Miracle-dz/UniFAR-FTUs huggingface dataset:
Uncertainty in preindustrial abundance of tropospheric ozone: Implications for radiative forcing calculations

Recent model calculations of the global mean radiative forcing from tropospheric ozone since preindustrial times fall in a relatively narrow range, from 0.3 to 0.5 W m−2. These calculations use preindustrial ozone fields that overestimate observations available from the turn of the nineteenth century. Although there may be calibration problems with the observations, uncertainties in model estimates of preindustrial natural emissions must also be considered. We show that a global three-dimensional model of tropospheric chemistry with reduced NOx emissions from lightning (1–2 Tg N yr−1) and soils (2 Tg N yr−1) and increased emissions of biogenic hydrocarbons can better reproduce the nineteenth century observations. The resulting global mean radiative forcing from tropospheric ozone since preindustrial times is 0.72–0.80 W m−2, amounting to about half of the estimated CO2 forcing. Reduction in the preindustrial lightning source accounts for two thirds of the increase in the ozone forcing. Because there is near-total titration of OH by isoprene in the continental boundary layer of the preindustrial atmosphere, isoprene and other biogenic hydrocarbons represent significant ozone sinks. The weak or absent spring maximum in the nineteenth century observations of ozone is difficult to explain within our understanding of the natural ozone budget. Our results indicate that the uncertainty in computing radiative forcing from tropospheric ozone since preindustrial times is larger than is usually acknowledged.
Pharmacodynamic and predictive markers of ipilimumab on melanoma patients' T-cells.

2503 Background: The purpose of this retrospective study was to identify peripheral blood biomarkers associated with the therapeutic effect of ipilimumab, a human antibody against cytotoxic T lymphocyte antigen-4 (CTLA-4). Immunophenotypic changes in CD4+ and CD8+ T cells from advanced melanoma patients treated with ipilimumab were identified by gene expression profiling and subsequently validated by flow cytometry Methods: CD4+ and CD8+ T cells were purified by flow cytometry sorting from peripheral blood pre- and post- ipilimumab treatment from stages IIIC/IV melanoma patients rendered free of disease on an adjuvant trial. Microarray analysis of purified CD4+ and CD8+ T cells to identify gene profiling changes induced by ipilimumab were performed in 18 patients. Flow cytometry analysis of a larger, overlapping cohort of 36 patients was performed to confirm effects on T cell phenotypes Results: Ipilimumab augmented total CD4+ T cells and decreased CD4+ and CD8+ naïve T cells. Mean fluorescence intensity (MFI) of proliferation marker Ki67, the Inducible T cell Co-Stimulator (ICOS), and the polarizing regulatory molecule GATA3 were significantly up-regulated on CD4+ and CD8+ T cells (p<0.01 Wilcoxon). Percent expression and MFI of Granzyme B in CD8+ T cells was increased and EOMES (eomesodermin) was decreased on CD8+ T cells (both p<0.04). The MFI of CCR7 and IL-7R on CD4+ T cells was decreased (p<0.001). Increased expression of ICOS and Ki-67 in CD8+ T cells were negatively associated with developing immune related adverse events (p=0.04, Wald), and increased EOMES on CD8+ T cells was associated with shorter relapse free-survival (RFS)(p=0.04). Higher baseline EOMES CD8+ expression was predictive of favorable RFS (p=0.03) Conclusions: Increased expression of proliferation and polarization markers in CD4+ and CD8+ cells, decreased CCR7 and IL-7R on CD4+ T cells and up-regulated Granzyme B in CD8+ T cells may serve as pharmacodynamic indicators of the effects of ipilimumab. Increased activation markers ICOS and EOMES were significantly associated with fewer adverse events and less favorable outcome, respectively, but baseline elevated expression of EOMES appears to predict favorable relapse-free survival in this analysis.
Myocardial cooling for reperfusion injury protection achieved by organ specific hypothermic autologous perfusion

Objective—Whole body hypothermia has been suggested to reduce myocardial injury in patients with ST‐segment elevation myocardial infarction. Because of the large human thermal mass, induction of generalized hypothermia is slow and the technique has encountered considerable side effects. The aim was to develop and validate a method for regional cooling during myocardial reperfusion using hypothermic autologous blood. Design—In a myocardial ischemia‐reperfusion pig model (n = 10), arterial blood was cooled in a closed circuit, and returned to the myocardium during reperfusion either through a perfusion catheter or through the guiding catheter. Myocardial temperatures were recorded using temperature electrodes. Results—Stabile regional myocardial cooling was induced without complications within 4 min. Both flow rate and blood temperature had significant impact on temperature in the reperfused myocardium but did not influence systemic temperature. Conclusion—A method for organ specific hypothermic autologous arterial blood reperfusion has been developed and validated. The method is a simple and much faster alternative to systemic cooling and may have the potential to reduce myocardial injury in patients with acute myocardial infarction.
Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase‐4 inhibitor linagliptin *

Aim: This study assessed the influence of various degrees of renal impairment on the exposure of linagliptin, a dipeptidyl peptidase‐4 (DPP‐4) inhibitor with a primarily non‐renal route of excretion, in subjects with type 2 diabetes mellitus (T2DM).
Clarifying the Concept of Human Dignity in the Care of the Elderly: A Dialogue between Empirical and Philosophical Approaches

The need for dignity is frequently mentioned in policy documents relating to the care of the elderly. It is also described as an important value in professional codes. Yet concerns about the standards of care for an important number of elderly people abound, despite global ageing being a challenging phenomenon. Not least among these is how to ensure that the elderly will be able to live out their days with dignity. In the present paper, we begin with an empirical exploration of the meaning of human dignity as experienced by older Europeans and their professional caregivers. Thereafter, we discuss the meaning and relevance of these empirical research findings from a care ethics perspective.
The Oxford handbook of close relationships

The Oxford Handbook of Close Relationships, 846 pages, OUP USA, 2013, 0195398696, 9780195398694, Jeffry A. Simpson, Lorne Campbell, 2013, The Oxford Handbook of Close Relationships provides the best, most in-depth, and most comprehensive summary of the study of close relationships. The book is divided into eight sections: introductory comments, major theoretical approaches to relationships, attraction in relationships, models of relationship functioning and processes, daily relationship functioning, psychological and physical well-being in relationships, relationships across development and time, and concluding comments. The 37 chapters showcase the most important classic and contemporary theories, models, and empirical research that have been conducted across three dozen major topic areas within the field of close relationships. Chapter topics range in scope from evolutionary approaches to understanding relationships, the "battle between the sexes," cultural influences on relationships, female sexuality, personality in relationships, intimate partner violence, relationships and health, social development, and adult relationship outcomes. Each chapter is structured around three themes: (1) the most important and foundational principles, ideas, and findings on each chapter topic, (2) the most important and novel emerging themes and issues relevant to each topic, and (3) the newest and most promising directions for future research. Current, comprehensive, and with heretofore unmatched breadth and depth, this volume will serve as a roadmap for future theory and research in the study of close relationship during the next decade. file download rym.pdf
Ellipsoidal collapse and an improved model for the numberand spatial distribution of dark matter

The Press{Schechter, excursion set approach allows one to make predictions about the shape and evolution of the mass function of bound objects. The approach combines the assumption that objects collapse spherically with the assumption that the initial density uctuations were Gaussian and small. While the predicted mass function is reasonably accurate at the high mass end, it has more low mass objects than are seen in simulations of hierarchical clustering. We show that the discrepancy between theory and simulation can be reduced substantially if bound structures are assumed to form from an ellipsoidal, rather than a spherical collapse. In the original, standard, spherical model, a region collapses if the initial density within it exceeds a threshold value, sc. This value is independent of the initial size of the region, and since the mass of the collapsed object is related to its initial size, this means that sc is independent of nal mass. In the ellipsoidal model, the collapse of a region depends on the surrounding shear eld, as well as on its initial overdensity. In Gaussian random elds, the distribution of these quantities depends on the size of the region considered. Since the mass of a region is related to its initial size, there is a relation between the density threshold value required for collapse, and the mass of the nal object. We provide a tting function to this ec (m) relation which simpliies the inclusion of ellipsoidal dynamics in the excursion set approach. We discuss the relation between the excursion set predictions and the halo distribution in high resolution N-body simulations, and use our new formulation of the approach to show that our simple parametrization of the ellipsoidal collapse model represents a signiicant improvement on the spherical model on an object-by-object basis. Finally, we show that the associated statistical predictions, the mass function and the large scale halo-to-mass bias relation, are also more accurate than the standard predictions.
Sleep Deprivation Causes Behavioral, Synaptic, and Membrane Excitability Alterations in Hippocampal Neurons

Although the function of sleep remains elusive, several lines of evidence suggest that sleep has an important role in learning and memory. In light of the available data and with the prevalence of sleep deprivation (SD), we sought to determine the effect of SD on neuronal functioning. We found that the exposure of rats to 72 hr of primarily rapid eye movement SD impaired their subsequent performance on a hippocampus-dependent spatial learning task but had no effect on an amygdala-dependent learning task. To determine the underlying cellular level mechanisms of this hippocampal deficit, we examined the impact of SD on several fundamental aspects of membrane excitability and synaptic physiology in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. We found that neuronal excitability was severely reduced in CA1 neurons but not in granule cells and that the production of long-term potentiation of synaptic strength was inhibited in both areas. Using multiple SD methods we further attempted to differentiate the effects of sleep deprivation from those associated with the nonspecific stress induced by the sleep deprivation methods. Together these data suggest that failure to acquire adequate sleep produces several molecular and cellular level alterations that profoundly inhibit hippocampal functioning.
Convex Co-embedding

We present a general framework for association learning, where entities are embedded in a common latent space to express relatedness by geometry -- an approach that underlies the state of the art for link prediction, relation learning, multi-label tagging, relevance retrieval and ranking. Although current approaches rely on local training applied to non-convex formulations, we demonstrate how general convex formulations can be achieved for entity embedding, both for standard multi-linear and prototype-distance models. We investigate an efficient optimization strategy that allows scaling. An experimental evaluation reveals the advantages of global training in different case studies.
Failure to Connect: How Computers Affect Our Children's Minds -- and What We Can Do About It

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New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado–Joseph disease)

Purpose of reviewThis review summarizes recent neuropathological findings in spinocerebellar ataxia type 3 and discusses their relevance for clinical neurology. Recent findingsThe extent of the spinocerebellar ataxia type 3 related central nervous neurodegenerative changes has been recently systematically investigated in a series of pathoanatomical studies. These studies showed that the extent of the central nervous degenerative changes of spinocerebellar ataxia type 3 has been underestimated so far. The newly described pattern of central nervous neurodegeneration includes the visual, auditory, vestibular, somatosensory, ingestion-related, dopaminergic and cholinergic systems. These pathological findings were correlated with clinical findings and explain a variety of the spinocerebellar ataxia type 3 symptoms observed in clinical practice. SummarySystematic pathoanatomical analysis of spinocerebellar ataxia type 3 brains helps to understand the structural basis of this neurodegenerative disease and offers explanations for a variety of disease symptoms. This better understanding of the neuropathology of the condition has implications for the treatment of spinocerebellar ataxia type 3 patients and represents a basis for further biochemical and molecular biological studies aimed at deciphering the pathomechanisms of this progressive ataxic disorder.
Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model

Background Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson’s disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila. Methods Elav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter. The effects of Drp1 on the lifespan, motor ability and neuronal degeneration of the transgenic Drosophila were explored by over-expressing Drp1 in the Aβ42 transgenic Drosophila. ATP levels in the brain tissues of Aβ42 transgenic Drosophila were detected using high performance liquid chromatography (HPLC). Results Exogenous expression of Drp1 promoted crawling ability, reduced the levels of ATP in Drosophila brain and suppressed the neuronal degeneration. Conclusion The protective effect of Drp1 on the Aβ42 transgenic Drosophila was achieved by protecting the mitochondrial function, suggesting that Drp1 may be a potential therapeutic strategies for AD.
Hierarchical Pitman-Yor Language Model for Machine Translation

The hierarchical Pitman-Yor process-based smoothing method applied to language model was proposed by Gold water and by The, the performance of this smoothing method is shown comparable with the modified Kneser-Ney method in terms of perplexity. Although this method was presented four years ago, there has been no paper which reports that this language model indeed improves translation quality in the context of Machine Translation (MT). This is important for the MT community since an improvement in perplexity does not always lead to an improvement in BLEU score, for example, the success of word alignment measured by Alignment Error Rate (AER) does not often lead to an improvement in BLEU. This paper reports in the context of MT that an improvement in perplexity really leads to an improvement in BLEU score. It turned out that an application of the Hierarchical Pitman-Yor Language Model (HPYLM) requires a minor change in the conventional decoding process. Additionally to this, we propose a new Pitman-Yor process-based statistical smoothing method similar to the Good-Turing method although the performance of this is inferior to HPYLM. We conducted experiments, HPYLM improved by 1.03 BLEU points absolute and 6% relative for 50k EN-JP, which was statistically significant.
Neutralizing antibody complex of infectious bronchitis virus.

The reaction between infectious bronchitis virus-42 (Beaudette) and neutralizing antibody, and dissociation of the antigen-antibody complex, was studied by the plaque technique using chicken embryo kidney cell cultures. Neutralization was a first-order reaction dependent upon time and concentration of antibody. When the complex was diluted, there was a slight but statistically significant dissociation. The complex clarified by centrifugation did not dissociate after dilution. Complexes were readily dissociated by acid with a direct relationship to H+ ion concentration. Maximum dissociation occurred within 1 min at pH 1.7 with a recovery of 60% of the original infectious virus. Virus and antibody dissociated at low pH could be reassociated at neutrality. The complexes adsorbed to cells. Brief acidification dissociated neutralizing antibody from the complexes allowing virus to infect the cells.
Chromogranin B in Heart Failure: A Putative Cardiac Biomarker Expressed in the Failing Myocardium

Background—Chromogranin B (CgB) is a member of the granin protein family. Because CgB is often colocalized with chromogranin A (CgA), a recently discovered cardiac biomarker, we hypothesized that CgB is regulated during heart failure (HF) development. Methods and Results—CgB regulation was investigated in patients with chronic HF and in a post–myocardial infarction HF mouse model. Animals were phenotypically characterized by echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5.2-fold increased in the noninfarcted part of the left ventricle of HF animals compared with sham-operated animals (P<0.001). CgB mRNA level in HF animals correlated closely with animal lung weight (r=0.74, P=0.04) but not with CgA mRNA levels (r=0.20, P=0.61). CgB protein levels were markedly increased in both the noninfarcted (110%) and the infarcted part of the left ventricle (70%) but unaltered in other tissues investigated. Myocardial CgB immunoreactivity was confined to cardiomyocytes. Norepinephrine, angiotensin II, and transforming growth factor-&bgr; increased CgB gene expression in cardiomyocytes. Circulating CgB levels were increased in HF animals (median levels in HF animals versus sham, 1.23 [interquartile range, 1.03 to 1.93] versus 0.98 [0.90 to 1.04] nmol/L; P=0.003) and in HF patients (HF patients versus control, 1.66 [1.48 to 1.85] versus 1.47 [1.39 to 1.58] nmol/L; P=0.007), with levels increasing in proportion to New York Heart Association functional class (P=0.03 for trend). Circulating CgB levels were only modestly correlated with CgA (r=0.31, P=0.009) and B-type natriuretic peptide levels (r=0.27, P=0.014). Conclusions—CgB production is increased and regulated in proportion to disease severity in the left ventricle and circulation during HF development.
Double-network gels and the toughness of terrestrial slug glue

ABSTRACT The terrestrial slug Arion subfuscus produces a defensive secretion that is sticky and tough, despite being a dilute gel. It is unusual in having high stiffness for a gel, yet retaining the high extensibility typical of mucus. In tensile tests, it sustains an average peak stress of 101 kPa, and fails at an average strain of 9.5. This gives the gel toughness; it requires much greater strain energy to fracture than most gels. This toughness may arise from a double-network type mechanism. In this mechanism, two separate, interpenetrating networks of polymers with different properties combine to give toughness that can be several orders of magnitude greater than either network individually. Native gel electrophoresis suggests that A. subfuscus glue consists of two networks: a network of negatively charged proteins ranging in Mr from 40×103 to 220×103 that can be dissociated by hydroxylamine and a network of heparan sulfate-like proteoglycans. The two networks are not tightly linked, though proteins of Mr 40×103 and 165×103 may associate with the carbohydrates. Targeted disruption of either network separately, using enzymatic hydrolysis, disulfide bond breakage or imine bond disruption completely disrupted the glue, resulting in no measurable toughness. Thus, the two networks separately provide little toughness, but together they work synergistically to create a tough material, as predicted in the double-network mechanism. Summary: The gel-based glue of Arion subfuscus combines two separate networks: a deformable proteoglycan network and a cross-linked protein network. These work together to achieve far greater toughness than each can produce separately.
Patterns and controls of lotic algal stable carbon isotope ratios

Spatial and temporal variations in stable carbon isotope ratios (i.e., δ13C) of primary producers are common but poorly understood features of isotopic characterizations of aquatic food webs. I investigated factors that control δ13C of algae (concentration and δ13C of inorganic carbon, algal fractionation, and growth rates) in riffle habitats across a gradient in stream size and productivity in northern California. There was considerable seasonal and spatial variation in δ13C of the green alga Cladophora glomerata, microalgal‐influenced epilithic biofilms, and their herbivores. Algal and herbivore δ13C were depleted in 13C in small, unproductive tributary streams (−44‰ to −30‰) compared with more productive sites downstream (−31‰ to −23‰). The majority of variation in algal δ13C of Cladophora and epilithic biofilms was determined by dissolved CO2 (CO2aq) via effects on δ13C of CO2aq and photosynthetic fractionation. In contrast, two other taxa (the cyanobacterium Nostoc pruniforme and the red alga Lemanea sp.) showed little variation in δ13C or fractionation in response to varied inorganic carbon availability because of their distinct modes of inorganic carbon acquisition. Although variation in algal δ13C might complicate use of δ13C to resolve consumer diet sources under some circumstances, better understanding of such variation should improve the use of δ13C techniques in aquatic food web studies.