165 research outputs found

    Gate-source distance scaling effects in H-terminated diamond MESFETs

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    In this paper, an analysis of gate-source and gate-drain scaling effects in MESFETs fabricated on hydrogen-terminated single-crystal diamond films is reported. The experimental results show that a decrease in gate-source spacing can improve the device performance by increasing the device output current density and its transconductance. On the contrary, the gate--drain distance produces less pronounced effects on device performance. Breakdown voltage, knee voltage, and threshold voltage variations due to changes in gate-source and drain-source distances have also been investigated. The obtained results can be used as a design guideline for the layout optimization of H-terminated diamond-based MESFETs

    A pilot study of IL-1 inhibition by anakinra in acute gout

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    Monosodium urate crystals stimulate monocytes and macrophages to release IL-1β through the NALP3 component of the inflammasome. The effectiveness of IL-1 inhibition in hereditary autoinflammatory syndromes with mutations in the NALP3 protein suggested that IL-1 inhibition might also be effective in relieving the inflammatory manifestations of acute gout. The effectiveness of IL-1 inhibition was first evaluated in a mouse model of monosodium urate crystal-induced inflammation. IL-1 inhibition prevented peritoneal neutrophil accumulation but TNF blockade had no effect. Based on these findings, we performed a pilot, open-labeled study (trial registration number ISRCTN10862635) in 10 patients with gout who could not tolerate or had failed standard antiinflammatory therapies. All patients received 100 mg anakinra daily for 3 days. All 10 patients with acute gout responded rapidly to anakinra. No adverse effects were observed. IL-1 blockade appears to be an effective therapy for acute gouty arthritis. The clinical findings need to be confirmed in a controlled study

    imaging the coupling of terahertz radiation to a high electron mobility transistor in the near field

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    We used AlGaN/GaN high electron mobility transistors as room-temperature direct detectors of radiation at 0.15 THz from a free electron laser, hence 5 times higher than their cutoff frequency of 30 GHz. By near-field active mapping we investigated the antenna-like coupling of the radiation to the transistor channel. We formulate a model for the detection based on self-mixing in the transistor channel. The noise equivalent power is found in the range of 10^{-7} W/Hz^{0.5} without any optimization of the device responsivity. Present day AlGaN/GaN fabrication technology may provide operation at higher frequency, integration of amplifiers for improved responsivity and fast switches for multiplexing, which make the detector here described the basic element of a monolithic terahertz focal plane array

    The B6 database: a tool for the description and classification of vitamin B6-dependent enzymatic activities and of the corresponding protein families

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    BACKGROUND: Enzymes that depend on vitamin B6 (and in particular on its metabolically active form, pyridoxal 5'-phosphate, PLP) are of great relevance to biology and medicine, as they catalyze a wide variety of biochemical reactions mainly involving amino acid substrates. Although PLP-dependent enzymes belong to a small number of independent evolutionary lineages, they encompass more than 160 distinct catalytic functions, thus representing a striking example of divergent evolution. The importance and remarkable versatility of these enzymes, as well as the difficulties in their functional classification, create a need for an integrated source of information about them. DESCRIPTION: The B6 database http://bioinformatics.unipr.it/B6db contains documented B6-dependent activities and the relevant protein families, defined as monophyletic groups of sequences possessing the same enzymatic function. One or more families were associated to each of 121 PLP-dependent activities with known sequences. Hidden Markov models (HMMs) were built from family alignments and incorporated in the database. These HMMs can be used for the functional classification of PLP-dependent enzymes in genomic sets of predicted protein sequences. An example of such analyses (a census of human genes coding for PLP-dependent enzymes) is provided here, whereas many more are accessible through the database itself. CONCLUSION: The B6 database is a curated repository of biochemical and molecular information about an important group of enzymes. This information is logically organized and available for computational analyses, providing a key resource for the identification, classification and comparative analysis of B6-dependent enzymes

    Fusion of 60Ni + 100Mo below barrier

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    The fusion cross section of 60Ni + 100Mo has been measured down to microbarn level, looking for hindrance at low energy, in a system with positive Q-values for neutron transfer. The measured cross sections look similar to those of the nearby 64Ni + 100Mo, but no conclusive statement can be made at this stage, as to the onset of hindrance in this system

    The prognostic value of four interleukin-1 gene polymorphisms in caucasian women with breast cancer – a multicenter study

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    <p>Abstract</p> <p>Background</p> <p>The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown.</p> <p>Methods</p> <p>We studied the influence of four common gene polymorphisms (<it>IL1A </it>-889C/T, <it>IL1B </it>-511C/T, <it>IL1B </it>+3953E1/E2, and <it>IL1RN </it>long/2) of the IL-1 family on survival in 262 Caucasian patients with breast cancer by univariate and multivariate survival analysis. The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis.</p> <p>Results</p> <p>In the present study 38 cases of cancer related death and a median time of follow-up (range) of 55.3 (0.4–175.8) months was observed. <it>IL1RN </it>2/2 (homozygous mutant) gene polymorphism was associated with shortened disease free and overall survival in a univariate (p = 0.001 and p = 0.01, respectively) and multivariate analysis (p = 0.002, Odds Ratio [95% Confidence Interval] = 3.6 [1.6–8.0] and p = 0.05, Odds Ratio = 3.0 [1.1–9.3], respectively). Presence of the homozygous mutant genotype of the <it>IL1A </it>-889 and <it>IL1B </it>+3953 gene polymorphism was associated with overall survival in the univariate (p = 0.004 and p = 0.002, respectively), but not in the multivariate analysis. No association was observed between all possible haplotype combinations and overall survival.</p> <p>Conclusion</p> <p>Carriage of the mutant alleles of <it>IL1RN </it>was independently associated with shortened disease free and overall survival rates in Caucasian patients with breast cancer.</p

    Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status

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    <p>Abstract</p> <p>Background</p> <p>The interleukin-1 (IL-1) family of cytokines is involved in the inflammatory and repair reactions of skeletal muscle during and after exercise. Specifically, plasma levels of the IL-1 receptor antagonist (IL-1ra) increase dramatically after intense exercise, and accumulating evidence points to an effect of genetic polymorphisms on athletic phenotypes. Therefore, the IL-1 family cytokine genes are plausible candidate genes for athleticism. We explored whether IL-1 polymorphisms are associated with athlete status in European subjects.</p> <p>Methods</p> <p>Genomic DNA was obtained from 205 (53 professional and 152 competitive non-professional) Italian athletes and 458 non-athlete controls. Two diallelic polymorphisms in the IL-1β gene (<it>IL-1B</it>) at -511 and +3954 positions, and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (<it>IL-1RN</it>) were assessed.</p> <p>Results</p> <p>We found a 2-fold higher frequency of the <it>IL-1RN </it>1/2 genotype in athletes compared to non-athlete controls (OR = 1.93, 95% CI = 1.37-2.74, 41.0% vs. 26.4%), and a lower frequency of the 1/1 genotype (OR = 0.55, 95% CI = 0.40-0.77, 43.9% vs. 58.5%). Frequency of the <it>IL-1RN </it>2/2 genotype did not differ between groups. No significant differences between athletes and controls were found for either -511 or +3954 <it>IL-1B </it>polymorphisms. However, the haplotype (-511)C-(+3954)T-(VNTR)2 was 3-fold more frequent in athletes than in non-athletes (OR = 3.02, 95% CI = 1.16-7.87). Interestingly, the <it>IL-1RN </it>1/2 genotype was more frequent in professional than in non-professional athletes (OR = 1.92, 95% CI = 1.02-3.61, 52.8% vs. 36.8%).</p> <p>Conclusions</p> <p>Our study found that variants at the IL-1ra gene associate with athletic status. This confirms the crucial role that cytokine IL-1ra plays in human physical exercise. The VNTR <it>IL-1RN </it>polymorphism may have implications for muscle health, performance, and/or recovery capacities. Further studies are needed to assess these specific issues. As VNTR <it>IL-1RN </it>polymorphism is implicated in several disease conditions, athlete status may constitute a confounding variable that will need to be accounted for when examining associations of this polymorphism with disease risk.</p

    Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

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    Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling
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