Theoretical Studies of Sodium Metal Clusters.

Theoretical methods were used to study small sodium metal clusters. The goal was to find a simple way to model the electronic structure in these clusters that can be used to study large sodium clusters. Monte Carlo studies using Feynman\u27s path integral formulation of quantum mechanics with Bose-Einstein statistics were used to study sodium metal clusters whose valence electrons with opposite spins were paired as bosons. Next, non-atom-based Gaussian s orbitals were used in a Hartree-Fock Monte Carlo procedure. Based on these results, standard quantum chemistry programs were used to test the utility of using non-atom-based basis sets made up of both s and p Gaussian functions to represent the valence electron density in sodium clusters. The Hartree-Fock Monte Carlo procedure was then modified to include Gaussian p functions in addition to the Gaussian s functions. Neutral and cationic clusters with three to six and eight atoms were studied to determine the geometries of the most stable isomers, the correlated energies, and the ionization potentials. Geometries were compared with published geometries and the ionization potentials were compared with experimental and theoretical ionization potentials. The small, non-atom-based basis set was found to be successful in modeling the electronic structure of small sodium metal clusters, and it is applicable to large sodium clusters and other metal systems

Development, Justification, and use of a Projection Operator in Path Integral Calculations in Continuous Space

A projection operator, similar to one previously used by us for problems with a finite set of basis functions, is suggested for use with continuous basis sets. This projection operator requires knowledge of the nodes of the density matrix at all temperatures. We show that a class of nodes, determined from the noninteracting density matrix and present at high temperatures in the interacting system are preserved to first order in the interaction at low temperatures. While we cannot show that the nodes are present at intermediate temperatures, we suspect they do exist and, as a test of this conjecture, we perform a calculation of two electrons confined in a harmonic well, using the projection operator. We find that accurate results are obtained at a range of temperatures, suggesting that our conjecture is indeed correct. We find that the error limits determined using the projection operator are 1–2 times smaller than those obtained with straightforward Monte Carlo integration (corresponding to a reduction in time of 1–4 in obtaining a desired level of accuracy)

Nuance and behavioral cogency: How the Visible Burrow System inspired the Stress-Alternatives Model and conceptualization of the continuum of anxiety

By creating the Visible Burrow System (VBS) Bob Blanchard found a way to study the interaction of genetics, physiology, environment, and adaptive significance in a model with broad validity. The VBS changed the way we think about anxiety and affective disorders by allowing the mechanisms which control them to be observed in a dynamic setting. Critically, Blanchard used the VBS and other models to show how behavioral systems like defense are dependent upon context and behavioral elements unique to the individual. Inspired by the VBS, we developed a Stress Alternatives Model (SAM) to further explore the multifaceted dynamics of the stress response with a dichotomous choice condition. Like the VBS, the SAM is a naturalistic model built upon risk assessment and defensive behavior, but with a choice of response: escape or submission to a large conspecific aggressor. The anxiety of novelty during the first escape must be weighed against fear of the aggressor, and a decision must be made. Both outcomes are adaptively significant, evidenced by a 50/50 split in outcome across several study systems. By manipulating the variables of the SAM, we show that a gradient of anxiety exists that spans the contextual settings of escaping an open field, escaping from aggression, and submitting to aggression. These findings correspond with increasing levels of corticosterone and increasing levels of NPS and BDNF in the central amygdala as the context changes.Whereas some anxiolytics were able to reduce the latency to escape for some animals, only with the potent anxiolytic drug antalarmin (CRF1R-blocker) and the anxiogenic drug yohimbine (α2 antagonist) were we able to reverse the outcome for a substantial proportion of individuals. Our findings promote a novel method for modeling anxiety, offering a distinction between low-and-high levels, and accounting for individual variability. The translational value of the VBS is immeasurable, and it guided us and many other researchers to seek potential clinical solutions through a deeper understanding of regional neurochemistry and gene expression in concert with an ecological behavioral model

Utilization of case presentations in medical microbiology to enhance relevance of basic science for medical students

Background : Small-group case presentation exercises (CPs) were created to increase course relevance for medical students taking Medical Microbiology (MM) and Infectious Diseases (ID) Methods : Each student received a unique paper case and had 10 minutes to review patient history, physical exam data, and laboratory data. Students then had three minutes to orally present their case and defend why they ruled in or out each of the answer choices provided, followed by an additional three minutes to answer questions. Results : Exam scores differed significantly between students who received the traditional lecture-laboratory curriculum (Group I) and students who participated in the CPs (Group II). In MM, median unit exam and final exam scores for Group I students were 84.4% and 77.8%, compared to 86.0% and 82.2% for Group II students (P < 0.018; P < 0.001; Mann-Whitney Rank Sum Test). Median unit and final ID exam scores for Group I students were 84.0% and 80.0%, compared to 88.0% and 86.7% for Group II students (P < 0.001; P < 0.001). Conclusion : Students felt that the CPs improved their critical thinking and presentation skills and helped to prepare them as future physicians

Multi-level manifestations of sexual stigma among men with same-gender sexual experience in Ghana

Sexual stigma and discrimination toward men who have same-gender sexual experiences are present across the globe. In Ghana, same-gender sexual desires and relationships are stigmatized, and the stigma is sanctioned through both social and legal processes. Such stigma negatively influences health and other material and social aspects of daily life for men who have sex with men (MSM). However, there is evidence that stigma at the interpersonal level can intersect with stigma that may be operating simultaneously at other levels. Few studies provide a comprehensive qualitative assessment of the multi-level sexual stigma derived from the direct narratives of men with same-gender sexual experience. To help fill this gap on sexual stigma, we qualitatively investigated [1] what was the range of sexual stigma manifestations, and [2] how sexual stigma manifestations were distributed across socioecological levels in a sample of Ghanaian MSM. From March to September 2020, we conducted eight focus group discussions (FGDs) with MSM about their experiences with stigma from Accra and Kumasi, Ghana. Data from the FGDs were subjected to qualitative content analysis. We identified a range of eight manifestations of sexual stigma: (1) gossiping and outing; (2) verbal abuse and intrusive questioning; (3) non-verbal judgmental gestures; (4) societal, cultural, and religious blaming and shaming; (5) physical abuse; (6) poor-quality services; (7) living in constant fear and stigma avoidance; and (8) internal ambivalence and guilt about sexual behavior. Sexual stigma manifestations were unevenly distributed across socioecological levels. Our findings are consistent with those of existing literature documenting that, across Africa, and particularly in Ghana, national laws and religious institutions continue to drive stigma against MSM. Fundamental anti-homosexual sentiments along with beliefs associating homosexuality with foreign cultures and immorality drive the stigmatization of MSM. Stigma experienced at all socioecological levels has been shown to impact both the mental and sexual health of MSM. Deeper analysis is needed to understand more of the lived stigma experiences of MSM to develop appropriate stigma-reduction interventions. Additionally, more community-level stigma research and interventions are needed that focus on the role of family and peers in stigma toward MSM in Ghana

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN