116 research outputs found

    Влияние ледового сжатия на составляющие скорости движения жидкости под ледяным покровом в бегущей периодической изгибно-гравитационной волне конечной амплитуды

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    Методом многих масштабов с точностью до величин третьего порядка малости получены асимптотические разложения, определяющие составляющие скорости движения жидкости под плавающим ледяным покровом при распространении периодической поверхностной изгибногравитационной волны конечной амплитуды в условиях ледового сжатия. Рассмотрена зависимость распределений составляющих скорости вдоль профиля волны от величины сжимающего усилия и характеристик начальной гармоники. Показано, что с увеличением сжимающего усилия происходит уменьшение амплитудных значений составляющих скорости и отставание фазы колебаний.Методом багатьох масштабів з точністю до величин третього порядку малості отримані асимптотичні розкладання, які визначають складові швидкості руху рідини під плаваючим льодяним покривом при розповсюдженні періодичної поверхневої згинально-гравітаційної хвилі кінцевої амплітуди в умовах льодяного стиснення. Розглянуто залежність розподілів складових швидкості вздовж профілю хвилі від величини стискаючого зусилля та характеристик початкової гармоніки. Показано, що із збільшенням стискаючого зусилля відбувається зменшення амплітудних значень складових швидкості та відставання фази коливань.Using the method of multiple scales, the asymptotic expansions are obtained up to the values of the third order. The expansions condition the components of fluid movement velocity under floating ice cover at propagation of periodic surface flexural-gravity wave of finite amplitude in the condition of ice compression. Dependence of distribution of velocity components along the wave profile upon the compressive force value and the initial harmonic characteristics is considered. It is shown that rise of compressive force is accompanied by decrease of amplitude values of velocity components and lag of oscillations’ phase

    Developments in lung transplantation over the past decade

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    With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of ex vivo lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade

    Corneal Pachymetry by AS-OCT after Descemet's Membrane Endothelial Keratoplasty

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    Corneal thickness (pachymetry) maps can be used to monitor restoration of corneal endothelial function, for example after Descemet's membrane endothelial keratoplasty (DMEK). Automated delineation of the corneal interfaces in anterior segment optical coherence tomography (AS-OCT) can be challenging for corneas that are irregularly shaped due to pathology, or as a consequence of surgery, leading to incorrect thickness measurements. In this research, deep learning is used to automatically delineate the corneal interfaces and measure corneal thickness with high accuracy in post-DMEK AS-OCT B-scans. Three different deep learning strategies were developed based on 960 B-scans from 50 patients. On an independent test set of 320 B-scans, corneal thickness could be measured with an error of 13.98 to 15.50 micrometer for the central 9 mm range, which is less than 3% of the average corneal thickness. The accurate thickness measurements were used to construct detailed pachymetry maps. Moreover, follow-up scans could be registered based on anatomical landmarks to obtain differential pachymetry maps. These maps may enable a more comprehensive understanding of the restoration of the endothelial function after DMEK, where thickness often varies throughout different regions of the cornea, and subsequently contribute to a standardized postoperative regime.Comment: Fixed typo in abstract: The development set consists of 960 B-scans from 50 patients (instead of 68). The B-scans from the other 18 patients were used for testing onl

    Identification of genes that contribute to the pathogenesis of invasive Pneumococcal Disease by In Vivo transcriptomic analysis

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    Streptococcus pneumoniae (the pneumococcus) continues to be responsible for a high level of global morbidity and mortality resulting from pneumonia, bacteremia, meningitis, and otitis media. Here we have used a novel technique involving niche-specific, genome-wide in vivo transcriptomic analyses to identify genes upregulated in distinct niches during pathogenesis after intranasal infection of mice with serotype 4 or 6A pneumococci. The analyses yielded 28 common, significantly upregulated genes in the lungs relative to those in the nasopharynx and 25 significantly upregulated genes in the blood relative to those in the lungs in both strains, some of which were previously unrecognized. The role of five upregulated genes from either the lungs or the blood in pneumococcal pathogenesis and virulence was then evaluated by targeted mutagenesis. One of the mutants (ΔmalX) was significantly attenuated for virulence in the lungs, two (ΔaliA and ΔilvH) were significantly attenuated for virulence in the blood relative to the wild type, and two others (ΔcbiO and ΔpiuA) were completely avirulent in a mouse intranasal challenge model. We also show that the products of aliA, malX, and piuA are promising candidates for incorporation into multicomponent protein-based pneumococcal vaccines currently under development. Importantly, we suggest that this new approach is a viable complement to existing strategies for the discovery of genes critical to the distinct stages of invasive pneumococcal disease and potentially has broad application for novel protein antigen discovery in other pathogens such as S. pyogenes, Haemophilus influenzae type b, and Neisseria meningitidis

    MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines

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    Copyright ©1995-2014 Baishideng Publishing Group Inc. All rights reserved. Articles published by this open-access journal are distributed under the terms of the Creative Commons Attribution-Noncommercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/4.0/AIM: To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines. METHODS: An in-vitro model of acquired chemotherapy resistance in esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) cells was used, and microRNA expression profiles for cisplatin or 5-fluorouracil (5-FU) resistant variants vs chemotherapy sensitive controls were compared using microarray and quantitative real-time polymerase chain reaction (PCR). The expression of chemotherapy-relevant genes potentially targeted by the dysregulated microRNAs in the chemotherapy resistant variants was also evaluated. RESULTS: Chemotherapy resistant sublines were found to have specific miRNA signatures, and these miRNA signatures were different for the cisplatin vs 5-FU resistant cells from the same tumor cell line, and also for EAC vs ESCC cells with resistance to the same specific chemotherapy agent. Amongst others, miR-27b-3p, miR-193b-3p, miR-192-5p, miR-378 a-3p, miR-125a-5p and miR-18a-3p were dysregulated, consistent with negative posttranscriptional control of KRAS, TYMS, ABCC3, CBL-B and ERBB2 expression via these miRNAs. CONCLUSION: The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer. Keywords: Esophageal cancer, MicroRNA, Chemotherapy, Resistance, Targe

    Intracerebroventricular Administration of Neuropeptide Y Induces Hepatic Insulin Resistance via Sympathetic Innervation

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    OBJECTIVE—We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The downstream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY administration modulates the suppressive action of insulin on EGP via hepatic sympathetic or parasympathetic innervation

    Future Scenarios of Nitrogen in Europe

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    The future effects of nitrogen in the environment will depend on the extent of nitrogen use and the practical application techniques of nitrogen in a similar way as in the past. Projections and scenarios are appropriate tools for extrapolating current knowledge into thefuture. However,these tools will not allow future system turnovers to be predicted. Approaches• In principle, scenarios of nitrogen use follow the approaches currently used for air pollution,climate ,or ecosystem projections. Short term projections (to 2030) are developed using a ‘baseline’ path of development,which considers abatement options that are consistent with European policy. For medium-term projections (to 2050) and long-term projections, the European Nitrogen Assessment (ENA) applies a ‘storyline’ approach similar to that used in the IPCC SRES scenarios. Beyond 2050 in particular, such story lines also take into account technological and behavioral shift s.Key findings/state of knowledge• The ENA distinguishes between driver-oriented and effect-oriented factors determining nitrogen use. Parameters that cause changes in nitrogen fixation or application are called drivers. In a driver-based approach, it is assumed that any variation of these parameters will also trigger a change in nitrogen pollution. In an effect-based approach, as the adverse effects of nitrogen become evident inthe environment, introduction of nitrogen abatement legislation requiring the application of more efficient abatement measuresis expected. This approach needs to rely on a target that is likely to be maintained in the future (e.g.human health). Nitrogen abatement legislation basedon such targets will aim to counter any growth in adverse environmental effects that occur as a result of increased nitrogen application.• For combustionand industry, technical fixes forabatement are available. Allscenarios agree in projecting a decrease in NOx emissions.Yet agricultural nitrogen use is expected to remain the leading cause of nitrogen release to the environment, as options to reduce emissions are limited. Thus, major changes will occur only if the extent of agricultural production changes, which may possibly be triggered by decreasing population numbers in Europe.The scenarios presented here project modest changes in NH 3 and N 2 O emissions, or nitrateleaching, but do not agree on the direction of these changes.•Agricultural activity (and thus nitrogen loads to the environment) may decrease strongly if the European population adopts a healthier‘low meat’ diet leading to lower nitrogenlosses related to animal husbandry. Change to a ‘healthy diet’ across the EU, which consists of 63% less meat and eggs, would reduce ammonia emissions from animal production by 48%. However, if an agricultural area previously used for animal feed production is utilized for biofuel crops, additional nitrogen fertilizer maybe required, which will partially offset reductions of nitrogen leakage to the environment. Major uncertainties/challenges• International trade in nitrogen-containing goods (agricultural as well as industrial) represents a key uncertainty and is difficult to project. Estimating the demand for such goods for Europe alone may not at all reflect European production and related environmental effects. The industrial use of nitrogen is alsovery poorly understood, but it is expected to continue to grow considerably. The respective environmental impacts of such products cannot be clearly discerned from statistical information.Recommendations• Scenarios need to be continuously updated in terms of economic, technical, and societal trends to reflect improved understanding of these factors. Using nitrogen budgets as tools could improve the consistency of scenarios.JRC.DDG.H.2-Climate change and air qualit

    An intracellular pH gradient in the anammox bacterium Kuenenia stuttgartiensis as evaluated by 31P NMR

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    The cytoplasm of anaerobic ammonium oxidizing (anammox) bacteria consists of three compartments separated by membranes. It has been suggested that a proton motive force may be generated over the membrane of the innermost compartment, the “anammoxosome”. 31P nuclear magnetic resonance (NMR) spectroscopy was employed to investigate intracellular pH differences in the anammox bacterium Kuenenia stuttgartiensis. With in vivo NMR, spectra were recorded of active, highly concentrated suspensions of K. stuttgartiensis in a wide-bore NMR tube. At different external pH values, two stable and distinct phosphate peaks were apparent in the recorded spectra. These peaks were equivalent with pH values of 7.3 and 6.3 and suggested the presence of a proton motive force over an intracytoplasmic membrane in K. stuttgartiensis. This study provides for the second time—after discovery of acidocalcisome-like compartments in Agrobacterium tumefaciens—evidence for an intracytoplasmic pH gradient in a chemotrophic prokaryotic cell

    Terminating Tableaux for Graded Hybrid Logic with Global Modalities and Role Hierarchies

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    We present a terminating tableau calculus for graded hybrid logic with global modalities, reflexivity, transitivity and role hierarchies. Termination of the system is achieved through pattern-based blocking. Previous approaches to related logics all rely on chain-based blocking. Besides being conceptually simple and suitable for efficient implementation, the pattern-based approach gives us a NExpTime complexity bound for the decision procedure

    Genome-wide gene expression profiling identifies overlap with malignant adrenocortical tumours and novel mechanisms of inefficient steroidogenesis in familial ACTH-independent macronodular adrenal hyperplasia.

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    ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of sporadic or familial late-onset Cushing's syndrome. It is a cytologically benign disease, of unknown pathogenesis, and characterised by inefficient steroidogenesis, ascribed to differential cellular localisation of steroidogenic enzymes. The objectives were to determine the molecular mechanisms involved in the pathogenesis of familial AIMAH tumours and the mechanisms of their inefficient steroidogenesis. Using Affymetrix Human GeneChip® HumanGene 1.0 ST arrays, we compared the genome-wide gene expression profile of two AIMAH nodules from each of three affected siblings with normal adrenal cortex and analysed the data for differential expression and using Ingenuity Pathway Analysis, Gene Set Enrichment Analysis and Motif Activity Response Analysis. Expression profiling identified: (i) that amongst the most highly differentially expressed genes were ones known to have involvement in tumorigenesis and metastasis; (ii) enrichment for differentially expressed genes in sporadic AIMAH and other benign and malignant adrenocortical tumours and (iii) reduced activity of key transcriptional regulators (Steroidogenic factor-1, SF-1 and transcription factor Sp1, Sp1) of steroidogenic enzymes. Genome-wide gene expression studies of familial AIMAH nodules have identified overlap with malignant adrenocortical tumours, which is intriguing given the benign biological behaviour of these tumours. This requires further study. Novel mechanisms of inefficient steroidogenesis were also identified
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