Multicultural Histories and Legacies of London and Rome 2018

STEP Category: Education AbroadThe Multicultural Histories and Legacies of London and Rome was a one month program in May 2018 in which we traveled to the United Kingdom and Italy to sight see, volunteer, and learn about the vast differences of their social, political, religious, and educational structures.The Ohio State University Second-year Transformational Experience Program (STEP)Academic Major: Marketin

Genome-Wide Systems Genetics of Alcohol Consumption and Dependence

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence. The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks in the mesolimbocortical system of acute alcohol-treated mice and human genetic alcohol dependence association data. This study successfully identified ethanol-responsive gene expression networks with overrepresentation of genes suggestively associated with alcohol dependence in an independent human sample, indicating that gene expression networks in mouse models are informative for identifying mechanistic networks relevant to the risk for developing dependence. The second study aimed to identify quantitative trait loci for voluntary alcohol drinking behaviors under an intermittent ethanol access paradigm, in the genetically complex Diversity Outbred mice. After determining high heritability for alcohol consumption and dependence amongst the progenitor strains, we identified several specific genetic loci associated with these traits. One locus replicated results from a human association study of alcohol consumption, and provided insight to the potentially contributing genes. Finally, we identified alcohol consumption-correlated gene expression networks in the prefrontal cortex of these mice. We also mapped quantitative trait loci for network expression levels, some of which overlapped with the behavioral loci, indicating that the functions represented by these modules mediate the relationship between the genotypes in that region and drinking behaviors. Overall, our studies revealed neuroplastic and ubiquitin-related genes pathways involved in alcohol consumption in mice and humans, and that likely contribute to the risk for developing dependence

Resistance in Candida albicans: exploring the cell wall barrier by proteomics

The incidence of candidiasis has dramatically increased and bloodstream infections due to different species of Candida are becoming a prime cause of morbidity and mortality in different types of immunocompromised patients. Azole and echinocandin drug resistance accounts for the dramatic increase in incidence of nosocomial bloodstream candidiasis found in recent years. Cell wall constitutes the barrier between the yeast and the host and resistant strains change the proteome of this compartment. In the last decade different proteomic platforms have been applied to study cell wall and markers of resistance to drugs have been pointed out. Modulation of these proteins seem to suggest that although resistance is based on a specific mutation able to counteract the toxicity of the antifungal drug, a set of other molecular modifications takes place contemporary or subsequently the establishment of the resistance and seems to support the viability of the resistant yeast. Profiled proteins by proteomics may be valuable in design therapy using classical antifungal along with complementary drugs able to abolish pathways that strengthen the resistance and attenuate virulence of the mutated cell

Procedure for the Alignment of an Ultrasonic Beam for Nondestructive Applications

Most of the nondestructive evaluation (NDE) work using ultrasonic waves generally involves detection and sizing of flaws (e.g., cracks, voids, etc.), and analysis of waves scattering from boundaries with different elastic properties inside a material. Alignment of the ultrasonic measuring system by maximizing the amplitude of the received signal is adequate for these measurements. For characterization of the material properties, one must determine the elastic constants of the material. If the material is anisotropic (e.g., composites), assuming orthorhombic symmetry, one needs a complete set of 9 elastic constants for the characterization.</p

Membrane protein remodeling in microglia exposed to amyloid peptides

Infection, neurodegeneration, and other conditions associated with loss of brain homeostasis, induce changes in microglial morphology, gene expression and function, generally referred to as “activation”. Alzheimer’s disease (AD) is the most common dementia and is characterized by neuroinfammatory changes, including alterations in the morphology and distribution of microglia and astrocytes, and deposition of complement and other infammatory mediators. Our previous observations show that microglial cells challenged in vitro with amyloid peptides clustered and rounded up, dramatically changing their morphology. Besides, in these cells we observed the early acetylation and then the phosphorylation of STAT3 which is required for the expression of the epsilon isoform of 14-3-3, a marker of Abeta-activated microglia (1, 2). We applied afnity partitioning approach combined with high throughput mass spectrometric analysis in order to identify variation of proteins on plasma membrane of BV2 immortalized microglia upon treatment with amyloid peptides. By this method several proteins up- or down-regulated by amyloid treatment were identifed in microglial plasma membrane. Among them annexins (5 and 7), IFITM3 and MARK3. These data have been confrmed in primary microglial cultures. In microglia, plasma membrane plays a relevant role in the cross-talking with the external neuronal environment and in the resulting trophic or infammatory response of these sentinel cells. As such, knowledge of the microglia responsiveness to beta amyloids in term of changes in its plasma membrane proteome is imperative for unveiling the molecular landscape in which AD occurs

Acoustic Tomographic Reconstruction of Fiber Angle in Orthotropic Composite Materials

Composite materials are complex structures widely utilized in modern industry. Numerous nondestructive testing techniques are used to examine these composites for manufacturing flaws, including ultrasonic testing. Normally the reinforcing fibers in a composite material are aligned in a prescribed fashion, from a simple unidirectional composite to a complex composite laminate lay-up. Defects caused by manufacturing or in-service use can result in buckling or warping of the fibers. This is an important concern when dealing with thick composites

Immune cell gene signatures for profiling the microenvironment of solid tumours

The immune composition of the tumor microenvironment regulates processes including angiogenesis, metastasis, and the response to drugs or immunotherapy. To facilitate the characterization of the immune component of tumors from transcriptomics data, a number of immune cell transcriptome signatures have been reported that are made up of lists of marker genes indicative of the presence a given immune cell population. The majority of these gene signatures have been defined through analysis of isolated blood cells. However, blood cells do not reflect the differentiation or activation state of similar cells within tissues, including tumors, and consequently markers derived from blood cells do not necessarily transfer well to tissues. To address this issue, we generated a set of immune gene signatures derived directly from tissue transcriptomics data using a network- based deconvolution approach. We define markers for seven immune cell types, collectively named ImSig, and demonstrate how these markers can be used for the quantitative estimation of the immune cell content of tumor and nontumor tissue samples. The utility of ImSig is demonstrated through the stratification of melanoma patients into subgroups of prognostic significance and the identification of immune cells with the use of single-cell RNA-sequencing data derived from tumors. Use of ImSig is facilitated by an R package (imsig)

DesyreML: a SysML profile for heterogeneous embedded systems

International audienceWe propose a novel language for the formal description of heterogeneous embedded systems (DesyreML). As the main contribution, the language is formally described in terms of semantics and concrete syntax based on the SysML language. We define the concept of thick connector to allow for heterogeneous components communication and computation for multiple semantic domains (synchronous reactive, continuous time, discrete time, discrete-event). As technological application, a verification flow based on model-transformation techniques is described showing the use of an enriched version of the SystemC-AMS simulation kernel that is capable of simulating heterogeneous systems containing combinatorial loops. Finally, the language and the analysis flow are applied to a cruise control case study