Homeless young people aged up to 30 encounter difficulties when looking for work. The U-District Job Co-op is a design vision that seeks to overcome these difficulties by connecting homeless youth to short-term employment opportunities. Unlike other job search websites, the U-District Job Co-op accommodates the needs of homeless young people by inviting community members to offer mini-jobs and a system of support. Mini-jobs will help homeless young people develop life-skills and work experience that may lead to long-term, permanent employment. Support is provided by employers who offer mini-jobs and feedback, and service providers who assist with the job search and application process, facilitating communication between youths and potential employers. The initial design of the U-District Job Co-op was articulated through wireframes, representations of the layout and structure of the website. Content for the wireframes was drawn from community workshops where homeless young people and other community members discussed barriers and solutions homeless youth encounter in securing work. Three sets of wireframes were developed to show the different perspectives of how a homeless young person, service provider, and employer might interact with the U-District Job Co-op. Eight homeless young people participated in co-design activities (2 participants per activity) that provided assessment of the wireframes. In the co-design activities, homeless young people responded to designer prompts by sketching information they want to present to potential employers through the U-District Job Co-op. Quantitative analysis of the co-design data mapped the number of occurrences of features presented by homeless youth to existing wireframe features. This data informs the refinement of the wireframes. Future work includes developing the U-District Job Co-op into a fully functional website based on the refined wireframes and exploratory field deployments.

Sensory hair cells in our inner ear are necessary to detect sound, and hair cell death is the primary cause of hearing loss. A certain class of antibiotics, including neomycin, induces hair cell death. Understanding the mechanisms involved in preventing hair cell death may yield pharmacological advancements to protect sensory hair cells when these antibiotics are administered. Zebrafish are often used to study hair cells because fish have readily accessible hair cells on their exterior that are analogous to sensory hair cells within our inner ear. This project investigated the effects of heat shock on neomycin-induced hair cell death. Heat shock can trigger several signaling pathways known to protect cells against cellular insults. We hypothesized that applying heat shock prior to exposing the hair cells to neomycin would inhibit damage by increasing cellular defense mechanisms as seen in other organisms. The data were obtained by placing 5-day-old zebrafish in a 38 degree Celsius water bath for one hour (heat shock), followed by an hour break for recovery, and then a 30-minute incubation period in neomycin. We quantified the degree of damage to the hair cells 5 hours after neomycin treatment by scoring (ranking) hair cell clusters based on cluster size and counting the number of hair cells located in specific areas. Our results suggest that heat exposure partially inhibits neomycin-induced hair cell damage. Further research may yield insight toward pharmacological advances that prevent antibiotic-induced hair cell damage.

Drift algal material is expected to play a significant trophic role in ecosystems adjacent to kelp beds. The contribution of drift algae to the overall nutritional state of various invertebrates can be assessed using phenotypic traits such as gonad index (larger gonad mass with better nutrition) and for sea urchins, jaw diameter (larger jaws with inconsistent food supplies). In this study, we collected green urchins (Strongylocentrotus droebachiensis) within kelp beds (5m depth) in the shallow subtidal photic environment (SSPE) and outside of kelp beds in nearby deep subtidal environments (DSE; 100m depth) during spring and winter seasons. SSPE and DSE sampling stations were less than 1 km apart. In the initial spring analyses, urchins in the DSE had significantly larger gonads but also larger jaws than SSPE animals. Winter gonad indices showed a reverse pattern, in which SSPE urchins had larger gonad indices, but still had smaller jaw indices than the DSE urchins; gonads in all urchins on this sampling date were much larger than those in the previous spring. These results suggest that food supplies may vary among seasons, especially in deep habitats, where the subsidy of algal material exported from shallow water may be inconsistent; the jaws from DSE urchins concur with this hypothesis. Gut content analyses from winter samples will be used to evaluate the types of foods available to deep vs. shallow-water animals.

 Vesicular Glutamate Transporters (vGluts) are proteins that package glutamate into vesicles prior to synaptic transmission. Three isoforms have been identified in mammals (vGlut-1-3), with 1 and 2 showing a mostly complementary pattern of expression, and 3 co-localizing in a small number of cells with both 1 and 2. Knockout mice for the vGlut1 gene die shortly after weaning, indicating a crucial role for vGlut1 in development. Intriguingly, avian genomes contain no vGlut-1 orthologs, despite the fact that lizards, a common ancestor of both mammals and birds, have orthologs of both vGlut-1 and -2. The fact that birds function without vGlut1 suggests there may be an increased functional role for vGlut2 in the avian brain. To further demonstrate the presence and potential role of vGlut2 in avian pallial circuitry, we used immunocytochemical methods to study the brain distribution of vGlut2 protein in zebra finch. To confirm the specificity of antibodies to vglut2, we first performed co-localization of anterograde tracer with vGlut-2 in known glutamatergic terminals in RA that originated from pallial song nucleus HVC. Electron microscopy further confirmed that labeling was restricted to synaptic terminals containing vesicles, and in situ hybridization was used to confirm the presence of mRNA in somata. We found that a large number of vGlut2-positive cells are present throughout the zebra finch pallium, and also found evidence for vGlut-2 positive synapses in three different song nuclei (nucleus HVC, Area X, and robust nucleus of the arcopallium), which were imaged and analyzed for size, and the potential identity of post-synaptic elements. Our results are consistent with the notion that avian vGlut2 has largely taken over vGlut1 functions. We believe our study contributes important facts to the long disputed evolutionary relationship between the avian pallium and the mammalian cortex.

Hybrid organic/inorganic composites of conjugated polymers with quantum dots are of interest due to their potential for low-cost, solution processable solar cells and photodetectors. We use photoinduced absorption (PIA) spectroscopy to study charge generation in hybrid bulk heterojunction blends of the conjugated polymers with PbS quantum dots. We have previously shown that selective excitation of the quantum dots leads to formation of positively charged polarons on the conjugated polymer. By computing the relative yields of long-lived holes following photoexcitation of both the polymer and quantum dot phases, we estimate that more long-lived polarons are produced per absorbed photon by the polymer phase than the quantum dot phase. In this study, we aim to determine whether the formation of long-lived charge carriers due to quantum dot photoexciation is wavelength-dependent by investigating the polaron yield resulting from selective PbS excitation at varying energies in the near infrared. These results will give insight into the process of hole transfer from photoexcited quantum dots to the organic host polymer.

A major obstacle in the efficient delivery of genes using non-viral vectors is sequestration and subsequent degradation of the vector in the endosomal/lysosomal trafficking pathway. While incorporation of membrane-lytic peptides into gene delivery vectors has been shown to increase transgene expression by disrupting the endosomal vesicles, non-specific membrane-disruption caused by these modified vectors leads to significantly increased toxicity. One approach to mitigating this increased toxicity is to mask the membrane-lytic peptides inside a pH-responsive micellar core that destabilizes during vesicle acidification in the endosomal/lysosomal pathway, revealing the membrane-lytic segments only when internalized. Incorporating pH-responsive imidazole elements in the hydrophobic micelle core which become charged under acidifying conditions can disrupt the micellar structure by electrostatic repulsion, leading to display of the active peptide, membrane lysis, and increased DNA delivery to the cytoplasm. After synthesis of the pH-responsive motif a panel of representative DNA delivery polymers will be evaluated for pH-responsiveness, transfection efficiency, and cytotoxicity.

Collective oscillations of conduction electrons in a metal nanoparticles, known as localized surface plasmon resonances (LSPRs), have been the source of much scientific study over the last decade due to their immediate and significant applications in biosensing, surface-enhanced Raman Spectroscopy (SERS), and light absorption engineering in semiconductor nanodevices used in solar cells. Due to the diffraction limit, many properties of LSPRs are undetectable by optical spectroscopies, creating a need for detection via electron-based probes. LSPRs can be generated as a result of high-energy electrons, such as those in an electron energy-loss (EEL) microscope, transferring energy to a nanometal’s electron cloud. This energy can follow a variety of pathways: it can be stored in the electric near-field of the nanoparticle (possibly generating "hot spots" - regions of very high electromagnetic field), radiated into the far field (becoming visible as light), or lost to thermal excitation of the metal. The purpose of this work is to study how nanoparticles distribute energy amongst these decay paths and to quantify the interactions between two adjacent nanoparticles. An interaction of significance is  the Fano effect - a destructive interference between the electric fields generated by two adjacent nanoparticles that leads to electromagnetically induced transparency. The Fano effect is studied from a theoretical perspective and is discussed in the context of energy transfer between different modes of a collective LSPR that spans both nanoparticles.

Solar technology is a potential way to help meet the growing demand for clean, renewable energy. Hybrid composites of inorganic quantum dots, with organic semiconducting polymers offer a potential means of producing low-cost, solution-processable photovoltaics. The synthesis of quantum dots typically involves the use of large surfactant molecules to facilitate particle growth and solubility. These native ligands act as electrical insulators that impede charge transport in photovoltaic devices. Therefore, it is necessary to exchange these large ligands with small molecules to achieve efficient charge carrier photogeneration and transport. In this research, we examine bulk heterojunction blends of low band gap PbS quantum dots with the conjugated polymer poly((4,8-bis(octyloxy)benzo(1,2-b:4,5-b')dithiophene-2,6-diyl)(2-((dodecyloxy)carbonyl)thieno(3,4-b)thiophenediyl)) (PTB1) treated with different ligands including cetyltrimethlammonium bromide (CTAB), tetrabutylammonium thiocyanate (TBAT), and 3-mercaptopropionic acid (MPA). We aim to elucidate how these different ligands influence the photovoltaic performance of PbS/PTB1blends by studying the differences in long-lived charge generation and recombination kinetics associated with the quantum dot ligand treatments using transient photovoltage (TPV) and photoinduced absorption (PIA) spectroscopy, respectively. We will also determine whether different ligand treatments influence film morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). We hope to gain a better understanding of how quantum dot ligand treatments may be used to optimize the performance of hybrid photovoltaics.

Cancer genomic analyses performed by our team have allowed us to identify frequently mutated genes in Small Cell Lung Cancer (SCLC). Among these genes, MLL2 was found to undergo loss of function mutations suggesting it could act as a tumor suppressor. MLL2 is a histone methyl transferase that transfers a methyl group to a histone on a DNA strand. This process regulates chromatin state and transcription. More specifically, MLL2 methylates the lysine 4 of histone H3 leading to the activation of gene expression. Interestingly, MLL2 was also recently found mutated in squamous cell lung carcinoma, non-Hodgkin lymphoma, medulloblastoma and cell renal carcinoma pointing out that it could be a novel major tumor suppressor. To investigate this hypothesis, both in vivo (mouse models) and in vitro (cell based assays) will be used. The mouse model consists of a conditional, tissue specific inactivation of two prototype tumor suppressors namely p53 and Rb, which are found highly mutated in SCLC. The role of MLL2 will be studied in this mouse model by generating triple mutants (Rb, p53, and MLL2) mice. The survival of control SCLC mice (p53 and Rb inactivated) will be compared to the survival of the triple mutant (MLL2, Rb, and p53) mice. This critical experiment should enlighten us on the functional role of MLL2 during SCLC development. Molecular and histopathological analyses will also be performed. Additionally, in vitro approaches with human and mouse cells will be used to identify and understand the biological processes and pathways regulated by MLL2. Altogether, it should help us decipher the role of MLL2 in SCLC and it might ultimately lead to the identification of novel treatments and/or preventive options for SCLC.

The goal of the New Muon (g-2) Experiment at Fermilab is a fourfold precision increase of the measurement of the anomalous magnetic dipole moment of the muon, with the hope of achieving a 5σ deviation from theory. Such a discovery would provide a basis for the exploration of new physics beyond the Standard Model. Many candidates exist for explaining this discrepancy, such as supersymmetry, dark photons, or lepton substructure. My work involves the characterization and analysis of Silicon Photomultipliers (SiPM’s) in support of the development of the (g-2) calorimeters — the central detector systems required to make the measurement. These avalanche photodiode arrays are a significant change from the previously used vacuum photomultiplier tubes (PMT’s). SiPM’s are extremely compact and can be mounted directly inside the magnetic field of the muon storage ring; characteristics such as these them a distinct advantage over PMT’s. A thorough study of pulse resolution, temperature dependence, gain, rate, and other properties is necessary to understand how SiPM’s may be most effectively utilized in the (g-2) experiment. Analyzing pulse resolution and gain involves exciting the SiPM with two laser pulses spaced 2 to 100 nanoseconds apart and determining how closely the pulses can overlap before a significant amount of information contained in the output of the SiPM is lost. Variations in the size and strength of each pulse have also been introduced in the study, such as saturating the SiPM circuit with a blast of laser light and studying how long it takes the device to recover.

Gamma activity refers to high-frequency neural activity (30-100 Hz) typically measured by electroencephalography (EEG). Evoked gamma activity is time-locked to stimulus onset which often reflects processing of stimulus properties such as the presence of edges and local luminance contrast. However, induced gamma activity is not time-locked to stimulus onset and evidence suggests it may reflect activation of the perceptual representation of the object presented. Here, we investigated whether induced gamma was altered by in-depth rotations of objects to elucidate the role of such activity in object perception. If induced gamma reflects a high-level object representation then it should not differ with rotation. However, if induced gamma reflects a representation of object features then induced should be modulated by in-depth rotation. We presented pairs of stimuli: an initial adapting stimulus followed by a test stimulus. Stimulus pairs were images of the same or different cars with the test stimulus rotated 0°, 90°, or 180° from the initial adapting stimulus. EEG gamma activity was measured using a 32-channel active electrode Biosemi, Active Two system. We analyzed gamma activity using Morlet wavelet decomposition that allows the measurement of induced gamma activity. The results revealed that induced gamma activity was related to the amount of rotation, with the lowest induced gamma activity during trials with no rotation and highest for trials with 180° rotation. This pattern suggests that induced gamma activity is related to processing of object features below the representation of the whole object. Moreover, the results suggest the cortical generator for the gamma oscillations may be lateral occipital object-selective regions that have similar sensitivity to in-depth rotation across similar paradigms and stimuli using fMRI. The results suggest a link between EEG induced gamma activity and object-selective visual cortex, and provide important information on the temporal dynamics of object-processing brain regions.

Obesity is a growing epidemic. Consequently, the percentage of Americans living with Type 2 Diabetes Mellitus (T2DM) has increased; 25.8 million Americans suffer from diabetes, and 90-95% of adult diabetes is T2DM. Bariatric surgeries--gastrointestinal operations designed to encourage weight loss by rerouting and reconnecting various parts of the stomach and small intestine--have been developed in response to increased obesity. A ramification of these surgeries is the elimination of T2DM; 84% of patients with T2DM experienced complete remission of diabetes after bariatric surgery. At RYGB Mechanisms (RYGBM) Animal Lab, we seek to understand the mechanisms of weight loss and T2DM remission in bariatric surgery through the development of an animal model. The animal models selected for this research are Ossabaw pigs. These pigs, raised on high fat diets, are obese and naturally develop insulin intolerance similar to T2DM in humans. There are two leading hypotheses for the causal relationship of bariatric surgery and the elimination of T2DM: the Lower Intestinal Hypothesis and the Upper Intestinal Hypothesis. To test these hypotheses, we perform five variations of bariatric surgery on the animal models: Gastrojejunostomy (GJ), GJ with Duodenal Exclusion, Roux-En-Y Gastric Bypass (RYGB), RYGB with Vagotomy, and Sham operation. We perform these variations of surgeries in attempts to identify which procedures will decrease T2DM while being the least invasive and most recoverable. Pre-operative and post-operative weights indicate if the surgery worked as a weight loss mechanism, while the pre-operative and post-operative changes in insulin sensitivity and gut peptide hormones--ghrelin, PYY, GLP1--indicate if the procedure succeeded as a T2DM loss mechanism. Since the start of the study, survival rates have improved, and RYGBM compilation of data has increased, thus enhancing conclusive findings, though data to support either hypothesis is still in progress.

With efforts being made to remove human impact on the ecosystems surrounding us, underwater ambient noise is a topic of interest. Understanding and even mitigating this ambient noise has come to be of foremost importance in various fields. To understand underwater noise, it is best to first have a well-developed understanding of noise in general and what it is about noise that we should concern ourselves with. Starting first with sources of sound, such as that of a person singing, can provide an introduction into how to process sound measurements underwater. By working with recordings in “.wav” form I was able to convert to a spectrum, or spread of frequencies, that can be read in terms of the frequency and underwater pressure, two important aspects when studying underwater ambient noise. Using a numerical computation language (GNU Octave) to analyze sound data, I was then able to see plots of these spectra as well as to generate Pressure Spectral Density plots. I was then provided guidance regarding how to interpret these plots and apply this knowledge to various locations, a necessary introductory step in the overall process. Understanding ambient noise in general, as I was able to start doing this summer, and then taking it further to understand ambient noise in our area, is the first step towards curbing disturbances to our marine ecosystems.

 Human aortic diseases such as aneurysms (abnormal dilation of the aorta) dissections (tears in the wall of the aorta) are often life-threatening. These diseases present significant challenges because: 1) their pathogenesis is not well understood; 2) they are difficult to diagnose, often presenting at an advanced, life-threatening stage; 3) they have limited treatment options; and 4) the treatments are all associated with major complications. Our work focuses on achieving a better understanding of the pathogenesis of aortic aneurysms and dissections, with a long-term goal of preventing or stabilizing these diseases. Signaling pathways initiated by transforming growth factor beta (TGF-β) in smooth muscle cells (SMC) of the aorta are essential for normal vascular development. Mouse embryos lacking SMC TGF-β signaling exhibit abnormal aortic structure, including dilation of the distal aorta. However, the role of SMC TGF-β signaling in maintaining the structural and functional integrity of the adult aorta is unclear. We use a transgenic mouse model to test the hypothesis that TGF-β signaling in adult aortic SMC preserves aortic health and prevents aortic aneurysms and dissections. With this model we can delete a gene that is critical for TGF-β signaling specifically in SMC of adult mice, and thereby discover the role of SMC TGF-β signaling in the regulation of SMC gene expression and aortic structure. We expect to find abnormal gene expression and aortic structure in adult mice with loss of SMC TGF-β signaling. Our study may uncover signaling pathways and gene expression patterns that maintain aortic health. These pathways may eventually be exploited to develop therapies that prevent aortic aneurysms and dissections.

The goal of our research is to understand mechanisms of the earthworm immune system responsible for distinguishing symbionts from potential pathogens. The Hygiene hypothesis, proposed by David Strachan and published in British Medical Journal in 1989, fundamentally expanded our view on microorganisms and natural development of immune system. The hypothesis states that early childhood exposure to microorganisms is essential for acquiring healthy immunity. Studies in mice showing that host-specific bacteria in the gut are required for full maturation and function of the immune system support this hypothesis. Although numerous symbioses of beneficial bacteria with animals have been studied, the role of symbionts in the development of host immunity remains uncertain. Additional models are needed to study the roles and regulation of the immune responses to host-specific beneficial bacteria. The earthworm offers a tractable system in which to study immune system development and responses to both beneficial symbionts and potential pathogens. Eisenia fetida, a common composting worm, has an effective immune system that eliminates bacteria from the coelom. E. fetida also harbors specific bacterial symbionts in the excretory organs (nephridia) that process coelomic fluid, thus potentially exposing the bacteria to immune elements in the fluid. We hypothesize that the immune system adapts to the symbiotic bacteria in order to avoid eliminating them, or cause unnecessary inflammation in the nephridial tissue. Therefore, we investigated the contribution of the bacterial symbiont Verminephrobacter eiseniae to the development of immune system responses in E. fetida. Coelomocytes were extracted from symbiont-containing earthworms and symbiont-free earthworms, and were examined for differences in their binding and engulfment responses to V. eiseniae and non-symbionts. We believe further studies of the role of immunity in symbiont recruitment mechanisms in the earthworm would help us understand more about the co-evolution of beneficial microbiota and the host organisms in other species. 

During the postembryonic transformation from larva to adult, zebrafish undergo a dramatic metamorphosis in pigment pattern. New pigment cells differentiate, interact, and migrate to form stripes of black cells (melanophores) and the interstripe regions of yellow cells (xanthophores); this pigment pattern characterizes adult zebrafish. My project investigates the roles of thyroid hormone (TH) in this dramatic transformation. We have produced a stable transgenic line expressing a transgene for nitroreductase exclusively in the thyroid gland. When I expose these transgenic fish to the drug metronidazole, toxic byproducts are produced in the thyroid gland, causing cell death and ablating the gland and preventing the fish from producing any TH. Using these thyroid ablated fish, I have characterized pigment cell differentiation and pattern formation in the absence of TH. I find that these thyroid ablated individuals do not develop xanthophores and show resulting disruptions in stripe boundary formation. Our lab has also found a zebrafish pigment mutant (opallus), which produces an excess of xanthophores. Mapping data from this mutant leads us to hypothesize that the phenotype is caused by a gain-of-function mutation in the receptor that stimulates TH production in the thyroid gland. I test the prediction that the excess xanthophore phenotype is caused by overproduction of TH by blocking TH synthesis using the drug methimazole, and show that these treatments rescue the opallus pigment phenotype, returning them to a wild-type pigment pattern. Moreover, I test the prediction that exposing wild-type zebrafish to exogenous TH produces an opallus-like pigment pattern. Thus, by quantifying the number of melanophores and xanthophores and their distribution across the flank in these hypothyroid and hyperthyroid backgrounds, I show that TH is both necessary and sufficient for xanthophore differentiation, and that both too much and too little thyroid hormone during the adult transformation grossly disrupts the formation of adult stripes.

Skeletal muscle myosin can use a variety of nucleotides to varying effectiveness as substrates for contraction. We previously demonstrated that complete replacement of ATP with 2 deoxy-ATP (dATP) in activation solutions increases contraction of demembranated rabbit skeletal muscle and that enhanced performance results from increased myosin binding and cycling kinetics, especially during sub-maximal calcium activation. Here we report on a transgenic mouse (Tg-RR) that overexpresses the enzyme, ribonucleotide reductase, which converts ADP to dADP, which is rapidly phosphorylated to dATP. This results in a 10-fold increase in dATP content of skeletal muscle, which still constitutes less than 2% of the adenosine triphosphate nucleotide pool. We are examining the contractile and metabolic properties of skeletal muscle in this transgenic model. Preliminary data indicates the phosphocreatine to ATP (PCr:ATP) ratio of Tg-RR mice is significantly elevated relative to wild type mice, suggesting the Tg-RR mice may have an energetic advantage due to increased high energy phosphate reserves. Furthermore, the Tg-RR mice ran for a longer period of time at increased speed and for longer distances in a graded exercise test. Direct in situ stimulation of the gastrocnemius muscle indicates improved resistance to fatigue, consistent with both the exercise and the metabolic (PCr:ATP) findings. Interestingly, our preliminary experiments suggest the Tg-RR mice produce significantly less peak force and show signs of atrophy. Ongoing experiments are examining changes in mitochondrial content and function as well as contractile properties of isolated muscles to determine the mechanisms underlying the increased fatigue resistance of the Tg-RR mice. These results suggest a new direction for developing interventions to improve exercise tolerance in human patients.

Do you worry more about getting cancer or having heat stroke? If you chose cancer, you are among the majority because cancer has a relatively higher risk perception. Risk perception describes how people emotionally and psychologically perceive hazards. It is different from risk assessment, which often analyzes risks quantitatively. Therefore, some risks may have minimal hazards but elevated risk perceptions, and vice versa. Understanding how businesses perceive climate risks is crucial to effectively approach climate change. My research aimed to determine whether businesses perceive climate change as a substantial risk to alter business behaviors. As such, I first interned at the U.S. Environmental Protection Agency to evaluate the risk perception associated with polychlorinated biphenyls (PCBs) and whether higher risk perception encourages action. I discovered that PCB contaminations in NY schools were associated with a high risk perception, which consequently pressured authorities to take proactive and remediation measures. Alongside my internship, I conducted a literature reveiw and verified that higher risk perception triggers higher chances of action. However, there are limited evidences that willingness to act may plunge when people find benefits associated with risks, entrust others to manage risks, or lack resources. In applying these findings, I conducted additional literature review to evaluate the willingness to invest by businesses for climate change, through looking at their risk perceptions. My results indicate that businesses have moderate risk perception of climate change, but low willingness to act. Most managers believe that regulators will tell them what to do, implying that they entrust the government to manage climate change. I conclude that businesses will not pay to prepare for climate change at this point in time. This implies that government must mandate businesses to change. Future studies must assess willingness of businesses to take actions as climate risks become greater.