756 research outputs found

    ITPKA expression is a novel prognostic factor in hepatocellular carcinoma

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    Dent disease: A window into calcium and phosphate transport

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    This review examines calcium and phosphate transport in the kidney through the lens of the rare X-linked genetic disorder Dent disease. Dent disease type 1 (DD1) is caused by mutations in the CLCN5 gene encoding ClC-5, a Cl- /H+ antiporter localized to early endosomes of the proximal tubule (PT). Phenotypic features commonly include low molecular weight proteinuria (LMWP), hypercalciuria, focal global sclerosis and chronic kidney disease; calcium nephrolithiasis, nephrocalcinosis and hypophosphatemic rickets are less commonly observed. Although it is not surprising that abnormal endosomal function and recycling in the PT could result in LMWP, it is less clear how ClC-5 dysfunction disturbs calcium and phosphate metabolism. It is known that the majority of calcium and phosphate transport occurs in PT cells, and PT endocytosis is essential for calcium and phosphorus reabsorption in this nephron segment. Evidence from ClC-5 KO models suggests that ClC-5 mediates parathormone endocytosis from tubular fluid. In addition, ClC-5 dysfunction alters expression of the sodium/proton exchanger NHE3 on the PT apical surface thus altering transcellular sodium movement and hence paracellular calcium reabsorption. A potential role for NHE3 dysfunction in the DD1 phenotype has never been investigated, either in DD models or in patients with DD1, even though patients with DD1 exhibit renal sodium and potassium wasting, especially when exposed to even a low dose of thiazide diuretic. Thus, insights from the rare disease DD1 may inform possible underlying mechanisms for the phenotype of hypercalciuria and idiopathic calcium stones

    A Low Power Multi-Class Migraine Detection Processor Based on Somatosensory Evoked Potentials

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    Migraine is a disabling neurological disorder that can be recurrent and persist for long durations. The continuous monitoring of the brain activities can enable the patient to respond on time before the occurrence of the approaching migraine episode to minimize the severity. Therefore, there is a need for a wearable device that can ensure the early diagnosis of a migraine attack. This brief presents a low latency, and power-efficient feature extraction and classification processor for the early detection of a migraine attack. Somatosensory Evoked Potentials (SEP) are utilized to monitor the migraine patterns in an ambulatory environment aiming to have a processor integrated on-sensor for power-efficient and timely intervention. In this work, a complete digital design of the wearable environment is proposed. It allows the extraction of multiple features including multiple power spectral bands using 256-point fast Fourier transform (FFT), root mean square of late HFO bursts and latency of N20 peak. These features are then classified using a multi-classification artificial neural network (ANN)-based classifier which is also realized on the chip. The proposed processor is placed and routed in a 180nm CMOS with an active area of 0.5mm(2). The total power consumption is 249 mu W while operating at a 20MHz clock with full computations completed in 1.31ms

    Threshold FlipThem:when the winner does not need to take all

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    We examine a FlipIt game in which there are multiple resources which a monolithic attacker is trying to compromise. This extension to FlipIt was considered in a paper in GameSec 2014, and was there called FlipThem. Our analysis of such a situation is focused on the situation where the attacker’s goal is to compromise a threshold of the resources. We use our game theoretic model to enable a defender to choose the correct configuration of resources (number of resources and the threshold) so as to ensure that it makes no sense for a rational adversary to try to attack the system. This selection is made on the basis of the relative costs of the attacker and the defender

    Small interfering RNA targeting mcl-1 enhances proteasome inhibitor-induced apoptosis in various solid malignant tumors

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    <p>Abstract</p> <p>Background</p> <p>Targeting the ubiquitin-proteasome pathway is a promising approach for anticancer strategies. Recently, we found Bik accumulation in cancer cell lines after they were treated with bortezomib. However, recent evidence indicates that proteasome inhibitors may also induce the accumulation of anti-apoptotic Bcl-2 family members. The current study was designed to analyze the levels of several anti-apoptotic members of Bcl-2 family in different human cancer cell lines after they were treated with proteasome inhibitors.</p> <p>Methods</p> <p>Different human cancer cell lines were treated with proteasome inhibitors. Western blot were used to investigate the expression of Mcl-1 and activation of mitochondrial apoptotic signaling. Cell viability was investigated using SRB assay, and induction of apoptosis was measured using flow cytometry.</p> <p>Results</p> <p>We found elevated Mcl-1 level in human colon cancer cell lines DLD1, LOVO, SW620, and HCT116; human ovarian cancer cell line SKOV3; and human lung cancer cell line H1299, but not in human breast cancer cell line MCF7 after they were treated with bortezomib. This dramatic Mcl-1 accumulation was also observed when cells were treated with other two proteasome inhibitors, MG132 and calpain inhibitor I (ALLN). Moreover, our results showed Mcl-1 accumulation was caused by stabilization of the protein against degradation. Reducing Mcl-1 accumulation by Mcl-1 siRNA reduced Mcl-1 accumulation and enhanced proteasome inhibitor-induced cell death and apoptosis, as evidenced by the increased cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase.</p> <p>Conclusions</p> <p>Our results showed that it was not only Bik but also Mcl-1 accumulation during the treatment of proteasome inhibitors, and combining proteasome inhibitors with Mcl-1 siRNA would enhance the ultimate anticancer effect suggesting this combination might be a more effective strategy for cancer therapy.</p

    Observation of CR Anisotropy with ARGO-YBJ

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    The measurement of the anisotropies of cosmic ray arrival direction provides important informations on the propagation mechanisms and on the identification of their sources. In this paper we report the observation of anisotropy regions at different angular scales. In particular, the observation of a possible anisotropy on scales between \sim 10 ^{\circ} and \sim 30 ^{\circ} suggests the presence of unknown features of the magnetic fields the charged cosmic rays propagate through, as well as potential contributions of nearby sources to the total flux of cosmic rays. Evidence of new weaker few-degree excesses throughout the sky region 195195^{\circ}\leq R.A. 315\leq 315^{\circ} is reported for the first time.Comment: Talk given at 12th TAUP Conference 2011, 5-9 September 2011, Munich, German

    Morphology Analysis of Si Island Arrays on Si(001)

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    The formation of nanometer-scale islands is an important issue for bottom-up-based schemes in novel electronic, optoelectronic and magnetoelectronic devices technology. In this work, we present a detailed atomic force microscopy analysis of Si island arrays grown by molecular beam epitaxy. Recent reports have shown that self-assembled distributions of fourfold pyramid-like islands develop in 5-nm thick Si layers grown at substrate temperatures of 650 and 750°C on HF-prepared Si(001) substrates. Looking for wielding control and understanding the phenomena involved in this surface nanostructuring, we develop and apply a formalism that allows for processing large area AFM topographic images in a shot, obtaining surface orientation maps with specific information on facets population. The procedure reveals some noticeable features of these Si island arrays, e.g. a clear anisotropy of the in-plane local slope distributions. Total island volume analysis also indicates mass transport from the substrate surface to the 3D islands, a process presumably related to the presence of trenches around some of the pyramids. Results are discussed within the framework of similar island arrays in homoepitaxial and heteroepitaxial semiconductor systems

    Preparation of Fe3O4Spherical Nanoporous Particles Facilitated by Polyethylene Glycol 4000

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    Much interest has been attracted to the magnetic materials with porous structure because of their unique properties and potential applications. In this report, Fe3O4nanoporous particles assembled from small Fe3O4nanoparticles have been prepared by thermal decomposition of iron acetylacetonate in the presence of polyethylene glycol 4000. The size of the spherical nanoporous particles is 100–200 nm. Surface area measurement shows that these Fe3O4nanoporous particles have a high surface area of 87.5 m2/g. Magnetization measurement and Mössbauer spectrum indicate that these particles are nearly superparamagnetic at room temperature. It is found that the morphology of the products is greatly influenced by polyethylene glycol concentration and the polymerization degree of polyethylene glycol. Polyethylene glycol molecules are believed to facilitate the formation of the spherical assembly
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