691 research outputs found

    PUK7 IMMUNOSUPPRESSANT THERAPY PATTERNS AND ITS COSTS IN POST KIDNEY TRANSPLANT PATIENTS IN THE NATIONAL TRANSPLANT PROGRAM IN BRAZIL

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    Buku kerja modul manajemen implementasi kurikulum 2013 jenjang SMP (B5 M1)

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    Buku Kerja Modul ini terdisi dari dua bagian, bagian pertama berisi prinsip penyusunan kurikulum 2013 meliputi ; analisis dokumen SKL, DI-KD, dan IPK; analisis materi dalam buku teks pelajaran; analisis penilaian dan pengelolaan hasil belajar; analisis penerapan model pembelajaran; perancangan pembelajaran. Pada bagian kedua berisi pengembangan strategi penyusunan kurikulum 2013 yang meliputi strategi pengelolaan implementasi kurikulum 2013 dan strategi penyempurnaan buku KTSP

    Searching for plasticity in dissociated cortical cultures on multi-electrode arrays

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    We attempted to induce functional plasticity in dense cultures of cortical cells using stimulation through extracellular electrodes embedded in the culture dish substrate (multi-electrode arrays, or MEAs). We looked for plasticity expressed in changes in spontaneous burst patterns, and in array-wide response patterns to electrical stimuli, following several induction protocols related to those used in the literature, as well as some novel ones. Experiments were performed with spontaneous culture-wide bursting suppressed by either distributed electrical stimulation or by elevated extracellular magnesium concentrations as well as with spontaneous bursting untreated. Changes concomitant with induction were no larger in magnitude than changes that occurred spontaneously, except in one novel protocol in which spontaneous bursts were quieted using distributed electrical stimulation

    Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

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    Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers

    Numerical Unsaturated Flow Model of Railway Drainage Systems

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    Substandard drainage assets are considered to be a major cause of flooding, earthwork failures, and deficient track geometry. Considering the deterioration of track materials due to cyclic loads and tamping forces, the impact of more frequent extreme rainfall events is likely to lead towards higher rates of hydraulic overloads in the drainage system, earthwork failures, and service disruptions. Therefore, the development of a numerical model could be able to describe the ageing track bed materials and provide an alternative tool for the simulation of the flow through the porous media used in the construction of railway tracks. In this paper the model HYDRUS is tested to simulate the drainage of trackbed materials under laboratory controlled conditions prior its application on actual railway drainage case studies

    HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

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    The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

    Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

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    The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

    Unravelling the alcohol harm paradox: a population-based study of social gradients across very heavy drinking thresholds

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    Background: There is consistent evidence that individuals in higher socioeconomic status groups are more likely to report exceeding recommended drinking limits, but those in lower socioeconomic status groups experience more alcohol-related harm. This has been called the ‘alcohol harm paradox’. Such studies typically use standard cut-offs to define heavy drinking, which are exceeded by a large proportion of adults. Our study pools data from six years (2008–2013) of the population-based Health Survey for England to test whether the socioeconomic distribution of more extreme levels of drinking could help explain the paradox. Methods: The study included 51,498 adults from a representative sample of the adult population of England for a cross-sectional analysis of associations between socioeconomic status and self-reported drinking. Heavy weekly drinking was measured at four thresholds, ranging from 112 g+/168 g + (alcohol for women/men, or 14/21 UK standard units) to 680 g+/880 g + (or 85/110 UK standard units) per week. Heavy episodic drinking was also measured at four thresholds, from 48 g+/64 g + (or 6/8 UK standard units) to 192 g+/256 g + (or 24/32 UK standard units) in one day. Socioeconomic status indicators were equivalised household income, education, occupation and neighbourhood deprivation. Results: Lower socioeconomic status was associated with lower likelihoods of exceeding recommended limits for weekly and episodic drinking, and higher likelihoods of exceeding more extreme thresholds. For example, participants in routine or manual occupations had 0.65 (95 % CI 0.57–0.74) times the odds of exceeding the recommended weekly limit compared to those in ‘higher managerial’ occupations, and 2.15 (95 % CI 1.06–4.36) times the odds of exceeding the highest threshold. Similarly, participants in the lowest income quintile had 0.60 (95 % CI 0.52–0.69) times the odds of exceeding the recommended weekly limit when compared to the highest quintile, and 2.30 (95 % CI 1.28–4.13) times the odds of exceeding the highest threshold. Conclusions: Low socioeconomic status groups are more likely to drink at extreme levels, which may partially explain the alcohol harm paradox. Policies that address alcohol-related health inequalities need to consider extreme drinking levels in some sub-groups that may be associated with multiple markers of deprivation. This will require a more disaggregated understanding of drinking practice

    The Evolution of Compact Binary Star Systems

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    We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

    Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer

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    <p>Abstract</p> <p>Background</p> <p>Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues and correlated it with clinicopathologic data.</p> <p>Methods</p> <p>pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively.</p> <p>Results</p> <p>pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues (6 out of 80, 7.5%; <it>P </it>< 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5 in CRC tissues was significantly correlated to the depth of invasion (<it>P </it>= 0.001), lymph node metastasis (<it>P </it>< 0.001), distant metastasis (<it>P </it>< 0.001) and high preoperative CEA level (<it>P </it>< 0.001). Consistently, the pMEK5 level in CRC tissues was increased following stage progression of the disease (<it>P </it>< 0.001). Analysis of the survival curves showed a significantly worse 5-year disease-free (<it>P </it>= 0.002) and 5-year overall survival rate (<it>P </it>< 0.001) for patients whose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic factor for CRC (DFS: <it>P </it>= 0.139; OS: <it>P </it>= 0.071).</p> <p>Conclusions</p> <p>pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.</p
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