Phase evolution of the direct detection noise figure of a nondegenerate fiber phase-sensitive amplifier

International audienceWe experimentally investigate the evolution of the direct detection noise figure of a nondegenerate phase-sensitive amplifier based on a nonlinear fiber, as a function of the relative phase between the signal, idler, and pump, all other parameters remaining fixed. The use of a fiber with a high stimulated Brillouin scattering threshold permits us to investigate the full range of phase-sensitive gain and noise figure without pump dithering. Good agreement is found with theory, both for signal only and combined signal and idler direct detections

Sno/scaRNAbase: a curated database for small nucleolar RNAs and cajal body-specific RNAs

Small nucleolar RNAs (snoRNAs) and Cajal body-specific RNAs (scaRNAs) are named for their subcellular localization within nucleoli and Cajal bodies (conserved subnuclear organelles present in the nucleoplasm), respectively. They have been found to play important roles in rRNA, tRNA, snRNAs, and even mRNA modification and processing. All snoRNAs fall in two categories, box C/D snoRNAs and box H/ACA snoRNAs, according to their distinct sequence and secondary structure features. Box C/D snoRNAs and box H/ACA snoRNAs mainly function in guiding 2′-O-ribose methylation and pseudouridilation, respectively. ScaRNAs possess both box C/D snoRNA and box H/ACA snoRNA sequence motif features, but guide snRNA modifications that are transcribed by RNA polymerase II. Here we present a Web-based sno/scaRNA database, called sno/scaRNAbase, to facilitate the sno/scaRNA research in terms of providing a more comprehensive knowledge base. Covering 1979 records derived from 85 organisms for the first time, sno/scaRNAbase is not only dedicated to filling gaps between existing organism-specific sno/scaRNA databases that are focused on different sno/scaRNA aspects, but also provides sno/scaRNA scientists with an opportunity to adopt a unified nomenclature for sno/scaRNAs. Derived from a systematic literature curation and annotation effort, the sno/scaRNAbase provides an easy-to-use gateway to important sno/scaRNA features such as sequence motifs, possible functions, homologues, secondary structures, genomics organization, sno/scaRNA gene's chromosome location, and more. Approximate searches, in addition to accurate and straightforward searches, make the database search more flexible. A BLAST search engine is implemented to enable blast of query sequences against all sno/scaRNAbase sequences. Thus our sno/scaRNAbase serves as a more uniform and friendly platform for sno/scaRNA research. The database is free available at

Association of MDR1 Gene SNPs and Haplotypes with the Tacrolimus Dose Requirements in Han Chinese Liver Transplant Recipients

BACKGROUND: This work seeks to evaluate the association between the C/D ratios (plasma concentration of tacrolimus divided by daily dose of tacrolimus per body weight) of tacrolimus and the haplotypes of MDR1 gene combined by C1236T (rs1128503), G2677A/T (rs2032582) and C3435T (rs1045642), and to further determine the functional significance of haplotypes in the clinical pharmacokinetics of oral tacrolimus in Han Chinese liver transplant recipients. METHODOLOGY/PRINCIPAL FINDINGS: The tacrolimus blood concentrations were continuously recorded for one month after initial administration, and the peripheral blood DNA from a total of 62 liver transplant recipients was extracted. Genotyping of C1236T, G2677A/T and C3435T was performed, and SNP frequency, Hardy-Weinberg equilibrium, linkage disequilibrium, haplotypes analysis and multiple testing were achieved by software PLINK. C/D ratios of different SNP groups or haplotype groups were compared, with a p value<0.05 considered statistically significant. Linkage studies revealed that C1236T, G2677A/T and C3435T are genetically associated with each other. Patients carrying T-T haplotype combined by C1236T and G2677A/T, and an additional T/T homozygote at either position would require higher dose of tacrolimus. Tacrolimus C/D ratios of liver transplant recipients varied significantly among different haplotype groups of MDR1 gene. CONCLUSIONS: Our studies suggest that the genetic polymorphism could be used as a valuable molecular marker for the prediction of tacrolimus C/D ratios of liver transplant recipients

A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia

ObjectivesThis study aims to assess the efficacy of tofacitinib (TOF) plus iguratimod (IGU) in rheumatoid arthritis (RA) with usual interstitial pneumonia (UIP) (RA-UIP).MethodsThis was a prospective observational cohort, single-center study. Data from 78 RA-UIP patients treated with TOF plus IGU, IGU plus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and csDMARDs were analyzed. Clinically relevant responses in RA activity assessment, pulmonary function tests (PFTs), and high-resolution computed tomography (HRCT) assessment at baseline and follow-up were compared between groups to evaluate the efficacy of TOF plus IGU.ResultsA total of 78 patients were followed up for at least 6 months after treatment. There were significant changes in sedimentation rate (ESR), C reactive protein (CRP), and disease activity score (DAS) 28-CRP during the follow-up within each treatment group, but there was no statistically significant difference between the two groups. After 6 months of TOF plus IGU treatment, forced vital capacity (FVC)% (84.7 ± 14.7 vs. 90.7 ± 15.4) and HRCT fibrosis score (7.3 ± 3.4 vs. 7.0 ± 5.6) showed a significant improvement compared to the csDMARDs group (P = 0.031, P = 0.015). The TOF plus IGU-treated patients had a significantly higher regression and lower deterioration than the csDMARDs-treated patients (P = 0.026, P = 0.026) and had a significantly higher response (regression + stability), with overall response rates of 66.7% (16/24) vs. 35.7% (10/28) (P = 0.027), respectively.ConclusionOur results indicate that TOF plus IGU can simultaneously relieve RA and RA-UIP and be better than the csDMARDs with a higher response rate in RA-UIP, which may be a potential choice for “dual treat-to-target”

Nonlinear response of a gallium phosphide nanopatterned photonic waveguide in the CW regime

International audienceThe third-order Kerr nonlinear response in gallium phos-phide nanoscale waveguides is measured through continuous wave (CW) four-wave mixing. The extracted nonlinear coefficient ranges from about 800 W −1 m −1 to 1400 W −1 m −1 , consistently with an estimated material nonlinearity n 2 ˆ 3.5 × 10 −18 W −1 m 2. The roles of the residual absorption and the related thermal effects are discussed

Origin and anatomy of two different types of mass-transport complexes: a 3D seismic case study from the northern South China Sea margin

Integration of 2D and 3D seismic data from the Qiongdongnan Basin along the northwestern South China Sea margin has enabled the seismic stratigraphy, seismic geomorphology and emplacement mechanisms of eight separate, previously undocumented, mass-transport complexes (MTCs) to be characterized. These eight MTCs can be grouped into two types:. (1) Localized detached MTCs, which are confined to submarine canyons and cover hundreds of km, consist of a few tens of km remobilized sediments and show long striations at their base. They resulted from small-scale mass-wasting processes induced by regional tectonic events and gravitational instabilities on canyon margins.(2) Regional attached MTCs, which occur within semi-confined or unconfined settings and are distributed roughly perpendicular to the strike of the regional slope. Attached MTCs occupy hundreds to thousands of km and are composed of tens to hundreds of km of remobilized sediments. They contain headwall escarpments, translated blocks, remnant blocks, pressure ridges, and basal striations and cat-claw grooves. They were created by large-scale mass-wasting processes triggered by high sedimentation rates, slope oversteepening by shelf-edge deltas, and seismicity.Our results show that MTCs may act as both lateral and top seals for underlying hydrocarbon reservoirs and could create MTC-related stratigraphic traps that represent potential drilling targets on continental margins, helping to identify MTC-related hydrocarbon traps

Systems-Scale Analysis Reveals Pathways Involved in Cellular Response to Methamphetamine

Background: Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced. Methodology/Results: We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis/ contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level. Conclusion: Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion

The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban