20,388 research outputs found
P2X receptors: epithelial ion channels and regulators of salt and water transport.
When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels
A Similarity Measure for GPU Kernel Subgraph Matching
Accelerator architectures specialize in executing SIMD (single instruction,
multiple data) in lockstep. Because the majority of CUDA applications are
parallelized loops, control flow information can provide an in-depth
characterization of a kernel. CUDAflow is a tool that statically separates CUDA
binaries into basic block regions and dynamically measures instruction and
basic block frequencies. CUDAflow captures this information in a control flow
graph (CFG) and performs subgraph matching across various kernel's CFGs to gain
insights to an application's resource requirements, based on the shape and
traversal of the graph, instruction operations executed and registers
allocated, among other information. The utility of CUDAflow is demonstrated
with SHOC and Rodinia application case studies on a variety of GPU
architectures, revealing novel thread divergence characteristics that
facilitates end users, autotuners and compilers in generating high performing
code
Childhood secondhand smoke exposure and pregnancy loss in never smokers: The Guangzhou Biobank Cohort Study
published_or_final_versio
Effects of hydrogen bond and solvent polarity on the C=O strectching of bis(2-thienyl)ketone in solution
The optimized structural parameters, the absorption and the resonance Raman spectra have been investigated for the bis(2-thienyl)ketone in gas phase, in cyclohexane, methanol, and acetonitrile solvents by means of time dependent density functional theory calculations, the solvent electronic polarization effect on the solvation shift is examined and in well accordance with the calculation. The effect of increasing the polarity of the solvent is well represented by the polarizable continuum model, both for the absorption spectra and resonance Raman intensities. The Raman spectra of the C=O stretching mode, which is sensitive to the intermolecular interaction for bis(2-thienyl)ketone dissolved in solvents, were systematically studied. It was found that the hydrogen bond effect plays an important role in reducing the carbonyl stretching wavenumbers. The results of Raman shifts were interpreted through the dilution effect, solvation effects, and hydrogen bond-forming effects. Furthermore, the excitation profiles of several important Raman bands of bis(2-thienyl)ketone molecule in different solvents have been critically analyzed. The solvent effects on structural and symmetry properties of the molecule in S2 electronic state as well as the short-time photo relaxation dynamics have been discussed.published_or_final_versio
Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway
Objectives: Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour - stroma interaction. Methods: Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results: Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2 (+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 2003X microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition. Conclusions: TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.published_or_final_versio
Machine learning application in personalised lung cancer recurrence and survivability prediction
Copyright © 2022 The Authors. Machine learning is an important artificial intelligence technique that is widely applied in cancer diagnosis and detection. More recently, with the rise of personalised and precision medicine, there is a growing trend towards machine learning applications for prognosis prediction. However, to date, building reliable prediction models of cancer outcomes in everyday clinical practice is still a hurdle. In this work, we integrate genomic, clinical and demographic data of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) patients from The Cancer Genome Atlas (TCGA) and introduce copy number variation (CNV) and mutation information of 15 selected genes to generate predictive models for recurrence and survivability. We compare the accuracy and benefits of three well-established machine learning algorithms: decision tree methods, neural networks and support vector machines. Although the accuracy of predictive models using the decision tree method has no significant advantage, the tree models reveal the most important predictors among genomic information (e.g. KRAS, EGFR, TP53), clinical status (e.g. TNM stage and radiotherapy) and demographics (e.g. age and gender) and how they influence the prediction of recurrence and survivability for both early stage LUAD and LUSC. The machine learning models have the potential to help clinicians to make personalised decisions on aspects such as follow-up timeline and to assist with personalised planning of future social care needs.Funding from the UK Engineering & Physical Sciences Research Council (EPSRC) for the Future Targeted Healthcare Manufacturing Hub hosted at University College London with UK university partners is gratefully acknowledged (Grant Reference: EP/P006485/1). Financial and in-kind support from the consortium of industrial users and sector organisations is also acknowledged
Serum levels of WNT1-inducible signaling pathway protein-1 (WISP-1): a noninvasive biomarker of renal fibrosis in subjects with chronic kidney disease
WNT1-inducible signaling pathway protein-1 (WISP-1) is an extracellular matrix-related protein that plays multiple roles in cellular physiology and pathology. Accumulating evidence shows that WISP-1 is involved in the process underlying fibrotic diseases. However, the correlation between WISP-1 and renal fibrosis is unknown. In this study, we hypothesized that WISP-1 levels might be correlated with renal fibrosis and could be used as a noninvasive biomarker to screen for renal fibrosis in patients with chronic kidney disease (CKD). We first measured the WISP-1 expression levels using a transforming growth factor-β (TGF-β)-induced renal fibrosis tubular epithelial cell (TEC) model and a mouse model of obstructive nephropathy. We then evaluated the correlation between serum WISP-1 levels and fibrosis scores in biopsy-proven renal fibrosis of patients with CKD. Based on the findings from both in vivo and in vitro studies, the levels of WISP-1 and fibrotic parameters (collagen I, fibronectin and α-smooth muscle actin) were significantly increased in the fibrotic models. Consistently, patients with focal proliferative IgA nephropathy, focal segmental glomerular sclerosis and diabetic nephropathy displayed markedly elevated serum WISP-1 levels and fibrosis scores of renal biopsies compared with normal subjects and patients with minimal change disease (P<0.05). Importantly, the serum WISP-1 levels were positively correlated with fibrosis scores in the renal biopsies of these patients (r=0.475, P=0.0001). Thus, serum WISP-1 levels may be used as a potential noninvasive biomarker of renal fibrosis in patients with CKD.published_or_final_versio
Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor
Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in non-hematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP)). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects
Holographic Entanglement Entropy in P-wave Superconductor Phase Transition
We investigate the behavior of entanglement entropy across the holographic
p-wave superconductor phase transition in an Einstein-Yang-Mills theory with a
negative cosmological constant. The holographic entanglement entropy is
calculated for a strip geometry at AdS boundary. It is found that the
entanglement entropy undergoes a dramatic change as we tune the ratio of the
gravitational constant to the Yang-Mills coupling, and that the entanglement
entropy does behave as the thermal entropy of the background black holes. That
is, the entanglement entropy will show the feature of the second order or first
order phase transition when the ratio is changed. It indicates that the
entanglement entropy is a good probe to investigate the properties of the
holographic phase transition.Comment: 19 pages,15 figures, extended discussion in Sec.5, references adde
Mapping Patent Classifications: Portfolio and Statistical Analysis, and the Comparison of Strengths and Weaknesses
The Cooperative Patent Classifications (CPC) jointly developed by the
European and US Patent Offices provide a new basis for mapping and portfolio
analysis. This update provides an occasion for rethinking the parameter
choices. The new maps are significantly different from previous ones, although
this may not always be obvious on visual inspection. Since these maps are
statistical constructs based on index terms, their quality--as different from
utility--can only be controlled discursively. We provide nested maps online and
a routine for portfolio overlays and further statistical analysis. We add a new
tool for "difference maps" which is illustrated by comparing the portfolios of
patents granted to Novartis and MSD in 2016.Comment: Scientometrics 112(3) (2017) 1573-1591;
http://link.springer.com/article/10.1007/s11192-017-2449-
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