3,697 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

    Charities\u27 Changing Tort Immunity

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    The gatekeeper: individual differences are key in the chain from perception to behaviour

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    A basic assumption in mainstream social cognition is that the path from perception to behaviour is often automatic and direct, as supported for example by several experimental studies showing that priming can lead directly to a congruent behaviour without any need of conscious awareness of the process. However, we argue that the priming of a goal or an object activates individual differences in automatic evaluations at the associative level that in turn are the key predictors of action (gatekeeper model). A study (n = 90) on the American stereotype is presented to support the model. The results show that individual differences of the American stereotype as assessed with the IAT predicts a relevant action (essay evaluation) but only under condition of priming. Broader implications for predictive validity of implicit measures are also discussed

    Dispersion strengthening in vanadium microalloyed steels processed by simulated thin slab casting and direct charging. Part 2 - chemical characterisation of dispersion strengthening precipitates

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    The composition of the sub-15 nm particles in six related vanadium high strength low alloy steels, made by simulated thin slab direct charged casting, has been determined using electron energy loss spectroscopy (EELS). Such particles are considered to be responsible for dispersion hardening. For the first time, particles down to 4 nm in size have had their composition fully determined. In all the steels, the particles were nitrogen and vanadium rich and possibly slightly sub-stoichiometric carbonitrides. Equilibrium thermodynamics predicted much higher carbon to metal atomic ratios than observed in all cases so that kinetics and mechanical deformation clearly control the precipitation process. Thus it is important to formulate the steel with this in mind

    Reinforcement learning for bandits with continuous actions and large context spaces

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    We consider the challenging scenario of contextual bandits with continuous actions and large context spaces. This is an increasingly important application area in personalised healthcare where an agent is requested to make dosing decisions based on a patient’s single image scan. In this paper, we first adapt a reinforcement learning (RL) algorithm for continuous control to outperform contextual bandit algorithms specifically hand-crafted for continuous action spaces. We empirically demonstrate this on a suite of standard benchmark datasets for vector contexts. Secondly, we demonstrate that our RL agent can generalise problems with continuous actions to large context spaces, providing results that outperform previous methods on image contexts. Thirdly, we introduce a new contextual bandits test domain with multi-dimensional continuous action space and image contexts which existing tree-based methods cannot handle. We provide initial results with our RL agent

    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

    Three-Wheel Brush-Wheel Sampler

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    A new sampler is similar to a common snow blower, but is robust and effective in sample collection. The brush wheels are arranged in a triangle shape, each driven by a brushless DC motor and planetary gearhead embedded in the wheel shaft. Its speed can be varied from 800 - 2,000 rpm, depending on the surface regolith resistance. The sample-collecting flow path, and internal features, are designed based on flow dynamics, and the sample-collecting rates have consistently exceeded the requirement under various conditions that span the range of expected surface properties. The brush-wheel sampler (BWS) is designed so that the flow channel is the main body of the apparatus, and links the brush-wheel assembly to the sample canister. The combination of the three brush wheels, the sample flow path, and the canister location make sample collection, storage, and transfer an easier task
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