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Spectrum
H O R A C E M A N N ’ S P R E M I E R S C I E N C E P U B L I C AT I O N • M A R C H 2 0 1 3 1
NOTE from the EDITOR
Dear Readers, In the fall, I heard about how John B. Gurdon and Shinya Yamanaka won the Nobel Prize in Physiology or Medicine for their work with stem cells and cloning. Gurdon, in 1962, was able to inject an adult frog’s intestine’s nucleus into a frog egg, whose nucleus had been removed. Gurdon saw that the egg reprogrammed the nucleus so that it would perform the functions of growing egg, instead of the original intestine. After many years of research, he discovered that transcription factors, or genes that regulate other genes, were responsible for the reprogramming. Stem cells and induced pluripotent stem cells have extremely versatile uses, ranging from how scientists can use them to design and test cures for certain diseases, to how they can be used in tissue engineering and in cloning. Technology has so many different applications in medicine, ranging from creating different data systems to keeping medical records, to designing the instruments that surgeons use to perform open-heart surgery. The theme of this issue is medicine and technology. The articles show how they work together to make the world a better place. We hope you enjoy these articles and learn something new about medicine and technology. Every day, scientists use some form of technology in order to try to save people’s lives. Every scientific discovery made in the world begins with passionate scientists who strive to find an answer to their research questions. This issue features a preview of Horace Mann’s annual science fair, SciTech13. SciTech13 will include many student researchers who will present their work. These students have been working very hard exploring topics of their own choice outside the school curriculum. We hope that after reading these previews you are inspired to go out and try research. There is so much to discover. Let’s go explore. Deepti Raghavan Editor in Chief
Spectrum is a student publication. Its contents are the views and work of the students and do not necessarily represent those of the faculty or administration of the Horace Mann School. The Horace Mann School is not responsible for the accuracy and contents of Spectrum, and is not liable for any claims based on the contents or view expressed therein. The opinions represented are those of the writers and do not necessarily represent those of the editorial board. The editorial represents the opinion of the majority of the Editorial Board. All photos not credited are from creativecommons.org. All editorial decisions regarding grammar, content, and layout are made by the Editorial Board. All queries and complaints should be directed to the Editor-In-Chief. Please address these comments by e-mail, to hmspectrum@gmail.com. Spectrum recognizes an ethical responsibility to correct all its factual errors, large and small (even misspellings of names), promptly and in a prominent reserved space in the magazine. A complaint from any source should be relayed to a responsible editor and will be investigated quickly. If a correction is warranted, it will follow immediately.
Deepti Raghavan Editor-in-Chief
Jay Moon
Production Director
Jay Palekar Justin Bleuel Executive Editors
Michael Herschorn Managing Editor
Juliet Zou
Business Manager
James Apfel Senior Columnist
David Zask News Editor
Joanna Cho Yang Fei Ricardo Fernandez Jennifer Heon Mihka Kapoor Henry Luo Teddy Reiss Amanda Zhou Brenda Zhou Junior Editors
Dr. Jeff Weitz Faculty Advisor
Corrections: In Issue 5, Henry Luo, a junior editor, was mistakenly not included in the masthead.
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SECTION 1 • PAGE 5
TECHNOLOGY Autonomous Cars by Teddy Reiss
Technology in The Hobbit by Lauren Futter
5 6-7
Nanotechnology
8
Using Computers to Develop Medicine
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by James Kon
by Isabel Friesner
Robotic Prosthetics
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The REMPARK
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by Eliza Christman-Cohen
by Jenna Karp
Using Energy from the Body to Power Electronics by Jason Ginsberg
12-13
SECTION 2 • PAGE 13
BIOLOGY & MEDICINE Are We all the Same Species? by Ethan Gelfer
14-15
Artificial Life
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Epigenetics
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The Science of Acupuncture
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by Aditya Ram
by Sonia Sehra
by Cassandra Kopans-Johnson
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Meditation
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Vitamins
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iPS Cells from Kidney Cells
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by Lauren Hooda
by Grant Ackerman
by Dorothy Quincy
Neuroscience
22-23
Radiation Therapy
24-25
Stem Cells and Tissue Engineering
26-27
The Promise of Induced Pluripotent Stem Cells
28-29
by Elizabeth Xiong
by Abigail Zuckerman
by Lily McCarthy
by Samantha Stern
D. Radiodurans: The Extremophile by Ricardo Fernandez
Small Pox by Veer Sobti
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SECTION 3 • PAGE 32
RESEARCH Preview of SciTech ‘13
32-35
Our Mission: To encourage students to find topics in science that interest them and move them to explore these sparks. We believe that science is exciting, interesting and an intergral part of our futures. By diving into science we can only come out more knolwedgable.
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x1r8, Flickr Photo Sharing
Driverless Cars? BY Teddy Reiss
Google creates drverless NYC cabs.
Driverless cars, also known as autonomous cars, completely control themselves. In March 2012, Nevada became the first state to allow autonomous cars on public roads. The state gave Google’s driverless cars a license in May of that year. According to one Nevada law, an autonomous car is “a motor vehicle that uses artificial intelligence, sensors and global positioning system coordinates to drive itself without the active intervention of a human operator.” In other words, an autonomous car uses information it gathers from the world around it to drive. Autonomous cars are similar to autonomous robots since neither require human intervention. While autonomous robots can perform a wide range of possible tasks, autonomous cars only have to drive. Driving safely, however, includes responding to the actions of other drivers, which may not be always predictable or rational, according to PBS Nova. Many different organizations are working on bringing the autonomous car to life. Most prevalent among these groups are the Defense Advanced Research Projects Agency (DARPA), Google, and major car companies such as Ford, General Motors, and Volvo. In the early 2000’s, DARPA ran two autonomous car competitions, the Grand Challenge and the Urban Grand Challenge. The Grand Challenge was a race of autonomous cars in the desert. None of the cars completed the course in 2004 due to inaccuracies in their GPS. In 2005, the teams relied on different methods to keep the car on the road. In the Urban Grand Challenge, the cars navigated an urban environment. Google has also been working on an autonomous car project. Sebastian Thrun, a professor at Stanford and one of the university’s team leaders in the DARPA competitions, is helping run Google’s autonomous car project. Google has designed cars to navigate through city streets safely. Google’s cars have the ability to sense not only where the road is but also where buildings, signs, traffic lights, and people are. They use a combination of LIDAR, a method of measuring the distance to nearby objects with light, and RADAR
to sense the world around them. They also utilize encoders, GPS, and other position sensors that help detect where they are. These and other sensors feed into a computer that controls the car. This technology works during both day and night. Currently, for safety reasons, Google cars have a driver who is able to take control when necessary, but the cars have driven so well that the driver rarely needs to interfere. As of now, Google’s cars have driven over 140,000 miles autonomously with very little human influence. Large car companies including Ford, General Motors, and Volvo are working on their own autonomous cars. Volvo has been testing a “road train” system in which one car in front, driven by a human, is followed by multiple cars replicating its motions. According to a Business Inside article by Viknesh Vijayenthiran, from Motor Authority, “Volvo is paving the way for the implementation of Car-2Car...communication systems.” In other words, it is working on ways to make cars safer by having them communicate with each other. General Motors and Segway have been working on the EN-V, a type of vehicle that can be summoned with a phone call. Ford has been working on ways to improve parking and traffic jam navigation methods. Work on autonomous cars, in fact, began before the 21st century. One 1990’s autonomous car project, the VaMP, was able to drive through traffic for long distances. VaMP did not use GPS; it got all its information from analyzing camera images. Autonomous cars have the potential to be safer and faster than human driven ones for a few reasons. Most importantly, they can help eliminate the possibility of human error caused accidents because they will not get distracted. Robots can also react to situations on the road faster than humans. According to a Forbes article by Joann Muller, however, only Nevada, Florida and California have passed laws allowing autonomous cars on public roads. One challenge autonomous cars will have to overcome is restrictions on locations where they can be driven.
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Fortymillionsheep, Flickr Photo Sharing
e Th t i b b o H By Lauren Futter
This image depicts a scenic scene from the movie set.
In the recent release of The Hobbit: An Unexpected Journey, the editors of the film used a wide range of technology that had never before been utilized. Increasing the frame rate of films from 24 frames per second (fps) to 48 fps was the primary means by which the director of the film, Peter Jackson, changed the way the film was made. However, Jackson also used several other new types of technology that improved the quality of the film. Instead of using typical 3D filming cameras, Jackson used 30 Red Epic digital cameras. Finally, The Hobbit served as a platform for introducing a CGI (Computer Generated Image) Smaug, a giant dragon that lives in a cave that the main character, Bilbo Baggins, explores. When Jackson announced that he would be using 48 fps as opposed to the standard 24 fps, people everywhere lauded the achievement as the next major step in film technology according to screenrant. com. But what does 48 fps actually mean, and what is the body’s reaction to it? According to the American Optometric Association, movement is processed in the visual system when light enters the eye and goes through the cornea, the transparent part of the eye that covers the pupil and the iris. After going through the cornea, light is refracted, and an inverted image appears on the retina. In the retina, there are rod and cone proteins that process the color and the amount
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of light. After the retina processes the image, the optic nerve transfers the image to the back of the brain called the visual cortex. According to filmmaker James Kerwin, studies show that human eyes can do this about 66 times per second. Films act in a similar manner in that they take numerous pictures per second that are put together to make the picture move. Traditional film uses 24 fps, which adds more blur to the film, as opposed to the new 48 fps that the Hobbit uses. However, while increased clarity may appear to be a good thing, the film-goers often expressed a dislike of the way The Hobbit was filmed. Dr. Stuart Hameroff, from the University of Arizona’s Center for Consciousness Studies, argues that despite humans’ ability to process 66 frames per second, humans are only consciously aware of 40 frames per second. As a result, if the frame rate exceeds 40 frames per second, the film begins to look hyper-realistic, as opposed to a film rate of 24 frames per second, which looks artificial, according to movieline.com. While people like Jackson and James Cameron, director of The Titanic, believe that the realistic effect increases the cinematic value of the film, viewers of the film appear to have different opinions. Vincent Laforet of Gizmodo.com described his viewing experience as disappointing, stating that it was too real in a movie that was meant to be fantastical.
The Uncanny Valley hypothesis proposed by Masahi When The Hobbit was released, many peoro Mori, which argues that human beings do not like ple complained that there were too many Computer replicas of humans that look and act almost perfectly Generated Images (CGI’s) in the film. Although peolike humans, supports this position. Therefore, after a ple may have preferred the characters to be real as certain point, the visual quality of a film becomes too opposed to computer generated, CGI’s play a large realistic, leading to revulsion. So while the technology role in movies today. First, characters are molded that Jackson uses may increase the resolution, it may out of clay. If the director likes the clay character, the also cause discomfort for the viewers. animator will scan the clay model into the computer, In addition to using new fps technology, Jackor make a computer drawing that matches the clay son also used new Red Epic 3D Digital cameras. version. During filming while the character may not According to engadget.com, Red Epic cameras allow be present, actors who play the computer generated for not only higher definition for the Hobbit, but also character are equipped with equipment that allows sharper 3D images. According to howstuffworks.com, there movements to be captured and recorded so that eyes perceive depth because two separate images are the animated character has a reference point for how sent to each human eye. The eyes are about two inch- the movement should look. After working to combine es apart from one another, causing a slightly different the computer image of the character and the actor’s image to be sent to each eye. When the images are movements, the images are combined. Then the sent to the brain, the brain puts the images together, combined images are refined and are digitally added creating a slight overlap. This overlap allows humans to the live action film. In The Hobbit, Andy Serkis wore to perceive depth. Stereographer Angus Ward explains a motion capture suit for his portrayal of Gollum. The that to create 3D images, two Red Epic cameras are motion capture suit has points on the suit, which are needed so that they can be spaced apart in a similar recorded and used to animate the CGI characters. way that two eyes would be spaced apart. The images Although this technology was utilized in all of The are then laid over each other. According to Professor Lord of the Rings movies, the technology is always Phil Moriarty of the University of Nottingham, after evolving, according to the Cornell Center for Materials they are overlaid, the light from the images in the Research. left and right cameras are polarized so that the light The science behind many films such as the waves from each camera move in directions that are Hobbit is complex. In various ways such as fps, CGI, perpendicular to each other. However, this in itself and 3D, film tricks the mind into thinking that what does not make the movie 3D. When someone goes is fake is actually real. Although the difference may into a movie theater they need to put on 3D glasses. seem obvious, in the future the line between what is According to Edwin H. Land, these 3D glasses work real and fake may be hard to distinguish. The Hobbit because they are made of Polaroid film, which is is merely one step on the road to more creative and made of nitrocellulose polymer film. A polymer is a diverse films. long chain of a particular chemical, in this When humans watch 3D films, case, nitrocellulose. The polymer film is also using these 3D glasses, two different embedded with microscopic crystals called images are combined in the brain to iodoquinine sulfate or herapathite. In each create a false sense of depth. lens of the glasses, the herapathite is either vertical or horizontal. When heraphathite is placed in the nitrocellulose polymer, the film becomes dichroic, meaning that it only absorbs light waves that are parallel to the chains herapathite in the glasses. Professor Phil Moriarty of the University of Nottingham explains that when someone wears the 3D glasses, the left eye may only absorb light from the video filmed by the particular camera that was polarized, so the light waves move parallel to the crystal chain in that lens. As a result, two different images are sent to the brain, which the brain combines to create 3d-erlebnis, Wikimedia Commons a false sense of depth.
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Nanotechnology
In the early 1930s two scientists, Ernst Ruska and Max Knoll, created the first prototype of the electron microscope. With the invention of this microscope, researchers gained the ability to see at the nanoscale. Later in the 1980s, nanotechnology was created and popularized with the development of the scanning tunneling microscope (STM). Nanotechnology is the construction and usage of structures that are at the atomic or molecular levels. According to Professor Zhong L. Wang of the Georgia Institute of Technology, these structures interact with objects 1 to 100 nanometers long. To view these objects, scientists use scanning tunneling microscopes and atomic force microscopes (AFMs). The STM works by sending a probe close to the sample to create an electron tunnel between the probe and sample. The AFM uses a laser that is directed onto a sample and reflected onto a motion sensitive detector. This allows both microscopes to carefully map out the atoms or molecules. There are two ways that scientists and engineers can approach the construction of nanotechnology. The first method, top down, is the most traditional method of creating a device. The basic principle, stated by Columbia University, is to create a smaller device from a larger one. During this process, photolithography is used to create a pattern nanoscale structure that is carved onto a substrate. It works by transferring light through an opaque glass to a light sensitive chemical that is on the substrate. The substrate is later treated with chemicals that engrain the pattern. At the end, computer chips and film are most frequently produced. The other method, bottom up, is a relatively new procedure that relies on molecular self-assembly, that the Stanford University helped create. The procedure requires unique copolymers that become covalently bonded by sol-gel processing into a useful configuration. This creates a physical linkage that will prevent the copolymers from separating. This method has great practical use in modern medicine, because it can be used to manufacture many useful chemicals and drugs. Nanotechnology provides an effective and non-evasive procedure that deals with many different types of medical issues. One of the major developments is the diagnosis and treatment of cancer. Scientists, including some of the researchers at MIT,
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By James Kon have begun to design nano-devices that will attach to tumors and release peptides, marking the location of the tumor. NanoBioMagnetics, a nanobiomaterials company, has created another magnetic version of this device, for brain cancer. It will be able to attach itself to particles in the blood stream that have been released by cancer cells. Currently CytImmune Sciences and BIND Biosciences, two clinical-stage biopharmaceutical companies, are developing devices that will deliver chemotherapy, drugs, and heat to malignant cells. They are engineered to either attract the targeted cells or have infrared light directed at a tumor or tumor area. Most of these gadgets are built using a myriad of materials including proteins, nucleic acids, strands of DNA, and silver. This limits the damage caused by the chemotherapy’s drugs. The process is also quicker and cheaper. However, there have been concerns over the toxicity levels in some of the implements. The problem will most likely be resolved by using different metals. New advances in therapy treatments, anti-microbial techniques, and cell repair have been made through the usage of these machineries. Furthermore, nanotechnology is a versatile science. One of its most important applications is in the field of medicine where it can save millions of lives. Scientists have yet to realize the full potential of nanotechnology, but with growing interest in the field, its full potential can and will be reached. The photo illustrates the steps by which nanotechnology is used to treat cancer patients clinically, also clearly exemplifying how research and clinical studies can work together to produce a desired effect—the healing process of a patient.
Kristian Molhave, Creative Commons
Using Computers to Develop Drugs
Feixiong Cheng and others, published in a research article
If one were to use computers to store the medical data of patients treated with drugs, using computer science techniques, one would be able to produce comparative and relational body diagrams such as the one pictured below.
By Isabel Friesner
There are a countless number of companies working towards creating drugs to enhance our health. The assiduous work of computer scientists has enabled us to advance not only in the technological world but also in the medical world. Computer software has created advanced drugs that have changed the course of history. In order to make an effective drug, there has to be a foundation. Drugs are molecules that interact with other molecules, mostly proteins. In order for a drug molecule to interact with the protein, it needs a binding site. Binding sites are specific sections of a protein that, if targeted by a complementary molecule, can inhibit the protein. Diseases stem from two different sources. One source is proteins that are improperly coded either in the genome or during transcription. These proteins do not perform their duty. For example, they could produce an incorrect amount of the substance for which they are coded. Such a malfunction can have deleterious effects on the cell and individual. The second source is
Matthew (WMF), Wikimedia Commons
Computers are used for data analysis to develop drugs.
foreign proteins that enter the body through infection or bacteria and interfere with bodily functions. Drugs bind to these problematic proteins and alter them in a way that destabilizes their function and therefore cures the patient. Computers store databases of candidate molecules that allow us to determine the three-dimensional structure of a protein in order to determine how best to attack it. While computers enable us to search through millions of molecules or DNA sequences, they are not 100% correct and do not account for or know all of the side effects that could occur. Therefore, testing is always necessary with a newly developed drug. In the 1980s, when AIDS was a new disease, nearly all infected individuals died. Now drugs have been created that enable the victim to survive. Molecules,created from computer design, block proteins of the AIDS virus and prevent the virus from reproducing in the body or affecting the individual. However, there is always room for improvements, as using computers can be expensive. Computer drug design is a newly developing field that will enhance pharmaceutical development and make more effective ways of figuring out diseases and unknown proteins. In addition, computers allow us to look at models of drugs and work on shaping the structure more easily. Modeling cures for diseases on the computer is an important technique that is changing the world. 9
Ro b o t ic P rost h e t ic s: Ma king Le a ps an d Bo u n d s By Eliza Christman-Cohen This is a progression of lower limb prosthetic devices from 2010.
Flickr Photo Sharing
Webster’s Dictionary defines “robot” as “an automatic device that performs functions normally ascribed to humans or a machine in the form of a human.” This definition, while accurate, does not express the powerful impact that robots and the science of robotics have had on many industries including healthcare and medicine. Robots assist and perform surgery, provide medical training, deliver special education, and assist the deaf and blind. Robotics has also been central to the development of medical prostheses. Prosthetic limbs have become especially sophisticated from their beginnings in 1945. In 1945, the National Academy of Sciences created the Artificial Limb Program. According to Discovery News, the Artificial Limb Program was established in response to the large number of World War II amputees. At the time, amputees had two options: receive a wooden limb or be confined to a wheelchair. However, wheelchairs at the time did not have navigational tools or electronic systems. Over the last 30 years, cutting-edge devices and technologies have changed the lives of many amputees. For example, in foot prostheses, doctors are able to use carbon fiber, a more “life-like” material that allows amputees to have a feeling of life in their feet. In addition, thermoplastic sockets, which are pliable above a certain temperature, make amputees more comfortable where the prosthesis is attached. All these advancements have led to more comfort and practicability for the amputees.
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Lower limb prosthetics have improved tremendously in recent years, while the field of upper arm prosthetics is beginning to see incredible innovations. Perhaps the biggest innovation to date is the development of mind-controlled prosthetic arms. By using Targeted Muscle Reinnervation, or TMR, nerves from an amputated limb are reenergized in different locations in the body. All that an amputee needs to do with this device is think of a desired action. Thinking signals the nerves in the individual’s chest to react by sending a message to a microprocessor in the robotic limb that performs the action. Another mind-controlled prosthetic limb that uses a different technology is called the BrainGate system. As shown on PBS, this system involves inserting electrodes in the motor cortex, a portion of the brain controlling movement. The patient’s thoughts are communicated from the sensor to a computer. The computer then sends instructions to the robotic arm. Cathy Hutchinson, a 58-year-old quadriplegic, uses this robotic arm to sip coffee. She had not been able to drink anything without assistance in 15 years. Advances in robotic prosthetics have been incredible and are truly changing lives for the better. So what does the future hold? Perhaps the latest work at the Massachusetts Institute of Technology gives a hint. In the coming years, not only will we have improved versions of thought-powered artificial limbs, but those limbs might be also be powered by the glucose manufactured in our very own bodies.
A Modern Approach to Parkinson’s Disease By Jenna Karp
This is a cluster of a certain type of nerve cell. Parkinson’s is a disease that involves the destruction of nerve cells. Wellcome Images, Flickr Photo Sharing
Parkinson’s disease is caused by the destruction of nerve cells in the brain that produce dopamine, a chemical that controls muscle movement. This disease occurs most often in men and women above the age of 50. Although the symptoms of Parkinson’s disease vary from patient to patient, many Parkinson’s sufferers experience tremors, rigid muscles, and slow movement. People with Parkinson’s also often walk with small steps, have limited arm movement, and exhibit freezing of gait, where patients momentarily feel as if their feet are stuck to the ground. There is currently no cure for Parkinson’s disease. However, the REMPARK system, also known as the Personal Health Device for the Remote and Autonomous Management of Parkinson’s Disease, is being developed to help Parkinson’s patients identify their symptoms sooner and manage their disorder better. According to the official REMPARK website, “REMPARK is a European Union funded project that will develop a wearable monitoring system to identify in real time the motor status
of people with Parkinson´s.” The REMPARK system is composed of various sensors, such as a cellular telephone-sized sensor worn at the patient’s waist. These sensors will detect whether the patient’s movements are jerky or frozen. The REMPARK device will then provide a signal to the brain to normalize movement. The REMPARK team also plans to store the patients’ data as obtained from the REMPARK device onto a central server, making the data readily available to the patients’ neurologists for further analysis. The REMPARK project began in 2011 and is expected to last 42 months. Today, 60 patients are testing the REMPARK system throughout the European Union. By the end of the testing period, the REMPARK team hopes to have a fully working Personal Health System with detection, reaction, and treatment capabilities for easier management of Parkinson’s disease. If the team meets their goal, then the REMPARK system will serve as a tremendous advantage in the treatment of Parkinson’s disease.
This background image depicts a nerve transplant, one method to reconnect broken nerves. Parkinson’s Disease includes damaging nerve cells.
Pennstatelive, Flickr Photo Sharing
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Benefits of Harnessing Bio-Energy by Jason Ginsberg
William Vroman, Wikipedia Commons
A Chakra picture depicts different energies within the body.
son, the head of the environmental division at SCS, the train station’s ventilation system captures the body heat of the more than 250,000 people that pass through the terminal each day, using their body heat to warm water. The hot water produced in the ventilation system is then pumped to nearby buildings, keeping them warm in Sweden’s frigid winter while reducing energy costs by 25%. This design has been so successful at reducing costs in Stockholm that other cities have become eager to implement this system in their own crowded buildings. Similar research in the field of harnessing human energy is currently being executed at Cranfield University. Scientists at this institution are working on knee brackets that will allow soldiers to create power as they run, replacing the heavy batteries that weigh them down. According to Alice Daniels of Cranfield University, the energy induced by a soldier’s activity can be focused into a crystal. Due to a phenomenon known as the Piezoelectric Effect, mechanical stress causes the crystal to produce an electric current that can then be used to power the soldier’s devices and equipment. This technology, although still in development, has the potential to save lives on the front line where there is no time to switch batteries and where a
The ancient Hindu practice of yoga teaches the benefits of harnessing power from within. Yoga students believe that locating and mastering their energy fields, called chakras, gives them control over their bodies. As scientists are just beginning to truly recognize the body’s potential, yoga followers may be onto something. The average human at rest produces 100 watts This is a bioenergy park, or a facility that creates renewable energy of power, expending much of from organic waste. this energy to pump his or her heart, churn his or her stomach, and move his or her muscles. Not all of the energy produced, however, is used. The body wastes much of the energy produced by releasing heat. Currently, scientists are working on devices that capture the energy wasted by the body to generate electricity and create a renewable energy source. The resultant bio-energy is extremely safe for the environment. Such technology is already being implemented in Stockholm’s Central Station (SCS). According to the Klas Johnas-
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Francois Guibert, Flickr Photo Sharing
heavy pack can slow down a soldier in the line of fire. This device could potentially also be useful for civilians, replacing cell phone batteries and chargers, as humans will power their own electronics through movement. Innovations in bio-energy harvesting are also affecting the medical field. For example, millions of people currently rely on battery powered implanted devices, such as pacemakers. One of the biggest drawbacks to these devices, however, is the replacement surgery required to change a dead battery after 10 years. According to Dr. Gene Frantz, an engineer at Texas Instruments, tapping into the body’s energy source will make such operations unnecessary. Frantz, along with other scientists at Texas Instruments and the University of Michigan, envisions a pacemaker that will be powered by the pressure of a heartbeat’s rhythm. This pacemaker will implement a mechanism similar to the one produced by researchers at Canfield University, a device
that uses mechanical stress to power a battery. Human energy harvesting also has the potential to change the urban environment, as MIT researchers have shown. Their project, which won the Japan-based Holcim Foundation’s Sustainable Construction competition, captures the energy created by pedestrian foot traffic. This project uses a special flooring system that suppresses under the force of human. When people walk on this special flooring, they cause certain plates in the flooring to slide against each other, generating an electric current. The electricity generated by these floors would then be used to supply power for the city. Though many of these technologies are in their early stages, in the not-too-distant future, bio-energy will revolutionize our lives. People will power cities, charge the phones they depend on, and heat buildings they live in.
Flickr Photo Sharing
A Bioenergy Park showcases many of the new evolving technologies in renewable energy.
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Another Species of Human? By Ethan Gelfer
An evolution of humanity through the skulls of our ancestors.
davydubbit, Flickr Photo Sharing
Many animals on earth are confined to certain locations. The blue jay is a species of bird that lives in North America. It is commonplace to see a blue jay around in the eastern United States. However, the chances of seeing one in Europe are remarkably low. This applies to almost every category of organism on Earth: trees, flowers, whales, sharks, tigers and more. However, Homo sapiens are very different in this regard. It is possible to observe a human in America, and in Africa or Europe, or anywhere in the world perhaps. The idea of multiple human species might seem unlikely, unnecessary, or unimaginable at first, but given the state of other organisms, it really should not be too difficult to believe. According to Juan Enriquez, a leading authority on the economic and political impacts of life sciences, since the first humans evolved from primates about 2.8 million years ago, twenty nine species of human beings have existed, and more are being discovered at an fast rate. Even the current human species, Homo sapiens, has at one time coexisted with at least eight other human species. Why should the case now be that there is just one human species when there is so much precedent this theory?
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The answer to this dilemma starts with us. Up until the 1920’s, mankind thought that there were major differences between people, partly based on the work of Charles Darwin’s cousin, Francis Galton. This theory of differences between humans was highly misinterpreted and led to horrific crimes against humanity: the Holocaust, slavery in America and around the world, and many others. Since the 1940’s, we as a species have been trying to say that we are all exactly the same, that no one human is better than another, and that for better or for worse, we are all identical. Now, however, scientists are beginning to find that this is not the case. Another problem is in differentiating one species from another. One solution is to look at the amount of DNA it takes to be classified as a new species. The difference between the current Homo sapiens and Homo neanderthalensis, according to Mr. Enriquez and Svante Paabo, a Swedish biologist specializing in evolutionary genetics, is .004% of gene code, just minor differences in sperm and testes, smell, and skin. There are merely 14 different genes that separate us humans from our ancestors the Neanderthals. Our classification of the difference between species
affects the necessary size of mutations in order to cause a “new” organism. Mutations have already occurred in Homo sapiens. One such mutation in one gene 10,000 years ago by the Black Sea caused blue eyes. Enriquez explains how mutations are already affecting humanity in the form of athletics. The ACE gene, for example, is important because it is linked to athletic performance. According to A.G. Williams and his colleagues, in a journal article published on nature.com, a longer allele corresponds to better athletic performance. No one has ever climbed an 8,000-meter peak, without oxygen without the longer allele. The ACE gene raises questions about sports. Should people with genetic advantages be allowed to “win” just because they have a genetic advantage? This is a challenge that humanity will have to face very soon. As Mr. Enriquez tells us, the rate of evolution is becoming faster and faster, and mutations are becoming more pronounced. Enriquez believes that we are already changing into a new species, “a Homo evolutis that, for better or worse, is not just a hominid that is conscious of his or her environment,” but is “a hominid that is beginning to directly and deliberately control the evolution of its own species.” In the future, due to genetic mutations over time, our descendants may be a different species.
A phylogenetic tree shows the various branching points between all species of life. Another limb must be placed if a new species of Homo sapiens exists.
tweedle, Flickr Photo Sharing
The blue jay evolved from moths. It is a rare and beautiful sight for anyone outside of North America.
mikonT, Flickr Photo Sharing
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Yikrazuul, Wikimedia Commons
Artificial Life
This image depicts a molecular structure of a section of DNA.
By Aditya Ram
Craig Venter is a pioneer in bioengineering. According to a New York Times Magazine article by Wil S. Hylton, he has developed a basic form of a genetically modified species: yellow algae. The modification allows the algae to be grown over other algae plants, so the sunlight permeates to the bottom leaves. This is a minor modification, but it proves that successful genetic modification is possible. If an organism or plant could be modified to produce a significant resource, then the world would be able to mass-produce that product. There are many examples of plants and animals being genetically modified to be superior to their predecessors. Goats have been modified to produce spider silk, a very strong and useful resource. Pigs have been modified so that their meat contains more omega-3’s and fewer fatty acids. Many crops have been modified to produce organic pesticides that repel insects. This was done by identifying the right genes and inducing mutations. Although the basic gene set is known to be simple, it encompasses all the genes an organism needs to live without any redundant code. The isolation of the basic gene set is essential for synthetic life, a popular topic in research and technology. Even before scientists postulated the idea of the basic gene set, the idea of cloning was introduced by Scottish scientist Keith Campbell in 1996 when he cloned a sheep named Dolly. In layperson terms, cloning, one of the most common ways to synthesize life, is copying and pasting genetic information into a DNA-free somatic cell.
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The ideal applications of genetic engineering involve organisms that produce more and consume less, and thus have a competitive advantage for their survival. This can only be done when the animal’s genes can be altered. When the genes are altered, different proteins can lead to beneficial animal mutations. Creating ideal organisms to perform all of our tasks for us is one possible solution to labor shortages, famines, or a lack of resources. Humanity could be entirely self-sufficient, using our genetic engineering knowledge to fulfill its every need. This is an ideal future.
Precipitated DNA at the Natural History Museum in Berlin.
LoKiLeCh, Wikimedia Commons
EPIGENETICS
LoKiLeCh, Wikimedia Commons
Precipitated DNA at the Natural History Museum in Berlin.
BY SONIA SEHRA For a long time, people believed that the genome alone determined one’s biological blueprint and destiny. Scientific evidence from the last 20 years has confirmed that it is not only the genome that determines biological identity but also something called the epigenome. The epigenome determines where, when, and how hereditary information is expressed. This form of gene expression is called epigenetic regulation. According to an article in the Scientific American by JR Minkel, epigenetics is “molecular processes that control a gene’s potential to act,” and a notable form of epigenetic regulation is methlyation. Methyl groups bond to the DNA as epigenetic tags and control whether or not the gene in that region is expressed. However, the underlying DNA itself has not changed. When high amounts of methyl are present in the body during critical periods of cell differentiation, the epigenome can change, as more methyl tags are bound to the DNA. The shape of DNA, specifically how tightly or loosely DNA is coiled, also affects gene expression. DNA is spooled around proteins called histones, which are another key part of the epigenomic system. The histones also determine how tight the spool is. As explained by Epigenetics: A Molecular Link Between Environmental Factors and Type 2 Diabetes, by scientists Charlotte Ling and Leif Groop, when the histones are loosely wound, there is more gene expression, as it is easier for a RNA polymerase to bind to a promoter sequence on the DNA strand to produce mRNA. This mRNA will travel out of the nucleus to a ribosome where the protein will ultimately be produced. This end result indicates how proteins are expressed in a cell and ultimately determines how the epigenome shapes the genome. Scientists have used the concept of controlling gene expression in epigenetics to study new drugs and the origins of certain diseases. Epigenetics has also explained the connection between the environment
and its effect on cells, gene expression, and organisms through time. The epigenome is a complex system that can be easily altered by the choices a person makes and the environment in which he or she lives. This means that the environment can directly affect our gene expression. According to the University of Utah Genetic Science Learning center, epigenetic mutations that occur in one generation can be passed down to the next generation. This contradicts the idea that only genes are passed through the DNA. A 19th century study done in the northernmost part of Sweden studied the correlation between heart disease and diabetes with epigenetics. According to a Times Article titled “Why Your DNA Isn’t Your Destiny,” by John Cloud, Dr. Lars Olov Bygren , at the Karolinska Institute in Stockholm, did research on epigenetics in Sweden. In the 18th century, in Norbotten, Sweden, the fluctuations in crop yield during a generation changed the methyl and acetyl levels in the individuals’ many nuclei. Varying levels of these molecules modified cellular genome expression, through the epigenome. Such inconsistent diets lead to poorer gene expression and shorter life expectancy rates than their counterparts. The children and grandchildren of the individuals with erratic diets inherited the unique epigenomes of their parents. The children also had shorter life expectancies than their peers. The data seemed to show that one season of binging, causing one generation to have shorter lives, started a family line of shorter life spans. In this case, the epigenome passed on through generations. Scientists are starting epigenetic treatment for patients with forms of cancer and other deadly diseases by changing which genes are expressed. Epigenetics and the epigenome will serve as important tools for the treatment of diseases and understanding biology as a whole.
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This photo depicts a patient recieving acupuncture in Orlando, Florida.
cupuncture
By Cassandra Kopans-Johnson
Flickr Photo Sharing
Acupuncture, an alternative medicine methodology originating in ancient China, continues to successfully treat patients around the world. Acupuncture uses thin, solid needles that are inserted into the skin. It can alleviate pain, stop nausea and vomiting, prevent depression and anxiety, help with infertility, and assist with many more health problems. Although acupuncture has effectively cured people over the centuries, how it works remains a mystery. Its central dogma focuses on qi (chi). Qi refers to an organism’s life energy, life force, and energy flow. The needles used are inserted into the skin at certain points called acupoints. Acupoints tend to be located at the midpoint of a muscle, where the nerves enter the muscle, or where the muscle joins the bone. Trigger points or palpation, in order to measure tenderness, can also locate them. One theory of how acupuncture works is that the trigger points
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stimulate the meridian system. In Traditional Chinese Medicine, the meridians are a series of paths through which the life energy, qi, flows. In western medicine this flow is most commonly associated with electric stimuli. How the sensations are communicated throughout the body eases the pain. Acupuncture’s ability to cure nausea and stop vomiting is often associated with the nerve reflex theory. This theory suggests that the body’s periphery, skin, through the viscero-cutaneous reflex, is connected to the internal organs. According to an article in The Atlantic, Dr. Leena Mathew, a physician of Anesthesiology and Pain Medicine at New York Presbyterian Hospital/Columbia University Medical Center, states, “If you stimulate the periphery with acupuncture needles, you can change the blood flow pattern to the stomach and abdomen, which could explain the effect on
nausea and vomiting.” Another theory suggests that acupuncture may relieve stress, depression, and anxiety by causing the release of endorphins, neurotransmitters associated with euphoria, in the hypothalamus-pituitary-adrenal axis, part of the body’s stress response system. Throughout history, human touch has been known to calm and relax people. Just as a mother can relax her child just by her physical and emotion presence, a human, well-intentioned touch can also have the same effect. This may be a reason why acupuncture, a therapeutic touch, seems to be successful in relieving pain that is sometimes associated with fear, anxiety, and stress. It is amazing that acupuncture, an ancient medicinal practice, has survived the centuries and continues to heal the world. This practice shrouded in mystery awaits scientific understanding.
MEDITATION By Lauren Hooda Millions of years ago, humans progressed through life at nature’s pace. Time was observed by the life cycles of humans, the transition of seasons, the cycles of the moon, and the passages of the sun and stars across the sky. Life was comfortably connected to nature. However, through evolution and technology, humans’ affiliation with time has drastically changed. The demands of modern society show up in therapists’ and doctors’ offices every day. An increasing number of people struggle to balance between work and family. Peace of mind is destroyed. There is no time to rest or recover, which often leads to anxiety, depression, and a multitude of mental and physical ailments. Meditation is one of the best medicines for a stressed mind. Meditation is a deep state of relaxation often consisting of sitting quietly and focusing on one’s breathing, a word, or a single phrase. Herbert Benson, a doctor at Harvard University, states meditation elicits the opposite bodily reaction from a “fight of flight” response. This is the brain’s response to stress by releasing the hormones epinephrine (adrenaline) and norepinephrine (noradrenaline). These hormones cause an increase in blood pressure, pulse rate, breathing, and blood flow to the muscles. By inducing a myriad of biochemical and physical changes, meditation slows down breathing, metabolism, and blood pressure. It brings about an elevated level of self-acceptance and insight about oneself. This mental exercise requires practice, as one seeks to ignore the individual’s internal chatter. Just ten minutes a day, however, can help contain stress, decrease anxiety, improve cardiovascular health, and attain a greater capacity for relaxation. Meditation does more than calm people. It alters the structure and operation of the brain. Richard Davidson, a psychologist based at the University of Michigan, produced scientific evidence that meditation strengthens and rewires brain circuits through an increase in the circuits’ number and robustness. Meditation also significantly activates the limbic system (the brain’s emotional network) and increases serotonin levels, which are responsible for generating positive and calming emotions. These specific changes galvanize a brain region called the left-sided anterior region. A Penn State University researcher, Andrew Newberg, found that lengthy meditation sessions increase the size of the prefrontal cortex, the area of the brain that deals with attention, auditory, visual, and sensory input processing.
This permanently cultivates focus and intense concentration in practicing individuals. Regular meditation procedures may also slow age-linked thinning of the frontal cortex, leading to longer lasting executive function. Society is currently dependent on the pharmaceutical industry to improve health. Although often necessary, medicines are crammed with chemicals. It is uplifting to think that meditation is one of the most effective and lifelong “mental medicines” to clear away stress and summon inner peace while lacking the potential side effects of drugs. With this cathartic technique, people can experience life and its racing pace through a renewed, fresh lens of calmness and tranquility. This image delineates the conversion of stress into relation via meditation. It depicts the “flight or flight” response in contrast to the opposite bodily reaction, which leads to self-acceptance.
Aaron T. Newman, as printed in Popular Science
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Pyramidal cells that can be controlled with light using optogenetics.
Optogenetics in Neuroscience
Doneuron, Wikipedia Commons.
By Elizabeth Xiong Vivo recording of optogenetic silencing of a rat prefrontal cortical neuro at Cooper Laboratory.
Neuroscience, the study of the nervous system, is a vastly diverse and complex branch of science. At a microbiological level, the most basic unit of the nervous system is a neuron, a type of cell that, when stimulated, releases neurotransmitters that activate and send signals to other cells and neurons. Numerous approaches towards studying the brain and nervous system exist. One such approach is called optogenetics, which involves using the properties of genetics and light to control the neurons in organisms. Coined in 2006 by Karl Deisseroth, a professor of bioengineering at Stanford Universy, but first speculated by Francis Crick, a molecular biologist who played a major part in discovering the double helix structure of DNA, optogenetics has advanced exponentially in the past few years, despite being a relatively unknown branch of science. Among other awards, optogenetics was named “Method of the Year” in 2010 by the science publication Nature Methods. Furthermore, the 2012 InBev-Baillet Latour International Health Prize was awarded to scientist Gero Miesenböck for his work in optogenetics.
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Scientists have already developed electrical methods of stimulating and manipulating the brain such as deep brain stimulation, which involves sending electric signals to the brain to target the brain’s neurons. This stimulation is an FDA approved treatment for nervous and neurological disorders such as essential tremor, Parkinson’s disease, and dystonia. It is used to treat depression in clinical trials. Deep brain stimulation goes beyond the previous forms of chemical treatment for neurological and psychological disorders, such as ingestion of a drug to supplement a hormone imbalance. However, when electric impulses stimulate every neuron in the region, they can become crude and imprecise. For example, when the electric signal targets neurons other than the ones specifically desired, side effects such as voice alteration and excessive coughing result. While an electric remedy may seem to be a plausible solution, for certain areas in the brain such as the hypothalamus, an electric remedy would be particularly dangerous because the hypothalamus contains a mix of various neurons within close proximity of each other.
Julie Pryor, Flickr Photo Sharing
In such cases of electric instability, optogenetics comes into play, because it uses light instead of electric impulses to stimulate the brain. Various photosensitive channels and light-activated enzymes called opsins are the primary tools used in this area of science. These opsins react to specific wavelengths of light. For example, Channelrhodopsin, a light-gated ion channel found in unicellular green algae, opens in response to blue light, letting in positive sodium ions into a neuron. Such a response may trigger an action potential in the neuron, releasing neurotransmitters. Other opsins, such as halorhodopsin, result in a release of negative chlorine ions when exposed to yellow light, subsequently closing and turning off the neuron. Adeno-associated, harmless, noninfectious viruses, are used as viral vectors to transfer the genes for opsins into the genomes of infected cells. These viruses are significant because they can infect non-dividing cells such as neurons. In his renowned experiment on optogenetics, Deisseroth inserted a fiber optic cable, a thin fiber that can be used to project light onto a specific target, into a specific structure in the right side of a rat’s brain, the side that controls the motor functions of the left side of the rat’s body. The fiber optic cable shone a blue light into the rat’s brain. While the cable shone the light, the rat continued to turn left in a counterclockwise circle. When the cable was turned off, the rat returned to normal behavior. The results of the experiment were astounding. If developed more fully, optogenetics could greatly enhance scientific knowledge of the nervous system. Moreover, light could be used to activate different neurons one by one and observe their effect on mammalian behavior. Deisseroth, a seminal scientist in optogenetics, is currently working on using the technology to observe causes of psychiatric illnesses, which have long been known to have biological rather than mental roots. Other applications for optogenetics include
the ability to make in-vitro mouse heart cells beat in time to the flashing of a blue light and to make a skin cell grow towards a moving laser. Scientists have already used optogenetics to identify the neurons activated when a sleeping mouse wakes up and to observe changes in brain structure between mice with Parkinson’s and control mice. The significance of optogenetics highlights the importance of ecological conservation and basic science, the study of science purely for the purpose of increasing the knowledge about the universe. The opsins used in optogenetics microorganisms occupy small, specialized niches and have long been studied by microbiologists with no knowledge of their potential in neuroscience. Ethical and philosophical arguments against optogenetics must also be considered. The idea of being controlled with the flash of a light is terrifying, but the fact remains that the light has no power until neurons are genetically modified to react to it. A culmination of prior knowledge from other scientific fields, optogenetics is an incredibly powerful tool that can further enhance our understanding of the human nervous system and of neurological and psychiatric disorders. Mo Costandi, Flickr Photo Sharing
DIY optogenetics kit created by Backyard Brains.
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Take Your Vitamins?
Ragesoss, Wikimedia Commons
The Truth behind MVMs
This image depicts yellow colored Vitamin B tablets poured out from a bottle. Vitamin B12 is crucial in creating DNA.
By Grant Ackerman Nowadays, many Americans do not get enough vitamins and minerals. According to the Office of Dietary Supplements (ODS), over one-third of Americans take multivitamin/mineral (MVM) supplements to supplement this deficiency. The U.S. Department of Agriculture and the U.S. Department of Health and Human Services’ Dietary Guidelines for Americans, however, explicitly state that nutrients should come primarily from food. Most people take MVMs to feel healthier; they believe that it will prevent chronic diseases or ward off colds and the flu. However, there have been no scientific studies to date that have definitively concluded that MVMs have a substantial positive effect on health. People take MVMs to increase nutrient intake. A study done by the National Institute of Health showed that people who take supplements are more likely to get the recommended nutritional values than people who do not. Ironically, people who might benefit from the increased nutritional intake are the least likely to take them. Americans that take MVMs are usually those who have more education, higher incomes, healthier lifestyles and diets, and lower body-mass indexes. Even though many people who take MVMs get the recommended Daily Values from food alone, some like to think of MVMs as “nutritional insurance.� What some people do not realize, though, is that consuming too many vitamins and minerals is just as serious as being deficient in them.
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According to a New York Times Healthy Guide, there are 13 essential vitamins that the human body needs to function: Vitamins A, C, D, E, K, B6, B12, thiamine, riboflavin, niacin, folic acid, Pantothenic acid, and Biotin. Nine of these vitamins are water-soluble, meaning that they must be consumed immediately or else they will leave the body through urine. Vitamin B12 is the only exception in that it can be stored in the liver for many years. The other vitamins, Vitamin A, E, D, and K, are fat-soluble, which means they are stored in fatty tissue. While it is hard to consume deadly amounts of water-soluble vitamins, it is comparatively easy to take in too many fat-soluble vitamins. It is hard to overdose on vitamins, but large amounts, usually obtained by eating MVMs, can be lethal. A study done in 2006 at Johns Hopkins University showed that MVMs do not have any effect in preventing chronic diseases. Most people who analyze this data conclude that the evidence thus far is insufficient to take a stance for or against MVMs. Therefore, some doctors will say that buying MVMs is a waste of money, especially if the patient is getting his or her recommended nutritional intake. The only sure way to remedy worries about health and chronic health diseases is through better diet and exercise habits. Although MVMs may seem like a convenient nutritional alternative, there is currently no satisfactory substitute for a balanced diet.
iPS C ells f rom Kidney C e lls By Dorothy Quincy This picture depicts a rat kidney epithelial cell on a fibronectin surface pattern. Kidney epithelial cells now have the ability to transmute into pluripotent stem cells.
Ravi Desai, as Pictured in Popular Science
Recent discoveries by scientists in China suggest that less likely to cause a rejection of the therapy from the one of mankind’s most overlooked and readily availbody’s immune system. A previous impediment of the able natural resources, human urine, can be used to usage of kidney epithelial cells was that the retrovicure neurodegenerative diseases. Led by stem-cell ruses used to insert the pluripotency gene into the biologist Duanqing Pei, scientists at Guangzhou Insticells’ DNA had a tendency to cause the genetic maketutes of Biomedicine and Health, a government-fund- up of the cells to become somewhat erratic, potentialed research institute affiliated with the Chinese ly causing tumor development. Pei has exchanged the Academy of Sciences near Hong-Kong, have devised commonly used retrovirus technique with the employmethods of manipulating cells in urine into a plethora ment of auxiliary vectors, such as bacteriophages or of different types of stem and progenitor cells, which plasmids, that do not alter the genome of the cells. carry promise for curing various neural defects. Pei According to Pei’s lab’s results, the iPS cells have sucand his fellow scientists have reverted such cells into ceeded in developing into neural progenitor cells, the pluripotent neural stem cells, which have the ability to precursors of brain cells. They also have not causing differentiate into several types of highly sought after tumor-development in rats. The manipulated cell colcells that can be utilized by patients in need. onies developed into rosette-shaped cells, characterUnfortunately, ethical dilemmas surround stem cell istic of neural stem cell, in only 12 days, half the time technology because human embryos made “in vitro” that it takes cells to become iPS cells through prior or in a lab are destroyed during the extraction of stem methods. Four weeks later, the cells injected into cells. While adult stem cells are less controversial the rat brains had adapted to the correct cell shape because they do not require any deaths, they are not and had the accurate molecular markers of neurons. able to easily transform into as many different types of The cells also displayed no signs of tumor formation. cells. However, Pei’s team’s paper, published by the Nature Kidney epithelial cells, found in human urine, Methods online publishing group, does not prove what are now shown to have the ability to transform into the long-term mutations of the cell might be. induced pluripotent stem (iPS) cells or body cells that Although this process of creating stem cells is are manipulated into becoming pluripotent in a lab. only in its beginnings, the idea of using kidney cells to Compared to cultured skin and blood cells, which are create iPS cells is promising. It is cost-effective, relthe routine sources of iPS cells, kidney epithelial cells atively quick, and uncontroversial. It does not require are more accessible and can be better specialized to invasive surgery and can be individualized to each the individual in need. “The benefit of sourcing cells patient. Hopefully, many widespread and devastating in this way is that urine can be collected from nearly diseases, such as Alzheimer’s, cancer, and Parkinany patient,” notes Dr. Mark Lalande, an iPS scientist son’s, will be curtailed by something that is flushed This picture showsevery a rat day. kidney epithelial cell on a fibronectin surat the University of Connecticut Health Center. Usaway face age of an individual’s own cells for stem cells is pattern. also Kidney epithelial cells now have the ability to transmute into pluripotent cells.
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Radiation Therapy by Abigail Zuckerman
This beam of light is light amplification by stimulated emission of radiation.
ThePhotographersRepublic ™, Flickr Photo Sharing
Radiation has become a crucial part of cancer treatment. More than half of all cancer cases are now treated with some form of radiation. Specific treatments are tailored to individual patients and their cancers depending on cancer type, location, and level of severity. Radiation is a type of “local treatment.� It cannot cure metastatic cancer, cancer spread to distant parts of the body. The purpose of radiation is to shrink early stage cancer, stop cancer from recurring in another area, and treat symptoms caused by advanced cancer. Radiation is essentially energy carried by waves of particles. This energy damages the genes (DNA) of cancer cells to influence the oncogenic cell cycle, a process related to the growth and reproduction of cells. When cell DNA is disfigured by radiation, a cell will either be killed or grow/reproduce improperly so that new cells cannot be reproduced. As a result, tumor size is reduced. Radiation is most effective on cells in the middle of mitosis, the process of cell replication. In order to ensure that enough cells have been treated, radiation usually needs to be administered over long periods of time. Ionizing radiation, radiation used for cancer treatment, removes electrons from intracellular atoms and molecules to form ions that affect the cell cycle. According to the American Cancer Society, ionizing radiation can be sorted into two major types. The first type, by far the most widely used form of treatment, is photon radiation, which consists of x-rays and gamma rays. High-energy
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photon beams come from radioactive sources such as cesium, cobalt, or a machine called linear accelerator (or linac for short). The second type, particle radiation, is relatively experimental and used only for specific cancers. It includes electron, proton, and neutron beams, carbon ion radiation, also known as heavy ion radiation, and alpha and beta particles mainly produced by radioactive substances called radiopharmaceuticals, which may be injected, swallowed, or surgically implanted. Radiation can be administered in a few different ways. The most common method is external beam radiation. In this form, the radiation comes from a machine outside the body and is focused on the cancer. In order to minimize damage to surrounding tissue, custom-made molds or casts are used to restrain patients and limit movement. On the other hand, internal radiation, or brachytherapy, is used to deliver a high dose of radiation to a small area, mainly when external beam radiation at high intensity would be too damaging to the surrounding tissue. Other types of radiation therapy include interstitial radiation, in which the source of radiation is placed directly into or next to the tumor, and intracavitary radiation, in which a radioactive material is placed in a cavity of the body. Unfortunately, current technologies cannot completely limit the effects of radiation to only cancerous cells. Radiation can also harm the dividing cells of surrounding tissues, often resulting in unwanted side effects or even
Ecancermedicalscience, Flickr Photo Sharing
Ovarian cancer cells in the midst of dividing.
second cancers. Tissues that grow quickly, such skin and bone marrow, are usually affected right away. Nerve, brain, and bone tissue, meanwhile, may only show side effects later on. For this reason, radiation may produce detrimental side effects that may not become apparent until weeks, months, or even years after treatment is completed. New research and developments in radiation therapy are focused on limiting collateral damage to surrounding tissues while increasing the precision with which radiation can be administered to the cancer. According to Dr. Simon Powell, Chair of the Radiation Oncology Department at Memorial Sloan-Kettering Cancer Center, “Ideally, the
treatment is delivered in such a way that it damages as many cancer cells as possible while sparing the healthy tissue surrounding the tumor.� These ways may include radio-sensitizers, drugs that make cancer cells more sensitive to radiation, and radio-protectors, substances that protect healthy cells from radiation. Such new developments are becoming increasingly common, effective, and potentially instrumental in future progress. While enormous strides in radiation therapy have taken place in the last several years, with continued work in the field, further advancements will undoubtedly make radiation therapy safer and more effective for patients in the future.
These are metastatic breast cancer cells observed under a microscope.
Flickr Photo Sharing
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A (Re)Generation of Tissue Building By Lily McCarthy
This depicts embyronic stem cells.
Life Technologies Corp, Flickr Photo Sharing
The prospect of having the ability to regrow and regenerate one’s organs successfully has finally become a reality. Due to the hard work of scientists involved in new developments in the field of tissue engineering, stem cells have emerged as the foundation of this new field. Although the process is far from complete, a series of breakthroughs have recently occurred in the biomedical research arena. Tissue engineering employs the use of stem cells, unspecialized cells with the potential to differentiate into a variety of cell types and functions. It also uses knowledge of the body’s extracellular matrix (ECM), a large fibrous protein-formed scaffold encircling every tissue and organ in the body. Among other functions, the ECM triggers cell growth and repair and ensures that the cells it surrounds stay together.
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This protein can be collected from animal and human specimens. Doctors such as Peter Rubin and Stephen Badylak have used the ECMs derived from pig bladders to repair lost or damaged muscle tissue in wounded veterans who fought in the wars in Iraq and Afghanistan. Scar tissue from the original injury is eliminated to ensure normal tissue will be at the muscular site onto which the ECM is stitched and stretched. It will then eventually encounter the bloodstream. However, after a period of time, the ECM will inevitably start to degrade, forcing scientists to create a solution that involves using the patient’s own cells for prolonged cure. At the Karolinska Institute in Sweden in June 2011, scientists led by researcher Paolo Macchiarini have succeeded in applying this technique through copying a patient’s windpipe out of a plastic, bio-
artificial model and implanting it into his chest. His fellow colleagues at the University College London designed the windpipe itself. The patient, 39-year old Andemariam Beyene, had developed cancer in his windpipe two and a half years earlier. Stems cells were extracted from Beyene’s bone marrow and used to cover the model. It was then placed in an incubator known as a bioreactor and was soaked in nutrients for a little over a day. The idea behind using one’s own cells for this procedure is two-fold. First, using one’s own cells avoids the ethical issues and controversies that inevitably arise from the procuration of stem cells. Secondly, this method dramatically lessens the possibility that the immune system will reject the stem cells. As this is such a revolutionary procedure, the internal events that occur after the windpipe has been replaced are largely unknown. Macchiarini conjectures that the original stem cells exposed to the artificial windpipe might have died, but they have communicated with the bone marrow to release new cells to continue regeneration in their place. An
examination and subsequent tests confirmed that Beyene’s windpipe was creating a network of blood vessels, a promising sign. A tremendous amount of preparation, months in advance, was required to ensure a successful outcome. Preliminary Research at the laboratory included removing living cells from the hearts and lungs of rats. This allowed the uncovering, observation, and study of the hearts’ and lungs’ ECM’s. Currently, labs across the globe are investigating and experimenting with the artificial creation of more complex body parts such as blood vessels, livers, and kidneys. There are still many unknown aspects within tissue engineering. Macchiarini maintains that his utmost goal is to find drugs that would cause the human body to regrow tissues and organs without physical intervention through surgery. This goal may be realized sooner than one might think due to the ever-increasing speed at which groundbreaking medical discoveries are occurring.
This machine is a large bioreactor, meant for animal cells.
Paul Bentley, Flickr Photo Sharing
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iPS Cells By Samantha Stern Directly in front of the elevator in the research building where the New York Stem Cell Foundation (NYSCF), resides are bright red walls and emboldened letters, which line the hallway of its laboratories. At the end of the hall is a photograph of bright and rainbow-colored cells, marked by antigens. The scientists at NYSCF are determined to fulfill the mission statement of the organization, which is, “to find a cure for major diseases of our time through stem cell research.” The color which lines the walls of the lab and the bubbly yet serious personalities of the researchers are exactly what the non-profit offers, a “bright” promise for the future. In 2005, CEO Susan Solomon, who wanted to provide an environment for scientists to work with stem cells, founded NYSCF. Her son has diabetes, and she had family members who suffered from Alzheimers. NYSCF was a way for her to take action. In a TEDx conference she spoke in this summer, Susan said, “I truly believe that stem cell research is going to allow our children to look at Alzheimer’s and diabetes and other major diseases, the way in which we view polio today, which is as a preventable disease.” The lab now has affiliations worldwide and conducts research projects based primarily on diabetes, heart disease, Parkinson’s, Alzheimer’s, bone regeneration, and multiple sclerosis. In addition, two members of the lab, Dieter Egli and Daniel Paull, recently succeeded in finding a method to prevent the inheritance of mitochondrial diseases. What began as one small room has developed into a floor, filled with robots, freezers, and centrifuges. iPS cells, or induced pluripotent stem cells, have played a vital role in the research conducted at
NYSCF. iPS cells were developed in 2006, by Shinya Yamanaka, a Japanese scientist. As opposed to embryonic stem cells, iPS cells pose no ethical problem. According to the researchers at NYSCF, the cells are “made in a dish” rather than being taken from blastocysts. The cells are obtained through donated human skin samples, which are then cleaned and purified in the lab. Next, the skin cells are infected with a very potent sendai virus, which converts them into stem cells. Almost all scientists at NYSCF share a common basic method. After creating the iPS cells, they differentiate them into specialized cells by feeding the cells particular media, essentially food. Each medium promotes the development of specific cell types, such as cardiac cells, neurons, etc., depending on the interest of the researcher. The researchers are both creating iPS cells from the cells of non-diseased humans and diseased-humans, so that they can study the differences in behavior between the iPS cells created from these patients. They do not study the diseased and non-diseased cells directly, but rather, the stem cells created from these diseased and non-diseased cells. The eventual goal is to use observations based on the behavior of the iPS cells to discover genetic and molecular influences on different diseases and to find cures or drugs for different diseases. Scientist Valentina Fossati uses iPS cells to study multiple sclerosis. MS is a result of the demyelination of cells in the central nervous system. When an impulse is received by the dendrites of the neuron, it is passed along a myelin sheath, which is made of fat and acts as an insulator, to the axon terminal, where it can be transferred to another cell. As a result, the impulses
A dyed induced pluripotent stem cell is depicted here,
Life Technologies Corp. Flickr Photo Sharing
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BW Jones, Flickr Photo Sharing
A doctor preps to inject stem cells into a patient for gene therapy. can travel quicker, skipping across these regions of the axon and hitting the nodes in between the sheath. In MS, the myelin is destroyed, which results in the slowing down of impulses. It is believed that MS is a result of an attack on or a problem in the coding of oligodendrocytes, which synthesize and support the myelin. These neurons, coming from the Greek word “oligo� for glue, effectively act as glue, and hold cells together. Fossati uses the iPS cells in order to manufacture oligodendrocytes. She can then study their behavior more easily. According to the researchers at NYSCF, it is possible to create large numbers of oligodendrocytes from iPS cells. It is difficult to get many oligodendrocytes from human cells directly. With a large culture of oligodendrocytes to study, the scientists could potentially test cures on diseased iPS cells rather than on human cells. Fossatti, among other researchers, uses iPS cells to study diseased and non-diseased human cells. As of now, the process of creating the iPS cells is done mostly manually, and is extremely time-consuming, but the Stem Cell Array, currently being built
at NYSCF, will make the process more rapid for all the scientists. The array is composed of a group of robots, which are programmed to convert and store the cells. They distribute skin samples into plates, allow them to break down into cells, infect them with a virus, sort out the true stem cells from those that have not yet been converted into stem cells using a magnetic system, and then store the cells. The idea behind the system is not only to create an availability of stem cells for scientists but to build a bank of stem cell lines which will represent a diverse mix of people. The stem cell bank will eventually hold 2,500 stem cell lines. Rather than testing drugs on humans, the array will allow for drugs to be tested directly on the cells, which may lead to individualized medication. The stem cell field is exciting and constantly developing. Induced pluripotent stem cells offer a new approach to solving major diseases of our time.
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D. Radiodurans Wikimedia Commons
Kenyon Microbe Wiki
By Ricardo Fernandez
Thie photo to the left depicts a bioremediation facility. in the brown area there are bacteria that will fight pollution and have a potential for bioremediation, a process by which bacteria are used to consume contaminants in the environment. The photo to the right depicts D. Radiodurans
Deinococcus Radiodurans is a bacterium whose name, derived from Ancient Greek, essentially means “radiation surviving berry.” It can function normally in an environment with three thousand times the amount the lethal dose of ionizing radiation that can kill a human being. This organism, also known as Conan the Bacterium, is considered an extremophile. It can survive the most physically demanding conditions on earth. Moreover, D. Radiodurans is polyextremophilic because it has adapted a variety of extremophilic features. Not only does it survive in the extreme cold, but it also survives in acid, dehydration, and vacuumed environments. It is very easily cultured and studied in a lab setting. Intrigued by the bacterium’s claimed radiation resistance, scientists wanted to confirm and study this biological phenomenon. A joint study, published by the Nature Publishing Group, conducted between various biology departments at the University of Minnesota and the Department of Pathology at the Uniformed Services University of Health Sciences, confirmed the many biologically astounding characteristics of D. Radiodurans. The growth rate of E. coli and D. Radiodurans were compared in the presence of sixty grays of radiation, twelve times the lethal ionizing radiation dose for humans. Without radiation, both bacteria had a steady rate of growth. In the presence of radiation, the E. coli’s growth rate greatly decreased over 30 hours, while the D. Radioduran’s growth rate remained almost exactly the same. The bacterium’s ability to rapidly repair its DNA and keep normal growth rates under extreme conditions incited even more scientists to explore D. Radiodurans’ potential contributions to the field of bio-remediation. Bio-remediation is the use of naturally occurring or deliberately introduced microorganisms to consume and break down pollutants. Dr. Matthew Wallenfang, a biology professor at Horace Mann School, believes that enzymes that break down oil spills or
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any other causes of environmental contaminations can be “placed” into D. Radiodurans through recombinant engineering. D. Radiodurans would be able to help clean up environmental disasters without being affected by extreme environmental conditions due to its radio-resistance and polyextremophilic characteristics. So far, the bacterial mercuric reductase gene, used to detoxify the ionic mercury residue frequently found in radioactive waste generated from nuclear weapons manufacturing, has been cloned from E. coli into D. Radiodurans. In addition, according to Dr. Wallenfang, other bacteria, such as E. coli, could be manipulated to live normally in extreme environments. As the genome of D. Radiodurans has already been mapped out, scientists merely need to isolate the genes that allow it to be a polyextremophile. D. Radiodurans can perform its job and not be affected by the hazardous radioactive environment, one reason for its potentially unlimited utilization. Though we have learned much from the study of D. Radiodurans, one mystery remains: how could D. Radiodurans have possibly evolved over time to adapt to environmental conditions that are scarcely found on Earth? The photo below depicts D. Radiodurans, a bacterium resistant to radiation, at a microscopic level. The bacterium is in a tetrad (group of four).
Michael Daly. Wikimedia Commons
The SIGA-246 Smallpox Cure
By Veer Sobti
A smallpox virus stained with fluorescent orange is captured in this photograph. Although smallpox viruses have been eradicated, it can be altered into a lethal weapon. SIGA-246 is the prototype to a panacea that can destroy all types of smallpox.
Sanofi Pasteur, Flickr Photo Sharing
The deadly smallpox virus no longer poses as a threat to the world. Ever since its eradication in 1977, no cases of smallpox have been reported. However, two reported vials of smallpox still remain in the world, one in the Center of Disease Control in Atlanta and the other in a Russian facility in Siberia. In the unlikely event that these vials are used for violence, a smallpox outbreak may result in the death of millions. In an attempt to stop such an outbreak, SIGA Technologies created the SIGA-246 smallpox cure. “Smallpox is one of the great biowarfare threats, and SIGA-246 demonstrates SIGA’s leadership in efforts to counteract that threat,” said Donald Drapkin, chairman of SIGA. SIGA-246 is capable of curing any person infected with smallpox and stopping a smallpox outbreak right in its tracks. According to SIGA Technologies, the drug is the first of its kind to illustrate 100% protection against the human smallpox virus. SIGA-246 accomplishes this defensive mechanism by destroying the virus’s ability to spread to other cells, thereby preventing the virus from proliferating. Preventing the virus’s ability to spread allows
time for the immune system to create a response to fight the disease. In an experimental test, a high dosage of smallpox virus was injected into a cynomolgus monkey followed by the SIGA-246 treatment. The monkey showed no symptoms for 24 hours after the administering of the virus and drug. In multiple tests with mice, the SIGA-246 also proves to be 100% disease protective. After many tests with the drug, Dr. Dennis E. Hruby, chief scientific officer of SIGA stated, “We are particularly pleased because the amount of virus used in this study is equivalent to the level present in late-stage disease in humans, which we believe signals that SIGA-246 can be used to prevent disease in humans even several days after initial viral exposure.” He revealed that, as small pox has not naturally occurred since 1977, these tests, not administered to humans, are the closest alternative. Dr. Hruby and his colleagues have been working very hard to try and find cures to this deadly and possibly imminent disease. So far, SIGA-246 is a promising start.
31 CDC/ Fred Murphy, Wikimedia Commons
SCITECH13 Preview
April 12, 2013 Cohen Dining Commons, 6-9PM The students featured here, among others, will present their science research projects at SciTech13. Unless otherwise noted, all the students here have been working on their projects through the year. SciTech13 will include dinner and music.
Rachel Buissereth Throughout my life the ocean has been an instrumental part of my well being. From my childhood living in the islands to the present, I have always been interested in the oceans. My current science research project focuses on the anthropogenic environmental factors on coral reefs and sea urchins. The variables that I am working with are temperature and pH. I hope to be able to observe coral bleaching and see changes in the way that sea urchins spawn.
Adam Zachar I am researching space debris: manmade waste left in orbit that serves no useful purpose. It could be anything from spent external fuel tanks, to defunct antennae, to remains of satellite explosions. Specifically, I’m analyzing the distribution of space debris to find the altitude where the most (greatest mass of) space junk can be removed for the least cost. Currently, there are many proposals on how to clear Earth’s orbit of debris, ranging from NASA’s PHEONIX proposal that would dissemble defunct satellites and reuse parts, to giant lasers on the polar ice. My project will help weigh the costs & benefits of the different proposals. I have access to the European Space Agency’s MASTER-2009 & PROOF-2009 data and modeling tools that I use to examine the projected state of orbiting debris in the future.
Simone Aisiks and Julia Hirschberg Our project aims to compare Body Integrity Identity Disorder to other mental illnesses in the hopes to demonstrating that BIID sufferers are not “crazy.” BIID is a disorder in which sufferers feel that one of their limbs does not belong to the rest of their body. This is important because BIID sufferers are not given the proper treatment (the only successful treatment is amputation) needed for their condition. Without the option of amputation, many sufferers do not feel “whole” and attempt to self-amputate, which can be fatal.
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Allyson Kim As fossil fuels become depleted, countries search for new, viable solutions for the mass production and distribution of energy. In the past few decades, nuclear power has become a common alternative to energy production by fossil fuels. However, the use of nuclear energy has also contributed to the increase in nuclear waste, especially the contamination of water. The search of new adsorbents to decontaminate large water bodies is one of the biggest concerns of the scientific community. Small doses of radionuclides, such as uranium and thorium, remain in the ecosystem and produce distortion in living organisms. My research focuses on the use of common materials, such as used green tea bags and corn cobs that have little to no other function, to remove radiation and toxic heavy metals from water. The aim of this study is to evaluate the adsorption of thorium, uranium, and heavy metals such as copper by these adsorbents. These adsorbents possess great potential in the treatment of radioactive wastes.
Zoe Fawer The purpose of my science research project is to discover whether one retains more information when reading on paper or on the computer. As of now, my research shows that people under the age of forty-five retain more information when they read on paper and people over the age of forty-five retain more information when read on the computer. This is due to presbyopia, a visual condition in which loss of elasticity of the lens of the eyes causes defective accommodation and inability to focus sharply for near vision. Therefore, since the resolution on the computer screen is higher than the resolution of the printed-paper, people over the age of 45 found it easier to read and, thus, retain information from the article on the computer.
Alex Stein For my science research project, I am studying the genetics in a fingerprint. I have taken from multiple families, all of the relative’s fingerprints. I am working on finding any sort of pattern that I can draw comparisons between in a certain family. This could range from patterns between siblings, a child and a parent, to generations even further off. As of now, I have been able to find some simple patterns between the general pattern in a fingerprint in an immediate family and I am trying to see if there is a reason as to why some fingerprints in certain families follow the same pattern and others do not. I am also interested in looking at more complex patterns in the components in a fingerprint.
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Andrew Fabry We plan to use the MakerBot 3D printer to create space-fill models of molecules. The models we create would be better than the models currently used because they are more accurate representations of the molecules. We plan to test the by quizzing one of the 10th grade chemistry classes and seeing the results based on angles, size, and orientation.
Ikaasa Suri The purpose of this project is to create a battery that is not only flexible, but can be woven into material. As a current sophomore, the “flexible battery” project was intended to stretch over the course of my high school career. Today, Americans purchase almost three billion dry cell batteries annually to power radios, toys, cellular phones, watches, laptops, and portable power tools. But there isn’t only one type of standard battery that uses the same types of metals and substances to carry electric current. Batteries can range from single-use alkaline manganese cells to rechargeable batteries made from nickel-cadmium, portable electronic batteries made from lithium-ions to bigger, stronger batteries made from lead acid and nickel metal hydride to power car and hybrid vehicle batteries. Starting with lemons, potatoes, and basic foods, my goal for this year is to create a successfully conductive, homemade battery. I’ve started testing the voltage of different electrolytes, and building my way up from there, I’ve begun collecting a metal kit, for which I plan to start testing out the conductivity of certain materials. I joined this science research course because I love science. I wanted to pursue my career in chemistry and I decided to do so by creating a new and innovative battery. This project, although far stretched and requiring both creativity and knowledge, is not impossible and I plan to have made significant progress by the end of this year. Experimenting with different materials, I hope to come up with a way in which I can create a flexible battery that can be woven into materials.
Ashley Gerber Protein Powders have recently become a huge fad. However, since many of these powders are not regulated by the FDA, how can the consumer be sure they are ingesting safe substances? After reading a Consumer Reports article that reported to have found traces of heavy metals in several different protein powders, I decided to further investigate. I am testing the levels of heavy metals in two protein powders- Muscle Milk and Protizyme- at different concentrations. The four heavy metals I will be testing for are Mercury, Arsenic, Lead, and Cadmium. While I have my doubts about the safety of protein powders, I hope for the sake of protein powder junkies that these metals are not present in harmful levels.
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Thomas Eng Sustainable energy is becoming increasingly important as we look toward the future. As natural gases and fossil fuels decrease we need to look toward new materials to produce energy and power. This project is an effort to create usable fuels through the heating of plastic materials. When plastics are heated in oxygen free capsules, they break down into flammable hydrocarbon chains, which can later be converted into the fuels we use in everyday engines, such as diesel. With garbage waste rising just as quickly getting rid of plastics by converting them into combustibles just might help us as a future sustainable resource.
Vickram Gidwani: Summer Research The epidermal growth factor receptor (EGFR) spans the cell membrane and is activated when growth factors in the body bind to it on the outside of the cell. Activation of EGFR results in two different cascades of activation events of “downstream” proteins. These two cascades, or “signaling pathways” are known as the AKT and ERK pathways, which are essential in regulating cell survival and growth. Mutations in EGFR, the AKT pathway, or the ERK pathway cause hyper-activation of growth signals in the cell, resulting in the development of many different types of cancers, including lung adenocarcinoma. One of the most well known treatments for this disease is Tarceva, which blocks EGFR signaling. Though the cancer initially regresses, resistance invariably develops. Because these therapies only target EGFR, they are also ineffective against mutations in the AKT or ERK pathways downstream of EGFR; with mutations, these pathways can remain hyper-activated regardless of the status of EGFR. Inhibition of both the AKT and ERK pathways is also necessary for inducing significant programmed cell death (when the cell kills itself due to loss of signaling from these key pathways), yet few effective single-agent inhibitors of both pathways exist. Studies have shown that certain antidepressants, like Clomipramine (CIP), can inhibit both of these pathways and cause the cancers cells to undergo programmed cell death. However, treatment with CIP at doses required for cancer cell death results in high levels of anti-CNS (Central Nervous System) effects, preventing application of these compounds for the treatment of cancer. In my study, CIP was structurally modified to produce a novel derivative compound, TRC-382, that could still induce programmed cell death in cancer cells without causing the neuroleptic-associated toxicities. We showed that this compound could inhibit both the AKT and ERK pathways. With this unique property of dual-inhibition of the two pathways, our compound could be used to treat cancers with mutations in the two pathways as well as cancers with mutations in EGFR. The compound exhibited the ability to induce programmed cell death in many cancer types, including lung cancer, pancreatic cancer, and melanoma. Furthermore, the compound induced tumor regression in multiple mice with lung cancer by inhibiting the same proteins identified in cell culture, without the toxic antidepressant effects of the parent compound. However, we identified feedback mechanisms activated in response to treatment with the novel molecule that increased the activity of EGFR, which could have dampened the effect of our compound by increasing signaling to the AKT and ERK pathways. Treatment with our drug and Tarceva, the EGFR inhibitor, resulted in increased cancer cell death, identifying an effective clinical combination. Thus, we showed here that our compound can treat multiple cancer types and that a combinaacvvtion strategy with TRC-382 and Tarceva can provide an additional therapeutic benefit in these cancers. In 9th grade, my Biochemistry class listened to a presentation on cutting edge research in the field of biology. I was awed by the level of detail we, as humans, know about our bodies and the tools and methods we have developed to study them. That summer, I contacted Dr. Goutham Narla and got an opportunity to work in his genetics lab. Cover Photo Take From University of Santa Barbara Engineering
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H O R A C E M A N N ’ S P R E M I E R S C I E N C E P U B L I C AT I O N • M A R C H 2 0 1 3
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