60 research outputs found

    Taylor dispersion with absorbing boundaries: A Stochastic Approach

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    We describe how to solve the problem of Taylor dispersion in the presence of absorbing boundaries using an exact stochastic formulation. In addition to providing a clear stochastic picture of Taylor dispersion, our method leads to closed-form expressions for all the moments of the convective displacement of the dispersing particles in terms of the transverse diffusion eigenmodes. We also find that the cumulants grow asymptotically linearly with time, ensuring a Gaussian distribution in the long-time limit. As a demonstration of the technique, the first two longitudinal cumulants (yielding respectively the effective velocity and the Taylor diffusion constant) as well as the skewness (a measure of the deviation from normality) are calculated for fluid flow in the parallel plate geometry. We find that the effective velocity and the skewness (which is negative in this case) are enhanced while Taylor dispersion is suppressed due to absorption at the boundary.Comment: 4 pages, 1 figur

    Young children's explorations of average through informal inferential reasoning

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    This study situates children's early notions of average within an inquiry classroom to investigate the rich inferential reasoning that young children drew on to make sense of the questions: Is there a typical height for a student in year 3? If so, what is it? Based on their deliberations over several lessons, students' ideas about average and typicality evolved as meaning reasonable, contrary to atypical, most common (value or interval), middle, normative, and representative of the population. The case study reported here documents a new direction for the development of children's conceptions of average in a classroom designed to elicit their informal inferential reasoning about data

    El Pensamiento Probabilístico de los Profesores de Biología en Formación

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    Los futuros profesores de secundaria requieren de una formación acorde a las demandas de la sociedad del siglo XXI. Ello impone el desarrollo de un pensamiento que le permita interpretar y abordar los fenómenos de naturaleza aleatoria. El objetivo de este trabajo es determinar las tendencias de pensamiento probabilístico de los estudiantes de los profesorados de Biología de la provincia de Mendoza, Argentina. Para ello se aplicó un cuestionario a los 325 estudiantes que cursan esta carrera. El mismo consta de tres partes; la primera trata sobre las variables demográficas de los estudiantes, la segunda corresponde al reconocimiento de la aleatoriedad; y la tercera a la estimación de la probabilidad de diferentes sucesos. Las respuestas se analizaron a partir de la aplicación de diferentes técnicas estadísticas; el test de independencia, el análisis de la varianza, el test de Tukey, análisis de clusters y análisis discriminante. En primer lugar, se encontraron diferencias significativas entre el reconocimiento de la aleatoriedad y el contexto del suceso, siendo mayor en el contexto de juego que en el físico natural. Mientras que, en el contexto físico natural se afirma la aleatoriedad desde la causalidad, en el de juego se afirma desde la incertidumbre. En segundo lugar, no se encontró relación de dependencia entre el reconocimiento de la aleatoriedad y la edad de los estudiantes, como así tampoco con el nivel académico de los mismos. Respecto a la estimación de la probabilidad, los estudiantes argumentan fundamentalmente desde la equiprobabilidad y desde la contingencia. El análisis de clusters y análisis discriminante permitieron encontrar cuatro tendencias de pensamiento: incertidumbre, determinista, contingente y personalista

    Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

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    Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

    County-Based Priority Assessment Methodology for Phasing of Wellhead Protection Programs

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    ABSTRACT-Setting priorities to schedule and implement wellhead protection programs for municipal and community drinking water supplies is presented in the framework of a general risk assessment approach. This includes a hazard identification procedure representing the likelihood of contaminants being released to the surface environment, a hydrogeologic vulnerability assessment representing the risk of contaminants entering the groundwater supply, and an impact assessment, strongly linked to the population at risk. A methodology was developed to aggregate information on a county basis for Minnesota. The resulting composite risk index map shows a number of counties in the central part of the state roughly following a line from the Twin Cities Metropolitan area along two major transportation axes to the St. Cloud and Fargo-Moorhead area, and toward the south to the Rochester-Austin area to which a high priority for phasing-in of the program is recommended. These counties emerge in addition to those in the southeastern karst area of Minnesota that traditionally have been identified as vulnerable areas

    Two-Way Regionalized Classification of Multivariate Datasets and its Application to the Assessment of Hydrodynamic Dispersion

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    Zones of mixing between shallow groundwaters of different composition were unravelled by “two-way regionalized classification,” a technique based on correspondence analysis (CA), cluster analysis (ClA) and discriminant analysis (DA), aided by gridding, map-overlay and contouring tools. The shallow groundwaters are from a granitoid plutonite in the Fundão region (central Portugal). Correspondence analysis detected three natural clusters in the working dataset: 1, weathering; 2, domestic effluents; 3, fertilizers. Cluster analysis set an alternative distribution of the samples by the three clusters. Group memberships obtained by correspondence analysis and by cluster analysis were optimized by discriminant analysis, gridded over the entire Fundão region, and converted into “two-way regionalized classification” memberships as follows: codes 1, 2 or 3 were used when classification by correspondence analysis and cluster analysis produced the same results; code 0 when the grid node was first assigned to cluster 1 and then to cluster 2 or vice versa (mixing between weathering and effluents); code 4 in the other cases (mixing between agriculture and the other influences). Code-3 areas were systematically surrounded by code-4 areas, an observation attributed to hydrodynamic dispersion. Accordingly, the extent of code-4 areas in two orthogonal directions was assumed proportional to the longitudinal and transverse dispersivities of local soils. The results (0.7–16.8 and 0.4–4.3 m, respectively) are acceptable at the macroscopic scale. The ratios between longitudinal and transverse dispersivities (1.2–11.1) are also in agreement with results obtained by other studies

    Helicobacter pylori Depletes Cholesterol in Gastric Glands to Prevent Interferon Gamma Signaling and Escape the Inflammatory Response

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    Background and Aims Despite inducing an inflammatory response, Helicobacter pylori can persist in the gastric mucosa for decades. H pylori expression of cholesterol-aglucosyltransferase (encoded by cgt) is required for gastric colonization and T-cell activation. We investigated how cgt affects gastric epithelial cells and the host immune response. Methods MKN45 gastric epithelial cells, AGS cells, and human primary gastric epithelial cells (obtained from patients undergoing gastrectomy or sleeve resection or gastric antral organoids) were incubated with interferon gamma (IFNG) or interferon beta (IFNB) and exposed to H pylori, including cagPAI and cgt mutant strains. Some cells were incubated with methyl-b-cyclodextrin (to deplete cholesterol from membranes) or myriocin and zaragozic acid to prevent biosynthesis of sphingolipids and cholesterol and analyzed by immunoblot, immunofluorescence, and reverse transcription quantitative polymerase chain reaction analyses. We compared gene expression patterns among primary human gastric cells, uninfected or infected with H pylori P12 wt or P12Dcgt, using microarray analysis. Mice with disruption of the IFNG receptor 1 (Ifngr1–/– mice) and C57BL6 (control) mice were infected with PMSS1 (wild-type) or PMSS1Dcgt H pylori; gastric tissues were collected and analyzed by reverse transcription quantitative polymerase chain reaction or confocal microscopy. Results In primary gastric cells and cell lines, infection with H pylori, but not cgt mutants, blocked IFNG-induced signaling via JAK and STAT. Cells infected with H pylori were depleted of cholesterol, which reduced IFNG signaling by disrupting lipid rafts, leading to reduced phosphorylation (activation) of JAK and STAT1. H pylori infection of cells also blocked signaling by IFNB, interleukin 6 (IL6), and IL22 and reduced activation of genes regulated by these signaling pathways, including cytokines that regulate T-cell function (MIG and IP10) and anti-microbial peptides such as human b-defensin 3 (hBD3). We found that this mechanism allows H pylori to persist in proximity to infected cells while inducing inflammation only in the neighboring, non-infected epithelium. Stomach tissues from mice infected with PMSS1 had increased levels of IFNG, but did not express higher levels of interferon-response genes. Expression of the IFNGresponse gene IRF1 was substantially higher in PMSS1Dcgtinfected mice than PMSS1-infected mice. Ifngr1–/– mice were colonized by PMSS1 to a greater extent than control mice. Conclusions H pylori expression of cgt reduces cholesterol levels in infected gastric epithelial cells and thereby blocks IFNG signaling, allowing the bacteria to escape the host inflammatory response. These findings provide insight into the mechanisms by which H pylori might promote gastric carcinogenesis (persisting despite constant inflammation) and ineffectiveness of T-cell–based vaccines against H pylori.</p

    Helicobacter pylori depletes cholesterol in gastric glands to prevent interferon gamma signaling and escape the inflammatory response

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    Background and Aims Despite inducing an inflammatory response, Helicobacter pylori can persist in the gastric mucosa for decades. H pylori expression of cholesterol-aglucosyltransferase (encoded by cgt) is required for gastric colonization and T-cell activation. We investigated how cgt affects gastric epithelial cells and the host immune response. Methods MKN45 gastric epithelial cells, AGS cells, and human primary gastric epithelial cells (obtained from patients undergoing gastrectomy or sleeve resection or gastric antral organoids) were incubated with interferon gamma (IFNG) or interferon beta (IFNB) and exposed to H pylori, including cagPAI and cgt mutant strains. Some cells were incubated with methyl-b-cyclodextrin (to deplete cholesterol from membranes) or myriocin and zaragozic acid to prevent biosynthesis of sphingolipids and cholesterol and analyzed by immunoblot, immunofluorescence, and reverse transcription quantitative polymerase chain reaction analyses. We compared gene expression patterns among primary human gastric cells, uninfected or infected with H pylori P12 wt or P12Dcgt, using microarray analysis. Mice with disruption of the IFNG receptor 1 (Ifngr1–/– mice) and C57BL6 (control) mice were infected with PMSS1 (wild-type) or PMSS1Dcgt H pylori; gastric tissues were collected and analyzed by reverse transcription quantitative polymerase chain reaction or confocal microscopy. Results In primary gastric cells and cell lines, infection with H pylori, but not cgt mutants, blocked IFNG-induced signaling via JAK and STAT. Cells infected with H pylori were depleted of cholesterol, which reduced IFNG signaling by disrupting lipid rafts, leading to reduced phosphorylation (activation) of JAK and STAT1. H pylori infection of cells also blocked signaling by IFNB, interleukin 6 (IL6), and IL22 and reduced activation of genes regulated by these signaling pathways, including cytokines that regulate T-cell function (MIG and IP10) and anti-microbial peptides such as human b-defensin 3 (hBD3). We found that this mechanism allows H pylori to persist in proximity to infected cells while inducing inflammation only in the neighboring, non-infected epithelium. Stomach tissues from mice infected with PMSS1 had increased levels of IFNG, but did not express higher levels of interferon-response genes. Expression of the IFNGresponse gene IRF1 was substantially higher in PMSS1Dcgtinfected mice than PMSS1-infected mice. Ifngr1–/– mice were colonized by PMSS1 to a greater extent than control mice. Conclusions H pylori expression of cgt reduces cholesterol levels in infected gastric epithelial cells and thereby blocks IFNG signaling, allowing the bacteria to escape the host inflammatory response. These findings provide insight into the mechanisms by which H pylori might promote gastric carcinogenesis (persisting despite constant inflammation) and ineffectiveness of T-cell–based vaccines against H pylori.</p
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