Nobelium Volume 3

Spring 2018 1

Meet the Team Letter from the Editor Editor in Chief Dear Readers, Lev Sandler The Nobelium team greatly appreciates the time you took read through this issue of the magazine. Content Manager This publication is the result of months of hard work and an arduous writing, editing, and layout process. Julia Lyne In addition to our amazing team of dedicated writers, editors, and layout staff, we would not have been able Co-Chairs of Layout to publish without the constant support of our truly incredible faculty advisor, Ms. Tonge, who has guided Clara Guzman and Lindsey Qian us throughout this entire undertaking. We also would like to show our appreciation for the Nobles STEM Editors of Biology departments for their constant assistanceSarah Mansour and Emily St. John This issue of Nobelium features renowned “patient zeros,” a person credited with being the first Editor of Chemistry carrier of a pathogen, usually responsible for spread the disease. Since the Middle Ages, health workers Liam Smith have sought out patient zeros. When faced with wide- spread pathological devastation, societies have been Editor of Psychology quick to name and blame a convenient figure, often for biased reasons. As you will soon discover, this Michaela Sylvia scapegoating results in discrimination, victimization, and often death. Editor of Computer Science Meghan Pauly, Maddy King, and I have Talia Kee taken on the task of providing the true accounts of “infamous” patient zeros. Meghan Pauly has written Editor of Physics about Gaëten Dugas, widely, and likely falsely, considered to be the patient zero of the AIDS virus. Clara Lawry Maddy King has written about Good Woman Phillips, the patient zero of the Black Death. I have writtenstaff writers about Mary Mallon, or “Typhoid Mary,” the patient zero of the typhoid outbreak in the 1900s. The truthCasey Goldstein Meghan Pauly and events of the lives of these patient zero will likelyJennifer Do-Dai Lindsey Qian surprise you, and we hope you enjoy reading aboutAnnie Kahwand some of virology’s most notorious figures.Hannah Epstein Adam Qu Susan Rowley We hope you enjoy, Maddy King Michaela Sylvia Lev Sandler Sidnie Kulik Clara Lawry Vivian Tao Co-founderSarah Mansour hailey brown Editor-in-Chief Liam Nawara Anushka Harve Keren LuoLayout Staff Meghan Pauly Grace Smith Matt Cullinane Anna Perez Tate DonnellyNattalie Gualdron Vivian Li Jennifer Do-Dai2 Nobelium Magazine • Spring 2018

ContentsFeatures 4 Black Death Origin and EffectsBiology By Maddy KingChemistry 6 Typhoid MaryPsychologyPhysics By Lev SandlerComputerScience 8 Patient Zero: Gaëtan Dugas By Meghan Pauly 10 CTE: The Buried Disease By Casey Goldstein 12 Drug Discovery: A New Hope by Jennifer Do-Dai 14 The Myth behind the Sugar high By Laurel alpaugh and Isabel Kelly 16 Using Spinach Leaves as Heart Tissue By Emily St. John 18 One Possible Cause of Autism By Annie Khawand 20 A cure for Cancer? By Anushka Harve 22 Irresistible Reactions: the Chemistry of Pizza By Hailey Brown 25 The Placebo Effect By Sarah Mansour 26 Bipolar Disorder By Keren Luo 29 Flow By Adam Qu 30 California Earthquake By Sidnie Kulik 32 Physics of Photography By Will Whalen 34 Ai in Medicine By Vivian Tao 35 Invisibility Cloak By Hannah Epstein 3

By Maddy KingEdited by Julia LyneBlack DeathOrigin and Effects The infamous Plague, or, the Black Death, was man Phillips, the deceased’s husband, five shillings, aone of the most deadliest outbreaks in the Western Civ- small amount fit for a cheap wooden coffin. Phillip’silization. Throughout the middle ages, the Black Death family, a husband and two sons, were locked, or “shuttrepeatedly struck Europe, cutting down the population upp,” (Moote, The Great Plague) in their own home forbefore it was able to repopulate. As this disease rewrote at least forty days in the hopes to quarantine the plague.history, afflicted people blamed the events on a list of As doctors of the time believed that the plague was annon-medical occurrences, believing fallacies over reality. airborne disease, they would contain whole familiesIn particular, during the the Great Plague of London, inside in hopes of saving the general public. Also, ancitizens accused a patient zero for starting the horrific additional five shillings would be payed to the Phillip’sepidemic that took one fourth of London’s population. family for a weeks worth of food. This amount would be passed through a window by a guard to the family inside Being recorded as a patient zero establishes one’s to avoid contamination. The plague was finally broughtname in history for all the wrong reasons. Goodwoman to an end when the Great Fire of London purged both thePhillip’s story remains a mystery. However, her death is local residents and the city of the plague, itself.known in textbooks as the first recorded death duringThe Great Plague of London, which caused the death of With modern day science, we know that theover 100,000 people from 1665 to 1666. baseline of the bubonic plague originated from a bacte- ria called, Yersinia Pestis. This microbe is an extremely After getting reports from neighbors about a sick- noxious pathogen. Y. Pestis causes an antiphagocyticness, a group of women were sent by the church to check layer in its occupier’s blood, which prohibits the growthon Goodwoman Phillips. On Christmas Eve in 1664, they and development of phagocytes, a type of cell that ingestsarrived at her home and found her there, dead. Inside, harmful bacteria. Also, it’s worth mentioning that thethey discovered pus-filled sores on her body, the signs of Great Plague of London consisted of three main types ofa victim of the bubonic plague. In a frenzy, they locked plague; bubonic plague, septicemic, and pneumonic. Theup her house and then wrote on her front door, in bold bubonic plague being the most common, as it attacks thered paint, “Lord have Mercy on us.” These words sent a immune system, causing the lymph nodes to swell, andclear message to passerbyers that the Phillip’s household later burst. Additionally, the septicemic plague, whilewas contaminated with the plague. less common, derives from the bacteria entering the Later, on December 30th, the parish paid Good-4 Nobelium Magazine • Spring 2018

bloodstream. Howbeit, the pneumonic plague is the by National Geographic titled, “Maybe Rats Aren’t tomost deadliest and contagious, as it infects the respi- Blame for the Black Death”, Michael Greshko suggest-ratory system and can spread from coughing, which ed, “If fleas and lice picked up the plague by bitingwould allow the bacteria to be expelled into the air. an infected human, they could potentially hop onto a person in close quarters and transmit the disease”. Plagues originate due to a slight change in the When putting this theory into the situation of affectedDNA of a species of bacteria which we are exposed to families being locked together in a house, it’s easy toconstantly. Christopher Wills, an expert on diseases understand how the plague caused such devastation.and gene mutation, wrote, “Plagues can happen be-cause the organisms that cause them are only a few The death of a poor woman in the squalor out-steps away, genetically speaking, from their less harm- skirts of London unbeknownst to the public was theful relatives that inhabit all of us all the time” (Wills, start of a traumatic outbreak. While it is unknown howYellow Fever Black Goddess). Due to their common exactly Goodwoman Phillips contracted the plague,ancestor, the bacteria that cause plagues are often very evidence suggests that a slight change in DNA, perhapsgenetically similar to the bacteria found in humans. from contact with an infected insect, transferred theThis fact makes it much more difficult for the body’s bubonic plague unto her. In the atrocious events of theimmune system to fight the plague. The bubonic Great Plague of London, society preferred blaming theplague continues living today, most recently it ap- first victims over recognizing the reality of London’speared in August 2017 in Madagascar and caused the unsanitary overcrowded living conditions. This themedeath of approximately 200 people. However, victims of choosing a scapegoat to simplify a reasoning, orcan recover when administered antibiotics early on in make better a situation stands in relation to human na-the stages, and survive. ture. Meanwhile, with a simple mutation the bacteria, Yersina Pestis can transform into the black plague. Yet, Interestingly, it was originally thought that rats it stands to say, that Phillip’s passing created a snowballsingle handedly brought the Black Death to Europe. effect onto the lives of others that changed the historyWhile infected vermin did attribute to the growth of of London.the plague, studies today show that human lice andfleas made much more of an impact. In a recent article Feature Articles: Patient Zero 5

Typhoid, in- or typhoid side fever, is an of a extremely danger- host, ous bacterial infec- infecting tion caused by exposure others, while to Salmonella typhi, a par- leaving the host ticularly vicious strain of the unaffected, makes “Salmonella” bacteria. Symp- this disease particularly toms appear gradually, but quickly harmful. If the host remains become severe. Symptoms begin as healthy, he or she is known as low grade fevers, dizziness, and nausea, a “healthy carrier.” Salmonella but progress to diarrhea, vomiting, danger- typhi is one of the few known bac- ous fevers, and rapidly spreading skin rashes. terial strains in which infected hosts Once the bacteria enters the bloodstream, typically can remain asymptomatic, allowing them via food consumption, they settle in the host’s intesti- to unknowingly pass on the disease to oth-nal cells. The bacteria functions like any other patho- ers. Typhoid is usually diagnosed by testing thegen: multiplying and feeding off the host’s bodily nu- host’s stool, bone marrow, or blood for typhoidtrients until, if left untreated, the bacteria consumes bacterial DNA. Treatments for typhoid range fromall nutrients and kills the host. Salmonella harms the as simple as rehydration to as invasive as surgery tohost in a variety of ways, the most dangerous being repair the intestines.perforation of the intestines which causes excessive Typhoid is said to have existed for hundreds ofintestinal bleeding. The speed in which the patho- years; it is considered the possible cause of a plaguegen is transferred makes typhoid more dangerous in 430 BCE Greece that killed one third of the Athe-than most other diseases. Additionally, the bacteria’s nian population. However, the most deadly outbreakability to be transmitted through food, grow quickly in occurred in the twentieth century. In the early 1900’s,unsanitary and overpopulated environments, and live typhoid tore through crowded, unsanitary New York City, killing and infecting hundreds of people before the government could understand what was happen- ing. Within that outbreak, the most notorious case of typhoid is that of Mary Mallon, more commonly known as “Typhoid Mary.” Mallon was one of the few who carried the disease but showed none of its symp- toms. Immigrating from Ireland to the U.S. in 1884, Mary was employed as a chef in 1906 by a wealthy New York banker named Charles Henry Warren (NCBI). While Mary worked for a wealthy man, she experienced no such economic success. Living with eleven other people, it is most likely that Mary con- tracted typhoid in her apartment in Oyster Bay on Long Island. While it has since been discovered that six out of her eleven roommates were infected previ- ously with typhoid, Mary a “healthy carrier,” was the one blamed for the outbreak. Concerned with the prevalence of typhoid on his property, Warren decided to hire sanitary engi- neer George Soper to discover the root of the problem. Soperimmediately began conducting research of War-6 Nobelium Magazine • Spring 2018

-ren’s employees and found out that members of seven the age of 69 as a result of pneumonia.of the families that had previously employed Mary Mary’s story, while tragic, has had a lastingMallon subsequently contracted typhoid. These fam-ily members went on to infect twenty unrelated other influence in how disease outbreaks and patient zerospeople and caused the death of one girl (History). are treated today. Throughout the course of her lifeSoper hypothesised that, as a chef, Mary was contami- and series of quarantines, Mary became somewhat of anating the food she was preparing. The bacteria could notorious celebrity. Her visage was used on a numberthen easily enter the host’s body and cause disease of public health images and cartoons and she becameand infection. Sopen began to actively pursue Mallon, known as “Typhoid Mary” by the public. The term “Ty-asking her (unsuccessfully) for blood, urine, and stool phoid Mary” is now used colloquially to describe anysamples (NCBI). Having found no luck approaching patient zero. Her particular affliction was of extremeMary directly, Soper contacted Dr. Biggs of the N.Y. medical importance as she was the first asymptom-Department of Health who brought Mary into a hospi- atic carrier of typhoid. Scientists now believe that thetal for testing. Mary’s stool tested positive for Salmo- typhoid bacteria was “hiding” inside of Mary’s macro-nella, resulting in her immediate quarantine. phages (a type of large white blood cell), allowing the bacteria to thrive in the host’s body without killing it, During her first stint in quarantine at a health but still being able to spread to other hosts (Huffpost).clinic on North Brother Island from 1907-1910, doc- This anomaly is the main reason Mary was able totors attempted to remove Mary’s gallbladder, believ- spread the disease so effectively. While the numbering that this organ housed the typhoid contagion. of deaths that occurred as a result of Mary MallonMary refused, promoting the health professionals to is unknown, some speculate that the numberunsuccessfully treat her with a barrage of medicines, could be as high as 50. Typhoid has notincluding Hexamethylenediamine (a moderately toxic been completely eradicated, as thereorganic compound), laxatives, Urotropin (an antibiotic was a deadly outbreak in 2004 in theaimed at infections in the kidneys and bladder), and Democratic Republic of Congo.brewer’s yeast (NCBI). Living in complete isolation However, scientists have discov-under inhospitable, dangerous conditions, while re- ered a series of medicationsceiving harmful, invasive, and ineffective treatments, and treatments that haveMary attempted to sue the New York Health Depart- significantly loweredment (History). The New York Supreme Court denied the mortality rate ofher appeal, but, in 1910, Mary was released from the disease.quarantine under the condition that she would notwork in direct contact with food and/or other people.Changing her name to Mary Brown, she violated thisagreement, working, again, as a chef at Sloane Mater-nity in Manhattan. In the three weeks that she workedthere, Mary is reported to have infected at least 25people, two of whom died (NCBI). To avoid beingreinstituted, Mary frequently moved around,changing jobs often, leaving a trail of diseaseand destruction in her wake. On March 27,1915, health officials discovered Mary’sseries of health violations and institu-tionalized her at the same healthfacility on North Brother Island.While in quarantine, Marysuffered a tragic strokethat left her paralyzed.Mary remained inquarantine untilher death onNovember11, 1938at Feature Articles: Patient Zero 77

88 Nobelium Magazine • Spring 2018 By Meghan Pauly Nobelium Magazine • Spring 2018 Edited by Lev Sandler

Patient Zero: Gaëtan Dugas “Patient zero” is a term used to identify the Maryland, admits that “the history of diseases hasfirst known carrier of a widespread disease. It is always been, in part, that someone needs to beimportant for scientists to identify the patient zero blamed” (Nature).of communicable diseases so that they can under-stand the cause of the outbreak and seek to prevent However, the true story lies in the mis-similar diseases from spreading in the future. One communication of the letter “O”. During Darrow’sof the most famous patient zeros is Gaëtan Dugas, interviews, he decided assign each patient a letter,thought to have been the first patient to ever carry number, or combination of both to identify them.and spread the HIV virus in the United States. Du- The letter “O” was assigned to Dugas. Anoth-gas is credited with causing the devastating AIDS er scientist at the CDC misinterpreted Darrow’soutbreak in the 1980s. Gaëtan Dugas was a Cana- labeling; instead of “Patient O” (the letter), thedian flight attendant who frequently travelled to colleague read “Patient 0” (the number). Fromthe US for work. He and other gay flight attendants then on, Dugas was referred to as “Patient zero.”that he worked with frequently engaged in sexual Darrow claims that he and his team never meantrelationships across North America; Dugas, him- to suggest that Dugas was the first person to carryself, had over 2,500 sexual partners (Gladwell, The HIV in the US. In fact, later research revealed theTipping Point). virus had been present in the US as early as 1970 and most likely came from a strain originating in In 1981, William Darrow, a sociologist at Haiti. However, as a result of the anxiety ravagingthe US Centers for Disease Control and Prevention the United States and the widespread homophobia(CDC), conducted research to determine the cause in the 1980s, the blame was quickly assigned toof the spreading HIV virus. He and his colleagues the gay, Canadian man who could most easily berealized that the first cases of AIDS were present blamed. The Dugas name has since been clearedin couples having sexual relations, and used this of blame, but Gaëtan Dugas and his family stillinformation to theorize that the HIV virus must be had to bear the public’s sheer hatred throughouta sexually transmitted disease. Numerous patient the 1980s. Michael Worobey, research scientist atinterviews supported Darrow’s theory and, to his the University of Arizona, states that “he has beensurprise, one name seemed to reoccur in many of blamed for things that no one should be blamedthe stories: Gaëtan Dugas. for” (NPR). Afterward, Gaëtan Dugas was referred toas the “patient zero” for the AIDS epidemic in theUnited States. For years, the public blamed Dugasfor bringing the HIV virus into the US, spreadingthe deadly disease to thousands of people, andcausing a devastating number of deaths. As a resultof the hysteria following the AIDS outbreak andthe existing homophobia in the 1980s, the publicreadily assigned the blame to Dugas, especiallybecause he was a gay man. A shocking number ofpeople even believed that Dugas purposefully andmaliciously spread the virus throughout the Unit-ed States. Anthony Fauci, director of the NationalInstitute for Allergy and Infectious Disease in Feature Articles: Patient Zero 9

CTE: By Casey Goldstein Edited by Julia LyneThe Buried Disease An All American at the University of Florida, such as legendary Packers quarterback Brett Favre,Aaron Hernandez was drafted in the fourth round or Hall of Fame running back Tony Dorsett. Theseby the Patriots in 2010. As the youngest player on living individuals carry on with their lives knowingany active NFL roster, Hernandez dominated the that it is only a matter of time before the inevitableNew England tight end position, alongside rookie strikes; a life slowly rendered unlivable, due to aRob Gronkowski, and they became the first duo to combination of physical or emotional trauma.score at least five touchdowns in consecutive sea-sons on the same team. He even made an appear- The disease occurs as a result of repetitiveance at the Super Bowl. blows to the head over time, causing a protein called Tau to form clumps and spread around the Hernandez seemed to have it all, but at 23 brain, killing brain cells. The phenomenon hashe was arrested and charged for the murder of his been observed for nearly a century, as Dr. Harrisonfiancee’s sister’s boyfriend. He was 25 when he was Martland, an early 20th century pathologist, de-found guilty, and he was 26 when he was found scribed a group of boxers as having what he dubbeddead in his prison cell on April 19, 2017. In Septem- “punch drunk syndrome.” This is now recognized asber 2017, rounding what would be his 28th birthday, CTE.he was diagnosed with Chronic Traumatic Enceph-alopathy, or CTE. And even more recently, several CTE can result a variety of behavioral chang-sources have confirmed that his case of CTE was the es, such as aggression, depression, and paranoia.worst ever recorded for a man of his age. While the debilitating disease has taken various forms in each of its victims, it remains a serious Unfortunately, harrowing stories like Her- hindrance to one’s daily life. Dorsett, in an ESPNnandez’s are not uncommon around the profes- interview, conceded that “[his] quality of living hassional football league. If you have seen the movie changed drastically and it deteriorates every day.”Concussion, with Will Smith, you might be familiar Others have said that they experience “short-termwith CTE. The name was coined by Bennet Oma- memory loss, erratic behavior… and fogginess.”lu, a Nigerian American forensic pathologist, as hediagnosed the first evidence-supported case of the Surprisingly, CTE typically occurs as a resultnow deceased and former Pittsburgh Steeler Mike of non concussive, or subconcussive, trauma. In oth-Webster. er words, those who are hit but not diagnosed with a concussion are more likely to develop CTE. The The NFL remains under the spotlight for inflicted players tend to continue on, unknowinglyCTE cases. Tissue repository centers around the adding on to the long term brain damage.world, such as the VA-BU-CLF Brain Bank, contin-ue Omalu’s work to study the brains of deceased An NFL player sustaining blow after blowathletes. The results have been shocking; of the 111 will eventually develop irreparable damage to bothformer NFL player’s brains analyzed in this Boston the mind and body. As effects of CTE typically dobased Brain Bank, 110 of them have been diagnosed not begin until the victim is between 20 and 30with CTE. years old, the disease remains under the radar of the individual’s health concerns. Thus, many are un- Among living former football players diag- aware of possessing such trauma until well past thenosed with CTE, football fans will recognize names point of remediation.10 Nobelium Magazine • Spring 2018

This insanity,subconcussive will be the last oftrauma has amplified its kind.impact within youth, and hard-ly ever heals naturally in such athletes. Author’s Note: I hope that this article had noStudies have shown that head injuries occurring negative influence on your view of football. I havebefore the age of twelve have much more negative been playing for five years now, and I can honestlyeffect on the span of one’s life than those occurring say that there is infinitely more to the activity thanafter. That adorable tackle made by a seven year the risk of being diagnosed with a concussion ofold linebacker in Pop Warner may hold serious, life CTE. Please do not let this controversial topic deterlong implications to his or her health if not treated you from seeing the true spirit of contact sports.properly. Luckily, such organizations are workingtowards providing both the technology and meansto identify subconcussive trauma before it’s too late. CTE has long been swept under the rug inthe realm of sports, especially football. The NFL hasactively muted those who have tried to raise aware-ness about the issue, concerned that the consequentlawsuits could potentially disrupt its 60 billion dol-lar industry. CTE, as a result, remains a disease onlyrecently placed under the nation’s spotlight, and itwill take years, if not decades, for an amendment tocome into effect. The silver lining? We’re on the right track.The fact that a Golden Globe nominated moviecondemned the actions of the NFL demonstratesthat some ground is being madein the pursuit of the awareness ofthe disease. Roger Goodell, alreadya figure of controversy, continuesto grapple with the surge of dis-contentment from families of CTEdiagnosed football players andspectators alike. Now that the factsare all out in the open, remediationcan begin. Hopefully Hernandez’sstory, a tale of crime fueled by near Biology 11

Drug Discovery:By Jennifer Do-DaiEdited by Sarah Mansour One out of three people are at risk for develop- is too much, and how much will not work at all? Shoulding cancer in the US and one out of every five people are the drug be in tablet form or injected? What effects will itat risk of dying from cancer (cancer.org). Chronic my- have on different people? Will there be any detrimentalelogenous leukemia (CML) is a slow-developing cancer side effects? If there are other drugs for the same disease,caused by a mutation in blood-forming cells. Eventually, is this a better alternative?this mutation causes an excess of white blood cells inthe bone marrow. These white blood cells don’t grow or In 1960, Dr. Peter Nowell and Dr. David Hun-die normally like normal white blood cells. When these gerford were on the front lines of CML research whenwhite blood cells divide and build up in the bone marrow, they observed an “abnormally short chromosome in bonethe healthy cells are crowded out and the bone marrow marrow cells from patients with CML” (cancer.gov).is damaged. An estimated 90% of CML patients are still However, due to a lack of technology for genetic research,alive 5 years after starting treatment (cancer.gov). This the scientist’s knowledge about the chromosome and itshigh survival rate is due to the discovery of a new drug, relationship with CML at that time was limited. In 1973,imatinib, more commonly known as gleevec. Before the Dr. Janet Rowley discovered that chromosome 22 and 9discovery of imatinib, only 33% of people survived 5 in CML patients underwent a process called chromosom-years after a CML diagnosis. Gleevec gave a new hope for al translocation. In chromosomal translocation, parts ofsurvival after a CML diagnosis, and scientists continue to two different chromosomes switch or a part of one chro-attempt to find cures to other cancers today (cancer.gov). mosome breaks off and attaches itself to a different chro-The drug discovery and development process consists mosome. This creates a mutation in the chromosome.of five main steps: discovery and development, preclin- In the 1980s, Dr. Nora Heisterkamp and her colleaguesical research, clinical research, review by the FDA, and discovered that the translocation of chromosome 22post-market monitoring. and chromosome 9 created a new gene called BCR-ABL. In 1986, Dr. Owen Witte and his colleagues discovered The first step in the development process is the that the BCR-ABL gene instructs the body to producediscovery and development of the drug. To find a mo- “an abnormally active form of an enzyme called tyrosinelecular compound that could lead to beneficial effects, kinase that stimulates uncontrolled cell growth in whitescientists use new information released about the dis- blood cells” (cancer.gov). Since a symptom of chronicease or unexpected results from current treatments, myelogenous leukemia is an excess of white blood cells, ittest thousands of compounds, and experiment with new was obvious to Witte that the tyrosine kinase could causetechnologies. Next, scientists must conduct experiments CML. To cure CML, scientists needed to find a way toto learn more. How does the drug interact with other inhibit the enzyme. After testing hundreds of developedcompounds? What is the appropriate dosage - how much compounds in 1993, Dr. Nicholas Lydon and his team12 Nobelium Magazine • Spring 2018

A New Hopediscovered the compound STI571, later named as ima- stage, effectiveness and other side effects are monitoredtinib. It “would kill every CML cell in a petri dish, every in 300 to 3,000 volunteers for anywhere from one to fourtime.” (cancer.gov) years. The fourth and final phase consists of several thou- sand participants are involved and can last for as many The next stage in drug discovery is preclinical years as needed (fda.gov).research. Before the drug is tested on humans, scientists Clinical trials for imatinib began in 1998. In the first trial,must ensure that it is safe. There are two methods for imatinib restored 31 participants’ white blood cell count.this: in vitro or in vivo. In vitro means that testing occurs All 31 participants took a dosage of 300 mg a day (cancer.in a test tube or culture dish. In vivo means that the drug gov). In further clinical trials, around 95% of patientsis tested on a living organism, like a rat. This stage is not with CML in its beginning stages had normal bloodlarge-scale; yet, it is an important stage. Scientists must counts after taking imatinib (cancer.gov).determine that the drug is safe for testing on humans inclinical studies. The fourth step and fifth steps of drug testing are mostly completed by the FDA (fda.gov). After clin- Clinical trials span decades; scientists must ical trials are complete, the developer files a New Drugascertain that the drug leaves no long-term side effects. Application (NDA). This includes all research completedBefore clinical studies can begin, scientists must set on the drug. The FDA reviews the NDA and a reviewparameters on the trial: who qualifies to participate? team ensures that no data was withheld and the develop-How long with the study last? How and when should data ers followed safe procedures. This usually takes aroundbe collected? Once those questions are answered, the six to ten months and a senior FDA official makes thedevelopers must submit an application to the FDA (Food final decision. After FDA approval, and the drug has beenand Drug Administration). Within 30 days, the FDA will released, the FDA still monitors the drug post-marketeither give its approval, suggestions to improve, or a clin- (phase five).ical hold. In a clinical hold, the investigation is delayed orstopped completely. After receiving the FDA’s approval, While the road to discovery for a drug is a longclinical research can finally begin. and challenging process, any treatment can give a new hope to patients and their families. “Before the introduc- Clinical research typically occurs in four stages tion of imatinib, a diagnosis of CML amounted to a death- starting small and growing large scale in terms of time sentence” (cancer.gov). A 2011 study concluded that mostand participants (fda.gov). The first phase usually lasts patients were in remission within two years of treatment,several months with anywhere from 20 to 100 partici- meaning all symptoms of the cancer had disappeared.pants. The goal of this phase is to confirm the dosage and If scientists continue to develop new drugs, a cure to allsafety. The second phase, with around several hundred cancers may exist in about five to ten years (Professorparticipants, takes months to years. Its goal is to deter- Karol Sikora).mine the drug’s effectiveness and side effects. In the third Biology 13

The Myth Behind the Sugar High By Laurel alpaugh and Isabel Kelly Edited by Lev Sandler Have you ever been around children just after they ate a thick slice of cake or an overflowing fistful of candy? Afterwards, they seem to act more hyper, running around–practically bouncing off the walls. You proba- bly have felt a little hyper yourself after eating some flan at the castle. Your parents might have told you about “sugar highs”, explaining that it leads to hyperactivity in children. So, you probably assumed that they are having a “sugar high” and that is why they’re acting like this; however, the intake of sugar actually has no effect on one’s behavior. To further understand this myth and how it started, we must go way back to the 1970’s. In 1978, a study by the Journal Food and Cosmetics Toxicology was published examining sugar and hyperactivity in children. The study examined 265 hyperkinet- ic, or “hyper” children and their medical records. From the study, it was discovered that the hyperkinetic children seem to have low overall blood sugar levels, which can be caused by eating too much sugar (Sciencedirect). Low blood sugar can be caused by reactive hypoglycemia, or the drop in blood sugar that comes a few hours after eating (Health Line). So, it was assumed that the hyperactive children had eaten too much sugar and then their blood sug- ars had “crashed” causing the low blood sugar that the scientists observed. Low blood sugar is common in diabetic people but can be experienced among14 Nobelium Magazine • Spring 2018

non-diabetic people after eating too much sugar. The study concluded that the reac- tive hypoglycemia was from the excessive amounts of sugar the children must have been eating. However, later research conduct- ed found that the blood sugar levels among the children were actually at normal levels for children and not as low as previously thought, which dis- proved the Journal Food and Cosmetics Toxicology study (Spectator Heath). More recently, the “sugar high” was further debunked by a meta-analysis done by the Journal of the American Medical As- sociation. A meta-analysis is a procedure that uses data from other studies and merges it to- gether to show a consistent trend or effect. The meta-analysis done by the Journal of the Ameri- can Medical Association took 23 studies released in an 11 year period between 1983 and 1994 and found that no link existed between sugar and a significant behavioral change (Spectator Health). All of the stud- ies used for the meta-analysis compared children after eating a placebo pill, an artificial sweetener such as sac- charin or aspartame, and after eating sugar. The studies examined 14 different outcomes, such as mood, school performance, aggression, and of course, hyperactivity. But still, no connection could be found between sugar and ex- cessive energy (Spectator Health). In conclusion, the “sugar high” appears to be a lie. Your parents have lied to you, probably in an effort to stop having you stop eating sweets and flan. Parents who believe that their children are more hyper on sugar are just under the spell of the myth; that’s just what’s been told to them. Instead, kids may be acting more hyper based on the situation or the place they are in, not because of all the candy and cake they are eating. This does not mean that children or anyone can eat large amounts of candy with-out side effects, but hyperactivity is not one of them. Biology 15

Using Spinach LeavesA Key to Building Organs By Emily St. John edited by Lev Sandler Over 100,000 people are current- functional, individualized heart tissue thatly on the waiting list to receive an organ, could be used to repair small areas or evenand only 30,000 of them will receive an whole hearts (news.nationalgeographic.organ each year (unos.org). It can take com).up to 5 years to receive an organ, whichthe body may reject and leave the patient Vascular systems are vital in bothwithout a functioning organ (unos.org). plants and animals. They serve as a su-Alternative methods to donor organs, such perhighway for the nutrients, oxygen, andas 3D bioprinting, have been explored by molecules that are vital to cell develop-scientists; however, these technologies ment and tissue growth. One member ofare road blocked by the inability of scien- the team, Joshua Gershlak drew on thistists to create a viable vascular network connection, thinking about how the veinsto deliver blood in order to develop larg- and stem in a plant are similar to the hu-er-scale tissues, especially cardiac tissue man vascular system of veins and arteries(news.nationalgeographic.com). Dr. Glenn (wpi.edu). The team began by decellular-Gaudette, a professor at Worcester Poly- izing, or stripping the spinach leaves of alltechnic Institute, found a solution to this of its cells, to leave a cellulose scaffold byproblem using nature. He and his inter- injecting a detergent into the leaf’s veins.disciplinary team decellularized spinach This scaffold is the outline of the leaf’sleaves, using them as a cellulose scaffold major structure, therefore preserving theto culture, or inject and grow, beating veins in the leaf which serves as the vas-heart cells using fluids similar to human cular system of the new tissue. Celluloseblood. Although in its early stages, this is a sugar found in plants that is entirelytechnology is invaluable to help grow biocompatible; it is already used in many regenerative medicine applications, such1166 Nobelium Magazine • Spring 2018

as Heart Tissueas synthetic cartilage and bone engineer- ic.com). Being able to utilize the vascularing. (wpi.edu) The team then injected system of plants to create larger tissuesthe decellularized leaves with live human is a major stepping stone for scientistsheart cells and supplemented their growth to create entire organs. Then, because aby perfusing fluid and microbeads through patient’s own cells would be used to growthe leaf’s vascular system to supply the these tissues on the plant scaffold, the riskcells with vital nutrients to survive. Then, of organ rejection would be smaller be-miraculously, after five days the heart cells cause it is the patient’s own cells, identicalbegan to beat (wpi.edu). in genetic makeup. This unorthodox approach has a However, using spinach leaves asgreat potential to create larger-scale tis- functioning heart tissue is far from enter-sues that need vascular networking to sus- ing actual medical practice. In extremelytain themselves. By using plants that can early stages, the team at WPI wants tobe grown in mass quantities and inexpen- explore building a second vascular net-sively, this technology proves to be much work for the outflow of bloods and fluidsmore cost efficient and accessible than and using different types of cells to growother synthetic approaches such as bio- on spinach leaves (wpi.edu). Nevertheless,printing. Scientists at WPI have also used this technology is extremely valuable tothis same process successfully on parsley, the medical community as it can providepeanut hairy roots, and annua (Gersh- highly accessible solutions to growing lay-lak et al, 14). Due to the fact each plant ers of healthy tissue necessary to solve thehas a different vasculature and structure issue of organ transplantations.strength, they can be used to engineer dif-ferent types of tissue (wpi.edu). For exam-ple, cardiac tissue needs to have an exten-sive vascular system, therefore spinachleaves are ideal because of their complexvasculature. The vascular scaffold allowsfor blood and fluid containing nutrientsto perfuse deeper into the tissue, allowingscientists to create thicker and larger sam-ples than before (news.nationalgeograph- Biology 1177

One Possible Cause of Autism By Annie Khawand Edited by Julia Lyne1188 Nobelium Magazine • Spring 2018

Autism Spectrum Disorder, Sci-more commonly known as Autism, is a entistsdisability that occurs due to the improper have founddevelopment of the brain. Autism is distin- one gene thatguishable from other mental diseases because has eight differentit causes social, communicative, and behav- mutations in a narrowioral difficulties. There is no medical test to region that likely leads toidentify autism. Children are usually evaluated Autism, the TRIO gene. Theby certain specialists after parents notice that TRIO gene is responsible for thetheir children are not exhibiting normal be- coding of a protein called GEF1/havioral patterns. These include a child’s lack DH1. When the TRIO gene is mutated,of eye contact, lack of response to his or her the GEF1/DH1 protein is not synthesisedname, and lack of playing with toys. Autism correctly, so it does not function properly.is usually identified in children at around two One of GEF1/DH1’s jobs is to activate anotheryears old. protein called RAC1 which forms fibrins that help hold the structure of neurons and syn- Autism is a spectrum, meaning that aptic gaps. When RAC1 is not activated, theit affects children at different levels, and in connection between neurons become abnor-varying ways. In other words, autism is not mal because of the lack of fibrins. In rare casesstandard; it comes in many forms. Accord- connection can become stronger, but typicallying to the Center for Disease Control (CDC), it becomes weaker. Either way, the abnormali-autism affects one in every sixty eight kids in ties in these connections lead to a deficit in thethe United States. Unfortunately, the scien- neural development process. Information istific community has not been able to identify still transmitted from one neuron to another,one specific cause for Autism. There has been but the storage and synthesis of this informa-a rumor that vaccinations were the cause of tion becomes less reliable. This can lead toautism. This rumor seemed very plausible be- clinical symptoms that are associated with Au-cause sign of autism begin showing in children tism, more specifically, challenges with com-around the same time they began getting vac- munication, behavior, and in social situations.cinated. There have been many studies howev-er that prove that vaccines are completely safe,and that they do not lead to autism (CDC).Although there is no definite cause, many ge-netic mutations on different genes have beenfound to have a connection with Autism. Biology 1199

A Cure forCancer? Cancer is one of the most deadliest diseas- cells,es known to man because there is no one way to mod-cure it. Various types of cancer, like breast cancer ifyingand skin cancer, are so differentiated, that there them,is no “one-size-fits-all” cure. Worse, cancer cells andinside of even a singular tumor are heteroge- inject-neous, meaning different. Therefore, the cancer ing themthat exists in a person today may not even be the back intosame cancer in a week, or a month - making it the patient.very hard to treat. Every case is individual, be- The mostcause every immune system is individual as well effective type(The Jackson Laboratory). The immune system of ACT has beenis so important to consider in cancer treatment the creation of CARbecause it reacts in different ways to cancers and T cells (National Cancermedications. Institute). These are the patient’s own T cells, but with The immune system is equipped with a special receptors called Chimericway to fight cancer cells. T cells, a type of white Antigen Receptors (CAR) on their surface.blood cell, target tumor cells by latching onto the CARs more powerfully and intelligently identifyforeign antigens (proteins) on their surface and the foreign antigens on tumor cells, allowing thereleasing a toxic chemical to kill it. However, one T cells to initiate an immune system response toway that many cancer cells evade the immune kill it (Dana Farber).system is by either disguising themselves ashealthy cells, or by sprouting so many antigens A cancer patient starting the process ofon their surface that the T Cells are overwhelmed CAR T cell immunotherapy will have lots of Tand cannot attach (Dana Farber). cells extracted from their body in a process called apheresis. The patient’s blood will be drawn, Cancer researchers have found a ground- the T cells filtered out, and the remaining bloodbreaking way to see past these defense mecha- transfused back into the patient’s body. Once anisms to create a cure for cancer. They’ve devel- good number of T cells are collected, they areoped a new way of curing cancer called adoptivecell transfer (ACT), a type of immunotherapy.This treatment is essentially taking a patient’sown T20 Nobelium Magazine • Spring 2018

By Anushka HarveEdited by Lev Sandler genet- cells are being tested with a variety of tumors, ically but it seems to have worked best with acute engineered lymphoblastic leukemia (ALL) in children and in a lab, us- adults, and refectory non-Hodgkin lymphoma. ing an inactive CAR T cells are being used through clinical trials virus, to express for other forms of blood cancer as well (Dana the CARs. The lab Farber). is then able to produce hundreds of millions of 11-year-old Esmeralda Pineda, a patient CAR T cells. Afterwards, the T at the Memorial Sloan Kettering Cancer Center cells are then infused back into the in 2015, had pediatric ALL that chemotherapy patient like a blood transfusion. The whole did not seem to work for. This was because herprocess takes a couple of weeks, with chemother- cancer “carried a unique genetic signature thatapy in between while the patient waits for the made her particular disease resistant to tradi-T cells to be modified in the lab. The patient is tional treatments.” Once her “expected cure rate”monitored in the hospital for a period after the dropped from 90% to 30%, as a last resort, herinfusion (Dana Farber 2). doctors tried CAR T cell therapy. After treatment, This “living drug” is absolutely revolution- she showed no signs of cancer whatsoever. Yet,ary, holding promise to cure at least some types the doctors made her have a bone marrow trans-of cancer. Although this new method is restricted plant just to be sure. Esmeralda was able to finishto clinical trials, it could soon become the stan- school, and is apparently still cancer free. Thedard response to cancer, similar to the current immunotherapy saved her life because it caters touse of chemotherapy (Dana Farber 2). CAR T the individual cancer and doesn’t rely on a gen- eral treatment (Memorial Sloan Kettering Cancer Center). Although CAR T cell therapy, and immu- notherapy in general, have a long way to go, it has the potential to be the most effective cure for cancer since it uses the patient’s own cells. And unlike chemotherapy, it doesn’t destroy the body at the same time. Cancer destroys people and families, but that could be over (at least for blood cancers, as of now) with this newfound idea. Biology 21

Irresistible Reactions: The Chemistry of Pizza By Hailey Brown Edited by Liam Smith Whether it’s a thin crust with bubbling maximizing gluten development, which is donecheese on top, a tomato basil delight, or thick through kneading. Though moisture helpscrust covered with meats, there is something glutenin and gliadin combine successfully, thewonderfully delicious about pizza. Although components of the two molecules need to bepizzas can vary in toppings, sauces, and crusts, aligned properly, so that the gluten strandsthey are the result of a complex symphony of are organized in a way that will cause the crustchemical reactions resulting in incomparable to rise: tangled so that air pockets can expandtexture and flavor. but stay trapped in the dough. Kneading the dough improves the organization of the gluten Pizza dough is simple enough to make, strands, and then allowing the dough to restconsisting of four main ingredients: flour, salt, will cause it to rise.yeast, and water. The first step to a deliciouspizza crust is combining flour and water. The After the dough is massaged, the doughratio of these two ingredients can drastically rises through a process of fermentation, whichchange the pizza dough texture. Flour consists can only occur by adding yeast. Yeasts areof four main chemical components: endosperm, eukaryotic, single-celled microorganisms thatbran, germ, and water, but the most important obtain energy by carrying out fermentation - thebeing endosperm and water. The endosperm is breaking down of carbohydrates in the absencethe starchy center of the grain, which contains of oxygen, also known as anaerobic respiration.carbohydrates, protein, and a small amount The by-products of this fermentation ofof oil, and comprises about 83 percent of the dough carbohydrates by yeast include alcoholweight (Cook’s Science). The endosperm also (ethanol) and carbon dioxide (Bake Info). Thecontains almost all of the starch and proteins carbon dioxide creates the air pockets insidesuch as gliadin and glutenin. Glutenin is large the bread, causing the dough to rise. This isand coiled, providing strength and elasticity in the same metabolic process a brewer reliesdough, whereas gliadin is more tightly coiled on in making beer - but in bread-making, theand smaller, providing stretch. In the presence ethanol evaporates out of the bread during theof water, glutenin and gliadin change shape subsequent baking process. Yeasts are finickyand combine to form a loose, disorganized and require a narrow range of temperature tomatrix called gluten. Too much water can successfully carry out fermentation, not too coollead to diluted, weak gluten strands, whereas and too hot. Furthermore, if the fermentationtoo little water leads to a nonexistent gluten occurs too quickly, the yeast will producenetwork. Thus, it is essential to get the ratio of sour-smelling, flammable acids. In order towater to flour just right to achieve the elastic avoid this disaster and control the process,texture of pizza dough. fermentation initiators known as pre-ferments and cool-ferments are used. Pre-fermentsa, The next step to an excellent pizza dough is22 Nobelium Magazine • Spring 2018

which are also called “sponges,” are added at gas, which induces the production of naturalthe beginning of the dough-making process, pigments called lycophenes -- the sameand can be used to start multiple generations compounds that make ripe apples red! So whyof dough (Professional Baker’s Reference). can’t you just squeeze a tomato to get richCool fermentations are formulated such that tomato sauce? Because additional complexthe dough can undergo fermentation in low but delicious compounds are created whentemperature environments, such as rising tomatoes are cooked. However the issueovernight in the fridge. The benefit of this is with tomatoes is many people complain theirthat at lower temperatures, yeast produces stomach, throat, or mouth hurt when theyless carbon dioxide and more alcohols and have eaten too many, and this is because ofdesirable acids, making for a more decadent, the acidity. Tomatoes have a pH of below 4,rich, and flavorful dough. leaving a sour taste on our taste buds. If your tomato sauce is too bitter, some cooks add a bit The next step to a flavorful pizza is the tomato of more chemically basic ingredients such assauce. Tomatoes come in many different milk or cream -- or even a pinch of baking sodaforms and sizes, from cherry tomatoes to vine- (sodium bicarbonate) to reduce the acidityripened, and it is up to the chef to decide which -- but be careful! Too much baking soda andtype of tomato goes best with each pizza. The your sauce can become foamy (and lose flavor)one thing all chefs agree on, however, is that from the carbon dioxide gas released from thistomatoes have to be ripe in order to make chemical reaction.a good sauce, as many of the scrumptiousflavors we appreciate in a good tomato sauce The last step to a flavorful pizza is addingonly form during the ripening process. The the cheese. There are literally hundreds ofwonderful sweet-sour taste of a ripe tomato types of cheese in the world, all differing incomes from the complex combination of sugars levels of fat, moisture, texture, and flavor. Inand organic acids. Ethylene gas is produced by a scientific cooking book titled Cook’s Science:tomatoes during the ripening process, during How to Unlock Flavor in 50 of Our Favoritewhich starches in the sour, green fruits are Ingredients, it is clear that “When it comes toconverted into sweet sugars such as fructose. cheese, more age means more flavor” (Cook’sThe diffusion of ethylene gas explains why one illustrated). Different types of cheese melt inripe tomato can hasten the ripening ofnearby green tomatoes. That different ways. Some melt smoothly,beautiful red color while some do not melt atof a ripe tomato all. Moisture playsis also due to a significantethylene role, but the state of Chemistry 23

the state of a cheese’s proteins affects the Thus, rennet-coagulated cheeses are easier tolikelihood of it melting at all. There are two main melt. Acid-set cheeses, such as cream cheese,stages in the cheese-making process that affect while generally soft, are not as good at melting.the protein structure and, eventually, the cheese This is because the acids, having a lower pH,meltability: coagulation and the process of aging. dissolve the calcium ions that are between the casein proteins and change their electrical charge, Coagulation is the process by which milk which cause the proteins to scrunch up andthickens and turns into cheese and is done in two become clumpy. When acid-coagulated cheesesdifferent ways: with acids such as lemon juice or are placed in ovens, the heat causing the water tovinegar (acetic acid), or with an enzyme known evaporate, leaving the cheese dry and stiff.as rennet. Cheeses made by direct acidificationinclude soft cheeses such as cream cheese, or Once the dough is covered in sauce and isqueso fresco, and paradoxically can be harder to draped with cheese, the pizza is ready for themelt. Rennet is an enzyme derived from plantsor animals, and rennet-made cheeses include oven! When the pizza enters the oven, athose used most commonly on pizza, such special reaction called the Maillard Reactionas mozzarella and parmesan. When rennet occurs. The Maillard Reaction -- alsois added to milk, its enzymes work to tearapart the coils of protein in milk called known as non-enzymatic browning -- iscasein micelles. Once the casein micelles the process by which, at temperaturesare torn apart, they link together to above 140 degrees Celsius, sugars areform cheese curds, complex matricesconsisting of extensive tightly bound able to react with amino acids to createmolecular networks of proteins, flavor compounds that give pizzasurrounded by water and fat. its special and delicious flavor.TheThough this matrix is a solid,it is not very tightly wound, so caramelization of onions is a well-when the matrix is melted, known example of this reaction.it melts in two stages. First, Inside the oven the outer edge ofthe fat globules change the dough will begin to brownfrom solid to liquid whichmakes the cheese more and become crispy, due to waterbendable. Then, as the evaporation. What is amazingtemperature inside is that because of the moisturethe oven continues to from the sauce and cheese,rise, the somewhat-tightly wound casein the dough under the cheeseproteins loosen and sauce is left very softtheir grip on one and moist, adding to pizza’sanother and thecheese becomes complexity and interestinga gelatinous combination of textures.substance. As you crunch into your next delicious bite of pizza -crust, sauce and cheese- take a moment to appreciate the remarkable interplay of complex chemical reactions that have brought about such ascrumptious treat!24 Nobelium Magazine • Spring 2018

EBdyitSeadrbayhJMualinasLoyunreThe Placebo Effect A placebo is “medication” administered like sports. There is no medical evidence that this treat-a drug or medical treatment, but is actually inert, or ment actually has any physical benefits, but manyin other words contains no actual medicine. Often in people (including Olympic swimmer Michael Phelps)clinical trials, the placebo acts as the negative con- claim it helps with their sore muscles. Why might thistrol in order to see the effects of the tested drug. This be? In a 2015 study some patients were given a fakemedical phenomenon is known as the placebo effect; cupping treatment (with holes in the cups to renderthe scientifically proven idea of mind over matter. “It’s them ineffective) and some were given the real treat-not just positive thinking” (Harvard). Sometimes the ment. Both groups experienced the same level of painmere action of taking these pills can trigger the place- relief, showing that the effects may be more psycho-bo effect, even if the subjects are aware they are taking logical than physical. Just because the patients be-placebos. lieved they had been given the treatment, they felt the expected results. Even if someone is just taking a sugar pill, ithas been shown that pain relief can follow. This is This discovery has the potential to changebecause simply the act of taking a pill can trigger the the future of medicine, and more specifically, clini-placebo effect. When someone takes a pill, they have cal research. The protocols and data analysis may behigh expectations for the results, therefore dopamine, explained through the idea of placebo. Also, placebosa type of endorphin, is released in their brain. These may be used in the future as ways to minimize theendorphins attach to opioid receptors and act as a intake of medicine. If placebos can possibly have thepainkiller similar to morphine. It is believed that if same effect as advil (ibuprofen) for example, a bottlethe patient is aware they are taking a placebo, it will can be made with half placebos and half advil. Thisnot have the same effect. If the patient thinks they are way, the patient is unaware if they are receiving actualtaking a painkiller such as ibuprofen, but takes a sugar medicine or not, therefore minimizing their unneces-pill, they may have similar effects. sary pharmaceutical intake. This could be helpful as taking too much advil, or any pain medication for that An example you might have encountered is the matter, can be very dangerous to one’s health.alternative treatment, cupping. This is a very populartreatment for sore muscles among athletes of various Psychology 25

Meta-Analysis of Relative Brain Activity Levels in Bipolar Disorder» Introduction by keren luo edited by michaela sylvia Bipolar disorder, also known as manic depressive illness, is associated with dysfunctions in the prefrontal lobeand limbic system that cause abnormal changes in mood, energy, activity levels, and the ability to perform dailytasks. There are three primary types of bipolar disorder, including Bipolar I disorder, Bipolar II disorder, andCyclothymic Disorder, as well as other unspecified variations (Bipolar Disorder). All of them involve changesin mood, energy and activity levels. Bipolar patients generally suffer from two extreme psychological states:manic or hypomanic states and depressive states. Manic state usually refers to when patient is in a state ofheightened overall activation, in other words, the patient has abnormally high energy during the Manic Episode.On the other hand, a depressive episode is a period characterized by depressed mood. The length of each periodcan vary. Bipolar disorder usually first presents itself between the ages of 15 and 25. According to the NationalInstitute of Mental Health, bipolar disorder plagues 51 million people around the world; 1.1% of people abovethe age of 18 (Bipolar Disorder). Despite its wide prevalence, currently no cure exists for bipolar disorder. Thismeta analysis compares the fMRI whole brain studies of bipolar patient to those of healthy controls. Out ofthe fifty-four papers matching the purpose of the criterion, seven are chosen which utilized emotion-relatedtasks. The data is then classified into two concerning categories: hyperactivity and hypoactivity. Hypoactivity isan inhibition of behavioral or locomotor activity, while hyperactivity is the condition of being extremely active(Hypoactivity). This data was then run through GingerAle and displayed with Mango (both are tools used toextract data to generate fMRI scans). The purpose of this meta analysis is to investigate the main brain regionsthat a bipolar disorder patient is affected by which will eventually leads to the potential cure for bipolar disorder.» Table 1. Whole Brain Analyses of Bipolar Patients26 Nobelium Magazine • Spring 2018

Table 1 is the general information regarding each whole brain study of bipolar patients versus controls fora variety of emotion related task. The data is extracted from the seven chosen papers that utilized emotion-related tasks. The first column is the name of the article that is chosen, the second column shows the numberof participants; BP stands for bipolar disorder patient, while HC is healthy control. Most the of the papers havesame number of bipolar disorder patients and healthy controls so that it clearly establishes the contrasts betweenthe two. The third column provides the mean age of the two groups. All of the data is in the fMRI form and thenumber of regions that were investigated vary from 4 to 56. » Table 2. Brain Regions with Significant Activation Table 2 is a presentation of the brain structures that showed significant deviation from normal activityeither with hyperactivation (condition of being abnormally or extremely active) or hypoactivation (inhibitionof behavioral or locomotor activity) relative to healthy controls. Talairach coordinates, also known as Talairachspace, is a 3-dimensional coordinate system of human brain (Talairach Coordinate Space). It is usually used tomap out the structure of and location of brain regions independent from the overall shape of the brain. Here, thetalairach coordinate represent the weighted center of each cluster. Clusters were thresholded, the lowest levelof a stimulus that an organism could detect, with a p-value (the level of marginal significance) of 6.496E-7 forhyperactivity and 1.048E-6 for hypoactivity. With such low p-values for both hyperactivity and hypoactivity, theyindicate that the particular clusters likely show actual increased or decreased brain activation. » Figure 1. Brain Regions with Significance in Activation Figure 1 shows the brain regions of significant contrast between bipolar patients and healthy controls. According the data from table 2, clusters were thresholded with a p-value of 6.496E-7 for hyperactivity and 1.048E-6 for hypoactivity. In figure 1, red clusters represent hyperactivity with bipolar disorder patients greater than healthy controls, and blue clusters represent hypoactivity with bipolar disorder patients less than healthy controls. Top image of each brain region represents a medial or horizontal slice, bottom left represents coronal slice, and bottom right represents a sagittal slice. Psychology 27

» discussion According to Table 1, Table 2 and Figure 1, they show hypoactivity in the parahippocampal gyrus, culmen, and right inferior frontal gyrus. They also present hyperactivity in the parahippocampal gyrus. This contrast may be related to its complex emotional processing. In fact, a recent study explains why bipolar disorder patients are lithium responsive (LiR). The researchers used human induced pluripotent stem cells (hiPS) - regular cells that are taken from the parahippocampal region of the bipolar disorder patients and then programmed to behave like stem cells (Lithium Medication). Researchers found that CRMP2 protein was inactive in the bipolar disorder patient’s hiPS cells, however when the cells encountered Lithium, CRMP-2 protein became active. The CRMP2 protein is a member of the collapsin response mediator protein family that consists of five intracellular phosphoroteins (CRMP-1, CRMP-2, CRMP-3, CRMP-4, and CRMP-5) of similar size and highly identical amino acid sequence (Lithium Medication). They are predominantly expressive in the nervous system, and modulation of CRMP-2 expression becomes a new area of research that many scientists focus on. Essentially, by increasing or decreasing the expression of CRMP-2, scientists can reduce the effects of neurological disorder such as bipolar disorder. This method opened a new pathway, a molecular medication. If bipolar disorder patients take lithium supplements, they can be eventually cured. With further scientific research and investigation of the relationship between bipolar disorder and the complex emotional processing circuits of the brain, neuroscientists and neurologists alike can better work towards a clearer understanding of the disorder and a potential cure.2288 Nobelium Magazine • Spring 2018

By Adam QuFlow Edited by Michaela Sylvia What is happiness? Common definitions of the state characterize it as feelings of well-being stemmingfrom a meaningful, satisfactory life (Psychology Today). While the definition may seem simple, the difficultpart is obtaining such happiness and meaning in life. Fortunately, finding the intrinsic value in activities helpsto make life meaningful or simply provides a reprieve from one’s problems. Immersing oneself in such activi-ties can lead to a temporary escape from reality and also promote happiness. Natural escape from reality andpotential happiness can be achieved by being completely engaged in what one finds meaningful and entering astate of mind called flow, a concept first introduced by Hungarian psychologist Mihaly Csikszentmihalyi. Growing up during World War II, Mihaly Csikszentmihalyi, or MC for short, became interested in “whatcontributed to a life worth living” after witnessing the adults in his life live contented, satisfied lives despitehaving “their job, their home, their security” taken away by the war (TED2004). MC looked to facets of lifethat may make it worth living, such as religion, art, and money. MC’s search led him to “creative people,” likeartists, who are “essentially spending their lives” doing things without the expectation of “fame or fortune,” yetstill make their lives meaningful (TED2004). In an interview with an American composer, the composer de-scribed a “flow” he felt when composing music: “You are in an ecstatic state to such a point that you feel as though you almost don’t exist. I have experienced this time and again. My hand seems devoid of myself, and I have nothing to do with what is happening. I just sit there watching it in a state of awe and wonderment. And [the music] just flows out of itself” (Csikszentmihalyi 44). In MC’s analysis of the composer’s words, he attributes the composer’s feeling of nonexistence to thenervous system’s limited capacity for information intake; when someone is absorbed in a “completely engag-ing process”, he or she does not have enough “attention left over to monitor” anything unrelated to the currentactivity. MC concludes that “existence is temporarily suspended” when one isengaged in such an activity (TED2004). Simply focusing on something does not guarantee flow. Dr. Joachim I.Kreuger of Psychology Today summarizes MC’s findings surrounding flow asoccurring when a person “[1] is engaged in a doable task, [2] is able to focus, [3]has a clear goal, [4] receives immediate feedback, [5] moves without worrying,[6] has a sense of control, [7] has suspended the sense of self, and [8] has tempo-rarily lost a sense of time.” Considering all of these requirements, true instancesof flow are rare. However, MC’s research has led to the creation of a graph com-paring the challenge level of certain activities and how comfortable subjects felthandling them (skill level), which can be used to predict when someone will be inflow. This prediction is made by determining the average level (the point where the lines meet) of challengeand skill for someone. Once this “set point” is located, flow can be predicted by finding the points at which chal-lenge and skill levels are higher than average — “Only when the challenge level is high and you have the skillsto match, can a state of flow be achieved” (Nerdwriter1). If a person’s set point for some activity is not in the“Flow” section of the graph, the development of skills and increase of challenge can lead to flow for that activi-ty. For example, a person finding their set point in the “Arousal” or “Control” regions can enter flow by improv-ing or pushing themselves out of their comfort zone for that activity. While flow certainly provides temporary escapes from reality, it has been debated whether or notentering into flow can lead to the happiness people seek. “Experts,” such as the “creative people” interviewedby MC who often find themselves in flow, “may be respected and perhaps wealthy,” but not necessarily happy(Krueger). The loss of self-consciousness associated with flow makes it hard to determine if a person in flowis truly happy during that time. Whether it be only a reprieve from reality, or a means by which one achieveshappiness, by doing something meaningful to oneself, experiencing flow definitely makes life worth living. Psychology 2299

California Earthquake By Sidnie Kulik Edited by Lev Sandler The world is ending, or at least it seems like it is. There have been countless number of natural di- sasters over the past year. There were hurricanes, monsoons, mudslides, wildfires and earthquakes, killing and injuring thousands of people. Sadly, these calamities are not over with, scientists presume that there is still more to come. Earthquakes in 2017: It is predicted that California is up next for a deadly catastrophe. Scientists believe that the state will have an earthquake with a magnitude of 7.0 or higher by 2045. Though this may seem a while away, it will be within most of our lifetimes. The worst tremors of this year have occured at the Iraq-Iran bor- der and in central Mexico. The quakes had magnitudes of 7.3 and 7.1. There were a total of 814 deaths and over 7,000 injuries between the two, showing the horrific impact of earthquakes. How do earthquakes happen? Earthquakes occur on the outer layer, the crust, of the Earth. The crust is made up of tectonic plates, which line up together like puzzle pieces. These plates are moved by hot magma contained in the mantle, the layer below the crust.The mantle moves in a process called convection currents, or con- vection cells.The molten rock near the Earth’s core heats up and rises to the crust. Once reaching the crust, the lava cools back down and returns to the core. The activity from the mantle near the crust moves the plates in various directions. Earthquakes usually occur when two plates run into or slide past each other. Quakes can also develop near the edges of tectonic plates, in areas called faults.30 Nobelium Magazine • Spring 2018

Faults are cracks in the crust where a plate, or two plates, are moving in different directions. There are three typesof faults: normal, reverse and strike-slip. Normal faults occur when one plate is moving up and the other down,this usually happens as tectonic plates move away from each other. Reverse faults occur when one plate slidesunderneath or pushes up over another plate. Strike-slip faults happen when two plates are sliding past each oth-er; the San Andreas fault, located north of Las Angeles, is an example of this. Why California?California lies on the North American and Pacific tectonic plates, and contains the San Andreas faultline. Plate tectonics are constantly in motion, everyday they add more stress on the crust’s breaks.Eventually the accumulation of these stresses will lead to a brittle fracture in the crust, causing anearthquake. The San Andreas fault has not slipped since 1857 and the Hayward Fault, another fault inthe Bay Area, has not generated a major earthquake since 1868. This long stretch of time means that aquake is bound to materialize in California soon. Predicting Earthquakes:Though it is not a perfect science, we can hypothesize when and where an earthquake will occur. Onecan study the stresses along mapped fault lines or the history of previous earthquakes to anticipate anupcoming shock. Fortunately, there has been development of earthquake warning systems, which cannow find ground motion and send out an alert before the seismic shaking arrives, but they are not fullproof. California’s Means of Preparation:California is fully aware of the possibility for an earthquake, and has dealt with many in the past. Thelast sizeable quake had a magnitude of 7.8 and occurred in 1906. There are drills held annually inpreparation for a large earthquake. Home and car disaster kits have also been given to increase the se-curity of Californians. Though there are many safety precautions put into place, no one can ever trulybe prepared for the effects of an earthquake. Physics 31

Physics ofPhotography ByWillWhalen Edited By Liam Smith Visualizing images to transfer ideas, aspects of the photo in the lens, such as thefeelings and memories has existed as long as aperture (hole that allows either more orhumanity has. Starting from paintings on the less light into camera), as well as how fastwalls of caves all the way to the camera you the camera’s shutter will close to render ancarry in your pocket every day, being able image. The faster the shutter speed, the lessto capture our own experiences has become motion will be present in your picture; this isincreasingly streamlined as our understand- how artists can make subjects-such as a bas-ing of technology and physics has grown. By ketball player flying through the air-just asbeing able to manipulate light and environ- clean and crisp as if there was no movementment, photographers have learned how to at all. Once the shutter button is pressed,change any number of aspects of an image to the first mirror in the series drops down flat,tell their own story and communicate with changing the path of the light from the view-the people viewing their photos. finder to the back of the camera, where film in traditional cameras, or an image sensor Camera technology has evolved great- in digital cameras, is located. On the digitally throughout history. Until the end of the sensor, there are tens of millions of various1980s, photography was taken on rolls of colored segments called ‘detectors’ that emitlight-sensitive film, then chemically devel- a small electrical current if the color of lightoped in order to render the final image. Al- through the lens matches the specific colorthough the methods of getting the end prod- of that segment. Once all the light has beenuct have changed, the basics of your typical turned into electrical signals, the camera iscamera have stayed the same for hundreds then able to piece together what colors appearof years. Cameras function by reflecting and where, and make an image.refracting light until the moment the photog-rapher chooses to pull the shutter, allowingthat light to be captured. Here’s how it works: Once the camera is pointed at a sub-ject, some of the light that bounces off thatobject refracts into the lens of the camera andthrough a series of angled mirrors to be ableto put a preview of the image through a win-dow called a “viewfinder,” usually located atthe top back of the camera. The photographer can then change32 Nobelium Magazine • Spring 2018

If pingthe the reac-camera uses tion in the colorfilm, the light will go di- layers once the correctrectly onto the film and mark the shade is reached.area that it was ‘exposed’ as a different de-gree of gray depending on how much light hit As cameras become more ubiquitousthat area of film. Due to these different wave- in our everyday lives, it’s easy to forget alllengths of light, distinct images and details the physics happening each time you take acan be seen because of the precise refracting picture. Engineers are currently working onof the light through the lens to give the clear- being able to pack more detectors in a singleest photo. In color film, three light sensitive sensor for more detailed photos, as well aslayers, the three primary colors, supersede bioengineering projects to be able to capturethe normally black-and-white film in order to what your eye sees as a photograph. Storytell-map the amount of that specific wavelength ing has always been one of mankind’s greatestof light passed through the film at the time of skills, and with cameras progressing as fastpushing the shutter. After the photographer as they have, we will be able to share our ownis happy with their photo, the film is wound journeys with the push of a button.back into its roll to protect from light duringits travel from camera to development. To develop film, a “fixer” chemical isfirst applied to the camera’s exposed film inorder to prepare the images then be exposedto another chemical called “developer.” Inthis second step, the developer, which is heav-ily oxidized and designed to react with thefilm, enables each layer of the film to be dyedcommensurately to the correct hue of what-ever object the picture captures. If the subjectis not one of the three primary colors, the dyein each layer will stain the film accordingly sothe correct color is shown once light shinesthrough the film. A neutralizing agent knownas “stop bath” removes the developer, stop- Physics 33

ArtificialIntelligencein MedicineBy Vivian TaoEdited By Liam Smith Artificial intelligence is everywhere: it’s used Not only is AI practical in the medical field, in search engines, to give recommendations, and the use of AI in medicine is also gaining to organize information. Now it’s entering into the interest from investors. world of medicine to potentially save lives. Artificial intelligence, or AI, is currently being used to diag- The market for AI in the medical field is pro- nose breast cancer and its accuracy is constantly jected to grow 40% each year and is expected to be improving. worth 6.6 billion dollars by 2021 (Frost & Sullivan). Companies that specialize in the AI diagnosis of dif- AI comes into play ferent diseases are receiving investments from large companies like IBM Watson, Alphabet, and Phillips where humans fail. and also pharmaceutical companies and startups. Al- though AI is very expensive to develop and maintain, The AI is fed data from a database with companies like PathAI are receiving investments information about millions of patients, and the AI from many large companies. can then use that information to make personalized treatment plans. AI is currently being trained at MIT However, AI does have some downsides. Sci- and CalTech to identify cancerous cells more accu- entists still have concerns about the cost and avail- rately than humans can. The AI predicts if lesions ability of data. Hopefully in the future, scientists can (abnormal tissues) found in mammograms require overcome these troubles and will partner with AI to surgery or not. In an event last April that had the find breast cancer more efficiently in the future. PathAI (an AI that can diagnose diseases) compet- ing with an expert pathologist, the pathologist had a 3.5% error rate whereas the AI had a 7.5% error rate (CNBC). However, the system kept on improving and in a later competition in November, PathAI beat out the expert pathologist. One edge that AI has over humans is that AI is able to learn indefinitely where- as humans cannot. Humans and AI working together are a powerful force. When humans work with AI, the error rate decreased by 85%, yielding a 0.525% error rate which is a significant decrease from when the AI or the human worked separately (CNBC). Re- search shows that the AI is better at detecting tumors whereas humans are better at seeing whether or not the tumor is malignant.34 Nobelium Magazine • Spring 2018

Could the Invisibility Cloak Become a Reality?BY Hannah Epstein EDited by Lev sandlerThe invisibility cloak from (Israel 21c). The object is rendered invisible.Harry Potter is beginning This is only on the nano-level; so far, onlyto become a reality. Scien- an extremely small cylindrical item has beentists are working to create successfully “cloaked.” Scientists have showncomplete invisibility with “that it is possible to bend the light around anthe first ever invisibility object located on the cloak on an optical chip”cloak. (Dr. Alina Karabchevsky). The next major challenge is creating a prototype to render Achieving invisibil- much larger objects invisible.ity is not a revolutionaryconcept; over the years, This is not a completely new idea, butscientists have continu- it is a significant breakthrough. The cloakingously tried to make objects chip is an extension of technology in ra-invisible. Previous meth- dar-absorbing paints that are used for stealthods include modulating aircrafts, optical camouflage, and electromag-light waves near an object, netic wave scattering (Photonics Online).creating objects that emittheir own light to reduce reflections, or try- With this new technology, much largering to create a completely transparent object. things will be able to be rendered invisible inSo far, researchers have been successful in the near future. Soon enough, the invisibilitymanipulating light around an object. Since cloak will no longer be a fantasy.we see objects by light reflecting off of them,manipulating the light waves seems like the Computer Science 35most practical way to create invisibility. How-ever, scientists recently produced a cloakingchip which does not react with visible light,thus not producing any reflection and be-coming invisible. The idea behind this chip,theorized by researchers from the Ben-Guri-on University of the Negev, led by Dr. AlinaKarabchevsky, is that when the cloaking chipis engaged, any light that contacts the objectdoes not produce a visible reaction. The op-erational cloaking chip deflects and scattersthe light reflected off of the object, prevent-ing light from “interact[ing] with the object”

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“The important thing is not to stop questioning. Curiosity has its own reason for existence.” Albert Einstein38 Nobelium Magazine • Spring 2018