Miracle-dz/UniFAR-FTUs huggingface dataset:
Epitope‐specific anti‐nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine‐dependent

Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti‐mitochondrial antibodies (AMA), a significant number of patients have anti‐nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti‐nuclear antibodies as well as suggestive evidence that antibodies to gp210 predict a poor outcome. However, a further understanding of the significance of these autoantibodies has been hampered by limitations in accessing human subjects in a preclinical or early asymptomatic stage. To overcome this limitation, we have taken advantage of transgenic mice with abrogated transforming growth factor‐β signalling in T cells (dnTGF‐βRII) that develop histological features of PBC as well as the same AMA specificity. We studied these mice for serum ANA, including specific autoantibodies against gp210 and sp100. We further examined sera from dnTGF‐βRII mice with concurrent deletions of the genes encoding interleukin (IL)‐12p35, IL‐12p40, IL‐23p19, IL‐17, IL‐6, interferon (IFN)‐γ or tumour necrosis factor (TNF)‐α. Sera from all the dnTGF‐βRII mouse lines contained antibodies against gp210 and sp100. Of significance, mice with germline deletions of the genes encoding IL‐12p40, IL‐23p19, IL‐17, IL‐6 and TNF‐α had significantly lower titres of anti‐gp210 antibodies. These results provide a platform to dissect the mechanisms of gp210 and sp100 autoantibody production in dnTGF‐βRII mice as well as to study the possible role of ANA in the pathophysiology of PBC.
Evaluation of Isotopic Abundance Ratio in Biofield Energy Treated Nitrophenol Derivatives Using Gas Chromatography-Mass Spectrometry

Nitrophenols are the synthetic organic chemicals used for the preparation of synthetic intermediates, organophosphorus pesticides, and pharmaceuticals. The objective of the present study was to evaluate the effect of biofield energy treatment on the isotopic abundance ratios of PM+1/PM, and PM+2/PM in o- and m-nitrophenol using the gas chromatography-mass spectrometry. The o- and m-nitrophenol were divided into two parts - one part was control sample, and another part was considered as biofield energy treated sample, which received Mr. Trivedi’s biofield energy treatment (The Trivedi Effect®). The biofield energy treated nitrophenols having analyzed at different time intervals were designated as T1, T2, T3, and T4. The GC-MS analysis of both the control and biofield treated samples indicated the presence of the parent molecular ion peak of o- and m-nitrophenol (C6H5NO3+) at m/z 139 along with major fragmentation peaks at m/z 122, 109, 93, 81, 65, and 39. The relative peak intensities of the fragmented ions in the biofield treated o- and m-nitrophenol were notably changed as compared to the control sample with respect to the time. The isotopic abundance ratio analysis using GC-MS revealed that the isotopic abundance ratio of PM+1/PM in the biofield energy treated o-nitrophenol at T2 and T3 was significantly increased by 14.48 and 86.49%, respectively as compared to the control sample. Consequently, the isotopic abundance ratio of PM+2/PM in the biofield energy treated sample at T2 and T3 was increased by 11.36, and 82.95%, respectively as compared to the control sample. Similarly, in m-nitrophenol, the isotopic abundance ratio of PM+1/PM in the biofield energy treated sample at T1, T3, and T4 was increased by 5.82, 5.09, and 6.40%, respectively as compared to the control sample. Subsequently, the isotopic abundance ratio of PM+2/PM at T1, T2, T3 and T4 in the biofield energy treated m-nitrophenol was increased by 6.33, 3.80, 16.46, and 16.46%, respectively as compared to the control sample. Overall, the isotopic abundance ratios of PM+1/PM (2H/1H or 13C/12C or 15N/14N or 17O/16O), and PM+2/PM (18O/16O) were altered in the biofield energy treated o- and m-nitrophenol as compared to the control increased in most of the cases. The biofield treated o- and m-nitrophenol that have improved isotopic abundance ratios might have altered the physicochemical properties and could be useful in pharmaceutical and chemical industries as an intermediate in the manufacturing of pharmaceuticals and other useful chemicals for the industrial application.
Reproducibility of Benchmarked Deep Reinforcement Learning Tasks for Continuous Control

Policy gradient methods in reinforcement learning have become increasingly prevalent for state-of-the-art performance in continuous control tasks. Novel methods typically benchmark against a few key algorithms such as deep deterministic policy gradients and trust region policy optimization. As such, it is important to present and use consistent baselines experiments. However, this can be difficult due to general variance in the algorithms, hyper-parameter tuning, and environment stochasticity. We investigate and discuss: the significance of hyper-parameters in policy gradients for continuous control, general variance in the algorithms, and reproducibility of reported results. We provide guidelines on reporting novel results as comparisons against baseline methods such that future researchers can make informed decisions when investigating novel methods.
Morphological characterisation of the cell-growth inhibitory activity of rooperol and pharmacokinetic aspects of hypoxoside as an oral prodrug for cancer therapy.

Hypoxoside is the major diglucoside isolated from the corms of the plant family Hypoxidaceae. It contains an unusual E-pent-1-en-4-yne 5-carbon bridging unit with two distal catechol groups to which the glucose moieties are attached. It is non-toxic for BL6 mouse melanoma cells in tissue culture on condition that the fetal calf serum in the medium is heat-inactivated for 1 hour at 56 degrees C in order to destroy endogenous beta-glucosidase activity. The latter catalyses hypoxoside conversion to its cytotoxic aglucone, rooperol, which, when tested as a pure chemical, caused 50% inhibition of BL6 melanoma cell growth at 10 micrograms/ml. Light and electron microscopy revealed that the cytotoxic effect of rooperol manifested as vacuolisation of the cytoplasm and formation of pores in the plasma membrane. Indications of apoptosis were also found. Pharmacokinetic studies on mice dosed intragastrically with hypoxoside showed that it was deconjugated by bacterial beta-glucosidase to form rooperol in the colon. Surprisingly, no hypoxoside or rooperol was detectable in the serum. Only phase II biotransformation products (sulphates and glucuronides) were present in the portal blood and bile. In contrast, however, in human serum after oral ingestion of hypoxoside, the metabolites can reach relatively high concentrations. Rooperol metabolites isolated from human urine were non-toxic for BL6 melanoma cells in culture up to a concentration of 200 micrograms/ml. In the presence of beta-glucuronidase, which released rooperol from the metabolites, 50% growth inhibition was achieved at a 75 micrograms/ml metabolite concentration. The supernatant of a human melanoma homogenate could also cause deconjugation of the metabolites to form rooperol. (ABSTRACT TRUNCATED AT 250 WORDS)
High latitude meteoric δ18O compositions: Paleosol siderite in the Middle Cretaceous Nanushuk Formation, North Slope, Alaska

Siderite-bearing pedogenic horizons of the Nanushuk Formation of the North Slope, Alaska, provide a critical high paleolatitude oxygen isotopic proxy record of paleoprecipitation, supplying important empirical data needed for paleoclimatic reconstructions and models of “greenhouse- world” precipitation rates. Siderite δ 18 O values were determined from four paleosol horizons in the National Petroleum Reserve Alaska (NPR-A) Grandstand # 1 Core, and the values range between −17.6‰ and −14.3‰ Peedee belemnite (PDB) with standard deviations generally less than 0.6‰ within individual horizons. The δ 13 C values are much more variable, ranging from −4.6‰ to +10.8‰ PDB. A covariant δ 18 O versus δ 13 C trend in one horizon probably resulted from mixing between modified marine and meteoric phreatic fluids during siderite precipitation. Groundwater values calculated from siderite oxygen isotopic values and paleobotanical temperature estimates range from −23.0‰ to −19.5‰ standard mean ocean water (SMOW). Minor element analyses show that the siderites are impure, having enrichments in Ca, Mg, Mn, and Sr. Minor element substitutions and Mg/Fe and Mg/(Ca + Mg) ratios also suggest the influence of marine fluids upon siderite precipitation. The pedogenic horizons are characterized by gleyed colors, rare root traces, abundant siderite, abundant organic matter, rare clay and silty clay coatings and infillings, some preservation of primary sedimentary stratification, and a lack of ferruginous oxides and mottles. The pedogenic features suggest that these were poorly drained, reducing, hydromorphic soils that developed in coal-bearing delta plain facies and are similar to modern Inceptisols. Model-derived estimates of precipitation rates for the Late Albian of the North Slope, Alaska (485–626 mm/yr), are consistent with precipitation rates necessary to maintain modern peat-forming environments. This information reinforces the mutual consistency between empirical paleotemperature estimates and isotope mass balance models of the hydrologic cycle and can be used in future global circulation modeling (GCM) experiments of “greenhouse- world” climates to constrain high latitude precipitation rates in simulations of ancient worlds with decreased equator-to-pole temperature gradients.
Repetitive transcranial magnetic stimulation over the supplementary motor area modifies breathing pattern in response to inspiratory loading in normal humans

In awake humans, breathing depends on automatic brainstem pattern generators. It is also heavily influenced by cortical networks. For example, functional magnetic resonance imaging and electroencephalographic data show that the supplementary motor area becomes active when breathing is made difficult by inspiratory mechanical loads like resistances or threshold valves, which is associated with perceived respiratory discomfort. We hypothesized that manipulating the excitability of the supplementary motor area with repetitive transcranial magnetic stimulation would modify the breathing pattern response to an experimental inspiratory load and possibly respiratory discomfort. Seven subjects (three men, age 25 ± 4) were studied. Breathing pattern and respiratory discomfort during inspiratory loading were described before and after conditioning the supplementary motor area with repetitive stimulation, using an excitatory paradigm (5 Hz stimulation), an inhibitory paradigm, or sham stimulation. No significant change in breathing pattern during loading was observed after sham conditioning. Excitatory conditioning shortened inspiratory time (p = 0.001), decreased tidal volume (p = 0.016), and decreased ventilation (p = 0.003), as corroborated by an increased end-tidal expired carbon dioxide (p = 0.013). Inhibitory conditioning did not affect ventilation, but lengthened expiratory time (p = 0.031). Respiratory discomfort was mild under baseline conditions, and unchanged after conditioning of the supplementary motor area. This is the first study to show that repetitive transcranial magnetic stimulation conditioning of the cerebral cortex can alter breathing pattern. A 5 Hz conditioning protocol, known to enhance corticophrenic excitability, can reduce the amount of hyperventilation induced by inspiratory threshold loading. Further studies are needed to determine whether and under what circumstances rTMS can have an effect on dyspnoea.
Upregulation of GPR109A in Parkinson’s Disease

Background Anecdotal animal and human studies have implicated the symptomatic and neuroprotective roles of niacin in Parkinson’s disease (PD). Niacin has a high affinity for GPR109A, an anti-inflammatory receptor. Niacin is also thought to be involved in the regulation of circadian rhythm. Here we evaluated the relationships among the receptor, niacin levels and EEG night-sleep in individuals with PD. Methods and Findings GPR109A expression (blood and brain), niacin index (NAD-NADP ratio) and cytokine markers (blood) were analyzed. Measures of night-sleep function (EEG) and perceived sleep quality (questionnaire) were assessed. We observed significant up-regulation of GPR109A expression in the blood as well as in the substantia nigra (SN) in the PD group compared to age-matched controls. Confocal microscopy demonstrated co-localization of GPR109A staining with microglia in PD SN. Pro and anti-inflammatory cytokines did not show significant differences between the groups; however IL1-β, IL-4 and IL-7 showed an upward trend in PD. Time to sleep (sleep latency), EEG REM and sleep efficiency were different between PD and age-matched controls. Niacin levels were lower in PD and were associated with increased frequency of experiencing body pain and decreased duration of deep sleep. Conclusions The findings of associations among the GPR109A receptor, niacin levels and night-sleep function in individuals with PD are novel. Further studies are needed to understand the pathophysiological mechanisms of action of niacin, GPR109A expression and their associations with night-sleep function. It would be also crucial to study GPR109A expression in neurons, astrocytes, and microglia in PD. A clinical trial to determine the symptomatic and/or neuroprotective effect of niacin supplementation is warranted.
An exploration of the two-factor schematization of relation meaning and emotions among professional rugby union players

The aim of this paper was to explore Lazarus's two-factor schematization of losses and gains and the emotions generated in response to loss (threat and harm) and gain (challenge and benefit) relational meanings. Participants were 10 professional rugby union players aged between 24 and 35 years (M age = 26.8 years, SD = 5.92). The results revealed that at different times, the same stressor had different relational meanings. For instance, opponent, coach, playing an important match, and injury stressors were appraised as losses and gains. Furthermore, stressful loss relational meanings generated pre-dominantly negative emotions, whereas gain relational meanings generated mainly positive emotions. However, anxiety was the second most reported emotion generated in response to gain relational meanings. This finding suggests that not all gain relational meanings generate positively toned emotions.
A geometric Achlioptas process

The random geometric graph is obtained by sampling n points from the unit square (uniformly at random and independently), and connecting two points whenever their distance is at most r , for some given r = r(n) . We consider the following variation on the random geometric graph: in each of n rounds in total, a player is offered two random points from the unit square, and has to select exactly one of these two points for inclusion in the evolving geometric graph. We study the problem of avoiding a linear-sized (or “giant”) component in this setting. Speciﬁcally, we show that for any r (cid:2) (n loglog n) − 1 / 3 there is a strategy that succeeds in keeping all component sizes sublinear, with probability tending to one as n → ∞ . We also show that this is tight in the following sense: for any r (cid:5) (n loglog n) − 1 / 3 , the player will be forced to create a component of size ( 1 − o( 1 ))n , no matter how he plays, again with probability tending to one as n → ∞ . We also prove that the corresponding ofﬂine problem exhibits a similar threshold behaviour at r(n) = (cid:2)(n − 1 / 3 ) . These ﬁndings should be compared to the existing results for the (ordi-nary) random geometric graph: there a giant component arises with high probability once r is of order n − 1 / 2 . Thus, our results show, in particular, that in the geometric setting the power of choices can be exploited to a much larger extent than in the classical Erd˝os–Rényi random graph, where the appearance of a giant component can only be delayed by a constant factor.
Sensitivity of the folding/unfolding transition state ensemble of chymotrypsin inhibitor 2 to changes in temperature and solvent

To better characterize the transition state for folding/unfolding and its sensitivity to environmental changes, we have run multiple molecular dynamics simulations of chymotrypsin inhibitor 2 (CI2) under varying solvent conditions and temperature. The transition state structures agree well with experiment, and are similar under all of the conditions investigated here. Increasing the temperature leads to some movement in the position of the transition state along several reaction coordinates, as measured by changes in properties of the transition state structures. These structural changes are in the direction of a more native‐like transition state as denaturation conditions become more severe, as expected for a Hammond effect. These structural changes are not, however, reflected in the global structure as measured by the total number of contacts or the average S‐values. These results suggest that the small changes in average Φ‐values with temperature seen by experiment may be due to an increase in the sensitivity of the transition state to mutation rather than a change in the average structure of the transition state. A simple analysis of the rates of unfolding indicates that the free energy barrier to unfolding decreases with increasing temperature, but even in our very high temperature simulations there is a small free energy barrier.
Syndecan-3 and TFPI Colocalize on the Surface of Endothelial-, Smooth Muscle-, and Cancer Cells

Background Tissue factor (TF) pathway inhibitor (TFPI) exists in two isoforms; TFPIα and TFPIβ. Both isoforms are cell surface attached mainly through glycosylphosphatidylinositol (GPI) anchors. TFPIα has also been proposed to bind other surface molecules, like glycosaminoglycans (GAGs). Cell surface TFPIβ has been shown to exert higher anticoagulant activity than TFPIα, suggesting alternative functions for TFPIα. Further characterization and search for novel TFPI binding partners is crucial to completely understand the biological functions of cell associated TFPI. Methods and Results Potential association of TFPI to heparan sulphate (HS) proteoglycans in the syndecan family were evaluated by knock down studies and flow cytometry analysis. Cell surface colocalization was assessed by confocal microscopy, and native PAGE or immunoprecipitation followed by Western blotting was used to test for protein interaction. Heparanase was used to enzymatically degrade cell surface HS GAGs. Anticoagulant potential was evaluated using a factor Xa (FXa) activity assay. Knock down of syndecan-3 in endothelial,- smooth muscle- and breast cancer cells reduced the TFPI surface levels by 20-50%, and an association of TFPIα to syndecan-3 on the cell surface was demonstrated. Western blotting indicated that TFPIα was found in complex with syndecan-3. The TFPI bound to syndecan-3 did not inhibit the FXa generation. Removal of HS GAGs did not release TFPI antigen from the cells. Conclusions We demonstrated an association between TFPIα and syndecan-3 in vascular cells and in cancer cells, which did not appear to depend on HS GAGs. No anticoagulant activity was detected for the TFPI associated with syndecan-3, which may indicate coagulation independent functions for this cell associated TFPI pool. This will, however, require further investigation.
Comparing Distinctions and Similarities Across Websites of Newspapers, Radio Stations, and Television Stations

In the current Internet environment, media must not only compete with one another but with a host of newcomers, including online companies with no traditional media ties and a variety of other entrepreneurs. To what extent do the media reflect their traditional strengths and features? Furthermore, since the Internet allows for two-way communication, which of the media are taking advantage of this feature to connect with their audiences? This paper reports the results of a content analysis of 422 websites associated with local newspapers, radio stations, and television stations in twenty-five of the largest metro markets in the United States. Results show that each medium (including newspaper, radio station, and television station) has a relatively distinctive content emphasis, while each attempts to utilize its website to maximize institutional goals. Market size is found to be a relatively unimportant factor in shaping the content of these websites, but media type helps explain how these websites are differentiated.
Naturally Acquired Plasmodium knowlesi Malaria in Human, Thailand

We describe a case of naturally acquired infection with Plasmodium knowlesi in Thailand. Diagnosis was confirmed by the small subunit ribosomal RNA and the mitochondrial cytochrome b sequences. The occurrence of simian malaria in human has signified the roles of wild primate populations in disease transmission in some malaria-endemic areas.
Transformational Leadership and Work-Related Attitudes: The Moderating Effects of Collective and Self-Efficacy Across Cultures

In this study, we examined how collective and self-efficacy moderated the influence of transformational leadership on followers' work-related attitudes (i.e., organizational commitment and job satisfaction) using hierarchical linear modeling. Data for this study were collected from 37 bank branches and 644 individuals in China (n = 208), India (n = 194), and the United States (n = 242). Results revealed that transformational leadership and efficacy beliefs were positively related to followers' work-related attitudes. Aggregated collective and self-efficacy moderated the relationship between transformational leadership and followers' work-related attitudes. Limitations of the study and implications of these findings for practice and research are discussed. Key words: Transformational leadership, efficacy beliefs, and work attitudes.
Experimental measurements of multi-carrier power line communication systems

The article focuses on experimental measurement of multi-carrier narrowband Power Line Communication. The aim of experimental measurements was comparison of multi-carrier narrowband Power Line Communication from the view-point of possible communication distance, available data rate and impact of noise. The specifications G3-PLC and PRIME are considered. The field test results and data rate measurements are presented for different scenarios. They demonstrate consequences of noisy environment and complicated topology. Finally, the article identifies and analysis the fundamental issues for further development of PLC for Smart Grids and Smart Metering.
Literacy and reading performance in the United States, from 1880 to the present

THE AUTHORS review literacy and reading achievement trends over the past century and place current debates in a historical perspective. Although then-and-now studies are methodologically weak, they suggest that students' reading performance at a given age remained stable until the 1970s. The test score decline that then occurred was not as great as many educators think, and much of it can be explained by the changing demographics of test-takers. The decline pales when compared to the tremendous increase in the population's educational attainment over the past 40 years. However, the strategy of ever-increasing schooling to meet ever-increasing literacy demands may have run its course. High school dropout rates are increasing, and educational attainment has leveled off. Researchers have identified substantial mismatches between workers' skills and job demands, and between job and school literacy skills. In spite of their flaws, functional literacy tests suggest that 20 percent of the adult population, or 30 million people, have serious difficulties with common reading tasks. Upgrading literacy skills now requires new initiatives by coalitions of educators, community groups, employers, and government agencies.