Associations between WNT signaling pathway-related gene polymorphisms and risks of osteoporosis development in Chinese postmenopausal women: a case-control study.

BACKGROUND: The WNT signaling pathway is involved in the regulation of bone homeostasis, and the effect of WNT signaling pathway-related gene (WNT16 and LRP5) polymorphisms on osteoporosis risk among Chinese postmenopausal women is still unknown. Hence, we performed a case-control study to assess the association of WNT signaling pathway-related gene polymorphisms and osteoporosis risk. METHODS: A total of 1026 women (515 osteoporosis patients and 511 controls) of postmenopausal age who were randomly sampled from Xi'an 630 Hospital (Shaanxi Province, China) were involved in this study. Seven genetic polymorphisms in WNT16 (rs3779381, rs3801387, rs917727 and rs7776725) and LRP5 (rs2291467, rs11228240 and rs12272917) were selected and genotyped using the Agena MassARRAY iPLEX system. The association of the genetic polymorphisms and osteoporosis risk was assessed by odds ratios and 95% confidence intervals. The multifactor dimensionality reduction (MDR) method was conducted to analyze single nucleotide polymorphism (SNP)-SNP interaction. RESULTS: We found that LRP5 polymorphisms (rs2291467, rs11228240 and rs12272917) were significantly associated with a decreased risk of osteoporosis in homozygote, recessive and additive models (p < 0.05). Stratification analysis showed that LRP5 polymorphisms (rs2291467, rs11228240 and rs12272917) significantly decreased the osteoporosis risk in the subgroup of body mass index (BMI) ≤ 24 (p < 0.05) and that individuals carrying a heterozygote genotype of WNT16 polymorphisms (rs3779381, rs3801387, rs917727 and rs7776725) had a higher osteoporosis risk in the subgroup of BMI > 24 (p < 0.05). Two haplotypes (haplotype 1: rs3779381, rs3801387, rs917727 and rs7776725; haplotype 2: rs2291467 and rs11228240) were observed, yet only Trs2291467Trs11228240 and Crs2291467Crs11228240 had a strong association with a decreased risk of osteoporosis (p < 0.05). Additionally, MDR analysis revealed that LRP5 rs2291467 was the best model in single-locus MDR analysis. A seven-locus model including rs3779381-AG, rs7776725-TC, rs3801387-GA and rs917727-TC in WNT16 and rs11228240-CC, rs12272917-TC and rs2291467-CC in LRP5 was the best model in multiple-loci MDR analysis (p < 0.001). These two best models were the most significantly associated with osteoporosis risk. CONCLUSIONS: Our findings suggested that WNT16 and LRP5 genetic polymorphisms are associated with osteoporosis risk among Chinese postmenopausal women.

Urinary complement proteins and risk of end-stage renal disease: quantitative urinary proteomics in patients with type 2 diabetes and biopsy-proven diabetic nephropathy.

PURPOSE: To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). METHODS: Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). RESULTS: Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. CONCLUSION: Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.

Prognostic model for identifying candidates for hepatectomy among patients with hepatocellular carcinoma and hepatic vein invasion.

BACKGROUND: Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection. METHODS: Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts. RESULTS: Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus. CONCLUSION: The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.

ANTECEDENTES: La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas. RESULTADOS: De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

Comparative expression profile of microRNAs and piRNAs in three ruminant species testes using next-generation sequencing.

microRNA (miRNA) and piwi-interacting RNA (piRNA) are two classes small non-coding regulatory RNAs that play crucial roles in multiple biological processes such as spermatogenesis. However, there are no published studies on conjoint analysis of miRNA and piRNA profiles among cattle, yak and their interspecies (the dzo) using sequencing technology. Next-generation sequencing technology was used to profile miRNAs and piRNAs among those three ruminants to elucidate their functions. A total of 119, 14 and six differentially expressed miRNAs were obtained in cattle vs. dzo, cattle vs. yak and yak vs. dzo comparison groups, while there were 873, 1,065 and 1,158 differentially expressed piRNAs in those three comparison groups. The expression of three miRNAs was validated in the three ruminants, and the results suggested that the miRNA expression profiles data could represent actual miRNA expression levels. Moreover, the putative targets of differentially expressed miRNAs were predicted by their own genome, it is worth to note that both the cattle and yak genome were used for dzo, then the targets were subjected to GO enrichment and KEGG pathway analysis, revealing the likely roles for these differentially expressed miRNAs in spermatogenesis. In conclusion, this study provided a useful resource for further elucidation of the miRNAs and piRNAs regulatory roles in spermatogenesis. It may also facilitate the development of therapeutic strategies for dzo reproduction research.

The neurotoxicity of iron, copper and cobalt in Parkinson's disease through ROS-mediated mechanisms.

Parkinson's disease (PD) is the second most common neurodegenerative disease with gradual loss of dopaminergic neurons. Despite extensive research in the past decades, the etiology of PD remains elusive. Nevertheless, multiple lines of evidence suggest that oxidative stress is one of the common causes in the pathogenesis of PD. It has also been suggested that heavy metal-associated oxidative stress may be implicated in the etiology and pathogenesis of PD. Here we review the roles of redox metals, including iron, copper and cobalt, in PD. Iron is a highly reactive element and deregulation of iron homeostasis is accompanied by concomitant oxidation processes in PD. Copper is a key metal in cell division process, and it has been shown to have an important role in neurodegenerative diseases such as PD. Cobalt induces the generation of reactive oxygen species (ROS) and DNA damage in brain tissues.

Genetic diversity and classification of Tibetan yak populations based on the mtDNA COIII gene.

To determine the level of genetic diversity and phylogenetic relationships among Tibetan yak populations, the mitochondrial DNA cytochrome c oxidase subunit 3 (COIII) genes of 378 yak individuals from 16 populations were analyzed in this study. The results showed that the length of cytochrome c oxidase subunit 3 gene sequences was 781 bp, with nucleotide frequencies of 29.2, 29.4, 26.1, and 15.2% for T, C, A, and G, respectively. A total of 26 haplotypes were identified, with 69 polymorphic sites, including 11 parsimony-informative sites and 58 single-nucleotide polymorphism sites. No deletions/insertions were found in sequence comparison, indicating that nucleotide mutation types were transitions and transversions. Haplotype and nucleotide diversities were 0.562 and 0.00138, respectively, indicating a high level of genetic diversity in Tibetan yak populations. Phylogenetic relationship analysis indicated that Tibetan yak populations are divided into 2 groups.

Effects of corn and soybean meal types on rumen fermentation, nitrogen metabolism and productivity in dairy cows.

Twelve multiparous Holstein dairy cows in mid-lactation were selected for a replicated 4×4 Latin square design with a 2 ×2 factorial arrangement to investigate the effects of corn and soybean meal (SBM) types on rumen fermentation, N metabolism and lactation performance in dairy cows. Two types of corn (dry ground [DGC] and steam-flaked corn [SFC]) and two types of SBM (solvent-extracted and heat-treated SBM) with different ruminal degradation rates and extents were used to formulate four diets with the same basal ingredients. Each period lasted for 21 days, including 14 d for adaptation and 7 d for sample collection. Cows receiving SFC had a lower dry matter (DM) and total N intake than those fed DGC. However, the milk yield and milk protein yield were not influenced by the corn type, resulting in higher feed and N utilization efficiency in SFC-fed cows than those receiving DGC. Ruminal acetate concentrations was greater and total volatile fatty acids concentrations tended to be greater for cows receiving DGC relative to cows fed SFC, but milk fat content was not influenced by corn type. The SFC-fed cows had lower ruminal ammonia-N, less urea N in their blood and milk, and lower fecal N excretion than those on DGC. Compared with solvent-extracted SBM-fed cows, cows receiving heat-treated SBM had lower microbial protein yield in the rumen, but similar total tract apparent nutrient digestibility, N metabolism measurements, and productivity. Excessive supply of metabolizable protein in all diets may have caused the lack of difference in lactation performance between SBM types. Results of the present study indicated that increasing the energy degradability in the rumen could improve feed efficiency, and reduce environmental pollution.

Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis.

BACKGROUND: Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. METHODS: We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m(2)) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5-6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. FINDINGS: Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). INTERPRETATION: Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. FUNDING: None.

Unilateral mydriasis as the primary sign of neurosyphilis.

Syphilis can mimic most ocular disorders, and there is no characteristic to distinguish ocular syphilis from other eye diseases. We report a rare case of a 41-year-old man who presented with an Adie's-like pupil as the only feature of neurosyphilis. The patient met the criteria for the diagnosis of neurosyphilis by the finding of positive cerebrospinal fluid-Venereal Disease Research Laboratory (CSF-VDRL) and CSF-Treponema pallidum particle agglutination tests. The patient was then treated with 2 g intravenous ceftriaxone per day for 15 days because of penicillin allergy. Nine months after anti-syphilitic treatment alone, the diameter of the patient's left pupil reduced from 10 to 5 mm. The CSF-VDRL test was negative. It is highly recommended that any patients with ocular disease that does not respond to the routine treatment should undergo syphilis evaluation to avoid misdiagnosis.

Insertion depth of oral stomach tubes may affect the fermentation parameters of ruminal fluid collected in dairy cows.

Six rumen-fistulated dairy cows were used in 2 trials to validate the technique for the collection of ruminal fluid by an oral stomach tube (OST). Trial 1 was conducted to compare the differences of ruminal fermentation parameters among rumen sites (cranial dorsal, cranial ventral, central, ventral, caudal dorsal, and caudal ventral). The ruminal fluid was collected once per day for 3 consecutive days through rumen cannula (RC). The samples were analyzed for pH, volatile fatty acids (VFA), ammonia N, sodium, potassium, calcium, chloride, and phosphorus concentrations. The ruminal fermentation parameters varied significantly among rumen sites. Compared with the central or ventral rumen, the cranial dorsal rumen had significantly higher pH, ammonia, and sodium concentrations and lower acetate, propionate, and butyrate concentrations, indicating that the sampling site may be one of the main factors contributing to the difference in ruminal fermentation parameters between the samples collected via the OST and RC. In trial 2, the fermentation parameters of ruminal fluid collected via OST at 2 insertion depths (180 or 200 cm) were compared with those of ruminal fluid collected via RC (ventral sac). Ruminal fluid was collected once per week at 5 to 6h after morning feeding. When the OST was inserted to a depth of 180 cm, the OST head was located in the cranial dorsal (atrium) of the rumen. The ruminal fluid collected via the OST had higher pH and sodium concentrations but lower VFA, potassium, calcium, and phosphorus concentrations than that collected via RC. However, when the OST was inserted to a depth of 200 cm, the OST head could pass through the front rumen pillar and reach the central rumen for sampling. No differences were found in pH, VFA, ammonia N, and ion concentrations between the samples collected via the 2 sampling methods. These results indicated that the OST should be inserted to reach the central rumen to obtain representative rumen fluid samples.

Improving early running-in wear characteristics for dental lithium disilicate glass-ceramics by ion-exchange.

OBJECTIVES: This study examined the effects of Li+→Na+ ion-exchange on the early wear performance of dental lithium disilicate (LD) glass-ceramics. METHODS: Specimens with different shapes were prepared using IPS e.max Press as the LD glass-ceramics. Ion-exchange was conducted by placing polished specimens in molten salt containing 25% NaNO3 and 75% KNO3 at 385 °C for 16 or 64 h. The ion-exchanged specimens were analyzed using X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS) to investigate the structure and the elemental distribution. Thereafter, the specimens were tested for flexural strength, Vickers hardness, and fracture resistance. A portion of the specimens were tested with a pin-on-disk tribometer with 10 N for 40 × 104 wear cycles in artificial saliva. Wear analysis of the specimens was performed using a 3D profilometer and analyzed with one-way analyses of variance and Tukey's post hoc pairwise comparisons. Worn surfaces were examined with scanning electron microscopy. RESULTS: The LD glass-ceramics exhibited strong time-dependent wear behavior, with typical running-in and steady wear stages. Ion-exchange treatments at 385 °C for 16 h and 64 h both enhanced the mechanical properties and decreased the wear rates of early running-in wear stage. The early wear performance of specimens treated with ion-exchange for long time (64 h) was improved significantly. CONCLUSION: A thicker ion-exchange layer may be obtained by processing ion-exchange for a long time. This protocol improves the early wear performance of the glass-ceramics effectively. CLINICAL SIGNIFICANCE: Dental restorations may fail prematurely due to excessive wear. It is important to improve the early wear performance of the glass-ceramics. Ion-exchange has the potential to strengthen dental LD glass-ceramics. Understanding the effect of ion-exchange on the early wear performance of glass-ceramics provides insight improving the early wear performance of these restorations.

The bonding property and cytotoxicity of a dental adhesive incorporating a new antibacterial monomer.

The incorporation of polymerisable cationic monomers has been attempted to generate dental resinous materials with antibacterial activity. This study tested whether the incorporation of a cationic monomer, methacryloxylethyl cetyl dimethyl ammonium chloride (DMAE-CB), into a commercial dental adhesive would influence the bonding property and biocompatibility of the parental adhesive, and whether DMAE-CB could leach out from the cured modified adhesive. Microtensile bond strengths of DMAE-CB-incorporated adhesive and its parental adhesive to dentin were compared. Dentin discs bonded with modified adhesive were incubated in artificial saliva at three different temperatures for 90 days to obtain eluents. The cytotoxicity of DMAE-CB monomer and adhesive eluents were tested with 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cleavage assay (MTT assay). High-performance liquid chromatography (HPLC) was performed with the eluents of the modified adhesive. The results indicated that the incorporation of DMAE-CB into the dental adhesive did not adversely influence its bonding strength to dentin (P > 0·05). Although DMAE-CB monomer exhibited toxicity against L929 cells at the concentration of 2 µg mL(-1) or higher (P < 0·05), the eluents of DMAE-CB-incorporated adhesive did not show significant influence on cell growth (P > 0·05). Moreover, HPLC analysis detected four substances' peak baseline separation for the eluents of modified adhesives, which was identical to the eluent of the parental adhesive, indicating no detectable DMAE-CB monomer leaching even after soaking for 90 days. Those results suggest that DMAE-CB could be incorporated into the dental adhesive stably without compromising the bonding efficiency and biocompatibility of its parental adhesive.

Cell division autoantigen 1 plays a profibrotic role by modulating downstream signalling of TGF-beta in a murine diabetic model of atherosclerosis.

AIMS/HYPOTHESIS: Excess accumulation of vascular extracellular matrix (ECM) is an important pathological process in cardiovascular diseases including diabetes-associated atherosclerosis. We explored how a recently identified molecule, cell division autoantigen 1 (CDA1), influences the profibrotic TGF-beta pathway leading to vascular ECM accumulation. METHODS: Expression levels of genes encoding for CDA1, TGF-beta and connective tissue growth factor (CTGF) were examined in aorta from Apoe(-/-) mice with or without diabetes. We used retroviral and adenoviral constructs to knockdown or overexpress Tspyl2, the gene encoding CDA1, in mouse vascular smooth muscle cells (VSMCs) with or without TGF-beta treatment in order to demonstrate the role of CDA1 in TGF-beta signalling. RESULTS: In vivo studies indicated that the mRNA levels of CDA1-encoding gene Tspyl2 and protein levels of CDA1 were elevated in the aorta of diabetic Apoe(-/-) mice, accompanied by increased levels of Tgf-beta (also known as Tgfb1), Ctgf and ECM accumulation. In vitro studies in vascular cells showed that TGF-beta treatment rapidly increased CDA1 protein levels, which then amplified TGF-beta signalling leading to upregulation of ECM genes. Knockdown of CDA1-encoding gene Tspyl2 to reduce cellular CDA1 level markedly attenuated TGF-beta-stimulated MAD homologue 3 (drosophila; SMAD3) phosphorylation and transcriptional activities. CDA1 overproduction increased and Tspyl2 knockdown decreased expression of TGF-beta receptor type I, TbetarI (also known as Tgfbr1), but not TGF-beta receptor type II, TbetarII (also known as Tgfbr2), providing a mechanism for CDA1's action in modulating TGF-beta signalling. Knockdown of CDA1-encoding gene Tspyl2 also blocked the profibrotic effect of TGF-beta in VSMCs. CONCLUSIONS/INTERPRETATION: CDA1 plays an important role in vascular ECM accumulation by amplifying TGF-beta signalling. This is critical for the profibrotic effect of TGF-beta in the vasculature. CDA1 is therefore a potential target for attenuating vascular ECM accumulation caused by enhanced TGF-beta action, as seen in diabetic atherosclerosis.

Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient mice.

Interleukin (IL)-6, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) are considered to act as endogenous pyrogens. Because of the complex pattern of cross-inductions between these cytokines, the relative role of the central and peripheral production of these cytokines in eliciting the fever response has not yet been clarified. The purpose of this study was to determine the role of IL-6 in the fever response by making use of mice carrying a null mutation in the IL-6 gene. The intraperitoneal injections of lipopolysaccharide (LPS) (50 micrograms/kg) and recombinant murine (rm) IL-1 beta (10 micrograms/kg), respectively, failed to evoke fever response in IL-6-deficient mice, whereas the same doses of LPS and rmIL-1 beta caused fever response in wild-type mice. The fever response could be induced in the IL-6-deficient mice by intracerebroventricular injection of recombinant human (rh) IL-6 (500 ng/mouse), whereas intracerebroventricular injection of rmIL-1 beta (100 ng/mouse) failed to produce fever response in the IL-6-deficient mice. These results suggest that central IL-6 is a necessary component of the fever response to both endogenous (IL-1 beta) and exogenous (LPS) pyrogens in mice and that IL-6 acts downstream from both peripheral and central IL-1 beta.

Event-by-event fluctuations of azimuthal particle anisotropy in Au+Au collisions at square root(sNN) = 200 GeV.

This Letter presents the first measurement of event-by-event fluctuations of the elliptic flow parameter v(2) in Au+Au collisions at square root(s(NN))=200 GeV as a function of collision centrality. The relative nonstatistical fluctuations of the v(2) parameter are found to be approximately 40%. The results, including contributions from event-by-event elliptic flow fluctuations and from azimuthal correlations that are unrelated to the reaction plane (nonflow correlations), establish an upper limit on the magnitude of underlying elliptic flow fluctuations. This limit is consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. These results provide important constraints on models of the initial state and hydrodynamic evolution of relativistic heavy ion collisions.

High transverse momentum triggered correlations over a large pseudorapidity acceptance in Au + Au collisions at square root(s(NN)) = 200 GeV.

A measurement of two-particle correlations with a high transverse momentum trigger particle (p(T)(trig) > 2.5 GeV/c) is presented for Au+Au collisions at square root(s(NN)) = 200 GeV over the uniquely broad longitudinal acceptance of the PHOBOS detector (-4 < Delta eta < 2). A broadening of the away-side azimuthal correlation compared to elementary collisions is observed at all Delta eta. As in p+p collisions, the near side is characterized by a peak of correlated partners at small angle relative to the trigger particle. However, in central Au+Au collisions an additional correlation extended in Delta eta and known as the "ridge" is found to reach at least |Delta eta| approximately = 4. The ridge yield is largely independent of Delta eta over the measured range, and it decreases towards more peripheral collisions. For the chosen (p(T)(trig) cut, the ridge yield is consistent with zero for events with less than roughly 100 participating nucleons.

Committee machines-a universal method to deal with non-idealities in memristor-based neural networks.

Artificial neural networks are notoriously power- and time-consuming when implemented on conventional von Neumann computing systems. Consequently, recent years have seen an emergence of research in machine learning hardware that strives to bring memory and computing closer together. A popular approach is to realise artificial neural networks in hardware by implementing their synaptic weights using memristive devices. However, various device- and system-level non-idealities usually prevent these physical implementations from achieving high inference accuracy. We suggest applying a well-known concept in computer science-committee machines-in the context of memristor-based neural networks. Using simulations and experimental data from three different types of memristive devices, we show that committee machines employing ensemble averaging can successfully increase inference accuracy in physically implemented neural networks that suffer from faulty devices, device-to-device variability, random telegraph noise and line resistance. Importantly, we demonstrate that the accuracy can be improved even without increasing the total number of memristors.

Ti n+1C n MXenes with fully saturated and thermally stable Cl terminations.

MXenes are a rapidly growing family of 2D materials that exhibit a highly versatile structure and composition, allowing for significant tuning of the materials properties. These properties are, however, ultimately limited by the surface terminations, which are typically a mixture of species, including F and O that are inherent to the MXene processing. Other and robust terminations are lacking. Here, we apply high-resolution scanning transmission electron microscopy (STEM), corresponding image simulations and first-principles calculations to investigate the surface terminations on MXenes synthesized from MAX phases through Lewis acidic melts. The results show that atomic Cl terminates the synthesized MXenes, with mere residual presence of other termination species. Furthermore, in situ STEM-electron energy loss spectroscopy (EELS) heating experiments show that the Cl terminations are stable up to 750 °C. Thus, we present an attractive new termination that widely expands the MXenes' functionalization space and enables new applications.

A survey of extractable persistent organochlorine pollutants in Chinese commercial yogurt.

Eighteen Chinese commercial brands of yogurt were collected from supermarkets from December 2002 to April 2003, for characterization of organochlorine pesticides (OCP) and polychlorinated biphenyls (PCB). Besides monitoring OCP and PCB by gas chromatography, the levels of extractable persistent organochlorine (EPOCl; i.e., sulfuric acid-resistant EPOCl) were also determined by instrumental neutron activation analysis. The results indicated that the contamination pattern of the selected OCP and PCB were in the order of dichlorodiphenyltrichloroethanes (DDT) approximately hexachlorocyclohexanes (HCH) >> aldrin > or = chlordanes > or = heptachlor epoxide and 4-6 chlorinated biphenyls (CB) >> 7-10 CB, respectively. Furthermore, beta-HCH, and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene were the predominant isomers of HCH and DDT residues in yogurt, and PCB with 4,4'- and 2,3,5- substitution patterns were the predominant congeners of PCB residues. Also, the results indicated that the mean level of total chlorine in the identified organochlorine species was below 4% of EPOCl in yogurt, which implied that more than 96% of EPOCl measured in yogurt samples could not be accounted for by selected OCP and PCB.

Lattice Boltzmann modeling of three-phase incompressible flows.

In this paper, based on multicomponent phase-field theory we intend to develop an efficient lattice Boltzmann (LB) model for simulating three-phase incompressible flows. In this model, two LB equations are used to capture the interfaces among three different fluids, and another LB equation is adopted to solve the flow field, where a new distribution function for the forcing term is delicately designed. Different from previous multiphase LB models, the interfacial force is not used in the computation of fluid velocity, which is more reasonable from the perspective of the multiscale analysis. As a result, the computation of fluid velocity can be much simpler. Through the Chapman-Enskog analysis, it is shown that the present model can recover exactly the physical formulations for the three-phase system. Numerical simulations of extensive examples including two circular interfaces, ternary spinodal decomposition, spreading of a liquid lens, and Kelvin-Helmholtz instability are conducted to test the model. It is found that the present model can capture accurate interfaces among three different fluids, which is attributed to its algebraical and dynamical consistency properties with the two-component model. Furthermore, the numerical results of three-phase flows agree well with the theoretical results or some available data, which demonstrates that the present LB model is a reliable and efficient method for simulating three-phase flow problems.