The Collatz conjecture, named after Lothar Collatz, is one of the most deceptively difficult unsolved problems in mathematical number theory. The use of simple calculations and simple rules has left the mathematical community baffled for more than 80 years. Paul Erdős, a monumental 20th century mathematician, said that: "Mathematics may not be ready for such problems." He also offered $500 for its solution. In 2010, Jeffrey Lagarias claimed that based only on known information about this problem, "this is an extraordinarily difficult problem, completely out of reach of present day mathematics.” The Collatz conjecture’s simple rules are as follows; First, start with an integer. If it is even, divide by two. If it is odd, multiply by three and add one. Then, repeat this process for the result. Simple calculations. The conjecture states that every number will eventually reach one. For example: 5>16>8>4>2>1. This research aims to explore and observe the behavior of the Collatz problem as well as the “Collatz family.” The Collatz family are defined as iterative functions in the form: AX + B (X ≡ 1 (modulo Y)) and X/Z (X ≡ 0 (modulo Y)) Where X, A, B, and Y are integers. The Collatz conjecture is for the case: A=3, B=1, Y=2. This research does not attempt to find novel solutions to the problem using analytic number theory, rather we utilize computer programs to find structures and anomalies within the Collatz familly map. Hopefully, more discoveries surrounding the structure of the problem will give rise to its elusive patterns.

There is currently a lack of research in how transgender adolescent populations are affected by sleep and depressive symptoms. Sleep is incredibly important for teens, and there are links between depression and negative sleep outcomes. The purpose of this study is to examine correlations between gender, depression, and sleep in adolescents. I am using all data from a previous study that was comparing sleep and obesity in 100 cis-gendered adolescents aged 12 to 18. I am using this data to determine if a significant correlation exists between gender, objective sleep measures including total sleep time, sleep onset, wake after sleep onset, sleep efficiency (measured via Actigraphy), and depressive symptoms (measured via Center for Epidemiologic Studies Depression Scale, with scores of 16 or higher considered positive for significant depressive symptoms). An ANOVA test is being used to analyze for a significant correlation between gender, mean sleep time in minutes, and the presence or absence of depressive symptoms. The analysis of this data determines whether or not gender has a role in sleep and depressive outcomes, thereby determining the need for a further study of sleep and depressive symptoms in transgender adolescent populations.

Sleep is crucial for producing higher levels of concentration, performance, and overall health and safety. Yet, teens, a vulnerable population, get far less sleep than the recommended 8-10 hours and continuously incur a sleep debt that negatively impacts their health. This troubling issue led to a national public health initiative to delay high school start times to benefit teens’ health. Though the Seattle school district recently accepted and implemented this initiative, it remains to be seen if the time change had the expected impact on the teens’ sleep quantity and therefore overall performance and health. The purpose of our research was to explore any correlation between the later school start time and positive outcomes of improved sleep, health and performance. In order to address this question, we created a 22-item survey which asks questions regarding quantity of sleep, self-reported measurements of mood and mental health, academic and extracurricular activity performance. We used convenience sampling and recruited from the community, specifically high schoolers within the Seattle school district who experienced the time change, to complete this survey. We expect to find that the later school start time increased the quantity of sleep high schoolers obtained, contributing to improved overall health and performance. If we obtain our expected results, we hope the data can be used to encourage other school districts to also adopt the time change and promote the health of the teen population.

One of the main science goals of the Large Synoptic Survey Telescope (LSST) is to further understand the relationship between dark energy and the universe's expansion. In order to achieve this scientific goal of the LSST, accurate estimates of photometric redshifts, which are used as a proxy for cosmological distance, for galaxies are required. To improve its estimates of photometric redshifts, the LSST could incorporate near-infrared data from other surveys along with its optical measurements of galaxy brightness. In order to understand how photometric redshifts improve with the addition of near-infrared (NIR) data, we statistically compare the quality of photometric redshifts using simulated galaxy catalogs with optical-only and optical-plus-NIR data. In my poster, I quantify the expected improvements to photometric redshifts when LSST optical data is combined with NIR data from the future ESA Euclid or NASA WFIRST space telescopes. In general, WFIRST has less outlier galaxies because WFIRST’s NIR filters have a redder band and can cover deeper in the IR spectrum.

Humans have limited ability to regenerate many tissues. In instances such as limb loss or spinal cord injuries there is a dramatic decrease in quality of life and there are few therapeutic options to help recover from these serious injuries. My research characterizes how epigenetic changes affect tail regeneration in the frog, Xenopus tropicalis. Xenopus tadpoles have significant regenerative abilities when they are developing but that ability is lost as they age and undergo metamorphosis. This transition in regenerative ability makes them a great model for understanding the molecular differences between tissue that can regenerate and tissue that can not. Other advantages of Xenopus for epigenetic studies of regeneration include a well-characterized diploid genome and many well-established molecular tools. Previous work by our group has shown that the accessibility of chromatin undergoes drastic remodeling in which many of the genes are made inaccessible shortly after injury in the Xenopus tail. These genes are then reopened during regeneration. These changes are likely due in large part to histone deacetylases (HDACs) and histone acetyltransferases (HATs). We hypothesize that HDACs are necessary for causing the initial inaccessibility of the chromatin and that HATs are necessary for the reopening of chromatin for regeneration. We used an Assay for Transposase-Accessible Chromatin and sequencing (ATAC-Seq) to show that the chromatin does not undergo its normal shift toward inaccessibility over the course of regeneration when tadpoles are treated with HDAC inhibitors, coupled with a reduction in regenerative ability. This study will help us identify how histone acetylation directs changes in chromatin accessibility. Additionally, with immunohistochemistry we can study specific sites of histone acetylation and validate these antibodies for future epigenetic research. Our study of large-scale epigenetic changes during regeneration will help characterize how epigenetic gene regulation enables regeneration.

36.7 million people worldwide are living with HIV/AIDS, of which almost 15 million receive antiretroviral therapy (ART). These patients require regular HIV-1 viral load (VL) tests to monitor ART effectiveness and compliance. However, the majority of affected people live in low-resource settings where disease monitoring through medical laboratory-based systems, such as nucleic acid amplification tests (NAATs), are inaccessible. There is an increasing need for accurate, affordable HIV-1 VL tests at the point-of-care (POC). We previously demonstrated the ability to leverage an electrokinetic separation and preconcentration technique, isotachophoresis (ITP), and an isothermal nucleic acid amplification method to develop a proof-of-concept POC NAAT for extraction, amplification, and detection of nucleic acids from human serum. The limit of detection (LoD) of our paper-based test was hampered by the loss of nucleic acids during ITP across the paper membrane. This work is focused on lowering the LoD of our test by improving the isotachophoretic extraction of nucleic acids from human serum. We have addressed the adsorption of nucleic acids by screening membrane types and pre-treatment methods. We have observed significant nucleic acid entanglement of DNA greater than 50,000 base pairs in length, which we can mitigate using DNA shearing techniques. We have also developed specialized ITP chemsitries for increased extraction efficiency. The completion of this work will result in more effective separation and purification of nucleic acids from human serum, ultimately leading to a reduction of target loss and improved test sensitivity. Employing the ITP extraction techniques developed in this work will aid our lab's ongoing efforts to create a POC NAAT for monitoring HIV-1 viral load.

My research focused on the question: What can be learned about 19th century Middle Eastern and European medical practices from the personal diaries of Joseph Mattia Svoboda, a European resident in Iraq from 1860 to 1908? Joseph Mattia Svoboda’s diaries document a very detailed account of daily life and information in the Basra and Baghdad regions of modern day Iraq. Joseph himself suffered from a chronic gastrointestinal disease and frequently wrote about the medication prescribed to him by doctors and self-selected which he then self-administered. I used this information as a basis to piece together common medical practices and medications utilized in the 19th century. Using digital transcriptions of the diaries, I used data-mining techniques to extract references to medicines, doses, and usages. Then, using contemporary European newspapers, medical journals, advertisements, and historical records I traced these medicines and their ingredients back to their origin. I examined modern research on these medicines’ ingredients to look at the effect these medicines had on the body compared to the expected results of the time period. I found the medicinal practices of the time, especially in relation to patent medicines generally stem from Europe with many medications being produced and sold there. This allowed me to identify some of the ingredients and usages. However, some of the ingredients and medications were not native to Europe, indicating a larger trade system and medical practices from around the globe influencing medicine in Iraq. Future projects stemming from my research could look into the influence of Asian, Middle Eastern, and Native American herbalism and indigenous practices on 19th century medical practices and medicine trade. Regardless, I hope my work encourages others to explore beyond the eurocentric narrative of developing medicine in the 19th and 20th centuries.

Our project is on urothelial urinary bladder cancer, one of the more common types of cancers. Our lab focuses on protein synthesis control of ARID1A, a known tumor suppressor in the context of urothelial urinary bladder cancer. Our initial workup led us to believe that ARID1A loss is not important for tumor initiation but may be important for tumor progression. To prove this, we used CRE recombinase editing tool to knock out ARID1A after treatment with BBN, a known carcinogen that causes bladder cancer. The results confirmed our hypothesis. In our investigation of this mouse model, we discovered an unexpected relationship between ARID1A loss and lowered protein synthesis. There is a growing body of literature showing that high levels of protein synthesis are required for transformation. As such, we conducted an experiment with rpL24+/- mouse model to test this hypothesis. We found that rpL24+/- mice showed a significant delay in cancer initiation compared to wild type mice when treated with BBN, thus establishing the role of protein synthesis in cell transformation. Our focus now is to figure out the relationship between ARID1A loss and protein synthesis. Based on preliminary results that we have conducted, I hypothesize that ARID1A loss and decreased protein synthesis leads to a weakened cell state which makes them vulnerable to carcinogen induced DNA damage and cell death. This was shown by measuring DNA damage, apoptosis, and cell proliferation as cellular markers of cancer and then comparing them with protein synthesis levels in ARID1A knock out (KO) cells and WT cells upon short treatments with BBN. We used both a mouse model and in vitro model to address this hypothesis.

Chronic pain affects millions of people worldwide, and current treatments and ineffective and come with unwanted side effects. Modern research focuses on studying the mechanisms of pain sensation in the nervous system, with the goal of using our improved knowledge to develop more efficient analgesics. Our research focuses on neurons located in the trigeminal and dorsal ganglia, as they are known to play an important role in the sensation of touch and pain; we also study the genes that regulate the development and function of these neurons. Recent advances in gene editing methods, particularly the CRISPR/Cas9 system, allow us to mutate specific genes of interest in a living animal and monitor the effect of such mutations within a matter of days. To this end, we have developed a behavioral assay which determines the effect of CRISPR induced mutations on pain sensation in zebrafish larvae. CRISPR injected larvae are exposed to noxious stimuli such as AITC (mustard oil) and extreme temperatures. The CRISPR treated larvae’s response to the painful stimuli is compared to wild type larvae’s response to determine the impact that the gene we targeted had on their nociception. Through this assay we have identified a gene, zbtb7b, as potentially important to the sensation of noxious stimuli. Further experiments are now required to determine the precise mechanisms through which this genes plays a role in the sensation of pain, including other behavioral assays, RNA hybridizations, and imaging techniques. Several improvements can also be made to this assay to increase the efficiency of future runs.

Necroptosis is a lytic and immunogenic form of programmed cell death (PCD), characterized by pro-inflammatory cytokine production and the release of intracellular molecules, including cell-associated antigens. This form of death occurs after RIPK3, Receptor-Interacting Protein Kinase 3, activation. RIPK3 is a cell death regulator that promotes necroptosis. Previous studies have shown that necroptotic cells can promote maturation of antigen presenting cells (APCs) and are capable of priming antigen-specific CD8+ T cell responses. Understanding the downstream immunogenic effects of necroptosis allows for implicative applications within the field of tumor immunology. Previous work has shown that necroptotic NIH-3T3 fibroblasts produce inflammatory cytokines and chemokines, contributing to their immunogenicity. To recapitulate the immunogenic nature of 3T3s, we evaluated inflammatory chemokine and cytokine production via ELISA (enzyme-linked immunosorbent assay), quantifying these productions through antibodies and color-change, from necroptotic tumor cell line supernatants, including B16.F10 melanoma and LL/2 adenocarcinoma cells. Surprisingly, our results did not show significant chemokine or cytokine production from necroptotic tumor cells, suggesting that anti-tumor effects are not from signals derived from the tumor micro-environment (TME). This suggests that other forms of signaling downstream of RIPK3 activation, such as upregulation of non-chemokine transcriptional programs, could be the source of inflammatory signal production by necroptotic tumor cells. Further actions include RNA sequencing of necroptotic cancer cell lines to differentiate global changes between apoptotic and necroptotic forms of cell death, to provide unbiased analysis of transcriptional changes. With evidence of T cell-mediated immunity and the immunogenic nature of necroptosis, induction of this form of cell death within the TME will activate anti-tumor immune responses, potentially controlling tumor growth and contributing to the field of immunotherapy.

Plants recycle resources from dying organs to feed the development of new ones. For example, chloroplast degradation in senescing leaves is a major source of nitrogen for seeds. Darkness or shade can induce leaf senescence and chloroplast degradation, but if light returns soon enough, new chloroplasts are made and the leaf remains photosynthetically active. Phytochrome B (PHYB) is a protein that serves a key role in resource allocation throughout the plant. phyB null mutants of the model crop species Brassica rapa (Br) exhibit low chloroplast count, poor seed production, and a reduced increased growth response to high CO2, as compared to wild type. We will investigate the underlying cause of these phenotypes by comparing the transcriptomic response of chloroplast-biogenesis and nitrogen-assimilation-related genes in wild-type and BrphyB null mutants before and during dark-induced senescence, as well as after recovery. Establishing a deeper understanding of the scope of PHYB's role in resource recycling will help us isolate appropriate targets for engineering more drought-resistant and nutrient efficient crops.

Human immunodeficiency virus (HIV) infections are often paired with microbial translocation within the gastrointestinal tract (GI). In-vivo studies show that HIV-associated microbial translocation results from multiple immunopathological events occurring at the GI mucosa: early, detrimental, severe CD4(+) depletion in mucosal regions, mucosal immune hyperactivation and inflammation, and intestinal epithelium damage. Previous human studies have shown anti-inflammatory effects of cannabis, along with slowed GI tract disease progression. This project aims to further understand HIV infection and its response to patients’ cannabis use. We hypothesize the anti-inflammatory effects of cannabis should decrease the microbial translocation within HIV+ individuals. Using stool from HIV+ and HIV- patients, DNA and short chain fatty acid (SCFA) extractions were performed. The DNA was extracted using Power Fecal DNA extraction kits. In order to understand microbial community and how it relates to SCFA production, the extracted genomic DNA was PCR-amplified and will be sequenced with an Illumina MISEQ. SCFA extraction was done with ethyl acetate. We analyzed the samples using gas chromatography-mass spectrometry, and it showed HIV+ patients had a decrease in acetic (p=0.0057), propionic (p=0.0325), butyric (p=0.0007), iso-butyric (p=0.0039), and valeric acid (p=0.0133). When compared with HIV- patients, there’s an overall decrease in total SCFA (p=0.0012). These results demonstrate the detrimental effects HIV infection has on SCFA production, which can lead to a decrease in available energy for colon cells and disrupt gut microbial community health. However, amongst HIV+ with cannabis use, we saw an increase in acetic (p=0.0173), propionic (p=0.0087), butyric (p=0.0173), iso-butyric (p=0.0043), and total SCFA (p=0.0057). The HIV+ patients that used cannabis saw improvement in microbial community health, which is a promising sign that cannabis assists with the recovery of antiretroviral treatment.

Based on the Newbook Digital Texts: Joseph Mathia Svoboda Diaries, I expect to answer the question of how the route of the Tigris River traveled by Joseph, a man of Eastern European decent living in the Ottoman Empire in the last half of the 19th century, has changed in the last 100 years. The Svoboda Diaries provide an insight into life and travel in the Middle East. They contian the documentation of Joseph's travels in current day Iraq, detailing villages and towns passed on his regular routes. The purpose of this research is to show that some major changes in the river are due to economically and politically motivated policies made to control sections of the river. I hypothesize that economic and social policies since Joseph's time have impacted the river today. In my research, I use mapping software to visualize changes in modern-day Iraq. Through the program StoryMap, I highlight locations along the river and compare it today. Using maps from the late 19th century I will track changes and display them in comparison to an up-to-date map. Newbook currently has a few maps available, although I also plan on using articles from their past interns, one in particular that focuses on Hydraulic Policy in Iraq. Additionally, I will look for other maps available from the Library of Congress. Through my research, I expect to find changes in major dam projects, canals and irrigation projects as well as groups of people and tribes dislocated by changes to the river.

Degeneration of mechanosensory hair cells in the inner ear leads to complications in hearing and balance. Calcium plays an important role in hair cell function and failure to maintain calcium homeostasis is an underlying cause of hair cell death. We used hair cells in the zebrafish lateral line as our model, to explore the role of endoplasmic reticulum (ER)-mitochondrial calcium flow in hair cell damage. We utilized ER-GCaMP-150 for these studies, a new low-affinity calcium indicator made distinctly to look at calcium concentrations in the ER. Injection of zebrafish embryos with ER-GCaMP-150 expressed under a hair cell specific promoter allowed for visualization of ER Ca²⁺  concentrations under a high-resolution microscope. To date we have confirmed expression of ER-GCaMP in our zebrafish models and quantified Ca²⁺ transfer between the ER and mitochondria. Examining changes in calcium concentrations of hair cell organelles provides the opportuninty to gain more insight into the intracellular mechanisms underlying hearing loss.

Oncolytic adenoviruses such as serotype 5 adenoviruses (Ad5) selectively infect and destroy cancer cells and are widely used in preclinical and clinical trials for gene therapy. However, Ad5 has many downsides including preexisting anti-Ad5 immunity in humans, and the Ad5 receptor (CAR) is known to be down regulated in many aggressive tumors. Species B adenoviruses which use a different receptor than CAR are an alternative which shows great promise. These vectors avoid the immune response against Ad5 and show different cell tropism. Our lab has identified desmoglein2 (DSG2) as the main receptor for a group of species B adenoviruses, including Ad3. DSG2 is an epithelial junction protein and is highly expressed in malignant tumors. During Ad3 infection, binding of Ad3 fiber to DSG2 triggers the transient opening of these intercellular junctions and thus supports the lateral spread of the progeny virus. Our lab has recently developed an Ad3 fiber knob mutant (Y250F) which has an enhanced affinity to DSG2. We have shown that an increased affinity is correlated with a stronger ability to open these junctions. In this study, we developed an Ad3 based oncolytic vector containing fibers with enhanced affinity to DSG2 (> 400x higher than wild type Ad3.) We developed this vector using PCR site-directed mutagenesis and cloning the recombinant gene in E. coli. By inserting our gene into a Ad3 plasmid it allowed us to transfect the plasmid into human embryonic kidney cells (HEK 293 cells) and to amplify and recover the mutant oncolytic virus. We are working on in vitro experiments and in vivo tumor xenograft models to test our hypothesis that the oncolytic virus with an enhanced affinity to DSG2 will be translated to a significant improvement to the spreading of progeny virus, and thus a significant improvement to the effectiveness of oncolytic virotherapy.

The ease at which we appear to recognize and assess faces belies the difficulty underlying face recognition. Faces possess similar features (i.e. eyes, nose, mouth), yet we are able to identify separate individuals based on their featural configuration (i.e. T-shaped arrangement of features). Prior research using fMRI shows that featural and configural information is processed in different face-specific brain regions. Evidence suggests that the FFA responds to both featural and configural information, compared to the OFA and fSTS, which only respond to featural modification. However, precise response time of featural and configural face processing is unknown. Featural processing may occur before configural processing, or configural processing may occur before featural processing; conversely, they may occur simultaneously. Using a 2x2 factorial design we assessed the effects of changes in featural information, configural information, as well the interaction between the two. Participants saw four versions of a face: intact faces, faces with removed features, faces with distorted configuration, and faces with both modifications. Stimuli were presented while the brain activity of subjects was recorded using electroencephalography (EEG). This study specifically looked at temporal changes in a face-specific event related potential (ERP) called the N170, which consistently fires when presented with anything that resembles a face. We assessed the magnitude of the N170 to determine whether the face-processing brain regions explicitly processed information regarding features and configuration. In addition, timing of face-processing was assessed to detect any differences in how long it took the brain to process faces with featural or configural modifications. We tied together evidence from fMRI (spatial) and the N170 (temporal) to see how precise timing and location interact in the brain during face perception of facial features and feature configuration.

Changing developmental patterns is an essential strategy for plants to survive environmental stressors, and the hormone auxin coordinates much of plant development. In the auxin signaling pathway, Aux/IAAs are co-repressors that block expression of auxin target genes. When auxin is present, Aux/IAAs are ubiquinated by an E3 ligase and then degraded via the proteasome. This results in an increase of auxin response gene expression. Past research in the Nemhauser lab found that a dominant mutant in the Aux/IAA known as IAA28 alters the placement of lateral organs around the stem (a process called phyllotaxy). IAA28 loss-of-function mutants show no phenotype, so we hypothesized that another gene or genes could be acting in a redundant manner. IAA28 is closely related to two other Aux/IAAs called IAA18 and IAA26. Using CRISPR/Cas9 technology, I am making triple mutants that lack function of IAA18, IAA26, and IAA28. Once I have these mutants, I will measure phyllotaxy and other developmental phenotypes to look for differences when compared to wild-type plants.

Global climate change and population growth pose a significant risk to global food security. Estimates suggest that animal products alone, such as animal feed, must increase by 60-70% by 2050 to keep up with population growth. Crop species are needed to feed people directly and to feed livestock. How crop species respond to predicted climate change compounds the complexity of this challenge. Phytochrome B (phyB) is a photoreceptor that affects the plant’s ability to respond to changing resource availability. Plants with a reduced phyB function make less seeds, whether measured in the model plant, Arabidopsis thaliana, or in the crop, Brassica rapa. The reason for this seed yield phenotype is unknown. Characterizing reproductive structures in Brassica rapa from before fertilization through the production of viable seeds to identify the role phyB plays in seed production will give insight in this process. Doing this may ultimately lead to the identification of potential targets for engineering higher yielding oil seed varieties.

BrainNet is a system designed to be the first multi-person direct brain-to-brain interface in human brains. This interface combines electroencephalography (EEG) to record brain signals and Transcranial Magnetic Stimulation (TMS) to deliver information to the brain. Through this interface, three subjects will collaborate to complete a Tetris-like block game using direct brain-to-brain communication. Two of the three subjects are designated as "senders", whose brain signals are decoded by real time EEG data analysis. The decoding process extracts information about their decisions to rotate a Tetris block before it is dropped to fill the line. Then, this information is transmitted via TCP and directly delivered through magnetic stimulation of the occipital cortex to the brain of the "receiver", who cannot see the game screen. The receiver integrates the information s/he acquired from the senders and conveys this information back through EEG to the computer, which completes the intended action of either turning the block or keeping it in the same position. The performance of this brain network is evaluated in terms of the accuracies attained in (1) decoding decisions through EEG analysis, (2) delivering information through TMS, and (3) making correct group-level decisions during the block game. This interface enables for the very first time simple transmission of information directly among three brains without any verbal or physical action. Our preliminary result has shown proof of successful communication between the senders and the receiver with 14 out of 15 trails correct. BrainNet enables direct brain-to-brain communication of simple information between multiple humans, and is a step forward towards ultimate brain-to-brain communication. 

In order to yield the maximum number of high quality exoplanet observations, it is crucial to have the right data input based on pre-existing planetary models. Here we use a model of the solar system planets for modeling exoplanet observations that is as accurate as possible. However, the published model did not integrate how the observed spectra of an exoplanet would depend on its phase angle. Thus, we simulated planets with realistic atmospheric and surface features, and calculated high-resolution spectra at different phases. Interpolation further allows users of the Roberge “Haystacks” model to calculate values at exact phase angles. The results reveal how different types of scattering and surface features affect the reflected sunlight. In particular, our results for Venus, Earth, and Mars show that planets appear more reflective at crescent phases due to scattering by clouds and aerosols.