Journal of Organic Biochemistry at St. Andrew's, Volume 3

VOLUME 3, JULY 2022

Journal of Organic Biochemistry at St. Andrew’s Review articles researched and written by Upper School students.

A Note From the Editor

T

he annual Journal of Organic Biochemistry at St. Andrew’s showcases the diligent work and detailed learning of juniors and seniors in the Fundamentals of Organic Biochemistry course. Throughout the year, students read scientific journal articles related

to core course concepts, such as how combining our knowledge of carbohydrate metabolism with new studies in xylose fermentation techniques could improve biofuel yields. Students then present individual articles they found and read, showing an understanding of the key methodologies and results. For their final project, they review a variety of journal articles and academic sources to present a review-style article on a chemical or biochemical topic. This year’s submissions show the breadth of impacts chemistry has on our society, from the energy industry potential of hydrogen fuels, to the impact of air and herbicide pollution, to medical research, to the production of color and art preservation. Above all, we learn how science grows and progresses, with each new researcher adding their own contributions and ideas. May our young scientists continue to explore and make their own discoveries as they grow their science careers.

William Ferriby US Science Faculty Science Department Head

2

Table of Contents The Developmental and Reproductive Risks Associated with Glyphosate Exposure

by Aaron Lobsenz

Page 4

The Effects of Air Pollution on Cardiovascular Health

by Alex Behram

Page 7

Application and Practicality of Structural Coloration

by Brian Alewine

Page 10

Liver and Lung Disease as a Result of Alpha-1 Antitrypsin Deficiency

by Dylan Luchsinger

Page 13

Drug-Resistant Epilepsy: Potential Causes and Treatments

by Rose Ludecke

Page 16

Hydrogen Fuel as a Clean Alternative to Gasoline in Transportation

by Will Clark

Page 19

The Effects of Moisture on Cadmium Sulfide Based Oil-Paint Degradation

by Katie Skinner

Page 22

The Causal Relationship Between Lack of Sleep and Diabetes

by Zorina Sun

Page 25

The Effects of Calcium Supplementation on the Human Body

by Charlie Ryan

Page 27

3

The Developmental and Reproductive Risks Associated with Glyphosate Exposure

Aaron Lobsenz Abstract: Glyphosate is the primary active ingredient in many glyphosate-based herbicides (GBHs) including RoundUp, Touchdown, Glifloglex, and Glyphogan. When GBHs were first introduced to agriculture in the 1970s, they were regarded as harmless to humans. However, recent studies suggest that human exposure to GBHs may be associated with reproductive inhibition. This paper describes glyphosate and GBHs and the risks that they potentially pose to human reproduction and development.

Introduction: Plants use the shikitame pathway to synthesize the amino acids tryptophan, phenylalanine, and tyrosine (see Figure 1)1.

Glyphosate’s ability to actively inhibit 3phosphoshikimate 1-carboxyvinyltransferase (EPSP synthase) prevents this mechanism.

Figure 1: This diagram depicts the mechanism of the shikimate pathway, which glyphosate and GBHs act upon to inhibit the synthesis of three essential amino acids.

4

Researchers initially believed that GBHs would pose no significant health risks to humans, who do not use this pathway.

Because of the increasing usage of GBH resistant crops – to remove unwanted weeds and plants while protecting crops – GBHs’ utilization has significantly increased.

Between 1974 and 2014, overall glyphosate use in the United States (US) rose approximately 300-fold in agriculture.

Globally, the use of glyphosate increased from 12 to 20 million liters from 2008 to 20122.

With its increasing presence in the environment and food supplies, some studies that examined GBHs’ impact on human and animal health are finding concerning results.

Varying regulatory bodies have made different determinations regarding its safety.

In 2017, the International Agency for Research on Cancer classified glyphosate as “probably carcinogenic” to humans.

However, currently, the European Food Safety Authority and the US Environmental Protection Agency both consider glyphosate to pose no significant risks2.

Glyphosate Persistence in Humans: Glyphosate is frequently found within human urine, blood, and maternal milk, which primarily accumulates in the kidneys, liver, colon, and small intestine. Glyphosate in urine is detected at a rate of 0.16-7.6 µg/L in the general population, 0.26-73.5 µg/L in exposed workers, and up to 292 µg/L in workers in China involved in glyphosate production.

One of the few studies that directly tested glyphosate on humans discovered that it could remain in the body for at least 106 hours after initial consumption. The same study also found that, in comparison to prior animal studies, less glyphosate is removed from urine in humans than in animals, raising possible concerns over bodily absorption rate and lingering presence of glyphosate in humans3.

Effects on Cell Viability and Estrogen Synthesis: A 2005 study examined how cell viability changed depending on the amount of glyphosate concentration exposure at different durations of time3. Researchers used an MTT assay to test the effects of glyphosate and Roundup on JEG3 placental cells by incubating the cells with 250 µL MTT and varying concentrations of glyphosate, then using a spectrophotometer to measure cell viability. The study measured aromatase activity – which is involved in estrogen synthesis – by measuring the conversion of androstenedione to estrone. The study found that the toxicity of glyphosate and Roundup on JEG3 cells increased when exposed to higher glyphosate and Roundup concentrations for longer durations, particularly 24 to 48 hours. It also found a decrease in cell viability among cells treated with low glyphosate concentrations -- less than 10 times of what is typically used in agriculture (a 1-2% concentration). It further concluded that cells exposed to Roundup for only an hour had increased in aromatase activity, but the same cells had decreased in aromatase activity when exposed for 18 hours (see Figure 2).

These results make the researchers consider if Roundup should be labeled an endocrine disruptor, particularly when cells are exposed to glyphosate at the higher concentrations typically used in agriculture4.

Possible Effects on Male Reproductive Abilities: Multiple studies suggested that glyphosate may alter testicular morphology and testosterone levels.

A 2010 study5 divided 68 weaned male Wistar rats into four groups, where each group received a different concentration of diluted glyphosate-Roundup Transorb (GRT) from the twenty-third-day post-natal (PND23) until PND53. The researchers monitored their weights and balanopreputial separation -- which is used as an index to determine the onset of male puberty. At PND53, researchers performed a cardiac puncture of the rats to collect serum, which was later used in a radioimmunoassay analysis to determine hormone concentrations.

-There was little difference in overall body weight for rats when exposed to different GRT concentrations. However, the rats’ testicular weights were significantly greater in those exposed to higher concentrations of GRT. In addition, exposure to higher concentrations of GRT correlated with a delay in preputial separation and lower testosterone levels, but no change in estradiol presence (see Figure 3). The researchers found this particularly interesting as testosterone is a precursor of estradiol. This finding suggests that glyphosate consumption may pose a potential risk to male testosterone levels5.

Figure 2 The effects of Roundup and glyphosate on JEG3 aromatase activity at time lengths of 1 and 18 hours at varying concentrations in a serum-free medium.

5

Figure 3: Testosterone levels in mice treated with varying amounts of Roundup (RU) from PND 23 to PND53. 5 *P<0.005, ***P<0.001

Multigenerational Developmental Concerns from GBH Exposure: Multiple toxicology studies suggest the potential for morphological, functional, and biochemical alterations associated with increased GBH exposure. One research group found that mice (F1 generation) exposed prenatally to GBHs – where their mothers received a solution of 0.5% of the active ingredient glyphosate in their drinking water – had lower bodyweights at weaning.

Then, these F2 offspring, whose parents and F1 mice were both exposed perinatally to GBH formulation in doses of 200 mg/kg/bodyweight/day, often developed 1 Peillex, Cindy, and Martin Pellletier. "The Impact and

Toxicity of Glyphosate and Glyphosate-based Herbicides on Health and Immunity." Journal of Immunotoxicology, vol.

17, no. 1, 2020, pp. 163-74, www.tandfonline.com/doi/full/10.1080/1547691X.2020.1 804492. Accessed 25 Apr. 2022.

2 Richmond, Martha E. "Glyphosate: A Review of Its Global Use, Environmental Impact, and Potential Health Effects on Humans and Other Species." Journal of Environmental Studies and Sciences, 28 Sept. 2018, https://www.sciencedirect.com/science/. article/pii/S2667010021001281. Accessed 27 Apr. 2022.

3 Richard, S., Moslemi, S., Sipahutar, H., Benachour, N., & Seralini, G.-E. (2005). Differential effects of glyphosate and roundup on human placental cells and aromatase.

Environmental Health Perspectives, 113(6), 716–720. https://doi.org/10.1289/ehp.7728 Faniband, Moosa, et al. "Human Experimental Exposure to Glyphosate and Biomonitoring of Young Swedish Adults." International Journal of Hygiene and Environmental Health, Jan. 2021,

4

6

bodily anomalies including conjoined fetuses and maldeveloped limbs.

There are also concerns over glyphosate’s role in human neurodegenerative disorders.

One population-based case-control study found an increase in the likelihood of developing autism spectrum disorder in people prenatally exposed to glyphosate.6 Other studies performed on rats found a decrease in locomotor activity and anxiety, exacerbated emotionality, and impairment in recognition memory in prenatally exposed offspring. The authors suggest that this may occur because GBHs can induce gene deregulation, which causes changes in the concentrations of stress-related metabolites, including lysophosphatidylcholine and phosphatidylcholine, which are commonly associated with neurodegenerative diseases7.

Conclusion: There are concerns over the human health risks resulting from glyphosate exposure. As GBH use increases, further research is needed to better understand the multiple health effects associated with glyphosate exposure. Epidemiological studies are particularly needed to gain a more comprehensive understanding of the risks that glyphosate and GBHs pose to humans. file:///Users/a22lobse/Downloads/Humanexperimentale xposuretoglyphosateandbiomonitoringofyoungSwedishadul ts.pdf. Accessed 28 Apr. 2022.

5 Romano, R. M., et al. "Prepubertal Exposure to Commercial Formulation of the Herbicide Glyphosate Alters Testosterone Levels and Testicular Morphology."

Reproductive Toxicology, no. 84, 12 Dec. 2009, pp. 309-17, hhra.org/wp-content/uploads/Romano-Prepubertalexposure-to-commercial-form.pdf. Accessed 30 Apr. 2022.

6 von Ehrenstein, O. S., Ling, C., Cui, X., Cockburn, M., Park, A. S., Yu, F., Wu, J., & Ritz, B. (2019). Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: Population based case-control study.

BMJ, l962. https://doi.org/10.1136/bmj.l962 7 Milesi, Maria Mercedes, et al. "Glyphosate Herbicides: Reproductive Outcomes and Multigenerational Effects."

Frontiers in Endocrinology, vol. 12, 7 July 2021, pp. 1-22, www.frontiersin.org/articles/10.3389/fendo.2021.672532/ full. Accessed 30 Apr. 2022.

The Effects of Air Pollution on Cardiovascular Health Alex Behram

Abstract: Research indicates that that air pollution can have adverse effects on cardiovascular health. This paper evaluates the different types of air pollutants: gaseous pollutants, particulate matter, and metals, their sources, and the potential health hazards they pose to our cardiovascular health.

Introduction: Air pollution comes from a variety of different sources, including a mix of natural and human-generated emissions.

Most of the air pollution we face comes from either vehicular sources, such as cars, planes, and trains, or stationary sources, such as power plants and other industrial facilities.

Other sources of pollution, such as those created by agricultural work or those created by natural events like wildfires, are much less significant and do not create ongoing air pollution problems.1 Air Pollution is made up of various primary pollutants, such as nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO), as well as secondary pollutants such as ozone (O3). Air pollution also contains volatile and semivolatile organic aerosol compounds such as benzene, toluene, xylene, 1,3-butadiene, and polycyclic aromatic hydrocarbons.iii Particulate matter (PM) in the air is categorized into 3 categories: coarse particles (aerodynamic-mass median diameter, <10 μm [PM10]), fine particles (<2.5 μm [PM2.5]), and ultrafine particles (<0.1 μm [PM0.1]).iii Additionally, toxic metals such as lead, mercury, arsenic, and cadmium are also emitted into the air in industrial settings.iii

CVD is the leading cause of death globally, accounting for upwards of 30% of all global deaths each year.2 Recent studies have suggested that gaseous pollutants, PM, and metals are all dangerous parts of air pollution which can have detrimental health risks, most notably an increased risk for Cardiovascular Disease (CVD).3 A study done by the Global Burden of Disease found that pollution was responsible for 9 million deaths in 2019, with 61.9% of those deaths caused by CVD. The two primary types of CVD associated with pollution are ischemic heart disease, which contributed to 31.7% of the CVD deaths related to pollution in 2019, and stroke, which contributed to 27.7% of the deaths related to pollution in 2019.iii Although studies have verified the effects of these compounds on increasing the risk of CVD, more research must be done to understand the mechanisms by which these compounds cause an increased risk of CVD. Gaseous Pollutants: Gaseous pollutants commonly come from mobile and industrial sources. Primary gaseous pollutants, such as NOx, SO2, and CO are toxic on their own; however, they are also used in the formation of O3. The primary gaseous pollutants undergo a photochemical reaction with sunlight, volatile organic compounds, and other gaseous precursors to form ozone (See Figure 1).4

Figure 1: This graphic depicts the photochemical reaction in the atmosphere with primary gaseous pollutants and volatile organic compounds to form ozone.5

7

These primary gaseous pollutants, as well as ozone, have been linked to cardiovascular toxicity.vi Analyses have found a strong relationship between short-term exposure to ozone and acute myocardial infarction (MI, known colloquially as a heart attack).vi Individual gaseous pollutants affect cardiovascular tissues differently. Exposure to ozone impairs pulmonary gas exchange and leads to increasing myocardial (heart) work, which leads to an increased risk of MI. Conversely, SO2 exposure reduces cardiac vagal control, which increases susceptibility to ventricular arrhythmias.vi Although studies have established the effects of exposure to these gaseous pollutants, it remains unclear what mechanisms cause the exposure to these pollutants to be so detrimental to cardiovascular health.6 Particulate Matter: PM varies in its chemical composition depending on its source and location. PM is most concerning in urban and industrial area. The main source of PM in these places is combustion, whether it be from mobile vehicles or industrial facilities. Combustion-derived PM contains elemental and organic carbon, as well as mineral dusts, sea salt, ammonium, nitrates, and sulfates. Moreover, much of the PM formed in these industrial and urban areas come from vehicular exhaust, and much of the PM from these sources, especially those from diesel vehicles, are PM0.1, the smallest form thereof. These particles’ chemical composition, high surface area to mass ratio, and ability to penetrate deeply into the body suggest that these particles gave greater toxicity when compared to other sizes and sources of PM.7 A study done by Peters et al in the greater Boston area found a positive correlation between an exposure to an elevated concentration of PM2.5 and acute MI onset, highlighting its toxic effect to cardiovascular health. They discovered that an hourly 8

change of 25 μg/m3 in PM2.5 concentration led to an increase in the odds ratio of MI just hours after exposure to it (See Figure 2).8

Figure 2: This graph shows the change in odds of experiencing acute MI over the course of hours after exposure to an elevated concentration of PM2.5. It depicts a positive association between exposure to an increased concentration of PM2.5 and MI risk.vii

Although a positive correlation between increased PM exposure and CVD risk has been proven, it remains unclear what mechanism causes PM exposure to lead to CVD risk. A study done by O’Toole et al found that exposure to elevated levels of PM2.5 depletes circulating endothelial progenitor cells (EPCs) while increasing the platelet activation and plasma levels of highdensity lipoproteins.ix These changes in the circulatory system are linked to an increased risk of CVD, specifically risks to vascular dysfunction and endothelial injury, which are strongly linked to an effect of elevated PM exposure. However, they discovered that the decrease in EPC levels can be reversed, with the associated vascular injuries thus also reversible. Despite this, they concluded that the depletion of EPCs is likely correlated with other changes in lipids and protein levels in the cardiovascular system, which leads to vascular injury induced by PM. More research must be done to understand the mechanisms behind elevated PM exposure and an increase in CVD risk.9

Metals: Heavy metals such as cadmium, lead, and mercury are air pollutants commonly emitted as a result of industrial activity. They eventually make their way into soil and bodies of water, where they accumulate and make their way into the food-chain.10 Exposure to these metals, either in the air or through the food chain (as a result of air pollution), can cause severe risk of CVD. Cadmium is typically found in contaminated soils and tobacco smoke.

Experimental evidence has liked cadmium exposure to increased risk of artery disease, peripheral arterial disease, stroke, and other CVDs, even at very low exposures.iii Lead air pollution primarily comes from industrial sources such as smelters and waste incinerators, as well as the combustion of leaded gasoline and aviation fuel.11 Exposure to lead has been widely known to have adverse health effects. It leads to an increased risk of hypertension, and studies on animals have shown that lead exposure leads to increased blood pressure, thus increasing risk of CVD.iii Mercury is another toxic metal air pollutant, which is vaporized into the air

during processes such as the combustion of coal. It eventually precipitates into aqueous bodies, where it is converted into the highly toxic methylmercury. This methylmercury makes its way through the food chain, and humans eventually consume it. Recent data suggests that exposure increases the risks of death from CVD and MI. However, CVD is not the only effect of exposure to these toxic metals, as exposure can also cause cancer, neurobehavioral disorders, and renal disease.iii

Where Does Air Pollution Come From? (n.d.). Retrieved from https://www.nps.gov/subjects/air/sources.htm 2 Cardiovascular diseases (CVDs). (n.d.). Retrieved from https://www.who.int/news-room/factsheets/detail/cardiovascular-diseases-(cvds) 3 Rajagopalan, Sanjay, and Philip J. Landrigan. “Pollution and the Heart.” New England Journal of Medicine, edited

by Dan L. Longo , vol. 385, no. 20, Massachusetts Medical Society, 11 Nov. 2021, pp. 1881–1892. Crossref, doi:10.1056/nejmra2030281.

4 Bourdrel, T., Bind, M.-A., Béjot, Y., Morel, O., & Argacha, J.-F. (2017). Cardiovascular effects of air pollution. In Archives of Cardiovascular Diseases (Vol. 110, Issue 11, pp. 634–642). Elsevier BV. https://doi.org/10.1016/j.acvd.2017.05.003 5 Amann, Markus & Derwent, Dick & Forsberg, Bertil & Hänninen, Otto & Hurley, Fintan & Krzyzanowski, Michal & de Leeuw, Frank & Liu, Sally & Mandin, Corinne & Schneider, Jürgen & Schwarze, Per & Simpson, David.

(2008). Health risks of ozone from long-range transboundary air pollution.

6 Bhatnagar, A. (2006). Environmental Cardiology. In Circulation Research (Vol. 99, Issue 7, pp. 692–705). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/01.res.0000243586.99701.cf

Miller, M. R., & Newby, D. E. (2019). Air pollution and cardiovascular disease: car sick. In Cardiovascular Research. Oxford University Press (OUP). https://doi.org/10.1093/cvr/cvz228 8 Peters, A., Dockery, D. W., Muller, J. E., & Mittleman, M. A. (2001). Increased Particulate Air Pollution and the Triggering of Myocardial Infarction. In Circulation (Vol. 103, Issue 23, pp. 2810–2815). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/01.cir.103.23.2810 9 O’Toole, T. E., Hellmann, J., Wheat, L., Haberzettl, P., Lee, J., Conklin, D. J., Bhatnagar, A., & Pope, C. A., III. (2010). Episodic Exposure to Fine Particulate Air Pollution Decreases Circulating Levels of Endothelial Progenitor Cells. In Circulation Research (Vol. 107, Issue 2, pp. 200– 203). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/circresaha.110.222679 10 Health risks of heavy metals from long-range transboundary air pollution (2007). (2017, March 18).

Retrieved from https://www.euro.who.int/en/healthtopics/environment-and-health/airquality/publications/pre2009/health-risks-of-heavy-metalsfrom-long-range-transboundary-air-pollution-2007 11 Department of Health. (n.d.). Retrieved from https://www.health.ny.gov/environmental/lead/sources.h tm#air

1

Conclusion: Exposure to different types of air pollution, whether it be primary or secondary gaseous pollutants, PM, or heavy metals, can be particularly harmful to cardiovascular health and can increase the risk of getting a heart attack, stroke, or other CVD. Further research still needs to be done in order to understand the mechanisms behind what makes exposure to these different types of air pollution lead to an increased risk of CVD; however, current evidence clearly demonstrates that in order to reduce CVD, we must reduce air pollution.

7

9

Application and Practicality of Structural Coloration Brian Alewine

Abstract: Structural colors are created by the interference and absorption of light by nanostructures on a surface. The benefits of using structural color comes from the differences in its physical properties compared to dyes or pigments. Examples of structural color are commonly found in nature, yet some aspects of structural color synthesis have proved difficult. This review will cover the application and practicality of two types of structural color generation.

Introduction Color in pigments and dyes comes from the reflection and absorption of light by molecules. Structural color is produced by light interfering with nanostructures on the scale of the wavelength of visible light.1 Because the molecules in pigments and dyes absorb light energy to produce color, over time they break down, leading to color fading. Since dyes break down over time, they have to constantly be produced, causing sustainability and environmental concerns. Structural color stays colorful as long as the structure is intact, leading to long lasting color even over millions of years.

Structural colors can be made from a wider range of materials, such as metals which do not originally have bright colors, as it is the nanostructures that provide the color, not the types of molecules.

Nanostructures that create structural color have been found in many animals, from butterfly wings to peacock feathers; however, the complicated structures involved are challenging to replicate artificially, so most coloration methods simplify the structure.5 Simpler synthesis methods would be less expensive, better suited for mass production, 10

and able to be applied in more areas.

Structural color in nature is usually iridescent or non-iridescent which is caused by the structures being anisotropic or isotropic.23 For most applications, noniridescent color is desired because the color stays the same from different viewing angles.

While iridescent structures have richer colors at certain viewing angles, noniridescent structures provide consistent color across any angle. Two of the primary methods for creating structural color are discussed in detail: using photonic pigments with microspheres, and the creation of color via subwavelength hole array.

Structural Color from Photonic Pigments The most positive results in synthesis of artificial structural color have come from the formation of self-assembling crystalline structures. The distance between particles, determined by the diameter of each particle, changes the amount of light absorbed and scattered and thus shifts the resulting color.4 Because natural color structures can be extremely complex, the easiest way to replicate structural color artificially is to use self-assembling particles.5 A crystalline structure has the benefit of being easy to manufacture, not energy intensive, and highly repeatable. Crystals, also having amorphous properties, allow for bright colors without iridescence which can be used in a larger range of applications. The photonic nanoparticles that form the crystal are contained in a semi-permeable membrane which allows for changes in nanoparticle density with osmotic pressure.

After the desired color is reached, microspheres are then cured with UV light, preventing further color change.4

Figure 1: The osmotic pressure of the microsphere condenses the nanoparticles together, shifting the resulting color, and the microsphere is cured with UV light to lock the nanoparticles in place.

A benefit of the microsphere method is that the colors can be tuned in production all the way up until curing, unlike with chemical coloring which needs to be mixed with other colors or derived from a new source for a change in color.

See Figure 2 below.

Figure 2: As the diameter of the microspheres decreases and the nanoparticle concentration increases, the wavelength that the particles absorb shifts higher, resulting in a different color.

The color flexibility of microspheres is unique even in regard to other methods of structural coloration such as the hole-array method which is subtractive, meaning that once material is removed, it cannot be added back.

This method of structural color generation lets the photonic pigments be applied as a liquid, allowing for a greater range of application than coloration that is synthesized on a 2D plane. This method is best optimized for use inks or dyes as it is already in liquid form. One issue that was found was that red pigments were not as saturated as blue or green pigments, but this could be addressed in future studies by reducing incoherent scattering of light.

Incoherent light scattering increases the whiteness of the sample because the color of the sample is mixed with the incoherently scattered light, reducing saturation. The best use for this method of structural color would

be for inks that remain as a fluid, but a way to have the microspheres exist as a powder would be to make the shell out of a more rigid material so it does not compress under pressure.4 Structural Color from Subwavelength Hole Array Structural coloration can also be generated by an array of holes in a metal surface. This method differs from the microsphere method as it physically alters the structure of the material the color is on. By creating circular holes in the metal sheet with a diameter smaller than the wavelength of light using electron-beam lithography (EBL) or focused ion beam (FIB), the transmittance wavelength of the material can be changed.6 The amount of light that can pass through the hole determines what wavelengths get absorbed rather than scattered.

See Figure 2 below.

Figure 2: Holes in a dimple array generating the letters “h” and “v” in red and green. The lattice constant for red was 550 nm and for green was 450 nm.6 Changing the hole shape from square to triangle can increase the intensity of the colors by reducing backscattering from light diffusing on the opposite side of the material.

A change in the hole diameter is what has the greatest effect on the color produced.

Unlike other methods that use structures generated on top of a sheet of metal or nanoscopic polarizing filters, hole arrays are 11

less complex to produce while still showing a high brightness and range of colors. 6 The benefits of nanohole structural coloration are that it is extremely thin at 300 nm and can be used as an electrode because it is made of silver, as well as being resistant to chemicals and UV radiation.6 Hole arrays have the potential to be used in applications with intense UV light exposure or chemical bleaching agents. This method of coloration could be used to create ultrathin high resolution displays, security patterns, or high density information storage.

Conclusion These two methods of structural color production are effective because they generate color while still having a simple synthesis process. Although the techniques of creating the color differ, both methods can produce a range of colors. Structural color

offers more advantages than pigmented color in durability, longevity, thickness, and color specificity. The scale at which structural color can be produced as a whole allows for pixels below the resolution of the human eye. This would be useful in high resolution displays, however, it would be more difficult to manufacture for large displays. Due to the microspheres properties as a liquid and the production method that does not directly apply them to a surface compared to the hole array method, microspheres would be better suited for large displays and could even be adapted to work in existing printing technology.

Both of these methods show promise in a wide range of applications due to their color permanence, flexibility, and nanoscopic size.

1Xu,

Structural Colors through Colloidal Assembly." Angewandte Chemie International Edition, vol.

53, no. 11, 12 Feb. 2014, pp. 2899-903, https://doi.org/10.1002/anie.201309306.

5 Saito, Akira. "Material Design and Structural Color Inspired by Biomimetic Approach." Science and Technology of Advanced Materials, vol. 12, no. 6, Dec. 2011, p. 064709, https://doi.org/10.1088/1468-6996/12/6/064709.

6 Gu, Yinghong, et al. "Color Generation via subwavelength Plasmonic Nanostructures."

Nanoscale, vol. 7, no. 15, 2015, pp. 6409-19, https://doi.org/10.1039/C5NR00578G.

Ting, et al. "Structural Colors: From Plasmonic to Carbon Nanostructures." Small, vol. 7, no. 22, 20 Sept. 2011, pp. 3128-36, https://doi.org/10.1002/smll.201101068.

2 Forster, Jason D., et al. "Biomimetic Isotropic Nanostructures for Structural Coloration." Advanced Materials, vol. 22, nos. 26-27, 22 Apr. 2010, pp.

2939-44, https://doi.org/10.1002/adma.200903693.

3 Kohri, Michinari, et al. "Biomimetic Non-iridescent Structural Color Materials from Polydopamine Black Particles That Mimic Melanin Granules." Journal of Materials Chemistry C, vol. 3, no. 4, 2015, pp. 720-24, https://doi.org/10.1039/C4TC02383H. 4 Park, Jin-gyu, et al. "Full-Spectrum Photonic Pigments with Non-iridescent

12

Liver and Lung Disease as a Result of Alpha-1 Antitrypsin Deficiency Dylan Luchsinger

Abstract: Alpha-1 Antitrypsin Deficiency is a generally underdiagnosed condition where there is a lack of the alpha-1 antitrypsin protein in the bloodstream1. This is caused by multiple genetic mutations, the most common of which being the Z and S mutations of the 14th chromosome.2 The deficiency leads to complications in both the lungs and liver, generally manifesting themselves in older individuals with the homozygous PiZZ mutation. This review will cover the function of alpha-1 antitrypsin as well as its effects on lung and liver disease.

The Role of Alpha-1 Antitrypsin in the Body: Alpha-1 antitrypsin is a glycoprotein synthesized in the liver. Its function is to protect organ tissue from damage caused by neutrophil elastase. Neutrophil elastase is released into the lungs when inflamed or undergoing phagocytosis. Elastase that is released non-specifically poses a threat to the tissue of the lungs by causing lung blockages.2 In response, Alpha-1 Antitrypsin attaches to and is split by elastase, which deactivates the elastase by altering the active site, preventing it from causing blockages in the lungs2.

Alpha-1 Antitrypsin Deficiency (AATD) Alpha-1 antitrypsin deficiency is the product of a number of mutations of chromosome 142. The two most prevalent genes related to AATD are delineated as the “Z” and “S” mutations. The Z mutation is the mutation primarily responsible for both liver and lung disease, specifically the homozygous PiZZ genotype. The normal manifestation of this gene is the PiMM genotype.3 AATD is most

common amongst Caucasians, affecting around one in 3,000-5,000 people. The mechanism behind AATD varies depending upon the specific genetic mutation. Rarer mutations have been found that completely inhibit the production of alpha-1 antitrypsin, causing greater harm to individuals with this mutation2. The standard Z and S mutations, however, cause the improper folding of alpha-1 antitrypsin which prevents its export from the endoplasmic reticulum. The newly formed alpha-1 antitrypsin undergoes a rapid reaction which bonds the center loop of one antitrypsin molecule to the beta sheet of another. This forms a long polymer of Zalpha-1 antitrypsin which builds up in the endoplasmic reticulum of hepatocytes.4 This decreases the levels of alpha-1 antitrypsin both by reacting the molecule into the Z polymer, which is unusable, and by clogging affected hepatocytes and preventing the release of usable alpha-1 antitrypsins.4

Figure 1. The structure of the Z polymer is formed with two alpha-1 antitrypsin molecules. 1 Diagnosis and Symptoms AATD is difficult to spot in young children as the complications associated with the disorder do not manifest themselves until later in life. Young children with AATD can expect a completely normal life. However, in extreme cases, inhibited growth can occur.

In older children with the most severe PiZZ genotype, symptoms include chronic 13

hepatitis, poor growth, and hepatomegaly (or splenomegaly). As people with AATD age, more genotypes are at risk of even more severe symptoms. The PiZZ genotype is still at the most risk; however, the PiMZ and PiSZ genotypes can expect some complications if little to no care is taken in regards to liver and lung health. Older individuals with AATD can experience both liver and lung complications. However, lung issues are far more common symptom.

Overall, individuals with genotypes other than PiZZ can expect to live a normal lifespan; however, those with the PiZZ genotype are likely to have a shortened lifespan as a result of severe liver and lung complications1.

Lung Disease in Individuals With AATD The most frequent complication with AATD in general is Chronic Obstructive Pulmonary Disease (COPD). Individuals with AATD experience a 50% increased risk of developing COPD especially in cases of smokers and those with the PiZZ genotype1.

Additionally, there is a 50% increased risk of hospitalization from COPD for those with AATD.1 In individuals with COPD caused

by AATD, their symptoms are generally exacerbated drastically, and then hold steady from some time before being exacerbated again. Higher levels of elastase have been observed before and after these exacerbations, leading researchers to believe that elastase is the cause of these exacerbations.1 As it relates to emphysema, the same trend was observed. Individuals with homozygous null mutations for AATD (PiSS or PiZZ) were shown to experience more severe forms of emphysema. A study conducted by L. Fregonese, J. Stolk, R. Frants, and B. Veldhuisen5 displayed a clear link between homozygous AATD null mutations and the severity of emphysema.

This increased severity correlated directly with both age and smoking history. Older subjects experienced significantly worsened 14

emphysema as well as those who were either smokers or ex-smokers. As a result, the study concludes that patients with AATD homozygous null/null mutations “should be considered a subgroup at particularly high risk of emphysema within AATD.”5 The specific mechanism by which AATD increases the risk of COPD and emphysema is not yet fully understood6. Patients with AATD experience higher levels of three enzymes believed to be linked to the increased risk of disease: macrophage elastase, interstitial collagenase, and cysteine proteases. Most research seeking to further the understanding of the effects AATD has on lung disease has been conducted in genetically altered mice. Thus, while researchers believe these studies give insight into the mechanism by which AATD causes and worsens lung disease in humans, it is worth noting that there are likely discrepancies in how this deficiency affects mice and humans. The most thoroughly understood of these enzymes is elastase. It appears that the macrophage elastase causes airway neutrophil to obstruct the airways in the lungs (see figure 2).1

Figure 2. shows the current model for the mechanism by which AATD leads to emphysema. 1 Overtime this buildup leads to conditions like COPD and emphysema as the elastase is not regulated properly by alpha-1 antitrypsin7.

Liver Disease in Individuals with AATD Liver disease in individuals with AATD is far less common but still a significant risk factor associated with the condition. The two most common liver diseases associated with AATD are cirrhosis and fibrosis, with 31% of AATD patients dying with cirrhosis (although not necessarily from cirrhosis.) in extreme cases of AATD (mostly affecting those with the PiZZ genotype) where individuals can expect liver failure later in life.2 In the US approximately 60-90 liver transplants are conducted annually for individuals with PiZZ AATD2. These are not only conducted after liver failure, but in some cases, transplants are used as a curative measure in younger people with the PiZZ genotype and severely low levels of alpha-1 antitrypsin.2 Finally, there has been a suggested link between AATD and hepatocellular carcinoma. Problematically, however, there is a lack of population-based controls, making it hard to definitively state the magnitude of the risk increase. The mechanism by which AATD increases the risk of liver disease is much better understood than its effects on lung disease.

Liver disease is caused not by a lack of alpha-1 antitrypsin, but by the buildup of the Z polymer of antitrypsin. As the Z polymer builds up in the endoplasmic reticulum of hepatocytes, liver cells die (see figure 3).

1

Teckman, Jeffrey H., and Nisha Mangalat. "Alpha-1 antitrypsin and liver disease: mechanisms of injury and novel interventions." Expert Rev. Gastroenterol. Hepatol., pp. 1-6.

2 Stolk, Jan. "Alpha-1-antitrypsin deficiency." Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands., pp. 1+.

3 Serres, F., and I. de Blanco. "Role of alpha-1 antitrypsin in human health and disease."

Journal of Internal Medicine, pp. 1-9.

4 Fairbanks, Kyrsten D., and Anthony S. Tavill.

"Liver Disease in Alpha 1-Antitrypsin Deficiency: A

Figure 3. shows the buildup of Z polymer antitrypsin in the hepatocytes, leading to cellular death and liver disease. (Z polymer is stained pink)2 Treatment for liver disease caused by AATD is not specific. Most doctors utilize standard treatments for liver disease. The focus of treatment is primarily on mitigating symptoms. The symptoms include but are not limited to: portal hypertension, bleeding, ascites, pruritus, malnutrition, fat soluble vitamin deficiency, hepatocellular carcinoma, and growth disturbances (in younger children). 2 Conclusions Alpha-1 antitrypsin deficiency leads to an increased risk for long term complications in both the liver and lungs. Because the general understanding of how AATD impacts lung disease is limited, further research should be conducted, especially as it relates to treatment. As a final note, research into the ability to undo the improper folding of the Z antitrypsin using a single peptide is currently underway and could solve problems associated with the disorder1. However, in the meantime symptom mitigation will likely remain the focus of scientific inquiry.

Review." American Journal of Gastroenterology, 2008, pp.

1-5.

5 Fregonese, Laura, et al. "Alpha-1 antitrypsin Null mutations and severity of emphysema."

Respiratory Medicine, pp. 1-8.

6"Emphysema." Mayo Clinic, www.mayoclinic.org/diseasesconditions/emphysema/symptomscauses/syc-20355555. Accessed 1 May 2022.

7 "Chronic Obstructive Pulmonary Disease (COPD)."

Centers for Disease Control and Prevention

15

Drug-Resistant Epilepsy: Potential Causes and Treatments Rose Ludecke

Abstract: One in three people with Epilepsy are nonresponsive to drugs attempting to suppress their epileptic episodes. This is known as Refractory Epilepsy and is defined as when a patient is unresponsive to two sufficient trials of anti-seizure medications (ASMs).1 A variety of treatments are possible, and further research looks more closely into potential mechanisms that may cause this condition.

Introduction to Epilepsy Epilepsy is a condition that affects the Central Nervous System. Specifically, it is a neurological disorder in which the brain acts abnormally causing uncontrollable seizures, behaviors, sensations, and sometimes loss of awareness.2 The types of seizures or symptoms present among patients can vary in severity. Some will stare blankly, while others will twitch or seize uncontrollably.2 The brain operates through bursts of electricity between different neurons that work collectively to control thoughts, emotions, and movements. During an epileptic episode, something is disrupting this communication between the neurons, which can potentially cause a seizure to occur. There are two main categories for types of seizures: focal onset seizures and generalized onset. Focal onset seizures originally start in one specific area of the brain, and then spread across the brain.

Patients with focal onset seizures usually have had some sort of trauma to a specific part of the brain that is now the origin of focal onset seizures, like a stroke or meningitis.3 Further, some patients can feel focal seizures start to occur before the 16

symptoms become more intense. In generalized onset seizures, the activity occurs on both sides of the brain as opposed to originating in one specific part of the brain, and then spreading across the brain (Figure 1).

Figure 1: Generalized vs. Focal Seizures 4

Generalized onset seizures can be genetic, and usually start during childhood because of the brain’s inability to regulate the electricity between the neurons. Most patients who have epilepsy are able to be treated through medication. However, around 1/3 of the population with Epilepsy cannot be treated with medication, and instead have a form of Epilepsy known as Refractory Epilepsy.

Drug-Resistant Epilepsy Drug-resistant Epilepsy is clinically defined as when a patient has been unable to stay seizure-free after two sufficient trials of antiseizure medications.1 This condition affects about 1/3 of all patients with epilepsy. The reasons for drug-resistance to Epilepsy vary and have different contributing factors from patient-to-patient due to different circumstances, and theoretically the action site of the medication being used.4 Potential Causes to Drug-Resistant Epilepsy There is no consensus on the cause or causes of drug-resistant epilepsy. Simpler ideas put forth by doctors and scientists identify factors such as age, where older patients reported better results to the medication, and were more likely to be seizure-free.4

Multiple hypotheses have been put forth to attempt to explain the cause of Refractory Epilepsy. The target hypothesis, for example, puts forth the theory that the cause of this condition specifically related to how the anti-epileptic medication works. The theory is that the alteration of cellular targets causing the epileptic episodes by the medication leads to an eventual desensitization of the body to the treatment.

As the patient continues to use the medication, the less effective it becomes.

However, the target hypothesis presumes a total understanding of the mechanisms of antiepileptic drugs, which there is not.

Additionally, there are people who are resistant to multiple types of epileptic drugs that have different actions, which the hypothesis does not account for. These are two relatively big problems for the target hypothesis.

Another hypothesis currently being discussed is the transporter hypothesis, which postulates that, “drug resistance may be attributable to overexpression of multidrug efflux transporters at the epileptic focus.”4 One of the most studied efflux transporters is P-glyco-protein. The target hypothesis contends that while the transporter protein pumps normal amounts of xenobiotics from intracellular space back to the capillary lumen to maintain the integrity of the blood, the use of many medications used to regulate epileptic seizures alters the p-glyco-protein, causing the medication not to work because of the overexpression of these efflux transporters at the epileptic focus. This is consistent among many patients, found in resected samples of the brains of patients who had drug-resistant epilepsy. A conflicting explanation to this is that the gene that encodes the P-glycoprotein is the source of the poor response to the antiepileptic drugs. Another study was conducted that put forth reasoning behind

resistance to a common anti-epileptic drug known as Carbamazepine. Carbamazepine works by blocking the fast-sodium current in dentate granule cells, but was lost in the hippocampus of patients who were drugresistant to carbamazepine. This wasn't found in a drug that has similar actions to carbamazepine, called lamotrigine. The resistance to these drugs (as well as ones that use sodium channels) could have been associated to polymorphisms (a discontinuous genetic variation resulting in the occurrence of several different forms or types of individuals among the members of a single species) of the SCN2A gene.4 While there are many hypotheses and theories surrounding potential causes of refractoryepilepsy, there is not yet a definitive consensus, which may be attributed to the variety in patients who have drug-resistant epilepsy.

Current Available Treatments One of the main underlying issues regarding the treatment of Refractory Epilepsy is pseudoresistance. In order to determine whether a drug treatment is effective or not, you have to make sure that the person was not misdiagnosed. There are many disorders that have effects similar to those of epilepsy, and patients are subsequently misdiagnosed with some form of drug-resistant epilepsy because they are not being given the right medication for what illness they have.

Around 25% of people who are claimed to have drug resistant epilepsy actually have a different disorder.4 There are other potential causes such as the lifestyle of the patient (ex. abuse of drugs or alcohol, non-regulated use of medication or insufficient adherence to the medication) that can cause mistrials, and an eventual misdiagnosis of refractory epilepsy.

17

Figure 2: Nerve Cell Electrical Charge Movement

Once it is determined that the condition the patient has is, in fact, drug-resistant epilepsy, there are many ways potential treatment pathways. Patients should be evaluated early for the chance of a surgical remedy if they have conditions like unilateral hippocampal sclerosis or other lesions that can be resected. This decision should be weighed versus additional drug trials. In a randomized, controlled study, the prototype surgery of an anterior temporal lobectomy was shown to be better than medication in providing long-term relief from seizures in up to 70% of patients (adults) with Refractory Epilepsy.9 One issue with current antiepileptic drugs on the market is that they only focus on preventing seizures, and not necessarily at the right site. In some cases of epilepsy where there has not been an identified cause, there are autoantibodies involved in the neuronal excitation and inhibition that attack the ion channels,

causing differences in positive and negative electricity in the cell (Figure 2).

Patients who share this trait often do not respond to antiepileptic drugs, and immunotherapy trials have conflicting data surrounding their efficacy.

Another possible treatment plan is the combination of multiple anti-epileptic drugs.

Specifically, data from applied research of combination pharmaceutical therapy on animals suggests that the use of medication with two different modes of action, rather than multiple drugs with the same mode of action, could potentially help to cause patients to be seizure free, though highquality data supporting this theory is lacking.

Those with refractory-epilepsy do not have one singular course of action to become seizure-free, however clinical trials are still underway to attempt to find a cure.

1

Epilepsy Foundation. 5 Oct. 2020, www.epilepsy.com/treatment/medicines/drdrresistant-epilepsy. Accessed 28 Apr. 2022 2 Mayo Clinic Staff. "Epilepsy." Mayo Clinic, 7 Oct. 2021, www.mayoclinic.org/diseasesconditions/epilepsy/symptoms-causes/syc-20350093.

Accessed 28 Apr. 2022.

18

3

Johns Hopkins Staff, editor. "Types of Seizures."

Johns Hopkins Medicine, Johns Hopkins, www.hopkinsmedicine.org/health/conditions-anddiseases/epilepsy/types-of-seizures. Accessed 1 May 2022 4 Kwan, Patrick, et al. "Drug-Resistant Epilepsy."

Hydrogen Fuel as a Clean Alternative to Gasoline in Transportation Will Clark

Abstract: Carbon emissions from the transportation industry are a serious global concern. While electric cars are a potential solution, current limitations in range and charge time need to be improved. Hydrogen fuel could fix some of the flaws of electric cars. Hydrogen as a fuel source has been considered a replacement for gasoline due to the benign nature of water emissions. This paper evaluates the two different methods of harnessing hydrogen fuel, the chemistry of each method, and the overall viability of hydrogen fuel.

Why hydrogen fuel is being researched: Gasoline from transportation contributes to roughly 14% of global carbon emissions.12 The electric vehicle (EV) push in the transportation industry to reduced CO2 emissions from internal combustion is widespread, but electric cars are not perfect.

A long-range 2021 Tesla Model 3 has an estimated range of 315 miles. Recharge time for the Tesla Model 3 at a supercharging station, which provides 250 kW of maximum draw, is roughly 32 minutes to reach 80% capacity and double that to reach 100% capacity1. These factors make EV’s inconvenient on road trips and difficult to properly implement in the industrial and transportation sectors. Hydrogen fuel cells have been considered as an alternative, due to their shorter refueling times and higher range. There are currently two methods used for Hydrogen fuel.

12

Hydrogen fuel cells in EV’s: One method of harnessing hydrogen energy is through hydrogen fuel cells. Hydrogen is pumped out of a tank into a fuel cell, where a platinum catalyst on the anode side separates hydrogen into protons and electrons. This process generates an electrical current while only emitting water and unused oxygen, which is needed to complete the reaction. (see Figure 1)

Figure 1: a basic hydrogen fuel cell generating electricity 3 Platinum is expensive; however, that can be sidestepped with Molten Carbonate Fuel Cells (MCFC), which is the most complex fuel cell reaction available commercially.

(See Figure 2 below.)

19

EVs. However, they could be implemented in large industrial vehicles.

Standard fuel cells are the more viable method for consumer transportation, where they have already proved their viability.

Hydrogen-fueled EVs like the Toyota Mirai have much more range than a standard EV, with the Mirai having an estimated range of 402 miles.5

Figure 2: an MCFC. the reaction is like that of a standard fuel cell, but it is mediated by CO2 produced by the electrolyte. 4 MCFCs generate much more heat. The additional heat from the reaction in the fuel cell breaks down the electrolyte into CO2.

The electrolyte is made of alkali metal carbonates.4 2H2 + 2CO32- à 2H2O + 2CO2 + 4eThe CO2 from this reaction is sent back to the cathode side and reacts with O2 to regenerate carbonate ions in the electrolyte.

This happens based on this equation:4 O2 + 2CO2 + 4e- à 2CO32The reaction is similar to the basic fuel cell in Figure 1 but is mediated by carbonate ions from the electrolyte. This reaction also cannot be poisoned by carbon monoxide impurities, which instead form additional hydrogen through a shift reaction.4 CO + H2O à CO2 + H2 MCFC reactions do not generate any CO2 emissions as all CO2 is kept within a closed loop. These types of fuel cells are very efficient but not small enough to be adapted into personal vehicles, which currently use the simple hydrogen fuel cell design.4 Further study is needed on MCFCs to evaluate their full potential in consumer 20

Hydrogen-fueled Internal combustion engines (HICE): HICEs are much more chemically simple.

Much like a standard internal combustion engine (ICE), HICEs drive a piston with the following combustion reaction.

2H2 + O2 à 2H2O A typical engine cannot use hydrogen without significant problems. Hydrogen has very different properties than gasoline, and since it is gaseous at ambient temperature, it displaces more volume. See figure 3.

Figure 3: displacement comparisons of different engine configurations 6 Hydrogen has a stoichiometric air to fuel ratio of 34:1, which means a larger engine displacement and therefore larger engine block is needed to compete with the horsepower of a gasoline engine. Piston engines also have hot spots that can prematurely ignite the hydrogen. Engine knocking, or when a piston fires out of time, is also a problem with HICEs due to the volatility of hydrogen.

Some people propose using the Wankel Rotary Engine (WRE) in HICEs because it seems more naturally suited to hydrogens' unique properties. WRE’s are engines that are driven by triangle-shaped rotors that are put in a tapered oval and spin as opposed to pistons placed in an engine block that go back and forth. See figure 4.

Figure 4: A Wankel Rotary Engine (WRE) 7 WRE’s run cooler than orthodox ICEs, while also having a higher power per displacement volume, which means a WRE would benefit from a higher displacement requirement.7 Both orthodox ICEs and WREs have been tested with hydrogen fuel and need serious redesign to adapt properly to hydrogen. Companies like Toyota see hydrogen fuel as an alternative for automotive enthusiasts and have begun the development of a hydrogen-powered V8.8 Costs, Context, and Conclusion: Hydrogen fuel has proven itself to be a viable solution to the problems that afflict EVs, but are also face significant challenges.

Primarily, the issue with hydrogen fuel lies in the increased storage volume needed for hydrogen gas. Additionally, because of the volatility of hydrogen, storage tanks need to be carefully designed and built, which is a process that generates a lot of carbon emissions. At present, Hydrogen-fueled EVs are responsible for 15 kg of CO2 emissions per every 100km driven over a 150,000 km lifetime.9 This number accounts for the

emissions created when producing a hydrogen tank and the emissions that come from the production and transport of hydrogen fuel. Internal combustion engines, however, are responsible for 1.1 kg of CO2 per 100km driven.10 While total emissions may eventually be balanced out if the fuel cell vehicle is driven over 150,000 km, ICEs are less immediately harmful. Reducing total CO2 production costs for hydrogen-based vehicles is vital to their success. It would help to look into carbon fiber recycling to reduce the production emissions of a hydrogen tank. Hydrogen production that does not emit CO2 is also a vital path to pursue.

Hydrogen-based internal combustion is far less viable for two reasons. First, hydrogen combustion still produces emissions in the form of nitrogen oxide.11 This is because of the nitrogen that is naturally present in the earth's atmosphere, which is converted into various nitrogen oxides as a byproduct of combustion. Tank capacity also follows the same limits as hydrogen fuel cells, the difference being that hydrogen combustion is far less efficient than the reaction that occurs in hydrogen fuel cells, meaning decreased mileage and higher fuel costs.11 Unless emissions can be reduced, HICEs are not practical to apply in transportation.

Hydrogen fuel cell-based vehicles are primarily limited by cost. The Toyota Mirai costs approximately $50,000 MSRP,5 which will not be competitive with future electric cars. If the cost can be reduced and if access to hydrogen fuel can be expanded, hydrogen-based vehicles may become practical. Attention must also be paid to how the hydrogen fuel is sourced, as not all hydrogen produced is produced in a clean manner. Electric cars technology is advancing much more quickly, and is more promising. Hydrogen fuel is likely better applied in the industrial sector where electricity access may not be an option.

21

The Effects of Moisture on Cadmium Sulfide Based Oil-Paint Degradation Katie Skinner

Abstract: Cadmium Sulfide based oil-paint, which appears in shades of yellows, oranges, and even reds, is prone to degradation over extended periods of time. Degradation of cadmium sulfide paint can lead to major effects on famous works of art. This article will go over the effects that environments and moisture have on the degradation of Cadmium Sulfide based oil-paint.

Introduction In the late 19th and 20th century, Cadmium Sulfide (CdS) based oil-paint was used by many artists in their paintings due to its vibrant yellow and orange colors. Cadmium orange and cadmium yellow can be found in famous paintings such as The Scream by Edvard Munch1, Femme (Époque des !Demoiselles d"Avignon”) by Pablo Picasso2, Flowers in a blue vase by Vincent Van Gogh, Joy of Life by Henri Matisse3, and others. While CdS is now also used in a variety of different electronics such as lasers, light-emitting diodes, solar cells, and photodetectors as it is a key semiconductor because it is both chemically and thermally stable, it is mainly used as a pigment.2 Pure CdS based oil-paints tended to remain vibrant for a time, while light exposure caused poorer quality CdS paint to lose its color rapidly enough that paint producers and artists would notice right away.

These were some of the early signs of CdS degradation.

Other signs of degradation included areas pained with cadmium yellow becoming brittle, the formation of off-white and opaque crusts, chalking, discoloration, flaking, or the color darkening to a brownish-yellow. The 22

quality of the CdS paint, the humidity of the area the artwork is in, and light exposure are all factors that play into how fast the CdS paint degrades.

Creation of Cadmium Sulfide Paint and its Structures There are two processes used to produce CdS paints, the wet and dry methods. For the wet method, a soluble sulfide compound is combined with one or multiple types of cadmium salts in a precipitation reaction.1 For the dry method, cadmium carbonate, metallic cadmium, or cadmium oxide are calcined without oxygen with pure sulfur to form cadmium yellow pigment. Due to the various different combinations of cadmium salts and sulfide compounds and because neither reactants are ‘pure’, the wet method produces a much larger variety of cadmium yellow paints, but the paints produced through the wet method are more susceptible to chemical change than paints made through the dry method.1 Because of the large number of different types of CdS produced, each has a different rate of degradation, so it is difficult to pin down exactly how fast certain paintings that include CdS based oil-paints will discolor or degrade.2 Another factor that plays into the degradation process of CdS based oil-paints is their crystalline structures and the existence of “trap states.”2 CdS can have a crystalline structure that ranges from amorphous to the more common hexagonal and cubic. The shape of the structure not only influences what color the pigment is but also how chemically stable it is and therefore how it reacts with oxygen and water to cause degradation.4 Crystalline Structures and and How Moisture Affects CdS Degradation Moisture in the air greatly affects CdS based paints as it heightens the possibility of oxidation to occur. The exposed CdS crystalline structure is vulnerable to H2O and

O2. The larger amount of CdS atoms on the surface create “trap states” which are dangling CdS bonds that trap excited electrons. Because of different concentrations of electrons, vacancies of cadmium or sulfur atoms appear along the exposed ends of the structure (surface level paint).2 A vacancy of a cadmium atom in the structure causes water molecules to dissociate and fill the vacancy while a vacant sulfur atom on the outer ends of the structure is filled by one oxygen molecule (O2).4 This can be seen in Figure 1.

This causes the discoloration of the CdS based paints, including the degradation into a

brownish-yellow color.

Figure 1: hexagonal crystalline structure of hex-CdS affected by oxidation a) red oxygen molecule absorbed onto a cadmium atom vacancy creating an S-O2 bond; b) blue area is where the oxygen molecule has become charged and green areas are where the sulfur ion’s charge has been depleted4 The hexagonal structure is largely more stable, while the cubic structure allows for a higher density of dangling CdS bonds in one area and therefore is more vulnerable to degradation.2 While the difference between hexagonal and cubic structure degradation is a small factor, the quality of the CdS paint is a much greater factor in CdS degradation.

Higher quality CdS paint produced using the dry method show little to no signs of degradation over time whereas low quality CdS paint produced using the wet method, whether the CdS structure is hexagonal or cubic, is much more prone to degradation.1

Findings and Conclusion There are several ways that CdS paint degradation is studied, one of the ways is through an artificial aging process with mockup painting. Additionally, some of the same studies also performed macroscale spectroscopy studies using synchrotronradiation x-rays. In the mock-up aging studies, it was found that moisture in the air caused oxidation reactions changing CdS to the white CdSO4 and altering the paint. The oxidation reactions produce products such as sulfites and sulfates, even when not exposed to light. Different cadmium chloride compounds were also found to oxidize CdS while CdS pigment migration, recrystallization of watersoluble CdS phases, and dissolution were all secondary reactions caused by humidity.1 Moisture levels of around 95% relative humidity (RH) triggered CdS yellow to oxidize into CdSO4 white but RH levels of around 45%, which is considered to be ‘normal’ levels of humidity, did not oxidize.

This data can be seen in Figure 2. It was also found that electron-hole recombination and trap state repair happen when humidity decreases.3 Therefore, for the importance of maintaining art and art conservation, low or ‘normal’ humidity is the best way to store artworks to prevent CdS based oil-paint from degradation.

23

Fig. 2: results of 4 tests of artificial mock-up aging of hex-CdS and cub-CdS. Most aging appears when artificially aged with thermal 95% relative humidity (RH)3

Monico, Letizia, et al. "Probing the Chemistry of CdS Paints in The Scream by in Situ Noninvasive Spectroscopies and Synchrotron Radiation X-ray Techniques." Science Advances, vol. 6, no. 20, 15 May 2020. Science, https://doi.org/10.1126/sciadv.aay3514.

2 Comelli, Daniela, et al. "Degradation of Cadmium Yellow Paint: New Evidence from Photoluminescence Studies of Trap States in Picasso's Femme (Époque Des 'Demoiselles D'Avignon')." Analytical Chemistry, vol. 91, no. 5, 1 Feb. 2019, pp. 3421-28, https://doi.org/10.1021/acs.analchem.8b04914.

1

24

Monico, Letizia, et al. “Role of the Relative Humidity and the Cd/Zn Stoichiometry in the Photooxidation Process of Cadmium Yellows (CdS/Cd1−xZnxS) in Oil Paintings." Chemistry – a European Journal, vol. 24, no. 45, 25 July 2018, pp.

11584-93, https://doi.org/10.1002/chem.201801503.

4 Giacopetti, Laura, and Alessandra Satta.

"Reactivity of Cd-yellow Pigments: Role of Surface Defects." Microchemical Journal, vol. 137, Mar. 2018, pp. 502-08, https://doi.org/10.1016/J.MICROC.2017.12.013.

3

The Causal Relationship Between Lack of Sleep and Diabetes Zorina Sun

Abstract: Sleep Deprivation refers to the state when an individual does not get an adequate amount of good sleep. It is common in this fast-paced society, as people are spending a lot of time on studying, working and leisure activity. Thus, it is very significant to note the possible effects of lack of sleep on individual’s health. This paper evaluates the causal relationship between chronic lack of sleep and diseases, specifically, Type 2 Diabetes.

Introduction of Sleep Deprivation Sleep deprivation is very common in society today. There are several factors leading to this, including the increase in environmental light and electric light, use of electronic devices and the internet, and so on.

According to the 2009 Sleep in America Poll, Americans are more likely to be working longer hours or multiple jobs, and concerned about personal finance, employment, and the economy, in the current economic climate.1 Thus, sleep deprivation is partly self-imposed, as people choose to leave less time for sleep. Data from recent laboratory studies indicates that significant sleep loss exists in one-third or more of normal adults.2 According to recent polls from the US Centers for Disease Control and Prevention, approximately 29% of US adults sleep less than 7 hours per night, and about 60 million of them have chronic sleep and wakefulness disorders.3 People are sleeping less nowadays, and sleep disorders are on the rise.

Stages of sleep There are five stages of sleep, including rapid eye movement (REM) sleep and nonREM sleep (stages 1, 2, 3, and 4). In the non-REM sleep stage, stages 3 and 4 are the deeper stages, which are also known as slowwave sleep.4 Sleep has often been thought of as a “restorative” process for the mind and the body, and it also affects many metabolic and hormonal processes.

Lack of Sleep and Diabetes There is a very close relationship between sleep deprivation and diabetes. As Dr. Carol Touma and Dr. Silvana Pannain found, “people with diabetic should be systematically assessed for obstructive sleep apnea, and patients with known obstructive sleep apnea should be screened for diabetes.”4 The relationships between lack of sleep and diabetes can be explained by glucose tolerance and glucose metabolism.

1) Glucose Tolerance Glucose tolerance plays an important role in this causal relationship. It refers to the ability to maintain euglycemia. Normal glucose tolerance depends on the ability of the pancreatic beta cells to produce insulin. Beta cells are cells that make insulin, a hormone that controls the level of glucose (a type of sugar) in the blood. When pancreatic beta cells fail to compensate for a decreased insulin sensitivity, insulin secretion increases to maintain normal glucose levels, and diabetes becomes manifest.4 A research article from Nedeltcheva, Kessler, Imperial, and Penev examined the effects of less-severe sleep deprivation in sedentary middle-aged men and women.

The population of this study sleeps 5.5 hours per night for 14 nights. The lack of sleep is shown to decrease insulin sensitivity in the absence of adequate beta cell compensation.

This causes a decrease in glucose tolerance and eventually leads to diabetes.5 The short 25

lower parasympathetic activity, which are both associated with glucose metabolism.13 The sympathetic nervous system prevents insulin release while the parasympathetic system promotes it. Thus, these changes would cause an increase in glucose level, and therefore diabetes.14 Conclusion Sleep plays a very important role in glucose tolerance and metabolic function, as well as creating other problems on top of diabetes.

While it is important to note that there is a possible limitation to the present study because all the data collected was selfreported and thus might not be very Malik, Syed W., and Joseph Kaplan. "Sleep deprivation." Primary care: Clinics in office practice 32, no. 2 (2005): 475-490.

2 Bonnet, Michael H., and Donna L. Arand. "We are chronically sleep deprived." Sleep 18, no. 10 (1995): 908-911.

3 Centers for Disease Control and Prevention (CDC. "Perceived insufficient rest or sleep among adultsUnited States, 2008." MMWR. Morbidity and mortality weekly report 58, no. 42 (2009): 1175-1179.

4 Touma, Carol, and Silvana Pannain. "Does lack of sleep cause diabetes." Cleve Clin J Med 78, no. 8 (2011): 549-58.

5 Nedeltcheva AV, Kessler L, Imperial J, Penev PD. Exposure to recurrent sleep restriction in the setting of high caloric intake and physical inactivity results in increased insulin resistance and reduced glucose tolerance. J Clin Endocrinol Metab 2009; 94:3242– 3250.

6 Shankar, Anoop, Shirmila Syamala, and Sita Kalidindi. "Insufficient rest or sleep and its relation to cardiovascular disease, diabetes and obesity in a national, multiethnic sample." PloS one 5, no. 11 (2010): e14189.

7 Touma, Carol, and Silvana Pannain. "Does lack of sleep cause diabetes." Cleve Clin J Med 78, no. 8 (2011): 549-58.

8 "Clinic Chat: Counterregulatory Hormones." Type 1 Diabetes Family Centre. Last modified September 14, 2020. https://www.type1familycentre.org.au/post/clinicchat-counterregulatory-hormones.

9 Spiegel K, Leproult R, Colecchia EF, et al.

Adaptation of the 24-h growth hormone profile to a 1

26

accurate. People may include the time period of “trying to sleep” when they report, making the actual amount of sleep time lower. However, there is still a proven close relationship between sleep deprivation and disease. Based on data obtained by Shankar et al, “perceived insufficient rest/sleep was found to be independently associated with CHD, stroke, diabetes mellitus and obesity.”15 Thus, it is very important for us to get enough sleep (at least 7 hours), but not too much. Studies also show that the risk of diabetes is higher with either too little or too much sleep.16 Adequate amounts of good sleep should be a goal for a healthy lifestyle, especially for people with diabetes.16 state of sleep debt. Am J Physiol Regul Integr Comp Physiol 2000; 279:R874–R883.

10 Vgontzas AN, Papanicolaou DA, Bixler EO, et al.

Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab 1999; 84:2603–2607.

11 Vgontzas AN, Zoumakis E, Bixler EO, et al.

Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines.

J Clin Endocrinol Metab 2004; 89:2119–2126.

12 Dansinger, Michael. "Insulin Resistance: Symptoms, Causes, Tests, Treatment, and Prevention." WebMD, June 23, 2021.https://www.webmd.com/diabetes/insulinresistancesyndrome#:~:text=Insulin%20resistance%20is%20w hen%20cells,blood%20sugar%20levels%20go%20up .

13 Spiegel K, Leproult R, L’hermite-Balériaux M, Copinschi G, Penev PD, Van Cauter E. Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab 2004; 89:5762–5771.

14 Teff KL. Visceral nerves: vagal and sympathetic innervation. JPEN J Parenter Enteral Nutr 2008; 32:569–571.

15 Shankar, Anoop, Shirmila Syamala, and Sita Kalidindi. "Insufficient rest or sleep and its relation to cardiovascular disease, diabetes and obesity in a national, multiethnic sample." PloS one 5, no. 11 (2010): e14189.

16 Touma, Carol, and Silvana Pannain. "Does lack of sleep cause diabetes." Cleve Clin J Med 78, no. 8 (2011): 549-58.

The Effects of Calcium Supplementation on the Human Body Charlie Ryan

Abstract: The usage of calcium supplementation for the purpose of treating or preventing Osteoporosis has been studied to determine its efficacy and harmful side effects. The purpose of this article is to review these studies and call for further research into the effects of calcium supplements.

Introduction: Calcium plays a number of important roles in physiology, pathology, and especially as a structural component for bones.1 It is used in the processes of blood-clotting, muscle contraction, regulation of heart rhythms, and nerve functions.2 The body can attain calcium by either ingesting it through food and supplements or by removing calcium from the bones.2 The loss of bone mineral density (BMD) and the loss of muscle function are major causes of osteoporotic fractures, which are associated with disability, increased morbidity and a twenty percent increased mortality.3 Osteoporosis remains a common problem. Approximately forty percent of women aged fifty are expected to have an osteoporotic fracture in the remainder of their life.4 For years, a certain calcium and Vitamin D balance has been considered necessary for maintaining a healthy bone metabolism and for treating, as well as preventing, osteoporosis.3 There has been evidence that supplemental approaches to calcium, especially for those who receive inadequate amounts of it, may benefit bone mass and reduce fracture risk.5 Recent studies have, however, questioned the efficacy of calcium supplements.3 Moreover, further evidence

suggests possible gastrointestinal side effects, increased risk of kidney stones, and potential negative cardiovascular effects from calcium supplementation.3 Efficacy of Calcium Supplements: As a person ages, bones go through a remodeling process where they are repeatedly broken down and built up. 2 Osteoblast bone cells will continuously build bone up while osteoclast bone cells will constantly break bone down if calcium is needed in other parts of the body. 2 A typical healthy person will produce more bone than they lose until about the age of thirty, when they will have a negative calcium balance which can lead to bone loss and thus higher fragility in bones.2 Figure 1 depicts the negative feedback loop of calcium in the body.

Figure 1: A visual depiction of how the body regulates calcium levels. Note the effects of calcium levels on osteoclasts.2 Several studies have been performed to determine whether calcium supplementation has been shown to reduce the risk of osteoporotic fractures. Its effects when combined with Vitamin D supplemental intake may differ, as having 27

an adequate amount of Vitamin D is helpful for calcium absorption in the body.3 In their meta-analysis, the DIPART Investigator group viewed 68,500 patients from seven individual randomized controlled trials.5 For trials including the combined use of calcium and vitamin D supplements, there appeared to be a modest reduction in all fractures [Hazard Ratio (HR)–the ratio of hazard rates in the treated versus control group– 0.92 (95 % Confidence Interval (CI) 0.86, 0.99)] and hip fractures [HR 0.83 (95 % CI 0.69, 0.99)].5 This meta-analysis included individuals both in a community setting and in a nursing-home setting, indicating that there is an association between calcium supplements and reduced osteoporotic fractures in an average person’s environment.5 In order to determine whether calcium supplementation alone would differ from calcium supplementation combined with vitamin D supplementation, Tang et. Al. performed a meta-analysis separating the two approaches and comparing their results among seventeen trials.5 The authors of the meta-analysis took a sensitivity analysis comparing the effects of either approach.5 The relative risk of fracture for calcium and vitamin D supplements was 0.87 (95 % CI 0.77, 0.97) and, for calcium alone, it was 0.90 (95 % CI 0.80, 1.00). 5 Given the margin of error, there was no significant difference between the two types of therapies; however the reduced risk of fracture with calcium alone was borderline statistically significant. In a separate meta-analysis of random clinical trials conducted by members of the Department of Orthopaedic Surgery in China, the use of supplements that included calcium with or without vitamin D compared with a placebo or no treatment revealed that there was no significant association between calcium supplements and a reduced risk of bone fractures.4 As such, their findings do not support the use of 28

calcium supplements for community dwelling people, including those at higher ages who have the highest risk of Osteoporosis.4 In contrast, the metaanalysis done by Iacopo Chiodini and Mark J Bolland suggests that calcium supplements, specifically those combined with vitamin D supplements, lead to an increase in BMD and to a reduction of total fracture risk by fifteen percent and hip fracture risk by thirty percent.3 Therefore, without taking into account the possible adverse effects of calcium supplements, they claim that their findings suggest that only those who suffer from insufficient calcium uptake should take calcium supplements and that the evidence does not justify the use of population-level usage of calcium supplements, nor the prescribing of them to those who experience normal levels of calcium intake.

3 A similar review from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF) reflected this conclusion. 5 Harmful Effects of Calcium Supplements: Recent studies regarding the vascular and gastrointestinal side effects of calcium supplements have received more attention.

Calcium deposition in the vasculature has been a consistent feature of vascular disease and has shown to have adverse effects in other soft tissues such as with an increased risk of developing kidney stones.1 In order to prevent this, there is a complex system of inhibitors that react with calcium when it reaches high levels, however, as the body ages, the effectiveness of this system declines, especially in the vascular system.1 Furthermore, some studies claim that blood calcium levels influence the development of vascular diseases.1 One recent meta-analysis of nine studies regarding the relationship between serum

calcium and mortality from vascular disease revealed that calcium seemed to be an independent predictor of myocardial infarction, which are commonly referred to as heart attacks. Moreover, this meta analysis demonstrated a hazard ratio (HR) of death of 1.13 (95% confidence interval [CI], 1.09 to 1.18) for each standard deviation increase in serum calcium (approximately 0.1 mmol/L). 1 Many other studies also attribute serum calcium and circulating calcium to vascular calcification, and one study even directly attributed calcium supplements with an increased risk of developing coronary artery calcification.1 Further research is need to better determine what extent calcium supplements affect serum calcium levels. Many studies focusing on the direct relationship between calcium supplements and vascular health have been performed.

An example of which is presented in Figure 2.

Figure 2: Results of a meta-analysis revealing a significant difference between those who experienced a myocardial infarction after continuously taking calcium supplements and those who did not.

In contrast to this however, a Women’s Health Initiative study found no association between calcium supplementation and coronary artery calcium.6 The European Prospective Investigation into Cancer and Nutrition Study did find an association between calcium supplementation among women and myocardial infarction (RR = 1.86; 95% CI = 1.17–2.96) but depicted no significant relationship between calcium supplementation and strokes or cardiovascular disease mortality.6 In one of the studies incorporating results from patient level data, Bolland found that treatment of one thousand people with calcium for five years would cause an additional fourteen myocardial infarctions, ten strokes, and thirteen deaths while preventing twenty-six fractures.7 Although Bolland claims that the increased risk of cardiovascular disease is modest, he believes it could become a large problem given the widespread usage of calcium supplements. 7 Conclusion: Given the contrasting data on the efficacy of calcium supplements in preventing bone fractures and the important link between blood calcium levels and vascular disease, this review recommends that further research be done in regard to the effects of calcium supplements. An important focus should be put on calcium supplements and how they affect serum calcium. It is important to note that many of these studies were likely exposed to confounding variables, so more direct experimental research within the bounds of ethical standards appears to be necessary.

1 Reid,

Ian R. et al. "Calcium and Cardiovascular Disease." Endocrinology and Metabolism 32 (2017): 339 - 349.

2 The Nutrition Source. "Calcium." The Nutrition Source, Harvard T.H. Chan, www.hsph.harvard.edu/nutritionsource/calcium/ #:~:text=Calcium%20is%20a%20mineral%20mos t,heart%20rhythms%20and%20nerve%20function

29

s. Accessed 1 May 2022.

3 Chiodini, Iacopo, and Mark J. Bolland. "Calcium supplementation in osteoporosis: useful or harmful?" European Journal of Endocrinology, vol. 178, no. 4, Apr. 2018. European Society of Endocrinology, https://doi.org/10.1530/EJE-18-0113. Accessed 26 Apr. 2022.

4 Zhao, Jia-Guo et al. "Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis."

JAMA 318 (2017): 2466–2482.

5 Harvey, Nicholas C. et al. "The role of calcium supplementation in healthy musculoskeletal ageing." Osteoporosis International 28 (2016): 447-462.

6 Waldman, Talya et al. "Calcium Supplements and Cardiovascular Disease." American Journal of Lifestyle Medicine 9 (2015): 298 - 307.

7 Bolland, Mark J. et al. "Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis." The BMJ 341 (2010): n. pag.

30