CuInSe2 thin films produced by rf sputtering in Ar/H2 atmospheres

Structural, compositional, optical, and electrical properties of CuInSe2thin filmsgrown by rf reactive sputtering from a Se excess target in Ar/H2 atmospheres are presented. The addition of H2 to the sputtering atmospheres allows the control of stoichiometry of films giving rise to remarkable changes in the film properties. Variation of substrate temperature causes changes in film composition because of the variation of hydrogen reactivity at the substrate. Measurements of resistivity at variable temperatures indicate a hopping conduction mechanism through gap states for films grown at low temperature (100–250 °C), the existence of three acceptor levels at about 0.046, 0.098, and 0.144 eV above valence band for films grown at intermediate temperature (250–350 °C), and a pseudometallic behavior for film grown at high temperatures (350–450 °C). Chalcopyrite polycrystalline thin films of CuInSe2 with an average grain size of 1 μm, an optical gap of 1.01 eV, and resistivities from 10− 1 to 103 Ω cm can be obtained by adding 1.5% of H2 to the sputtering atmosphere and by varying the substrate temperature from 300 to 400 °C

Microvascular function is preserved in newly diagnosed rheumatoid arthritis and low systemic inflammatory activity

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease and may be affected in RA. It is, however, presently unknown at what point in the disease course the abnormalities in microvascular function occur. We determined whether microvascular function is already disturbed in early disease-modifying antirheumatic drugs (DMARD)-naive RA patients with low systemic inflammation. Fifteen consecutive RA patients with a median symptom duration of 5 months, a C-reactive protein level of ≤20 mg/l and without a history of cardiovascular disease, and age 15 and sex-matched healthy controls were recruited. Endothelium-dependent and endothelium-independent vasodilatation in skin was evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. CRP and ESR levels were mildly, but significantly elevated in patients compared to controls. No differences in both endothelium-dependent vasodilatation and capillary recruitment were observed between groups [709% (95% CI, 457–961%) vs 797% (95% CI, 556–1,037%), P = 0.59 and 37% (95% CI, 26–47%) vs 41% (95% CI, 31–50%), P = 0.59, respectively]. Skin microvascular function is preserved in early, DMARD-naive RA patients with moderately active RA but low systemic inflammatory activity. Both the extent of the systemic inflammation and disease duration, therefore, may be important determinants of microvascular dysfunction and subsequent increased risk for cardiovascular disease

SNP discovery in the bovine milk transcriptome using RNA-Seq technology

High-throughput sequencing of RNA (RNA-Seq) was developed primarily to analyze global gene expression in different tissues. However, it also is an efficient way to discover coding SNPs. The objective of this study was to perform a SNP discovery analysis in the milk transcriptome using RNA-Seq. Seven milk samples from Holstein cows were analyzed by sequencing cDNAs using the Illumina Genome Analyzer system. We detected 19,175 genes expressed in milk samples corresponding to approximately 70% of the total number of genes analyzed. The SNP detection analysis revealed 100,734 SNPs in Holstein samples, and a large number of those corresponded to differences between the Holstein breed and the Hereford bovine genome assembly Btau4.0. The number of polymorphic SNPs within Holstein cows was 33,045. The accuracy of RNA-Seq SNP discovery was tested by comparing SNPs detected in a set of 42 candidate genes expressed in milk that had been resequenced earlier using Sanger sequencing technology. Seventy of 86 SNPs were detected using both RNA-Seq and Sanger sequencing technologies. The KASPar Genotyping System was used to validate unique SNPs found by RNA-Seq but not observed by Sanger technology. Our results confirm that analyzing the transcriptome using RNA-Seq technology is an efficient and cost-effective method to identify SNPs in transcribed regions. This study creates guidelines to maximize the accuracy of SNP discovery and prevention of false-positive SNP detection, and provides more than 33,000 SNPs located in coding regions of genes expressed during lactation that can be used to develop genotyping platforms to perform marker-trait association studies in Holstein cattle

Myliobatis goodei, southern eagle ray

The Southern Eagle Ray (Myliobatis goodei) is a medium-sized (to at least 115 cm DW) coastal eagle ray that occurs in the Western Central and Southwest Atlantic Oceans from South Carolina and Florida, USA and Quintana Roo, Mexico to San Jorge Gulf, Santa Cruz, Argentina. It inhabits continental shelves from inshore to depths of 181 m. It is captured using artisanal longlines, gillnets, beach seines, and in industrial shrimp trawls. This species is inferred to be stable or increasing in the Western Central Atlantic, based on its similarity to the Bullnose Eagle Ray (Myliobatis freminvillei). In the Southwest Atlantic artisanal fisheries are intense, further there are largely unmanaged commercial trawl and longline fisheries in many areas. In Brazil, landings of eagle rays have been reduced by 60% over 2000?2012 in Santa Catarina State, and a reduction of 91% in Rio Grande do Sul since the 1980s. This inshore eagle ray has no refuge at depth and is exposed to intense and often unmanaged fishing pressure throughout the Atlantic South American portion of its range and there it is suspected that this species has undergone a population reduction of >80% over the past three generation lengths (44 years), but is stable in the Western Central Atlantic. Overall, based its range with the almost all threats found in the Southwest Atlantic, the suspected low productivity of the species, this species is suspected to have undergone a population reduction of 30 49% in three generation lengths (44 years) due to levels of exploitation, and it is assessed as Vulnerable A2d.Fil: Carlson, J.. National Marine Fisheries Service; Estados UnidosFil: Charvet, P.. Universidade Federal do Paraná; BrasilFil: Avalos Castillo, C.. Fundación Mundo Azul; GuatemalaFil: Blanco Parra, M. P.. Universidad de Quintana Roo; MéxicoFil: Briones Bell lloch, A.. Dirección de Regulaciones Pesqueras y Ciencias; CubaFil: Cardeñosa, D.. Florida International University; Estados UnidosFil: Chiaramonte, Gustavo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Hidrobiológica de Puerto Quequén (sede Quequén); ArgentinaFil: Cuevas, J.M.. Wildlife Conservation Society; Estados UnidosFil: Derrick, D.. University Fraser Simon; CanadáFil: Espinoza, E.. Galapagos National Park Directorate; EcuadorFil: Mejía Falla, P. A.. Wildlife Conservation Society; Estados UnidosFil: Morales Saldaña, J. M.. Smithsonian Tropical Research Institute; PanamáFil: Motta, F.. Universidade Federal Do Sao Paulo; BrasilFil: Naranjo Elizondo, B.. Universidad de Costa Rica; Costa RicaFil: Pacoureau, N.. University Fraser Simon; CanadáFil: Paesch, L.. Direccion Nacional de Recursos Acuaticos ; UruguayFil: Pérez Jiménez, J. C.. El Colegio de la Frontera del Sur; MéxicoFil: Rincon, G.. Universidade Federal Do Maranhao.; BrasilFil: Schneider, E. V. C.. Cape Eleuthera Institute; BahamasFil: Simpson, N. J.. Salvageblue; San Vicente y las GranadinasFil: Talwar, B. S.. Florida International University; Estados UnidosFil: Pollom, R.. University Fraser Simon; Canad

Transcriptome Profiling of Bovine Milk Oligosaccharide Metabolism Genes Using RNA-Sequencing

This study examines the genes coding for enzymes involved in bovine milk oligosaccharide metabolism by comparing the oligosaccharide profiles with the expressions of glycosylation-related genes. Fresh milk samples (n = 32) were collected from four Holstein and Jersey cows at days 1, 15, 90 and 250 of lactation and free milk oligosaccharide profiles were analyzed. RNA was extracted from milk somatic cells at days 15 and 250 of lactation (n = 12) and gene expression analysis was conducted by RNA-Sequencing. A list was created of 121 glycosylation-related genes involved in oligosaccharide metabolism pathways in bovine by analyzing the oligosaccharide profiles and performing an extensive literature search. No significant differences were observed in either oligosaccharide profiles or expressions of glycosylation-related genes between Holstein and Jersey cows. The highest concentrations of free oligosaccharides were observed in the colostrum samples and a sharp decrease was observed in the concentration of free oligosaccharides on day 15, followed by progressive decrease on days 90 and 250. Ninety-two glycosylation-related genes were expressed in milk somatic cells. Most of these genes exhibited higher expression in day 250 samples indicating increases in net glycosylation-related metabolism in spite of decreases in free milk oligosaccharides in late lactation milk. Even though fucosylated free oligosaccharides were not identified, gene expression indicated the likely presence of fucosylated oligosaccharides in bovine milk. Fucosidase genes were expressed in milk and a possible explanation for not detecting fucosylated free oligosaccharides is the degradation of large fucosylated free oligosaccharides by the fucosidases. Detailed characterization of enzymes encoded by the 92 glycosylation-related genes identified in this study will provide the basic knowledge for metabolic network analysis of oligosaccharides in mammalian milk. These candidate genes will guide the design of a targeted breeding strategy to optimize the content of beneficial oligosaccharides in bovine milk

Molecular mechanisms of extracellular adenine nucleotides-mediated inhibition of human Cd4+ T lymphocytes activation

We have previously reported that ATPγS, a slowly hydrolyzed analog of ATP, inhibits the activation of human CD4+ T lymphocytes by anti-CD3 and anti-CD28 mAb. In this report we have partially characterized the signaling mechanisms involved in this immunosuppressive effect. ATPγS had no inhibitory effect on CD4+ T-cell activation induced by PMA and anti-CD28, indicating that it acts proximally to the TCR. It had no effect on the calcium rise induced by CD3/CD28 stimulation, but inhibited the phosphorylation of three kinases, ERK2, p38 MAPK and PKB, that play a key role in the activation of T cells. The receptor involved in these actions remains unidentified

Trabectedin and RAdiotherapy in Soft Tissue Sarcoma (TRASTS): Results of a Phase I Study in Myxoid Liposarcoma from Spanish (GEIS), Italian (ISG), French (FSG) Sarcoma Groups

Background: Myxoid liposarcoma (ML) exhibits a special sensitivity to trabectedin (T) and radiation therapy (RT). Preclinical data suggest a synergistic effect. We aimed to study safety, feasibility and activity of the administration of pre-operative concurrent T and RT in patients affected by localized resectable ML. Methods: Patients received 3 cycles (C) of T in combination with RT (45 Gy) in 25 fractions (1.8 Gy/fraction). Dose Levels for T were: 12 1 (1.1 mg/m2), 0 (1.3 mg/m2) and 1 (1.5 mg/m2). Primary endpoint was safety; antitumor activity was assessed by RECIST and Choi criteria. This study is registered at ClinicalTrials.gov, number NCT02275286. The phase 1 part of the study is complete and phase 2 is ongoing. Findings: From February 2015 to May 2016, 14 patients (M/F 7/7), median age 36 years (range 24\u201370) and median tumor size 12.5 cm (range 7\u201317 cm), were enrolled. One dose limiting toxicity (G3 transaminitis) occurred at Level 0 and one (sepsis due to catheter infection) at Level 1. All patients completed RT. Five patients achieved PR (36%), 8 SD (57%), 1 distant PD (7%) by RECIST, while 12 achieved PR (86%), 1 SD (7%) and 1 distant PD (7%) by Choi criteria. Twelve patients underwent surgery. Median viable residual tumor was 5% (0\u201360). Interpretation: T in combination with RT showed a favorable safety profile and antitumor activity in localized ML. T dose of 1.5 mg/m2 is the recommended dose for the phase 2 study, which is ongoing. Funding: This study was partially supported by Pharmamar

Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

<p>Abstract</p> <p>Background</p> <p>Growth hormone (GH) is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy) could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD) and explored the underlying molecular mechanisms.</p> <p>Methods</p> <p>Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW) adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism.</p> <p>Results</p> <p>Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; <it>P </it>< 0.001). GH1 therapy reversed HMW adiponectin levels to the normal levels in the alcohol-fed group. Alcohol feeding significantly reduced hepatic adipoR2 mRNA expression compared with that in the control group (0.71 ± 0.17 vs. 1.03 ± 0.19; <it>P </it>< 0.001), which was reversed by GH therapy. GH1 therapy also significantly increased the relative mRNA (1.98 ± 0.15 vs. 0.98 ± 0.15) and protein levels of SIRT1 (2.18 ± 0.37 vs. 0.99 ± 0.17) in the alcohol-fed group compared with those in the control group (both, <it>P </it>< 0.001). The alcohol diet decreased the phosphorylated and total protein levels of hepatic AMP-activated kinase-α (AMPKα) (phosphorylated protein: 0.40 ± 0.14 vs. 1.00 ± 0.12; total protein: 0.32 ± 0.12 vs. 1.00 ± 0.14; both, <it>P </it>< 0.001) and peroxisome proliferator activated receptor-α (PPARα) (phosphorylated protein: 0.30 ± 0.09 vs. 1.00 ± 0.09; total protein: 0.27 ± 0.10 vs. 1.00 ± 0.13; both, <it>P </it>< 0.001), which were restored by GH1 therapy. GH therapy also decreased the severity of fatty liver in alcohol-fed mice.</p> <p>Conclusions</p> <p>GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.</p

An integration of enhanced social force and crowd control models for high-density crowd simulation

Social force model is one of the well-known approaches that can successfully simulate pedestrians’ movements realistically. However, it is not suitable to simulate high-density crowd movement realistically due to the model having only three basic crowd characteristics which are goal, attraction, and repulsion. Therefore, it does not satisfy the high-density crowd condition which is complex yet unique, due to its capacity, density, and various demographic backgrounds of the agents. Thus, this research proposes a model that improves the social force model by introducing four new characteristics which are gender, walking speed, intention outlook, and grouping to make simulations more realistic. Besides, the high-density crowd introduces irregular behaviours in the crowd flow, which is stopping motion within the crowd. To handle these scenarios, another model has been proposed that controls each agent with two different states: walking and stopping. Furthermore, the stopping behaviour was categorized into a slow stop and sudden stop. Both of these proposed models were integrated to form a high-density crowd simulation framework. The framework has been validated by using the comparison method and fundamental diagram method. Based on the simulation of 45,000 agents, it shows that the proposed framework has a more accurate average walking speed (0.36 m/s) compared to the conventional social force model (0.61 m/s). Both of these results are compared to the real-world data which is 0.3267 m/s. The findings of this research will contribute to the simulation activities of pedestrians in a highly dense population