960 research outputs found

    A NUMBER THEORETIC FUNCTION AND ITS MEAN VALUE PROPERTY

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    Studying the asymptotic properties of a mean value, and giving an interesting asymptotic formula for it

    Identifying high-risk areas of N leaching in the Salt Lake Valley

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    Nitrogen (N) fertilization of urban turf areas, and potential nitrate (NO3-N) leaching, may pose a hazard to groundwater quality. This research utilized a Geographic Information System (GIS) approach to estimate NO3-N leaching mass from urban turf areas based on a one-dimensional N leaching model and to classify the NO3-N leaching risk in the Salt Lake Valley, Utah, USA, based on soil texture. The methodology integrated a calibrated and verified Hydrus-1D N model, soil textures and urban turf areas to predict NO3-N leaching to groundwater. Thirty United States Geological Survey (USGS) residential wells were installed and sampled in 1999 for NO3-N concentration. A relationship between estimated NO3-N leaching from urban landscapes and groundwater NO3-N concentration was developed to determine the effect of soil texture and landscaped area on NO3-N leaching from urban landscapes. The GIS approach was used to estimate the NO3-N leaching risk to groundwater under efficient irrigation and fertilization scenarios and over-irrigation and over-fertilization scenarios. The results showed that soil texture played a role in NO3-N leaching from urban landscapes to groundwater, and shallow groundwater was more susceptible to surface contamination compared to deep groundwater. The GIS technique identified areas where improved irrigation and fertilization management could reduce landscape NO3-N leaching significantly, resulting in fewer NO3-N leaching risk areas in the Salt Lake Valley, Utah, USA

    The Anorexigenic Fatty Acid Synthase Inhibitor, C75, Is a Nonspecific Neuronal Activator

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    C75, a recently derived compound that potently suppresses feeding and induces weight loss, has been proposed to act mainly by inhibiting fatty acid synthase (FAS) in central neurons that control feeding. For example, normal, fasting- associated, hypothalamic increases in neuropeptide Y (NPY)/Agouti-related protein (AGRP) expression and decreases in proopiomelanocortin (POMC)/cocaine and amphetamine regulated transcript (CART) expression were reported to be blocked by C75. Using loose-patch extracellular recording in acute slices, we tested the effect of C75 on anorexigenic POMC neurons and orexigenic NPY neurons of the hypothalamic arcuate nucleus, which were identified by promoter-driven GFP expression, as well as on feeding-unrelated cerebellar Purkinje neurons. We expected C75 to activate POMC neurons, inhibit NPY neurons, and have no effect on Purkinje neurons. Instead, C75 activated all cell types, suggesting that it lacks target specificity. This activation was probably not caused by FAS inhibition, because the classical FAS inhibitor, cerulenin, did not have this effect when tested on POMC and NPY neurons. Nonspecific neuronal activation and resulting neurological effects might contribute to the decreased feeding reported to follow centrally administered C75. Injection, ip, of C75 induced severe loosening or liquefaction of stools, weight loss, and decreased food intake in both wild-type and melanocortin-4 receptor knockout mice. In contrast, cerulenin failed to loosen stools, even at a molar dose over 9-fold greater than C75, and had a much smaller effect on body weight. FAS inhibitory activity, by itself, seems to be insufficient to reproduce all of the effects of ip-injected C75

    СИСТЕМНОЕ РЕФОРМИРОВАНИЕ КИТАЙСКОГО АНТИКОРРУПЦИОННОГО ЗАКОНОДАТЕЛЬСТВА И ПРАВОПРИМЕНИТЕЛЬНОЙ ПРАКТИКИ

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    The subject. The article is devoted to the analysis of ongoing systematic reform of Chinese anticorruption legislation and practice of its enforcement.The purpose of the article is to formulate ways of improvement Chinese anti-corruption legislation.The methods of legislation analysis and synthesis of legislative gaps and contradictions are used.The results, scope of application. Nowadays, China is moving from the struggle against corruption by political means to the struggle by legal means. In attempt to construct a system of anti-corruption legislation, China is actively forming a dualistic normative system and a mechanism for the interaction between party norms and state legislation. A multilevel vertical-integrated system of anti-corruption legislation with "The anti-corruption law" as a core was created; the Party is stressing the priority status of preventive legislation and the auxiliary role of legislation on control over power. This system should became the basis for building Chinese anti-corruption legislation. The author formulated a system of principles of Chinese anti-corruption legislation, including the principles of efficiency, consistency, economy and gradualism. The importance of the anti-corruption legislative program, the task formulated in 2015, is underlined. The list of the main anti-corruption legislative acts has been determined, including legislation in the aspects "do not dare to take [bribes]", "cannot take [bribes]" and "do not want to take [bribes]". The problem of improving the legislation in the "do not dare to take" aspect have been specially considered, including improvement of criminal legislation, adoption of the law on accountability and responsibility of public servants, as well as the adoption of an anti-corruption law. The main alternatives and problems of improving legislation in the context of "not being able to take" are considered, such as adoption of laws on declaration of property of public servants, on pre-vention of conflict of interests, on transparency of the administration, on public hearings, and the improvement of party norms.Conclusions. China is experiencing a crucial turning point in the fight against corruption since the beginning of the modernization transformation and is in the strategic "window of opportunities". Active and systematic construction of anti-corruption legislation, the transit from formal counteraction to real counteraction is the key to overcoming the current "corruption crisis with Chinese characteristics".Выявляются направления совершенствования китайского антикоррупционного законодательства и практики его применения. Обозначены принципы антикоррупционного законодательства. Дается оценка создаваемой в настоящее время в Китае многоуровневой комплексной вертикальной системы антикоррупционного законодательства, ядром которой должен стать приоритетный статус профилактического законодательства, а законодательство о контроле над властью должно выполнять вспомогательную роль

    Effect of pressure profile of shock waves on lipid membrane deformation

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    Use of shock waves to temporarily increase the permeability of the cell membrane is a promising approach in drug delivery and gene therapy to allow the translocation of macromolecules and small polar molecules into the cytoplasm. Our understanding of how the characteristics of the pressure profile of shock waves, such as peak pressure and pulse duration, influences membrane properties is limited. Here we study the response of lipid bilayer membranes to shock pulses with different pressure profiles using atomistic molecular dynamics simulations. From our simulation results, we find that the transient deformation/disordering of the membrane depends on both the magnitude and the pulse duration of the pressure profile of the shock pulse. For a low pressure impulse, peak pressure has a dominant effect on membrane structural changes, while for the high pressure impulse, we find that there exists an optimal pulse duration at which membrane deformation/disordering is maximized

    Pulmonary Retention of Adipose Stromal Cells Following Intravenous Delivery Is Markedly Altered in the Presence of ARDS

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    Transplantation of mesenchymal stromal cells (MSCs) has been shown to effectively prevent lung injury in several preclinical models of acute respiratory distress syndrome (ARDS). Since MSC therapy is tested in clinical trials for ARDS, there is an increased need to define the dynamics of cell trafficking and organ-specific accumulation. We examined how the presence of ARDS changes retention and organ-specific distribution of intravenously delivered MSCs isolated from subcutaneous adipose tissue [adipose-derived stem cells (ADSCs)]. This type of cell therapy was previously shown to ameliorate ARDS pathology. ARDS was triggered by lipopolysaccharide (LPS) aspiration, 4 h after which 300,000 murine CRE+ ADSCs were delivered intravenously. The distribution of ADSCs in the lungs and other organs was assessed by real-time polymerase chain reaction (PCR) of genomic DNA. As anticipated, the majority of delivered ADSCs accumulated in the lungs of both control and LPS-challenged mice, with minor amounts distributed to the liver, kidney, spleen, heart, and brain. Interestingly, within 2 h following ADSC administration, LPS-challenged lungs retained significantly lower levels of ADSCs compared to control lungs (∼7% vs. 15% of the original dose, respectively), whereas the liver, kidney, spleen, and brain of ARDS-affected animals retained significantly higher numbers of ADSCs compared to control animals. In contrast, 48 h later, only LPS-challenged lungs continued to retain ADSCs (∼3% of the original dose), whereas the lungs of control animals and nonpulmonary organs in either control or ARDS mice had no detectable levels of ADSCs. Our data suggest that the pulmonary microenvironment during ARDS may lessen the pulmonary capillary occlusion by MSCs immediately following cell delivery while facilitating pulmonary retention of the cells

    Thyroid hormone-regulated gene expression in juvenile mouse liver: identification of thyroid response elements using microarray profiling and in silico analyses

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    <p>Abstract</p> <p>Background</p> <p>Disruption of thyroid hormone signalling can alter growth, development and energy metabolism. Thyroid hormones exert their effects through interactions with thyroid receptors that directly bind thyroid response elements and can alter transcriptional activity of target genes. The effects of short-term thyroid hormone perturbation on hepatic mRNA transcription in juvenile mice were evaluated, with the goal of identifying genes containing active thyroid response elements. Thyroid hormone disruption was induced from postnatal day 12 to 15 by adding goitrogens to dams' drinking water (hypothyroid). A subgroup of thyroid hormone-disrupted pups received intraperitoneal injections of replacement thyroid hormones four hours prior to sacrifice (replacement). An additional group received only thyroid hormones four hours prior to sacrifice (hyperthyroid). Hepatic mRNA was extracted and hybridized to Agilent mouse microarrays.</p> <p>Results</p> <p>Transcriptional profiling enabled the identification of 28 genes that appeared to be under direct thyroid hormone-regulation. The regulatory regions of the genome adjacent to these genes were examined for half-site sequences that resemble known thyroid response elements. A bioinformatics search identified 33 thyroid response elements in the promoter regions of 13 different genes thought to be directly regulated by thyroid hormones. Thyroid response elements found in the promoter regions of Tor1a, 2310003H01Rik, Hect3d and Slc25a45 were further validated by confirming that the thyroid receptor is associated with these sequences <it>in vivo </it>and that it can bind directly to these sequences <it>in vitro</it>. Three different arrangements of thyroid response elements were identified. Some of these thyroid response elements were located far up-stream (> 7 kb) of the transcription start site of the regulated gene.</p> <p>Conclusions</p> <p>Transcriptional profiling of thyroid hormone disrupted animals coupled with a novel bioinformatics search revealed new thyroid response elements associated with genes previously unknown to be responsive to thyroid hormone. The work provides insight into thyroid response element sequence motif characteristics.</p

    Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury.

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    Adenosine has been implicated in the pathogenesis of chronic lung diseases such as asthma and chronic obstructive pulmonary disease. In vitro studies suggest that activation of the A2B adenosine receptor (A2BAR) results in proinflammatory and profibrotic effects relevant to the progression of lung diseases; however, in vivo data supporting these observations are lacking. Adenosine deaminase-deficient (ADA-deficient) mice develop pulmonary inflammation and injury that are dependent on increased lung adenosine levels. To investigate the role of the A2BAR in vivo, ADA-deficient mice were treated with the selective A2BAR antagonist CVT-6883, and pulmonary inflammation, fibrosis, and airspace integrity were assessed. Untreated and vehicle-treated ADA-deficient mice developed pulmonary inflammation, fibrosis, and enlargement of alveolar airspaces; conversely, CVT-6883-treated ADA-deficient mice showed less pulmonary inflammation, fibrosis, and alveolar airspace enlargement. A2BAR antagonism significantly reduced elevations in proinflammatory cytokines and chemokines as well as mediators of fibrosis and airway destruction. In addition, treatment with CVT-6883 attenuated pulmonary inflammation and fibrosis in wild-type mice subjected to bleomycin-induced lung injury. These findings suggest that A2BAR signaling influences pathways critical for pulmonary inflammation and injury in vivo. Thus in chronic lung diseases associated with increased adenosine, antagonism of A2BAR-mediated responses may prove to be a beneficial therapy
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