2,099 research outputs found

    Proteomic analysis of the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

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    So far, only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) has been accepted as diagnostic criterion for Creutzfeldt-Jakob disease (CJD). However, this assay cannot be used for screening because of the high rate of false-positive results, whereas patients with variant CJD are often negative for 14-3-3 proteins. The aim of this study was to compare the spot patterns of CSF by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to search for a CJD-specific spot pattern. We analyzed the CSF of 28 patients {[}11 CJD, 9 Alzheimer's disease ( AD), 8 nondemented controls (NDC)] employing 2D-PAGE which was optimized for minimal volumes of CSF (0.1 ml; 7-cm strips). All samples were run at least three times, gels were silver stained and analyzed by an analysis software and manually revised. We could consistently match 268 spots which were then compared between all groups. By the use of 5 spots, we were able to differentiate CJD from AD or NDC with a sensitivity of 100%. CJD could also be distinguished from both groups by using a heuristic clustering algorithm of 2 spots. We conclude that this proteomic approach can differentiate CJD from other diseases and may serve as a model for other neurodegenerative diseases. Copyright (C) 2007 S. Karger AG, Basel

    Estimating CO₂ emissions for 108000 European cities

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    City-level CO₂ emissions inventories are foundational for supporting the EU's decarbonization goals. Inventories are essential for priority setting and for estimating impacts from the decarbonization transition. Here we present a new CO₂ emissions inventory for all 116572 municipal and local-government units in Europe, containing 108000 cities at the smallest scale used. The inventory spatially disaggregates the national reported emissions, using nine spatialization methods to distribute the 167 line items detailed in the National Inventory Reports (NIRs) using the UNFCCC (United Nations Framework Convention on Climate Change) Common Reporting Framework (CRF). The novel contribution of this model is that results are provided per administrative jurisdiction at multiple administrative levels, following the region boundaries defined OpenStreetMap, using a new spatialization approach

    Ontology based Approach for Precision Agriculture

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    In this paper, we propose a framework of knowledge for an agriculture ontology which can be used for the purpose of smart agriculture systems. This ontology not only includes basic concepts in the agricultural domain but also contains geographical, IoT, business subdomains, and other knowledge extracted from various datasets. With this ontology, any users can easily understand agricultural data links between them collected from many different data resources. In our experiment, we also import country, sub-country and disease entities into this ontology as basic entities for building agricultural linked datasets later

    Visualization of the intracavitary blood flow in systemic ventricles of Fontan patients by contrast echocardiography using particle image velocimetry

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    <p>Abstract</p> <p>Background</p> <p>Flow patterns in univentricular hearts may have clinical value. Therefore, it is our objective to asses and characterize vortex flow patterns with Fontan circulation in comparison with healthy controls.</p> <p>Methods</p> <p>Twenty-three patients (8 Fontan and 15 normal patients) underwent echocardiography with intravenous contrast agent (Sonovue<sup>®</sup>) administration. Dedicated software was used to perform particle image velocimetry (PIV) and to visualize intracavitary flow in the systemic ventricles of the patients. Vortex parameters including vortex depth, length, width, and sphericity index were measured. Vortex pulsatility parameters including relative strength, vortex relative strength, and vortex pulsation correlation were also measured.</p> <p>Results</p> <p>The data from this study show that it is feasible to perform particle velocimetry in Fontan patients. Vortex length (VL) was significantly lower (0.51 ± 0.09 vs 0.65 ± 0.12, <it>P </it>= 0.010) and vortex width (VW) (0.32 ± 0.06 vs 0.27 ± 0.04, <it>p </it>= 0.014), vortex pulsation correlation (VPC) (0.26 ± 0.25 vs -0.22 ± 0.87, <it>p </it>= 0.05) were significantly higher in Fontan patients. Sphericity index (SI) (1.66 ± 0.48 vs 2.42 ± 0.62, <it>p </it>= 0.005), relative strength (RS) (0.77 ± 0.33 vs 1.90 ± 0.47, <it>p </it>= 0.0001), vortex relative strength (VRS) (0.18 ± 0.13 vs 0.43 ± 0.14, <it>p </it>= 0.0001) were significantly lower in the Fontan patients group.</p> <p>Conclusions</p> <p>PIV using contrast echocardiography is feasible in Fontan patients. Fontan patients had aberrant flow patterns as compared to normal hearts in terms of position, shape and sphericity of the main vortices. The vortex from the Fontan group was consistently shorter, wider and rounder than in controls. Whether vortex characteristics are related with clinical outcome is subject to further investigation.</p

    Polymorphisms of toll-like receptors 2 and 9 and severity and prognosis of bacterial meningitis in Chinese children

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    Toll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration <= 1.5 mmol/L and seizures) than those without (43.5% and 40.1% vs. 30.1% and 29.1%, p = 0.008 and p = 0.016, respectively). For TLR9 rs352139, patients who carried genotype AA and minor allele A developed seizures less often than those without (OR = 0.289, p = 0.003 and OR = 0.568, p = 0.004, respectively). However, for TLR9 rs352140, patients who carried genotype TT and minor allele T developed seizures more often than those without (OR = 3.385, p = 0.004 and OR = 1.767, p = 0.004, respectively). Our finding suggested that genetic variations in TLR2 and TLR9 are associated with severity and prognosis of bacterial meningitis in Chinese children. However, the results should be interpreted with caution since the number of subjects included was limited

    Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

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    Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

    PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

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    Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

    Dendritic and T Cell Response to Influenza is Normal in the Patients with X-Linked Agammaglobulinemia

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    Introduction Influenza virus is a potential cause of severe disease in the immunocompromised. X-linked agammaglobu-linemia (XLA) is a primary immunodeficiency characterized by the lack of immunoglobulin, B cells, and plasma cells, secondary to mutation in Bruton’s tyrosine kinase (Btk) gene

    Application of Graphene within Optoelectronic Devices and Transistors

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    Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures
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