205 research outputs found

    Lipid-modulated assembly of magnetized iron-filled carbon nanotubes in millimeter-scale structures

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    Biomolecule-functionalized carbon nanotubes (CNTs) combine the molecular recognition properties of biomaterials with the electrical properties of nanoscale solid state transducers. Application of this hybrid material in bioelectronic devices requires the development of methods for the reproducible self-assembly of CNTs into higher-order structures in an aqueous environment. To this end, we have studied pattern formation of lipid-coated Fe-filled CNTs, with lengths in the 1–5 µm range, by controlled evaporation of aqueous CNT-lipid suspensions. Novel diffusion limited aggregation structures composed of end-to-end oriented nanotubes were observed by optical and atomic force microscopy. Significantly, the lateral dimension of assemblies of magnetized Fe-filled CNTs was in the millimeter range. Control experiments in the absence of lipids and without magnetization indicated that the formation of these long linear nanotube patterns is driven by a subtle interplay between radial flow forces in the evaporating droplet, lipid-modulated van der Waals forces, and magnetic dipole–dipole interactions. Keywords

    Effect of Phosphate Buffered Saline Solutions on Top-Down Fabricated ZnO Nanowire Field Effect Transistor

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    ZnO based nanowire FETs have been fabricated by implementing a top-down approach, which uses optical photolithography, atomic layer deposition (ALD) of ZnO thin film, and anisotropic plasma etching. The effects of Phosphate Buffered Saline (PBS) solution on the surface of ZnO nanowire were investigated by measuring the FET characteristics at different PBS dilutions. The drain current, ION, exhibited an increase of 39 times in the highest PBS solution concentration compared to measurement in air. From the measured transfer characteristics and output characteristics in various PBS dilutions, the device was found to maintain n-type behaviour. These results indicate that the device can be effectively used for biomolecules sensing

    Fatigue in teriflunomide-treated patients with relapsing remitting multiple sclerosis in the real-world Teri-FAST study

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    BACKGROUND: Fatigue is a frequent and disabling symptom of multiple sclerosis (MS) often associated with impaired quality of life (QoL) in patients. Teriflunomide is a once-daily oral immunomodulator used for the treatment of relapsing remitting forms of MS. However, its effect on fatigue is not well known in real life practice. We evaluated the impact of teriflunomide on fatigue in patients with relapsing remitting MS (RRMS) after 2 years of treatment in the real-world Teri-FAST study. METHODS: Teri-FAST was a 2-year, prospective, observational study conducted in France in RRMS patients treated with teriflunomide 14 mg. Fatigue was assessed using the French version of the modified fatigue impact scale (EMIF-SEP). The primary endpoint was the change from baseline in EMIF-SEP score after 2 years of treatment. Secondary endpoints included evaluation of depression (Beck Depression Inventory [BDI]), health-related QoL (Two-Life Scale TLS-QoL 10), self-reported physical activity, and adverse events. RESULTS: 210 eligible patients were included in the study with a mean age of 45.4 years and a mean ± SD Expanded Disability Status Scale score of 1.76 ± 1.43 at baseline. About half (52.4%) of patients had no previous treatment for MS. In the 163 patients who completed at least 1 follow-up visit, the mean change in EMIF-SEP score at Year 2 was -1.54 (95% CI: -4.02, 0.94) indicating that fatigue remained stable. Similarly, there were no changes in depression level and QoL after 2 years of treatment. Physical activity slightly improved with 57% of patients reporting being physically active after 2 years as compared to 46% at baseline. The safety profile of teriflunomide was consistent with that seen during clinical development, and compliance with treatment was high. CONCLUSION: Fatigue scores remained stable in RRMS patients treated with teriflunomide 14 mg over 2 years in real-life setting. Teriflunomide did not negatively impact depression or QoL

    Characterization of the Prokaryotic Sodium Channel NavSp Pore with a Microfluidic Bilayer Platform

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    This paper describes the use of a newly-developed micro-chip bilayer platform to examine the electrophysiological properties of the prokaryotic voltage-gated sodium channel pore (NavSp) from Silicibacter pomeroyi. The platform allows up to 6 bilayers to be analysed simultaneously. Proteoliposomes were incorporated into suspended lipid bilayers formed within the microfluidic bilayer chips. The chips provide access to bilayers from either side, enabling the fast and controlled titration of compounds. Dose-dependent modulation of the opening probability by the channel blocking drug nifedipine was measured and its IC50 determined

    Fat induces glucose metabolism in nontransformed liver cells and promotes liver tumorigenesis

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    Hepatic fat accumulation is associated with diabetes and hepatocellular carcinoma (HCC). Here, we characterize the metabolic response that high-fat availability elicits in livers before disease development. After a short term on a high-fat diet (HFD), otherwise healthy mice showed elevated hepatic glucose uptake and increased glucose contribution to serine and pyruvate carboxylase activity compared with control diet (CD) mice. This glucose phenotype occurred independently from transcriptional or proteomic programming, which identifies increased peroxisomal and lipid metabolism pathways. HFD-fed mice exhibited increased lactate production when challenged with glucose. Consistently, administration of an oral glucose bolus to healthy individuals revealed a correlation between waist circumference and lactate secretion in a human cohort. In vitro, palmitate exposure stimulated production of reactive oxygen species and subsequent glucose uptake and lactate secretion in hepatocytes and liver cancer cells. Furthermore, HFD enhanced the formation of HCC compared with CD in mice exposed to a hepatic carcinogen. Regardless of the dietary background, all murine tumors showed similar alterations in glucose metabolism to those identified in fat exposed nontransformed mouse livers, however, particular lipid species were elevated in HFD tumor and nontumor-bearing HFD liver tissue. These findings suggest that fat can induce glucose-mediated metabolic changes in nontransformed liver cells similar to those found in HCC

    A high confidence, manually validated human blood plasma protein reference set

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    <p>Abstract</p> <p>Background</p> <p>The immense diagnostic potential of human plasma has prompted great interest and effort in cataloging its contents, exemplified by the Human Proteome Organization (HUPO) Plasma Proteome Project (PPP) pilot project. Due to challenges in obtaining a reliable blood plasma protein list, HUPO later re-analysed their own original dataset with a more stringent statistical treatment that resulted in a much reduced list of high confidence (at least 95%) proteins compared with their original findings. In order to facilitate the discovery of novel biomarkers in the future and to realize the full diagnostic potential of blood plasma, we feel that there is still a need for an ultra-high confidence reference list (at least 99% confidence) of blood plasma proteins.</p> <p>Methods</p> <p>To address the complexity and dynamic protein concentration range of the plasma proteome, we employed a linear ion-trap-Fourier transform (LTQ-FT) and a linear ion trap-Orbitrap (LTQ-Orbitrap) for mass spectrometry (MS) analysis. Both instruments allow the measurement of peptide masses in the low ppm range. Furthermore, we employed a statistical score that allows database peptide identification searching using the products of two consecutive stages of tandem mass spectrometry (MS3). The combination of MS3 with very high mass accuracy in the parent peptide allows peptide identification with orders of magnitude more confidence than that typically achieved.</p> <p>Results</p> <p>Herein we established a high confidence set of 697 blood plasma proteins and achieved a high 'average sequence coverage' of more than 14 peptides per protein and a median of 6 peptides per protein. All proteins annotated as belonging to the immunoglobulin family as well as all hypothetical proteins whose peptides completely matched immunoglobulin sequences were excluded from this protein list. We also compared the results of using two high-end MS instruments as well as the use of various peptide and protein separation approaches. Furthermore, we characterized the plasma proteins using cellular localization information, as well as comparing our list of proteins to data from other sources, including the HUPO PPP dataset.</p> <p>Conclusion</p> <p>Superior instrumentation combined with rigorous validation criteria gave rise to a set of 697 plasma proteins in which we have very high confidence, demonstrated by an exceptionally low false peptide identification rate of 0.29%.</p

    Spatio-Temporal Variation in Length-Weight Relationships and Condition of the Ribbonfish Trichiurus lepturus (Linnaeus, 1758): Implications for Fisheries Management

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    Knowledge of length-weight relationships for commercially exploited fish is an important tool for assessing and managing of fish stocks. However, analyses of length-weight relationship fisheries data typically do not consider the inherent differences in length-weight relationships for fish caught from different habitats, seasons, or years, and this can affect the utility of these data for developing condition indices or calculating fisheries biomass. Here, we investigated length-weight relationships for ribbonfish Trichiurus lepturus in the waters of the Arabian Sea off Oman collected during three periods (2001-02, 2007-08, and 2014-15) and showed that a multivariate modelling approach that considers the areas and seasons in which ribbonfish were caught improved estimation of length-weight relationships. We used the outputs of these models to explore spatio-temporal variations in condition indices and relative weights among ribbonfish, revealing fish of 85-125 cm were in the best overall condition. We also found that condition differed according to where and when fish were caught, with condition lowest during spring and pre-south-west monsoon periods and highest during and after the south-west monsoons. We interpret these differences to be a consequence of variability in temperature and food availability. Based on our findings, we suggest fishing during seasons that have the lowest impact on fish condition and which are commercially most viable; such fishery management would enhance fisheries conservation and economic revenue in the region

    First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

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    INTRODUCTION: Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. METHODS: A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. RESULTS: 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. CONCLUSIONS: Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies
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