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Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.
The feasibility of non-destructive detection and classification of in-shell insect-infested almonds was examined by using multispectral imaging (MSI) technology combined with chemometrics. Differentiation of reflectance spectral data between intact and insect-infested almonds was attempted by using analytical approaches based on principal component analysis and support vector machines, classification accuracy rates as high as 99.1% in the calibration set and 97.5% in the prediction set were achieved. Meanwhile, the in-shell almonds were categorized into three classes (intact, slightly infested and severely infested) based on the degree of damage caused by insect infestation and were characterized quantitatively by the analysis of shell/kernel weight ratio. A three-class model for the identification of intact, slightly infested and severely infested almonds yielded acceptable classification performance (95.6% accuracy in the calibration set and 93.3% in the prediction set). These results revealed that MSI technology combined with chemometrics may be a promising approach for the non-destructive detection of hidden insect damage in almonds and could be used for industrial applications.
The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.
Methods
Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.
Results
Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.
Conclusions
In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.
The unit-cell parameters of andalusite and sillimanite have been measured by high-T powder X-ray diffraction up to 1000°C at ambient pressure. Within the temperature range investigated, all the unit-cell parameters varied smoothly, indicating no phase transition. The volume-temperature data were fitted with a polynomial expression for the thermal expansion coefficient (αT = a0 + a1T + a2T-2). yielding a0 = 2.55(2) × 10–5K–1, al = 0 and a2 = 0 for andalusite, and a0 = 1.40(4) × 10–5K–1a1 = 7.1(8) × 10–9K–2 and a2 = 0 for sillimanite. Using the new thermal expansion data determined in the present study and compressional data from the literature, the P-T phase relations of the kyanite-andalusite-sillimanite system were calculated thermodynamically, with the invariant point located at ∼523°C and 3.93 kbar.
In vivo and in vitro trials were conducted to assess the effects of tributyrin (TB) supplementation on short-chain fatty acid (SFCA) concentrations, fibrolytic enzyme activity, nutrient digestibility and methanogenesis in adult sheep. Nine 12-month-old ruminally cannulated Small Tail ewes (initial body weight 55 ± 5.0 kg) without pregnancy were used for the in vitro trial. In vitro substrate made to offer TB at 0, 2, 4, 6 and 8 g/kg on a dry matter (DM) basis was incubated by ruminal microbes for 72 h at 39°C. Forty-five adult Small Tail ewes used for the in vivo trial were randomly assigned to five treatments with nine animals each for an 18-d period according to body weight (55 ± 5.0 kg). Total mixed ration fed to ewes was also used to offer TB at 0, 2, 4, 6 and 8 g/kg on a DM basis. The in vitro trial showed that TB supplementation linearly increased apparent digestibility of DM, crude protein, neutral detergent fibre and acid detergent fibre, and enhanced gas production and methane emissions. The in vivo trial showed that TB supplementation decreased DM intake, but enhanced ruminal fermentation efficiency. Both in vitro and in vivo trials showed that TB supplementation enhanced total SFCA concentrations and carboxymethyl cellulase activity. The results indicate that TB supplementation might exert advantage effects on rumen microbial metabolism, despite having an enhancing effect on methanogenesis.
The Proterozoic Sushina Hill Complex is the only agpaitic complex, reported from India and is characterized by a eudialyte-rinkite-bearing nepheline syenite. The complex is considered a ‘metamorphosed agpaitic complex'. This study describes the mineral assemblages formed during successive stages of evolution from magmatic to hydrothermal stages and low-temperature subsolidus re-equilibration assemblage. The primary-late magmatic assemblage is characterized by albite, orthoclase, unaltered nepheline, zoned diopside-hedenbergite, rinkite, late magmatic eudialyte and magnesio-arfvedsonite formed at ∼700°C with maximum aSiO2 of 0.60. In contrast, a deuteric assemblage (400-348°C) is represented by aegirine-jadeite-rich clinopyroxene, post-magmatic eudialyte, sodalite, analcime and the decomposition assemblages formed after eudialyte with decreasing aSiO2 (0.52-0.48). A further low-temperature subsolidus assemblage (≤250°C) represented by late-forming natrolite could be either related to regressive stages of metamorphism or a continuum of the subsolidus processes. Considering the P/T range of the greenschist - lower-amphibolite facies of metamorphism it is evident that the incorporation of a jadeite component within pyroxene is related to a subsolidus process between ∼400°C and 348°C in a silica deficient environment. We emphasize that the deuteric fluid itself acted as an agent of metamorphism and the decomposition assemblage formed after eudialyte is retained even after metamorphism due to the convergence of subsolidus and metamorphic domains. The formation of jadeite-rich aegirine is not considered to result from metamorphism. Overall it is near-impossible to discern any bona fide metamorphic textures or mineral assemblages in these syenites which appear to preserve a relict mineralogy regardless of their occurrence in country rocks which have experienced greenschist - amphibolite facies metamorphism. The Sushina complex is very similar in this respect to the Norra Kärr complex (Sweden).
Social networks facilitate the transmission of hepatitis C virus (HCV) in people who inject drugs (PWID). The aim of this study was to assess how certain network structural characteristics are related to HCV infections in PWID and to determine the most susceptible individuals for HCV transmission in a network of PWID. PWID (N = 80) from central China were recruited from a previous follow-up case-control study. Demographic and behavioural information was obtained from a computerized database for each group. HCV RNA was extracted from blood specimens. Sequences were used to construct a phylogenetic tree and to determine genetic distances. Socio-metric social links were established between participants. Network measures were calculated using UCINET. Three HCV genotypes were identified, covering five subtypes. The density of the social networks for the whole sample (N = 80), case group (n = 31) and control group (n = 49) was 0.038, 0.054 and 0.008, respectively. PWID infected with HCV were in frequent contact with others within their group. There were four pairs of nodes with genotypic distances of 0.000 that were identified and clustered in subtypes 6a and 1b; each subject pair was linked and found in one clique. Three of the five most active nodes were infected with HCV. These three nodes served as a bridge, contributing to the connection of other nodes. These findings identify susceptible individuals for HCV transmission in PWID based on their frequent contact with others in the network. These results provide data that could be used for modelling HCV transmission patterns and in public health policies.
Enterotoxigenic Escherichia coli (ETEC) is a type of pathogenic bacteria that cause diarrhea in piglets through colonizing pig small intestine epithelial cells by their surface fimbriae. Different fimbriae type of ETEC including F4, F18, K99 and F41 have been isolated from diarrheal pigs. In this study, we performed a genome-wide association study to map the loci associated with the susceptibility of pigs to ETEC F41 using 39454 single nucleotide polymorphisms (SNPs) in 667 F2 pigs from a White Duroc×Erhualian F2 cross. The most significant SNP (ALGA0022658, P=5.59×10−13) located at 6.95 Mb on chromosome 4. ALGA0022658 was in high linkage disequilibrium (r2>0.5) with surrounding SNPs that span a 1.21 Mb interval. Within this 1.21 Mb region, we investigated ZFAT as a positional candidate gene. We re-sequenced cDNA of ZFAT in four pigs with different susceptibility phenotypes, and identified seven coding variants. We genotyped these seven variants in 287 unrelated pigs from 15 diverse breeds that were measured with ETEC F41 susceptibility phenotype. Five variants showed nominal significant association (P<0.05) with ETEC F41 susceptibility phenotype in International commercial pigs. This study provided refined region associated with susceptibility of pigs to ETEC F41 than that reported previously. Further works are needed to uncover the underlying causal mutation(s).
The objective of the present study was to investigate the effect of dietary neutral detergent fibre (NDF) : crude protein (CP) ratio on duodenal microbial crude protein (MCP) flow and nitrogen (N) losses. The study was completed in a 5 × 5 Latin square design with five lactating Holstein dairy cows and 5 high-concentrate total mixed rations (TMR) with different forage combinations, typical for Northern China. The rations with a fixed forage-to-concentrate ratio (39 : 61) resulted in different dietary NDF : CP ratios: TMR1 3·03 : 1 (428·2 g NDF/kg : 141·4 g CP/kg); TMR2 2·74 : 1 (392·7 g NDF/kg : 143·2 g CP/kg); TMR3 2·55 : 1 (368·3 g NDF/kg : 144·4 g CP/kg); TMR4 1·84 : 1 (304·8 g NDF/kg : 165·8 g CP/kg); TMR5 1·60 : 1 (285·0 g NDF/kg : 178·0 g CP/kg). Rumen content, milk, blood, urine and faeces were sampled on the last 3 days of five 18-day periods. Purine derivatives in the urine samples were determined to estimate rumen MCP flow into the small intestine. Milk yield and milk protein yield increased linearly with decreasing dietary NDF : CP ratio although slight differences in dry matter intake were observed due to feed intake restriction. Diurnal ammonia N in the rumen and duodenal MCP flow increased linearly, but blood urea N, urinary N and faecal N linearly decreased with decreasing dietary NDF : CP ratio. The enhanced N utilization in the maize-silage-based TMRs (TMR4–5) in comparison with maize-stover-based TMRs (TMR1–3) increased milk yield and the synthesis of milk protein instead of milk fat in the lactating cows, probably due to high transfer of ammonia N into rumen MCP with a considerable increase of dietary non-fibre carbohydrate content and the decrease of NDF : CP ratio. The present results indicate that not only increasing dietary non-structural carbohydrate content but also adjusting the ratio of structural carbohydrate to CP ratio are important diet formulation strategies for mitigating N losses in lactating cows.
In 2009, we examined HIV and sexually transmitted infections (STIs) in 750 female sex workers (FSWs) in Shanghai using a cross-sectional survey. Participants (mean age 27 years) were interviewed and tested for HIV and selected STIs. Prevalence was: HIV 0·13%, chlamydia 14·7%, gonorrhoea 3·5% and syphilis 1·3%. In a demographic multivariate model, younger age, higher income and originating from provinces other than Zhejiang and Shanghai were independently associated with STI. In a social and sexual behavioural model, women working in small venues with fewer clients per week, use of drugs, and higher price charged per sex act indicated a greater risk for STI. Although HIV appears rare in Shanghai FSWs, chlamydial infection is common, especially in women aged <25 years (prevalence 19·6%). Since STI and HIV share similar risk factors, preventive intervention measures should be implemented immediately based on the venues and characteristics of FSWs to prevent future spread of HIV.
The effects of source field plates on AlGaN/GaN High Electron Mobility Transistor reliability under off-state stress conditions were investigated using step-stress cycling. The source field plate enhanced the drain breakdown voltage from 55V to 155V and the critical voltage for off-state gate stress from 40V to 65V, relative to devices without the field plate. Transmission electron microscopy was used to examine the degradation of the gate contacts. The presence of cracking that appeared on both source and drain side of the gate edges was attributed to the inverse piezoelectric effect. In addition, a thin oxide layer was observed between the Ni gate contact and the AlGaN layer, and both Ni and oxygen had diffused into the AlGaN layer. The critical degradation voltage of AlGaN/GaN High Electron Mobility Transistors during off-state electrical stress was determined as a function of Ni/Au gate dimensions (0.1-0.17μm). Devices with different gate length and gate-drain distances were found to exhibit the onset of degradation at different source-drain biases but similar electric field strengths, showing that the degradation mechanism is primarily field-driven. The temperature dependence of sub-threshold drain current versus gate voltage at a constant drain bias voltage were used to determine the trap densities in AlGaN/GaN high electron mobility transistors (HEMTs) before and after the off-state stress. Two different trap densities were obtained for the measurements conducted at 300-493K and 493-573K, respectively.
Gestation length and maternal ability are important to improve the sow reproduction efficiency and their offspring survival. To map quantitative trait loci (QTL) for gestation length and maternal ability related traits including piglet survival rate and average body weight of piglets at weaning, more than 200 F2 sows from a White Duroc × Erhualian resource population were phenotyped. A genome-wide scan was performed with 194 microsatellite markers covering the whole pig genome. QTL analysis was carried out using a composite regression interval mapping method via QTL express. The results showed that total number of born piglets was significantly correlated with gestation length (r = −0.13, P < 0.05). Three QTL were detected on pig chromosome (SSC)2, 8 and 12 for gestation length. The QTL on SSC2 achieved the 5% genome-wide significant level and the QTL on SSC8 was consistent with previous reports. Four suggestive QTL were identified for maternal ability related traits including 1 QTL for survival rate of piglets at weaning on SSC8, 3 QTL for average body weight of piglet at weaning on SSC3, 11 and 13.
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhoea in neonatal and postweaning pigs. F41 is one of ETEC fimbriae that adhere to the small intestinal epithelium and lead to development of diarrhoea. The genetic architecture of susceptibility to ETEC F41 remains elusive in pigs. In this study, we determined the in vitro adhesion phenotypes of ETEC F41 in a total of 835 F2 animals from a White Duroc × Erhualian intercross, and performed a genome scan using both F2 and half-sib analyses with 183 microsatellite markers to detect quantitative trait loci (QTL) for porcine susceptibility to ETEC F41. The two analyses consistently revealed a 1% genome-wide significant QTL on pig chromosome 4. Moreover, we determined F41 adhesion phenotypes in 14 purebred Erhualian and 14 White Duroc pigs. The results showed that both the founder breeds are segregating for the F41 adhesion phenotype, while less percentage of Erhualian pigs were adhesive to ETEC F41 compared to White Duroc pigs.
Adipocyte size and number are correlated with fat deposition, which is of major concern to human health and pork producers. To identify quantitative trait loci (QTL) for adipocyte size and number in pigs, a total of 341 F2 animals at 240 days in a White Duroc × Erhualian cross were measured for the area, perimeters, volume and number of adipocyte in abdominal fat. A genome scan was performed on these animals and their parents and grandparents with 183 microsatellite markers spanning the pig genome. Five chromosomal regions showed effects on the traits measured, predominantly on adipocyte size, on pig chromosome (SSC) 1, 4, 7 and 9. Neither of these QTL has been reported before this study. The QTL for adipocyte size detected in this study perfectly correspond to the previously reported QTL for fatness traits on SSC1, 4 and 7. The most significant association was evidenced at 58 cM on SSC7. At the locus, the favorable allele decreasing adipocyte size was unusually originated from the obese Erhualian breed. Only a suggestive QTL was detected for adipocyte number on SSC9. The results shed new lights on the understanding of the genetic basis of fatness traits in pigs.
Chloride ion concentration can be used as a biomarker for the level of pollen exposure in allergic asthma, chronic cough and airway acidification related to respiratory disease. AlGaN/GaN high electron mobility transistor (HEMT) with an InN thin film in the gate region was used for real time detection of chloride ion detection. The InN thin film provided surface sites for reversible anion coordination. The sensor exhibited significant changes in channel conductance upon exposure to various concentrations of NaCl solutions. The sensor was tested over the range of 100 nM to 100 μM NaCl solutions. The effect of cations on the chloride ion detection was also studied.
Five morphological fractions (leaf blade, leaf sheath, stem, husk and cob) of stover of five maize genotypes, namely waxy, conventional, fodder, sweet and high-oil maize, respectively, were used to test the effects of genotype and morphological fractions on chemical composition and in vitro fermentation characteristics. The waxy maize had a higher (P < 0.05) stem but lower (P < 0.05) leaf blade proportion and fodder maize had a higher (P < 0.05) leaf blade but lower (P < 0.05) leaf sheath proportion than other genotypes, respectively. Maize genotype had a significant effect (P < 0.001) on the chemical composition of stover parts except for organic matter (OM) concentration. Chemical composition of stover parts was affected (P < 0.001) by morphological fractions. The interaction effects between genotype and morphological fraction on the fiber content of stover parts were significant. Over 0.40 and 0.50 of phosphorus (P) and crude protein (CP) of whole-plant maize stover were averagely contributed by leaf blade. Leaf blade, stem and cob contributed over 0.75 of OM, CP, P and fiber in the whole plant. There were significant effects of genotype and morphological fraction on both in vitro gas production parameters and in vitro organic matter disappearance of maize stovers. The genotype and morphological fraction of maize stover and their interaction had significant effects on NH3-N and total volatile fatty acid concentration and the molar proportion of volatile fatty acid in the supernatant after 72 h of incubation except for valeric acid. The present data indicated that the genotype and morphological fraction of maize resulted in variation in the nutritive value of maize stover.
Simulations show that incorporating the pre-Gaia positional data into the Gaia astrometric data can significantly improve the efficiency of determining binary orbits, especially for those binaries with periods from 8 to 25 years.
The development of reliable and thermally stable Ohmic and Schottky contacts to ZnO is one of the critical issues related to the fabrication of ZnO-based UV light emitters/detectors and field effect transistors. To date, a number of different metallization schemes and surface cleaning procedures prior to metal deposition have been examined for rectifying contacts on n-ZnO. While these reports have shown that low reactive metals such as Au, Ag and Pd form rectifying contacts with Schottky barrier heights in the 0.6-0.8 eV range, the thermal stability of these contacts is usually extremely poor, with degradation occurring even at 60°C for Au/n-ZnO. One approach to achieving increased barrier heights that has proven successful for GaAs, InP, InGaAs and other compound semiconductors is the use of cryogenic deposition temperatures. In this context, we report in this work on the effect of cryogenic temperature metal deposition on the contact properties of Pd, Pt, Ti, and Ni on single-crystal n-type ZnO. Deposition at both room and low temperature produced contacts with Ohmic characteristics for Ti and Ni metallizations. In comparison, both Pd and Pt contacts showed rectifying characteristics after deposition. All rectifying contacts exhibited barrier heights around 1-2 eV and idealities between 1 and 2. Low temperature deposition gave higher resistances in comparison to room temperature deposition for all cases. Larger contacts also corresponded to an increase in resistance. Changes in contact behavior were measured on Pd to anneal temperatures of ∼300°C, showing an increase in barrier height along with a decrease in ideality with increasing temperature. This difference with annealing temperature is in sharp contrast to previous results for Au contacts to ZnO. There were no differences in near-surface stoichiometry for the different deposition temperatures; however low temperature contacts demonstrated some cracking in Pt and Pd, probably due to surface stress.