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Hepatocyte-specific HIF-1α ablation improves obesity-induced glucose intolerance by reducing first-pass GLP-1 degradation.
The decrease in incretin effects is an important etiologic component of type 2 diabetes with unknown mechanisms. In an attempt to understand obesity-induced changes in liver oxygen homeostasis, we found that liver HIF-1α expression was increased mainly by soluble factors released from obese adipocytes, leading to decreased incretin effects. Deletion of hepatocyte HIF-1α protected obesity-induced glucose intolerance without changes in body weight, liver steatosis, or insulin resistance. In-depth mouse metabolic phenotyping revealed that obesity increased first-pass degradation of an incretin hormone GLP-1 with increased liver DPP4 expression and decreased sinusoidal blood flow rate, reducing active GLP-1 levels in peripheral circulation. Hepatocyte HIF-1α KO blocked these changes induced by obesity. Deletion of hepatocyte HIF-2α did not change liver DPP4 expression but improved hepatic steatosis. Our results identify a previously unknown pathway for obesity-induced impaired beta cell glucose response (incretin effects) and the development of glucose intolerance through inter-organ communications
Hypoglossal schwannoma masquerading as a carotid body tumor.
Study Objective. To describe the clinical presentation, evaluation, and treatment of a hypoglossal schwannoma. Methods. We report an unusual case of a hypoglossal schwannoma presenting as a pulsatile level II neck mass at the bifurcation of the external and internal carotid arteries, mimicking a carotid body tumor. Radiologic findings are reviewed in detail. Results. A 59-year-old female presented to a tertiary care medical center with complaints of a pulsatile right-sided neck mass. An MRA of the neck was obtained demonstrating a 5 cm mass located at the carotid artery bifurcation and causing splaying of the internal and external carotids. Based on clinical presentation and imaging, a diagnosis of a carotid body tumor was conferred and the patient scheduled for excision. Intraoperatively, the mass was noted to arise from the hypoglossal nerve, remaining independent of the carotid artery. On histopathologic analysis, the mass was determined to be consistent with hypoglossal schwannoma. Conclusion. Though rare, the hypoglossal schwannoma should remain a consideration in the evaluation of a parapharyngeal space mass. As this report demonstrates, the clinical and radiologic presentation of a hypoglossal schwannoma may closely mimic that of the more common carotid body tumor
Research Framework for Consumer Satisfaction with Internet Shopping
Consumer satisfaction with Internet shopping has been conceptualized in a variety of ways. Studies in this area remain broad and appear relatively fragmented. In view of this, the purpose of this study is to propose a research framework that integrates both end-user computing satisfaction literature and service quality literature. This framework explicitly considers information quality, system quality, and service quality as the key dimensions of consumer satisfaction with Internet shopping. We believe the research framework and propositions serve as salient guidelines for researchers
SANDBOX CONTRACTING: AN EVALUATION OF GAMIFIED VS. TRADITIONAL CONTRACTING TRAINING METHODS AT THE USAF ENLISTED CONTRACTING TECHNICAL SCHOOL
This thesis involved an evaluation of gamified versus current (traditional) training methods employed by the instructors and faculty at the Air Force’s 344th Training Squadron (344 TRS) at Lackland Air Force Base, Texas, and by the professors at the Naval Postgraduate School (NPS) in Monterey, California. For our project, we designed and developed a first-person shooter (FPS) video game, titled Sandbox Contracting, that teaches the player basic contracting skills. Over the course of six weeks, we utilized this FPS video game to conduct an experiment in which a control group received the current (traditional) training methods employed by 344 TRS and NPS and a treatment group received the gamified version of the training. We assessed each student’s learning as well as their reaction to the assigned learning modality (traditional versus gaming) using post-training evaluation surveys. Traditional training methods outperformed gamified methods in most cases, but not all. We found that game design and mechanics impacted the student’s reactions and ultimately, the success of using gamified methods for learning. Additionally, the results demonstrated a genuine interest in using games for learning among the Air Force contracting students, given the right game design and mechanics. Lastly, we offer suggestions for areas in which further research should be conducted in the gamified versus traditional training arena.Outstanding ThesisCaptain, United States Air ForceCaptain, United States Air ForceCaptain, United States Air ForceApproved for public release. Distribution is unlimited
Variability in antifungal and antiviral use in hospitalized children
We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children’s hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed.Infect Control Hosp Epidemiol2017;38:743–746</jats:p
Molecular Mechanics Simulations and Improved Tight-binding Hamiltonians for Artificial Light Harvesting Systems: Predicting Geometric Distributions, Disorder, and Spectroscopy of Chromophores in a Protein Environment
We present molecular mechanics {and spectroscopic} calculations on prototype
artificial light harvesting systems consisting of chromophores attached to a
tobacco mosaic virus (TMV) protein scaffold. These systems have been
synthesized and characterized spectroscopically, but information about the
microscopic configurations and geometry of these TMV-templated chromophore
assemblies is largely unknown. We use a Monte Carlo conformational search
algorithm to determine the preferred positions and orientations of two
chromophores, Coumarin 343 together with its linker, and Oregon Green 488, when
these are attached at two different sites (104 and 123) on the TMV protein. The
resulting geometric information shows that the extent of disorder and
aggregation properties, and therefore the optical properties of the
TMV-templated chromophore assembly, are highly dependent on the choice of
chromophores and protein site to which they are bound. We used the results of
the conformational search as geometric parameters together with an improved
tight-binding Hamiltonian to simulate the linear absorption spectra and compare
with experimental spectral measurements. The ideal dipole approximation to the
Hamiltonian is not valid since the distance between chromophores can be very
small. We found that using the geometries from the conformational search is
necessary to reproduce the features of the experimental spectral peaks
LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage.
The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%-40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1-/- concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5-13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization
Task Solver or Socializer? The Impact of Camera Usage on Social Loafing in Hybrid Virtual Meeting Context
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