Miracle-dz/UniFAR-FTUs huggingface dataset:
Vasopressin type 1A receptor deletion enhances cardiac contractility, β-adrenergic receptor sensitivity and acute cardiac injury-induced dysfunction.

Vasopressin type 1A receptor (V1AR) expression is elevated in chronic human heart failure (HF) and contributes to cardiac dysfunction in animal models, in part via reduced β-adrenergic receptor (βAR) responsiveness. Although cardiac V1AR overexpression and V1AR stimulation are each sufficient to decrease βAR activity, it is unknown whether V1AR inhibition conversely augments βAR responsiveness. Further, although V1AR has been shown to contribute to chronic progression of HF, its impact on cardiac function following acute ischaemic injury has not been reported. Using V1AR knockout (V1AR KO) mice we assessed the impact of V1AR deletion on cardiac contractility at baseline and following ischaemic injury, βAR sensitivity and cardiomyocyte responsiveness to βAR stimulation. Strikingly, baseline cardiac contractility was enhanced in V1AR KO mice and they experienced a greater loss in contractile function than control mice following acute ischaemic injury, although the absolute levels of cardiac dysfunction and survival rates did not differ. Enhanced cardiac contractility in V1AR KO mice was associated with augmented β-blocker sensitivity, suggesting increased basal βAR activity, and indeed levels of left ventricular cAMP, as well as phospholamban (PLB) and cardiac troponin I (cTnI) phosphorylation were elevated compared with control mice. At the cellular level, myocytes isolated from V1AR KO mice demonstrated increased responsiveness to βAR stimulation consistent with the finding that acute pharmacological V1AR inhibition enhanced βAR-mediated contractility in control myocytes. Therefore, although V1AR deletion does not protect the heart from the rapid development of cardiac dysfunction following acute ischaemic injury, its effects on βAR activity suggest that acute V1AR inhibition could be utilized to promote myocyte contractile performance.
A randomised phase IIb study of mavrilimumab, a novel GM–CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis

Objectives Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte–macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. Methods In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)−C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28−CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24). Results 326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012–June 2013). Mavrilimumab treatment significantly reduced DAS28−CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: −1.90 (0.14), 100 mg: −1.64 (0.13), 30 mg: −1.37 (0.14), placebo: −0.68 (0.14); p<0.001; all dosages compared with placebo). Significantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (p<0.001)). Adverse events were reported in 43 (54.4%), 36 (42.4%), 41 (50.6%) and 38 (46.9%) patients in the mavrilimumab 150, 100, 30 mg eow and placebo groups, respectively. No treatment-related safety signals were identified. Conclusions Mavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential. Trial registration number NCT01706926; results.
Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

ABSTRACT To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-α (ERα), ERβ, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired non-neoplastic urothelial tissues. AR/ERα/ERβ/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (P < 0.001)/40% (P = 0.001)/85% (P = 0.001)/84% (P = 0.002)/13% (P = 0.489)]. There were no significant associations between each receptor expression pattern and histopathological characteristic of the tumors including tumor grade/stage. Kaplan-Meier and log-rank tests revealed no significant prognostic value of each receptor expression in these 99 patients. However, patients with UUTUC positive for either ERα or PR had a significantly higher risk of disease-specific mortality (P = 0.025), compared with those with UUTUC negative for both. PR positivity alone in pT3 or pT4 tumors was also strongly associated with the risk of disease-specific mortality (P = 0.040). Multivariate analysis further identified the expression of ERα and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P = 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ERα/ERβ/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERα and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.
Epsilon-Approximations & Epsilon-Nets

The use of random samples to approximate properties of geometric configurations has been an influential idea for both combinatorial and algorithmic purposes. This chapter considers two related notions---$\epsilon$-approximations and $\epsilon$-nets---that capture the most important quantitative properties that one would expect from a random sample with respect to an underlying geometric configuration.
Spatio-Temporal Wildland Arson Crime Functions

Wildland arson creates damages to structures and timber and affects the health and safety of people living in rural and wildland urban interface areas. We develop a model that incorporates temporal autocorrelations and spatial correlations in wildland arson ignitions in Florida. A Poisson autoregressive model of order p, or PAR(p) model, is estimated for six high arson Census tracts in the state for the period 1994-2001. Spatio-temporal lags of wildland arson ignitions are introduced as dummy variables indicating the presence of an ignition in previous days in surrounding Census tracts and counties. Temporal lags of ignition activity within the Census tract are shown to be statistically significant and larger than previously reported for non-spatial variants of the PAR(p) model. Spatio-temporal lagged relationships with current arson that were statistically significant show that arson activity up to a county away explains arson patterns, and spatio-temporal lags longer than two days were not significant. Other variables showing significance include weather and wildfire activity in the previous six years, but prescribed fire and several variables that provide evidence that such activity is consistent with an economic model of crime were less commonly significant.
Studies to determine whether an interaction exists among boron, calcium, and cholecalciferol on the skeletal development of broiler chickens.

Two experiments were designed to determine the effect of dietary boron on broiler cockerels and four experiments were conducted to determine whether an interaction exists among dietary boron, cholecalciferol, and calcium. The parameters measured were weight gain, feed efficiency, tibia bone ash, rickets, tibial dyschondroplasia, and plasma minerals. All experiments were conducted with tibial dyschondroplasia-inducing basal diets fed to broiler cockerels from 1 to 16 days of age. Experiments 1 and 2 had four levels of dietary boron (0, 20, 40, and 80 mg/kg (Experiment 1) and 0, 5, 10, and 20 mg/kg (Experiment 2). Boron had no effect on weight gain, feed efficiency, or plasma minerals in either experiment. In Experiment 2, increasing levels of boron had no influence on tibial dyschondroplasia but did exert a quadratic effect on bone ash with 5 and 10 mg/kg boron increasing bone ash. In Experiment 1, bone ash and the incidence of tibial dyschondroplasia were unaffected, but the severity of tibial dyschondroplasia linearly increased by increasing boron levels. Experiments 3 to 6 had a 2 x 2 x 2 factorial arrangement of treatments with calcium at . 65 and . 90%, cholecalciferol at 110 and 1,100 ICU/kg, and boron at 0 and 40 mg/kg (Experiments 3 to 5) or 0 and 3 mg/kg (Experiment 6). The higher levels of calcium and cholecalciferol improved weight gain, decreased the incidence of rickets, and decreased the incidence and severity of tibial dyschondroplasia. Feeding cholecalciferol at 1,100 ICU/kg increased plasma calcium and plasma dialyzable phosphorus and decreased plasma magnesium. Calcium at . 90% had no effect on plasma magnesium or plasma dialyzable phosphorus and increased plasma calcium only in Experiment 4. The only response to boron in Experiments 3 to 6 was a boron effect and a boron by cholecalciferol interaction on bone ash in Experiment 3, in which boron reduced bone ash at . 65% calcium and 110 ICU/kg cholecalciferol. From these experiments, there is no indication that an interaction among boron, cholecalciferol, and calcium exists in broiler cockerels.
Modeling neurodevelopmental cognitive deficits in tasks with cross‐species translational validity

Numerous psychiatric disorders whose cognitive dysfunction links to functional outcome have neurodevelopmental origins including schizophrenia, autism and bipolar disorder. Treatments are needed for these cognitive deficits, which require development using animal models. Models of neurodevelopmental disorders are as varied and diverse as the disorders themselves, recreating some but not all aspects of the disorder. This variety may in part underlie why purported procognitive treatments translated from these models have failed to restore functioning in the targeted patient populations. Further complications arise from environmental factors used in these models that can contribute to numerous disorders, perhaps only impacting specific domains, while diagnostic boundaries define individual disorders, limiting translational efficacy. The Research Domain Criteria project seeks to ‘develop new ways to classify mental disorders based on behavioral dimensions and neurobiological measures’ in hopes of facilitating translational research by remaining agnostic toward diagnostic borders derived from clinical presentation in humans. Models could therefore recreate biosignatures of cognitive dysfunction irrespective of disease state. This review highlights work within the field of neurodevelopmental models of psychiatric disorders tested in cross‐species translational cognitive paradigms that directly inform this newly developing research strategy. By expounding on this approach, the hopes are that a fuller understanding of each model may be attainable in terms of the cognitive profile elicited by each manipulation. Hence, conclusions may begin to be drawn on the nature of cognitive neuropathology on neurodevelopmental and other disorders, increasing the chances of procognitive treatment development for individuals affected in specific cognitive domains.
Effect of temperature and dietary energy on layer performance.

DeKalb XL White Leghorn hens 20 wk of age housed at 16.1, 18.9, 22.2, 25.0, 27.8, and 31.1 C were fed diets containing 2,645, 2.755, 2,865, and 2,976 kcal MEn/kg. Feed intake was 5.9 g lower (P less than .05) when dietary energy was increased from 2,645 to 2,976 kcal MEn/kg and was 21.7 g lower when temperatures were increased from 16.1 to 31.1 C. The MEn intake of hens at temperatures ranging from 16.1 to 31.1 C was 61.2 (P less than .05) kcal/hen per day lower in treatments with the higher temperatures. The MEn intake of hens was also 16.7 kcal/day higher (P less than .05) when energy density in the diet was raised from 2,645 to 2,976 kcal MEn/kg. Egg production was not affected by either temperature or dietary energy density. Egg weight increased . 78 g (P less than .05) with increases in dietary energy density from 2,645 to 2,976 kcal MEn/kg and decreased 3.18 g (P less than .05) when temperatures were raised from 16.1 to 31.1 C. Mean body weights and body weight gains were significantly (P less than .05) higher in treatments with higher energy density and lower in treatments with higher environmental temperatures. Feed conversion was increased . 41 g feed/g egg mass (P less than .05) at higher temperatures (16.1 and 31.1 C) and increased . 17 g feed/g egg mass at higher energy densities (2,645 and 2,976 kcal MEn/kg). Maintenance requirements were estimated at all temperatures.
Studying the Association between Green Space Characteristics and Land Surface Temperature for Sustainable Urban Environments: An Analysis of Beijing and Islamabad

Increasing trends of urbanization lead to vegetation degradation in big cities and affect the urban thermal environment. This study investigated (1) the cooling effect of urban green space spatial patterns on Land Surface Temperature (LST); (2) how the surrounding environment influences the green space cool islands (GCI), and vice versa. The study was conducted in two Asian capitals: Beijing, China and Islamabad, Pakistan by utilizing Gaofen-1 (GF-1) and Landsat-8 satellite imagery. Pearson’s correlation and normalized mutual information (NMI) were applied to investigate the relationship between green space characteristics and LST. Landscape metrics of green spaces including Percentage of Landscape (PLAND), Patch Density (PD), Edge Density (ED), and Landscape Shape Index (LSI) were selected to calculate the spatial patterns of green spaces, whereas GCI indicators were defined by Green Space Range (GR), Temperature Difference (TD), and Temperature Gradient (TG). The results indicate that both vegetation composition and configuration influence LST distributions; however, vegetation composition appeared to have a slightly greater effect. The cooling effect can be produced more effectively by increasing green space percentage, planting trees in large patches with equal distribution, and avoiding complex-shaped green spaces. The GCI principle indicates that LST can be decreased by increasing the green space area, increasing the water body fraction, or by decreasing the fraction of impervious surfaces. GCI can also be strengthened by decreasing the fraction of impervious surfaces and increasing the fraction of water body or vegetation in the surrounding environment. The cooling effect of vegetation and water could be explained based on their thermal properties. Beijing has already enacted the green-wedge initiative to increase the vegetation canopy. While designing the future urban layout of Islamabad, the construction of artificial lakes within the urban green spaces would also be beneficial, as is the case with Beijing.
Divergent biodiversity change within ecosystems

Significance The world’s biodiversity is under unprecedented threat due to human activities, yet we have an incomplete understanding of ecosystem change in response to these pressures. Here we present data from a new 5-y study of a tropical freshwater ecosystem showing that change in the two dimensions of biodiversity—assemblage diversity (number and abundance of species) and assemblage composition—is decoupled from and uncorrelated among taxa. Assemblage diversity is typically stable over time. However, in line with Darwin’s expectation that community composition is constantly changing, this stability can be accompanied by marked turnover in species identities. Our paper thus identifies an important question for future research: at what point does compositional turnover threaten ecosystem resilience? The Earth’s ecosystems are under unprecedented pressure, yet the nature of contemporary biodiversity change is not well understood. Growing evidence that community size is regulated highlights the need for improved understanding of community dynamics. As stability in community size could be underpinned by marked temporal turnover, a key question is the extent to which changes in both biodiversity dimensions (temporal α- and temporal β-diversity) covary within and among the assemblages that comprise natural communities. Here, we draw on a multiassemblage dataset (encompassing vertebrates, invertebrates, and unicellular plants) from a tropical freshwater ecosystem and employ a cyclic shift randomization to assess whether any directional change in temporal α-diversity and temporal β-diversity exceeds baseline levels. In the majority of cases, α-diversity remains stable over the 5-y time frame of our analysis, with little evidence for systematic change at the community level. In contrast, temporal β-diversity changes are more prevalent, and the two diversity dimensions are decoupled at both the within- and among-assemblage level. Consequently, a pressing research challenge is to establish how turnover supports regulation and when elevated temporal β-diversity jeopardizes community integrity.
CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field

Proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to treat the long-range and 1-4 nonbonded interactions. In this study, we systematically test the use of the C36 lipid FF in NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM. A wide range of Lennard-Jones (LJ) cutoff schemes and integrator algorithms were tested to find the optimal simulation protocol to best match bilayer properties of six lipids with varying acyl chain saturation and head groups. MD simulations of a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer were used to obtain the optimal protocol for each program. MD simulations with all programs were found to reasonably match the DPPC bilayer properties (surface area per lipid, chain order parameters, and area compressibility modulus) obtained using the standard protocol used in CHARMM as well as from experiments. The optimal simulation protocol was then applied to the other five lipid simulations and resulted in excellent agreement between results from most simulation programs as well as with experimental data. AMBER compared least favorably with the expected membrane properties, which appears to be due to its use of the hard-truncation in the LJ potential versus a force-based switching function used to smooth the LJ potential as it approaches the cutoff distance. The optimal simulation protocol for each program has been implemented in CHARMM-GUI. This protocol is expected to be applicable to the remainder of the additive C36 FF including the proteins, nucleic acids, carbohydrates, and small molecules.
Effect of enzyme supplementation on the performance and digestive tract size of broiler chickens fed wheat- and barley-based diets.

Three experiments were conducted to study the effects of crude enzyme preparations on the performance and gastrointestinal tract size of chicks fed wheat and barley diets. In the first experiment, enzyme addition (100 and 200 mg/kg of Roxazyme G and 1,000 mg/kg of Avizyme SX) to diets containing Bedford barley improved weight gain (6%) and the feed to gain ratio (5%) over a 6-wk period for both male and female broilers. In Experiment 2, enzyme addition to diets containing Scout (hulless) and Bedford (hulled) barley improved (P < or = .05) weight gains of Leghorn chicks by 25 and 11% and the feed to gain ratios by 10 and 6%, respectively. Feed consumption increased significantly (16%) only in the case of birds fed enzyme with Scout barley. Corresponding reductions in the relative weights of the crop and gizzards were 15 and 17% for birds fed Scout barley and 7 and 8% for those fed Bedford barley. Enzyme treatment of the diet containing Scout barley also reduced the relative length of the duodenum, jejunum, and ileum and the relative weight of the proventriculus, whereas a similar treatment of Bedford barley resulted in changes in the relative length of the duodenum and jejunum (P < .05). In the final broiler experiment (42 days), crude enzyme addition (100 mg/kg) to wheat and barley diets improved weight gains by 13 and 9% and feed to gain ratios by 7 and 10%, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy

Eribulin is indicated in the EU for advanced/metastatic breast cancer patients following ≥1 prior chemotherapy for advanced disease, and anthracycline and taxane in adjuvant/metastatic setting. We pooled 1644 patients from two phase III trials and found that eribulin significantly increased survival versus control, particularly in some subgroups of interest like HER2- and triple-negative disease.
Application of PROMETHEE-GAIA method for non-traditional machining processes selection

Article history: Received April 17, 2012 Accepted 11 June 2012 Available online June 12 2012 With ever increasing demand for manufactured products of hard alloys and metals with high surface finish and complex shape geometry, more interest is now being paid to non-traditional machining (NTM) processes, where energy in its direct form is used to remove material from workpiece surface. Compared to conventional machining processes, NTM processes possess almost unlimited capabilities and there is a strong believe that use of NTM processes would go on increasing in diverse range of applications. Presence of a large number of NTM processes along with complex characteristics and capabilities, and lack of experts in NTM process selection domain compel for development of a structured approach for NTM process selection for a given machining application. Past researchers have already attempted to solve NTM process selection problems using various complex mathematical approaches which often require a profound knowledge in mathematics/artificial intelligence from the part of process engineers. In this paper, four NTM process selection problems are solved using an integrated PROMETHEE (preference ranking organization method for enrichment evaluation) and GAIA (geometrical analysis for interactive aid) method which would act as a visual decision aid to the process engineers. The observed results are quite satisfactory and exactly match with the expected solutions. © 2012 Growing Science Ltd. All rights reserved.