2,408 research outputs found

    bak deletion stimulates gastric epithelial proliferation and enhances Helicobacter felis-induced gastric atrophy and dysplasia in mice

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    Helicobacter infection causes a chronic superficial gastritis that in some cases progresses via atrophic gastritis to adenocarcinoma. Proapoptotic bak has been shown to regulate radiation-induced apoptosis in the stomach and colon and also susceptibility to colorectal carcinogenesis in vivo. Therefore we investigated the gastric mucosal pathology following H. felis infection in bak-null mice at 6 or 48 wk postinfection. Primary gastric gland culture from bak-null mice was also used to assess the effects of bak deletion on IFN-γ-, TNF-α-, or IL-1β-induced apoptosis. bak-null gastric corpus glands were longer, had increased epithelial Ki-67 expression, and contained fewer parietal and enteroendocrine cells compared with the wild type (wt). In wt mice, bak was expressed at the luminal surface of gastric corpus glands, and this increased 2 wk post-H. felis infection. Apoptotic cell numbers were decreased in bak-null corpus 6 and 48 wk following infection and in primary gland cultures following cytokine administration. Increased gastric epithelial Ki-67 labeling index was observed in C57BL/6 mice after H. felis infection, whereas no such increase was detected in bak-null mice. More severe gastric atrophy was observed in bak-null compared with C57BL/6 mice 6 and 48 wk postinfection, and 76% of bak-null compared with 25% of C57BL/6 mice showed evidence of gastric dysplasia following long-term infection. Collectively, bak therefore regulates gastric epithelial cell apoptosis, proliferation, differentiation, mucosal thickness, and susceptibility to gastric atrophy and dysplasia following H. felis infection

    Oral iron exacerbates colitis and influences the intestinal microbiome

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    Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS

    Nitrogen cycle disruption through the application of de-icing salts on upland highways

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    It is hypothesized that episodic introductions of road salt severely disrupt the soil nitrogen cycle at a range of spatial and temporal scales. A field-scale study has confirmed impacts on the nitrogen cycle in soil, soil solution and river samples. There is evidence that ammonium-N retention on cation exchange sites has been reduced by the presence of sodium ions, and that ammonium-N has been flushed from the exchange sites. Increases in soil pH have been caused in naturally acidic uplands. These have enhanced mineralization of organic-N, especially nitrification, leading to a reduction in the mineralizable-N pool of roadside soils. There is evidence to support the hypothesis that organic matter content has been lowered over decades either through desorption or dispersal processes. Multiple drivers are identified that contribute to the disruption of nitrogen cycling processes, but their relative importance is difficult to quantify unequivocally. The influence of road salt on soil and soil solution declines with distance from the highway, but impacts on water chemistry in a local stream are still strongly evident at some distance from the road

    Radio-frequency powered glow discharge device and method with high voltage interface

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    A high voltage accelerating potential, which is supplied by a high voltage direct current power supply, is applied to the electrically conducting interior wall of an RF powered glow discharge cell. The RF power supply desirably is electrically grounded, and the conductor carrying the RF power to the sample held by the probe is desirably shielded completely excepting only the conductor\u27s terminal point of contact with the sample. The high voltage DC accelerating potential is not supplied to the sample. A high voltage capacitance is electrically connected in series between the sample on the one hand and the RF power supply and an impedance matching network on the other hand. The high voltage capacitance isolates the high DC voltage from the RF electronics, while the RF potential is passed across the high voltage capacitance to the plasma. An inductor protects at least the RF power supply, and desirably the impedance matching network as well, from a short that might occur across the high voltage capacitance. The discharge cell and the probe which holds the sample are configured and disposed to prevent the probe\u27s components, which are maintained at ground potential, from bridging between the relatively low vacuum region in communication with the glow discharge maintained within the cell on the one hand, and the relatively high vacuum region surrounding the probe and cell on the other hand. The probe and cell also are configured and disposed to prevent the probe\u27s components from electrically shorting the cell\u27s components

    Trinity University\u27s Summer Bridge Program: Navigating the Changing Demographics in Higher Education

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    Our article is divided into five sections. First, our study explores the demographic, economic, and cultural changes influencing higher education. We also explain the tangible and intangible benefits of a college education for first-generation, underrepresented students (FGUS). Second, we provide a brief discussion of the history of Trinity University and our Summer Bridge program. Third, our study describes our Summer Bridge program. Fourth, the data we collected examines how our Summer Bridge students’ grades and retention rates compare to our other first-year students. And, fifth, our article concludes with a discussion of future directions for our Summer Bridge program and how it may apply to other higher educational institutions. In particular, we offer recommendations for other student affairs professionals who also will be experiencing an increase in first-generation, underrepresented students

    Explainable Machine Learning for Real-Time Hypoglycemia and Hyperglycemia Prediction and Personalized Control Recommendations

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    BACKGROUND: The occurrences of acute complications arising from hypoglycemia and hyperglycemia peak as young adults with type 1 diabetes (T1D) take control of their own care. Continuous glucose monitoring (CGM) devices provide real-time glucose readings enabling users to manage their control proactively. Machine learning algorithms can use CGM data to make ahead-of-time risk predictions and provide insight into an individual’s longer term control. METHODS: We introduce explainable machine learning to make predictions of hypoglycemia (270 mg/dL) up to 60 minutes ahead of time. We train our models using CGM data from 153 people living with T1D in the CITY (CGM Intervention in Teens and Young Adults With Type 1 Diabetes)survey totaling more than 28 000 days of usage, which we summarize into (short-term, medium-term, and long-term) glucose control features along with demographic information. We use machine learning explanations (SHAP [SHapley Additive exPlanations]) to identify which features have been most important in predicting risk per user. RESULTS: Machine learning models (XGBoost) show excellent performance at predicting hypoglycemia (area under the receiver operating curve [AUROC]: 0.998, average precision: 0.953) and hyperglycemia (AUROC: 0.989, average precision: 0.931) in comparison with a baseline heuristic and logistic regression model. CONCLUSIONS: Maximizing model performance for glucose risk prediction and management is crucial to reduce the burden of alarm fatigue on CGM users. Machine learning enables more precise and timely predictions in comparison with baseline models. SHAP helps identify what about a CGM user’s glucose control has led to predictions of risk which can be used to reduce their long-term risk of complications

    Intestinal Preparation Techniques for Histological Analysis in the Mouse

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    The murine intestinal tract represents a difficult organ system to study due to its long convoluted tubular structure, narrow diameter, and delicate mucosa which undergoes rapid changes after sampling prior to fixation. These features do not make for easy histological analysis as rapid fixation in situ, or after simple removal without careful dissection, results in poor postfixation tissue handling and limited options for high quality histological sections. Collecting meaningful quantitative data by analysis of this tissue is further complicated by the anatomical changes in structure along its length. This article describes two methods of intestinal sampling at necropsy that allow systematic histological analysis of the entire intestinal tract, either through examination of cross sections (circumferences) by the gut bundling technique or longitudinal sections by the adapted Swiss roll technique, together with basic methods for data collection

    Self-control in decision-making involves modulation of the vmPFC valuation system

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    Every day, individuals make dozens of choices between an alternative with higher overall value and a more tempting but ultimately inferior option. Optimal decision-making requires self-control. We propose two hypotheses about the neurobiology of self-control: (i) Goal-directed decisions have their basis in a common value signal encoded in ventromedial prefrontal cortex (vmPFC), and (ii) exercising self-control involves the modulation of this value signal by dorsolateral prefrontal cortex (DLPFC). We used functional magnetic resonance imaging to monitor brain activity while dieters engaged in real decisions about food consumption. Activity in vmPFC was correlated with goal values regardless of the amount of self-control. It incorporated both taste and health in self-controllers but only taste in non–self-controllers. Activity in DLPFC increased when subjects exercised self-control and correlated with activity in vmPFC

    QSRlib: a software library for online acquisition of qualitative spatial relations from video

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    There is increasing interest in using Qualitative Spatial Relations as a formalism to abstract from noisy and large amounts of video data in order to form high level conceptualisations, e.g. of activities present in video. We present a library to support such work. It is compatible with the Robot Operating System (ROS) but can also be used stand alone. A number of QSRs are built in; others can be easily added
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