apparent detail [4].

Larger temporal phenomena are not the only ones that affect humans, however. One smaller phenomenon is the stopped-clock illusion, referring to how the second-hand of a clock seems to stop when stared at. This illusion is triggered by quick eye movements, occurring when there is a disconnect in the communication between sight and recognition in the brain. It suggests that reacting to new visual stimuli takes longer than reacting to known stimuli and is an exaggeration of the oddball effect, which takes place any time the brain experiences something unfamiliar. Much like new experiences, the brain pays more attention and takes note of more detail, so time appears to slow down. It is apparent with a new or stressful stimulus like a potential threat or mate. One theory suggests that the “fight or flight” response heavily involves the oddball effect, as the process of “slowing down” gives an advantage to making critical decisions because it gives humans “more” time to think and act. In fact, David Eagleman has proven that the brain processes information much faster in high-adrenaline situations [5]. Another experiment suggests that psychological time does not pass more slowly but is instead a trick of memory.

Participants in this experiment underwent Suspended Catch Air Device (SCAD) Diving, where they free-fell for fifteen stories and were given a perceptual chronometer, which is similar to a wristwatch that flashes numbers a little too fast to read on the

ground. If time were actually passing more slowly, the participants would be able to read the numbers. Since they were not able to read the chronometer, it appears that time did not actually slow down.

However, the participants reported a duration much longer than the real-time duration of the fall. The results suggest that, in a life-ordeath situation, the brain becomes hyperactive and records many more details than usual, so time seems slower upon reflection—a trick of memory [6]. Although real time does not actually slow down, relative person-to-person perception makes it seem like it does.

Einstein suggested that time can be relative from person to person based on factors like velocity. The ideas behind psychological time expand on his theory, implying that an elephant’s time, a fly’s time, or even the time experienced by two humans can differ drastically.

Time is dependent on emotions, activities, hormones, and a host of mysterious phenomena. Whatever the causes may be, temporal perception deviates from a clock, so each psychological second may not last for the same duration as the tick of a second hand. It seems that time can be relative in more ways than one.

References [1] “Quirks in Time Perception”. www.psychologytoday.com/blog/alternativetruths/201004/quirks-in-time-perception (2010) [2] “Psychology of Time”. www.exactlywhatistime.com/psychology-of-time/ (2017) [3] “The Psychology of Time”. www.jyi.org/issue/the-psychology-of-time/ (2004) [4] “Why Does Time Fly By As You Get Older”. www.npr.org/sections/ krulwich/2010/02/01/122322542/why-does-time-fly-by-as-you-get-older (2004) [5] “Temporal Illusions”. www.exactlywhatistime.com/psychology-of-time/ temporal-illusions/ (2017) [6] “Why A Brush With Death Triggers The Slow-Mo Effect”. www.npr.org/ templates/story/story.php?storyId=129112147 (2010)

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EDITOR-IN-CHIEF Stacy Hu

PRESIDENT Erica Hwang

ASSISTANT EDITORS-IN-CHIEF Colette Chiang, Sumin Hwang, Melba Nuzen

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CONTRIBUTING AUTHORS Jonathan Kuo, Arpad Kovesdy, Minha Kim, Isa Stelter, Alina Luk, Karishma Shah, Melba Nuzen, Sanil Gandhi, Natalia Rojas, Allison Jung, Kevin Ren, Poorvi Datta

DESIGN MANAGER William La

CONTRIBUTING EDITORS Jonathan Kuo, Colette Chiang, Jonathan Lu, Minha Kim, Maya Kota, Joshua Kim, Richard Li, Sumin Hwang, Edward Xie, Aditya Guru, Melba Nuzen

DESIGNERS Alexander Hong, Stacy Hu, Sumin Hwang, William La

STAFF ADVISOR Mr. Brinn Belyea

Dear Reader, We are excited to present to you the first JOURNYS issue of the 2017-18 school year! Although this issue was scheduled for publication last school year, we have had our fair share of setbacks - but all in efforts of producing a final version that is representative of our best work. JOURNYS is proud to serve as a forum for high school students around the world to share their research discoveries, dig deeper into topics that interest them, express their creativity through artwork, or demonstrate their eye for design with graphics and layout. We hope you have been inspired to learn more about a topic or consider a new idea you had never thought about before, and maybe even get involved in contributing to our next issue!

And now for some acknowledgements! Aside from our amazing writers, editors, and graphic artists, I would like to give a special shout out to Sumin Hwang, William La, Jessica Gang, and ALEXANDER HONG for the immense time and effort they have dedicated to the production of this issue (especially ALEXANDER HONG, if that was not clear already). I think Starbucks would also like to thank us for the sheer number of drinks we purchased from their establishment, which sustained us through the lengthy and numerous editing and layout sessions.

There are many more exciting things in store for this year, so keep your eyes peeled!

Sincerely, Stacy 31 | JOURNYS | FALL 2017

Journal of Youths in Science

2017-2018

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