Scientific Discoveries June - July

Issue 8

The Law of Chaos in Neuroscience Cryonics and Other Alternatives to Burial

Regenerative Medicine and Stem Cell Therapies the Latest Advances New Stem Cell and Nano Treatments for Brain and Spinal Cord Injuries

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

The Law of Chaos in Neuroscience and Other Fields The Law of Chaos in Neurroscience and Oher Fields Though chaotic systems follow a kind of order, the law of chaos determines that systems may not be necessarily predictable due to certain parameters.

Photojournalist: Loria Hilahm. All rights reserved.

For a system to be known as chaotic it must have the following characteristics: it must be sensitive to initial conditions, topologically mixing (meaning that due to its evolution any region of the system will overlap with any other given region, an example of a simple chaotic system is the mixing of fluids) and its periodic orbits must be dense (periodic orbits that are randomly close to each other).

7 Alterations in Primary Parameters

The law of chaos determines that systems may not necessarily be predictable because alterations in the primary parameters they are built on make them changeable. It establishes that their behaviour is related to their initial conditions. This law in physics observes the similarity of patterns in systems.

Quantum chaos is a field of study that is being applied to biology, engineering, sociology, economics, computer science, medicine, and ecology, among others. One of the pioneers of this theory was Edward Lorenz who, in 1961, became interested in chaos through his work on weather prediction.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Chaos Utilised in Neuroscience Neuroscience is one of the fields in which the study of chaos has been used to determine the selection, processing and creation of information in the brain, and this has caused a revolution in the way researchers in brain studies currently perceive the physiological and biochemical brain behaviour.

Contrary to the old belief that pathological brain malfunction was produced by chaos , it is important to realise, in fact, that it has now been established that deterministic chaos is essential for correct brain functioning, It is this physical state that allows the different perceptual activities to proceed in a rapid manner. Researchers have also discovered that chaotic basal activity influences the neuronal activity to exercise in order for neurones not to die. It can be stated that it is indispensable for the production of information.

The spatiotemporal form of neural activity is recreated by the brain itself and it can also select what input of information acquires. It has been proposed that chaos may be indispensable for the selection, processing and creation of information in the brain.

The Theory of Chaos Applied in a Variety of Fields In sociology, the application of nonlinear dynamic systems (chaos law) identifies when there are instabilities in social systems and it indicates, for example, how to adapt to changes in populations as well as how to influence social development at several levels.

In medicine, this law of physics is being used for a variety of purposes such as the monitoring of heart rate variability (HRV)) and the measurement of epileptic seizures.

In engineering, chaotic systems are used in communications, random number generators, and encryption systems.

In computer science it is being used as a new computing technique that allows a network of chaotic elements to "evolve" its answers.

As time goes by scientists and professionals in many fields are finding multiple uses for the chaos theory in a variety of fields. Believe it or not it is important to understand that chaotic systems follow a kind of order.

Copyright D. JL Novak and J. Johnson. All rights reserved.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Sources 

Boccaleti, S.,Grebogi, C., Lai, Y-C., Mancini, H., Maza, D. "The control of chaos theory and applications", Physics Reports 329, 2000.

 Skarda, C,A., Freemans, W,J. "Chaos and the new science of the brain", Concepts in Neuroscience, World Scientific Publishing, 1990.

This article was first published by Dinah JL Novak and John Johnson on October 2013. And has been revised and updated in June 2015 buy John Johnson for Scientific Discoveries.

We carefully researched the information in the references mentioned above and add our scientific research.

Contact Us for republishing, subscription or any other consultation to niirs.contact@gmail.com or call us on 02032862193.

Copyright D. JL Novak and J. Johnson. All rights reserved.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Cryonics and Other Options as an Alternative to Burial Cryonics and Other Options as an Aternative to Burial Cryonics intends to prevent death by lowering the temperature of the organs before they stop working. There are other options which are being in experimental phase Archives Investigative and Research Services, NIIRS Cryonics is a modern experiment that tries to preserve the body of a dead person by placing it at low temperatures (-120°C). At this point the biochemistry of their organs stops functioning. This process is achieved by injecting cryoprotectants. These substances allow the tissues to be frozen with little or no ice formation. The system is called vitrification.

This technique tries to arrest death and maintain cells (and therefore tissues and organs) at an optimal state to prevent damage so that the technology of the future can revive the brain or the entire body of an individual.

It was in 1967 that the first person, Doctor James Bedford, was cryopreserved in California. Since then hundreds of people of various age ranges and ethnicities have been placed in cryonic suspension.

It is thought that MNT (molecular nanotechnology) will be one of the main medical fields to be in charge of repairing and regenerating those who have been vitrified. As Ralph Merkel in Cryopreservation Revival Scenario Using Molecular Nanotechnology explains, “Advanced nanorobots will keep all human body cells in perfect repair, preventing disease and aging.” Therefore, in short, we could state that nanomedicine will be able to recover those cryopreserved individuals as nanorobots could be injected into the person in biostasis. With the aid of computerised systems both techniques will be able to restart the biochemical cycle of all the organs. After medical intervention and repair the individual will be gradually returned to the normal body temperature of 37°C.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

There are several companies that offer their services to those who decide to be cryopreserved as an alternative to a traditional burial. These include Alcor and Cryonics.

Not only humans have been vitrified but also pets and other animals as well as the freezing of single organs. Nitrogen is the main substance used to freeze the organs or bodies.

Cryonics intends to prevent death by lowering the temperature of the organs before they stop working.

It is important to understand that at present death is established approximately 5 minutes after the heart stops beating because it seemed quite impossible to resuscitate the brain beyond that length of time. Though at present several nations and institutions are revising their medical protocols on when to establish death.

The authors of this article would like to add from a scientific perspective that death is a stage that on its due time will be overcome. Due to advances and the implementation of new protocols. It is also important to remember that it is thought that already ancient civilizations believed and carried out certain rituals to surpass death.

There are other alternatives to cryonics too, one of them suspended animation. Though still on experimentation. If our readers would like to know more about this process they can refer to our April - May issue, and read the article Suspended Animation, A New Approach to Restore Health.

Avoiding Brain Damage However new experiments have demonstrated that brain damage can be avoided during 10 minutes of warm cardiac arrest. In the majority of US states, death is accepted when there is brain death and the heart and lungs stop functioning. As a matter of fact cryonics can only be carried out after legal death occurs. It is important to take into account that professionals in charge of this discipline differ in their opinion about legal death and speak of information-theoric death. They try to maintain the information (memory, personality‌) in the brain undamaged - a method that delays death in the hope that in future new fields such as nanomedicine will be able to revive the entire organism. The patients are placed in what are known as cryostats (compartmentalized units). The prices range from $80,000 for the brain to $150,000 for the body.

For those who believe that the future bring us an incredible advance in overcoming death cryopreservation could be one of the alternatives, preferably to be buried. In any case the choice should be always made after careful consideration as it is a decision in a life time.

Copyright D. JL Novak and J. Johnson. All rights reserved.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Sources 

The information for this article has been extracted from Alcor foundation website and also from the text of Ralph Merkel "Cryopreservation Revival Scenario Using Molecular Nanotechnology."

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The authors D JL Novak and John Johnson have revised and updated this report in July 2015, and have added their own scientific research and opinion to this updated version of Cryonics as an Alternative to Burial. At present, they are working on a research about the issues dealt in this article to publish shortly.

Contact Us for republishing, subscription or any other consultation to niirs.contact@gmail.com or call us on 02032862193.

Copyright D. JL Novak and J. Johnson. All rights reserved.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Stem Cell and Nano Therapies for Brain and Spinal Cord Injuries Stem Cell and Nano Therapies for Brain and Spinal Cord Injuries Biomaterials, with the aid of nanomedicine and stem cell therapies, are the key elements in restoring CNS (central nervous system) disorders.

Photojournalist: Loria Hilahm. All rights reserved.

In the near future nanogenerators will support nanorobots with the capability to repair DNA and to restructure impaired neurones and their organelles through gene regulation (gene expression specificity) to reactivate their molecular conformation and tasks. Most probably, as for acute disorders, complete cell exchange will take place and new stem cells will be delivered in the damaged area. Alternatively, nanotechnology and stem cells can stimulate the differentiation, migration and outgrowth of certain cells within our tissues.

Nanomedicine and Stem Cell therapy As a matter of fact, nanotechnology and stem cell therapy are already a reality in the laboratories and in some clinical trials are important treatments to rebuild cellular damage and promote regeneration in vivo. The medical integration of both fields can be utilized to repair intensive injuries in localized regions.

At present, the development of biomaterials that evoke cellular responses is increasingly important for the treatment of neurodegenerative disorders and brain repair. This article describes a series of systemic and local drug-delivery systems currently being used for promoting repair within the central nervous system (CNS). Nanoparticles, nanocarriers, cell immobilization systems, polymer scaffolds and a combination of polymer scaffolds and stem cells are the main biomolecules utilized for Parkinson's disease, Huntington's disorder, amyotrophic lateral sclerosis, and acute brain injuries.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Nanoparticles Nanospheres and nanocapsules can be included under the term polymeric nanoparticles.

They can be classified by the synthetic materials they are manufactured with: PLA, PLGA and PCPP-SA are the most common. Their size is appproximately between 10 nm and 1000 nm. Despite having a poor ability to cross the brain barrier the surface of these particles can be coated with special molecules to increase their access to the brain.

Nanocapsules are loaded with trophic factors such as NGF (neurotrophic growth factor), GDNF (glial derived neurotrophic factor), or with neurotransmitters such as dopamine or noradrenaline. When they reach their target they interact with the brain cells to protect and promote the survival of a wide variety of neurones.

Nanocarriers These can be solid lipid nanocarrier particles ( solid lipid matrices with surfactant structures which are in charge of lowering the interfacial liquid tension), micelles and dendrimeres.

These particles are special because they will only react once they reach a determined area of our body. The efficiency of solid lipid nanoparticles to enhance the uptake of other biochemical compounds such as HIV protease inhibitors (used in the treatment of AIDS) has been proved, and this has been extrapolated to deliver medication for neuroprotection, regeneration and repair.

As some nanocarriers are low in cytotoxicity level and have physical stability, this makes them highly suitable for drug release. Micelles are made of amphiphilic block copolymers with both hydrophilic and lipophilic parts, and are useful for encapsulating non-water soluble drugs for intravenous administration. These nanocarriers, as well as dendrimeres, are loaded with many different types of therapeutics such as proteins, oligonucleotides and imaging agents.

Cell-immobilization Systems These include micro and macroencapsulated structures. The first are cells enclosed in semipermeable thin spherical polymer films. They are built with polysacharides and thermoplastics which allow diffusion, kinetic release and cell viability. Macroencapsulated cells are cylindrical shapes filled with cells suspended in ECM -extracellular matrix. This is a connective tissue produced mainly with fibroblasts and astrocytes, which provides inhibitory and growth promoting signals to neurones and their extensions.

Surrounded with thick, permeable membranes, they are biodurable, and their large diameters provide long term implant stability. The capsule membranes prevent cell disruption, as antibodies cannot enter the molecule.

Copyright D. JL Novak and J. Johnson. All rights reserved.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

They are designed, however, for bidirectional diffusion of nutrients, oxygen and waste, and after implanting them in the damaged brain area, the final secretion of the encapsulated drug occurs.

These structures can also contain genetically engineered cells that discharge trophic factors such as GDNF (glial-cell derived neurotrophic factor) or CNTF (cilliary neurotrophic factor), biomolecules that seem to be essential for neuronal recovery in Parkinson's and Huntington's disease and amyotrophic lateral sclerosis. On the other hand, further clinical trials need to establish if cell survival is determined by the transplant region or the type of cell targeted.

Scaffolds These polymers are pre-designed to carry out multiple activities such as cell regulation, controlling tissue structure, as well as the control of diffusion of nutrients, metabolites and other molecules imitating the natural EMC functionality . They are produced as nanogels (gels made with nanoparticles) and sponges to be applied in brain areas, while channels are used for spinal cord axonal repair. Scaffolds can be implanted in cortical areas of the brain and work as a substrate for neurite formation and axonal growth.

The interaction of certain specific protein sequences such as PHSRNG6RGD1, between the polymer scaffold and other ECM proteins has demonstrated that this relationship promotes cell adhesion, differentiation and migration in the injured brain or spinal cord.

Nanotubes and nanofibres have also been tested to function as scaffold- like tissuebridging structures.

In these trials, nanofibres appeared to have interconnected the scaffold with the rest of the brain environment, developing axonal re-innervation through the ECM and the rest of the neural tissue. At the same time, these nanoparticles minimised glial scar formation, a cellular process that occurs after injury to the CNS.

Scaffolds with Neuronal Stem Cells Finally, treatment with scaffolds containing neuronal stem cells transplanted in the affected areas can improve spatial-learning behaviour, increase neurite pathways, and improve cell survival aiding to the prompt recovery of new brain tissue.

Copyright D. JL Novak and J. Johnson. All rights reserved.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Sources  Kreuter, J., 2003, 'Direct Evidence That Polysorbate-80-coated poly(butylcyanoacrylate) Nanoparticles Deliver Drugs to CNS via Specific Mechanisms Requiring Prior Binding of Drug to the Nanoparticles', Pharm. Res. 20, 409-416.  Bloch, J. et al. , 2004, 'Neuroprotective Gene Therapy for Huntington's Disease, Using Polymer-Encapsulated Cells Engineered to Secrete Human Ciliary Neurotrophic Factor: Results of a Phase I Study', Hum. Gene Ther. 15, 968-975.  Misra, A., Ganesh, S., Shahiwala, A. & Shah, S.P. , 2003, 'Drug Delivery to the Central Nervous System: a Review', J. Pharm. Pharmacol. Sci 6, 252-273.

This article was first published by Dinah JL Novak and John Johnson on October 2013.

And has been revised and updated in June 2015 buy John Johnson for Scientific Discoveries.

We carefully researched the information in the references mentioned above and investigated other scientific sources.

Contact Us for republishing, subscription or any other consultation to niirs.contact@gmail.com or call us on 02032862193.

Copyright D. JL Novak and J. Johnson. All rights reserved.

12

By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Stem Cell Therapy and Regenerative Medicine, New Treatments Stem Cell Therapy and Regenerative Medicine, New treatments The breakthrough in stem cell therapy and regenerative medicine has already began to prove essential to treat a wide variety of disorders Photojournalist: Loria Hilahm. All rights reserved.

Stem cell therapy and regenerative medicine seem to be the magic wands for health in this 21st century. Many disorders such neurodegenerative diseases, heart disorders, spinal cord injury, diabetes, blood cell illnesses, and cancer could improve or be cured by injecting patients with the right type of cell line manipulated and cultured previously in laboratories. Furthermore, stem cells can be used to model disorders and probe drugs in vitro.

There are two main factors that make stem cells unique in their behaviour: on one hand, every time they divide they are capable of self-renewal, the process of making copies of themselves. On the other hand, they synthesize specialized cells through differentiation.

These properties are of main importance for the maintenance of tissues, and therefore organs that undergo continuous cell replacement during the entire life of a human being.

Regenerative Medicine with Stem cells Blood, skin, muscle, our brain and other organs are all built by specialized cells that in the majority of cases do not replicate by themselves, therefore when they are damaged due to an injury or an illness they cannot replace themselves. Through regenerative medicine, stem cells can provide patients with healthy cells that will replace damaged tissues in any part of the body.

Embryonic stem cells known as ESCs, and adult stem cells are the two main groups of stem cells. The second ones can only give rise to the cells of a specific tissue.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Stem Cells Discovery In 1961 Dr Mcculloch , together with Dr Till, at Ontario Cancer Institute, Canada, wrote a first paper on the discovery of stem cells. Their findings were a step to launch regenerative medicine as a new field in science.

However, it was not until 1998 that James Thomson, a scientist at the university of Wisconsin, and his team, decided to remove cells from spare embryos at fertility clinics and grow them in the laboratory. They were pioneers in stem cell research and in fact they established the world's first human embryonic stem cell line which still exists today. In November 1998, the world known scientific journal Science published his research under the title "Embryonic stem cells lines derived from human blastocysts".

Though the discovery of ESCs has lead professionals to place embryonic stem cells as a main route to treat disorders which are still incurable, ethical issues have risen from certain communities who do not consider the destruction of human embryos in order to save lives a legal or a humane option.

An Alternative to hESC, iPSCs In 2006, Shinya Yamanaka and his group of researchers at Kyoto university, Japan, altered the biological cycle of adult mouse fibroblasts and genetically reprogrammed these cells by using only 4 factors (Oct 3/4, Sox 2, Kf4 and C-Myc). These scientists were able to convert specialized cells, (adult cells) into what in molecular biology is known as induced pluripotent stem cells (iPSC), unspecialized cells. A year later they generated hiPSC from human adult fibroblasts. Their research also demonstrated that a cell donors age does not affect the efficiency by which iPSC are obtained.

Unfortunately, at present, scientific evidence shows that there are still important differences between ESCs (embryonic stem cells) and iPSC (induced pluripotent stem cells).

Stem Cells Organizations In early 2000 the UK was the first country to set up a stem cell bank which supplies high quality starting materials for development of stem cell therapy. Moreover, there is a long list of organizations that support and promote stem cell research: the UK Stem Cell Foundation; the International Stem Cell Forum; and at the European level the Eurosystem project, a four year EU funded initiative of the EU framework 7, a consortium involving 20 EU institutions from both the public and private sectors.

Copyright D. JL Novak and J. Johnson. All rights reserved.

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By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

As Giovanni Amabile, and Alexander Meissner explain in their scientific paper, published in PubMed (US National Library of Medicine) in 2009, " The approach of generating patientspecific pluripotent cells will undoubtedly transform regenerative medicine in many ways."

In the years to come, new discoveries in stem cell therapy might allow us to store our own supply of hESCs or hiPSCs in authorized cell banks, scientifically reprogram them, and use such biological cultures for personalized treatments, in the event of an accident or illness.

This is a medical approach that will make organ donation unnecessary, radically improving health conditions and saving millions of lives.

Sources  Dr Mcculloch, Dr Till, University of Toronto, Canada,1961.  James Thomson, University of Wisconsin,1998.  Shinya Yamanaka, University of Kyoto, 2006.  Eurosystem project.  UK Stem Cell Foundation.  Yanhong Shi and Dennis O Clegg, Stem Cell Research and Therapeutics, Springer Science + Business Media B.V, 2008.

Stem Cell Therapy and Regenerative Medicine, New Treatments has been revised and updated by D JL Novak and J. Johnson on June 2015.

Contact Us for republishing, subscription or any other consultation to niirs.contact@gmail.com or call us on 02032862193.

Copyright D. JL Novak and J. Johnson. All rights reserved.

13

By Dinah JL Novak and John Johnson

Investigative and Research Services , NIIRS

21st Century

Walk along with us to the Incredible Adventure of what our Future brings

Photojournalist Loria Hilahm. All Rights Reserved.

We are sure you have enjoyed our latest advances in new

alternatives to burial, what the Law of Chaos demon� strates and its applications in a variety of fields. And the new advances in repairing brain and spinal cord injuries using Stem Cell and Nano Treatments. In the next issue, you will be able to visit and read our new sections as well as to participate in Scientific Discoveries.

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