Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative structural assessment of graded receptor agonism

Significance Pharmacological receptor theory models are used to predict and interpret how small-molecule ligands impact the function of cellular receptors. Theoretical models have been modified and extended over time to more accurately describe relationships between ligand affinity and receptor functional. However, structural studies are lacking that describe the influence of receptor conformation, or shape, as predicted by these models. Using NMR spectroscopy, we detected how the nuclear receptor transcription factor peroxisome proliferator-activated receptor γ (PPARγ) structurally responds to ligand binding. We observed a correlation between ligand affinity, function, and receptor conformation for chemically similar ligands but not chemical diverse ligands, revealing a potential limitation of theoretical receptor models. Ligand–receptor interactions, which are ubiquitous in physiology, are described by theoretical models of receptor pharmacology. Structural evidence for graded efficacy receptor conformations predicted by receptor theory has been limited but is critical to fully validate theoretical models. We applied quantitative structure–function approaches to characterize the effects of structurally similar and structurally diverse agonists on the conformational ensemble of nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). For all ligands, agonist functional efficacy is correlated to a shift in the conformational ensemble equilibrium from a ground state toward an active state, which is detected by NMR spectroscopy but not observed in crystal structures. For the structurally similar ligands, ligand potency and affinity are also correlated to efficacy and conformation, indicating ligand residence times among related analogs may influence receptor conformation and function. Our results derived from quantitative graded activity–conformation correlations provide experimental evidence and a platform with which to extend and test theoretical models of receptor pharmacology to more accurately describe and predict ligand-dependent receptor activity.
Are Causal Beliefs Associated With Stigma? A Test of the Impact of Biogenetic Versus Psychosocial Explanations on Stigma and Internalized Stigma in People Experiencing Psychosis

Individuals with psychosis are often subject to external stigma and discrimination and commonly also experience internalized stigma. Attempts to improve attitudes have tended to medicalize the experiences associated with psychosis; however, research increasingly indicates an association between biogenetic attitudes and stigma. This study aims to evaluate this approach by investigating the impact of two different etiological explanations on both internalized and external stigma in people experiencing psychosis. A total of 60 participants who have a diagnosis of schizophrenia or meet criteria for early intervention services for psychosis were randomly allocated to one of two conditions (psychosocial vs. biogenetic). Attitudes were assessed before and after the intervention. Both interventions resulted in a decrease in internalized stigma. Only the psychosocial intervention decreased external stigma. Although further research is necessary, providing education to individuals could be an effective way to reduce internal stigma. Antistigma campaigns should avoid a singular focus on biogenetic explanations of psychosis, and a psychosocial viewpoint may be a suitable alternative.
Children’s cognitive responses to constructive television news

Given the importance of news in preparing children for their role as active citizens in society, insight into how negative news can be delivered to children most optimally is warranted. In this regard, this study examined the usefulness of constructive news reporting (i.e. solution-based news stories including positive emotions). An experiment (N = 281 children, 9–13 years old) was conducted to investigate how constructive, compared to nonconstructive, news reporting affected recall of television news, and whether negative emotions elicited by this news mediated this relation. Analyses of covariance revealed that children in the constructive condition displayed a lower recall of the general information about the event. In contrast, their recall of constructive stories was better compared to the recall of comparable, but nonconstructive, stories by children in the nonconstructive condition. Fear and sadness elicited by the news did not mediate the relation between news reporting style and recall. Instead, constructive reporting directly induced smaller increases in fear and sadness than nonconstructive reporting. To conclude, the negative aspects of the news event were less prominently available in memory of children exposed to constructive news.
Discount or Premium? Diversification, Firm Value, and Capital Budgeting Efficiency

We model the internal capital market of a conglomerate where headquarters must rely on information reported by division managers to allocate limited resources across competing projects. Managers may exaggerate project quality to attract more capital, which limits the extent of winner-picking in capital budgeting. Focus (correlated projects) helps headquarters to infer information regarding project quality but makes winner-picking less crucial, whereas diversication (distinct projects) facilitates winner-picking but reduces managers’ incentive to report truthfully. We characterize conditions under which diversication improves and destroys rm value, and show that neither allocation eciency nor rm value varies with the degree of
Deep Sequencing of Small RNAs in Tomato for Virus and Viroid Identification and Strain Differentiation

Small RNAs (sRNA), including microRNAs (miRNA) and small interfering RNAs (siRNA), are produced abundantly in plants and animals and function in regulating gene expression or in defense against virus or viroid infection. Analysis of siRNA profiles upon virus infection in plant may allow for virus identification, strain differentiation, and de novo assembly of virus genomes. In the present study, four suspected virus-infected tomato samples collected in the U.S. and Mexico were used for sRNA library construction and deep sequencing. Each library generated between 5–7 million sRNA reads, of which more than 90% were from the tomato genome. Upon in-silico subtraction of the tomato sRNAs, the remaining highly enriched, virus-like siRNA pools were assembled with or without reference virus or viroid genomes. A complete genome was assembled for Potato spindle tuber viroid (PSTVd) using siRNA alone. In addition, a near complete virus genome (98%) also was assembled for Pepino mosaic virus (PepMV). A common mixed infection of two strains of PepMV (EU and US1), which shared 82% of genome nucleotide sequence identity, also could be differentially assembled into their respective genomes. Using de novo assembly, a novel potyvirus with less than 60% overall genome nucleotide sequence identity to other known viruses was discovered and its full genome sequence obtained. Taken together, these data suggest that the sRNA deep sequencing technology will likely become an efficient and powerful generic tool for virus identification in plants and animals.
Scaling theory of the Kondo screening cloud.

A scaling form for the local susceptibility, derived from renormalization group arguments, is proposed. The scale over which the uniform part of this scaling form varies can be viewed as a definition of the Kondo ``screening cloud" $\sim \xi_K$. The proposed scaling form interpolates between Ruderman-Kittel-Kasuya-Yosida (RKKY) results in the high temperature limit, $T\gg T_K$, and Fermi liquid results in the low temperature, long-distance limit, $T\ll T_K$, $r\gg \xi_K$. The predicted form of the Knight shift is longer range at low temperatures where the screening cloud has formed, than at high temperatures where it has not. Using weak and strong coupling perturbation theory combined with large scale density matrix renormalization group (DMRG) results we study the validity of the finite size version of the scaling form at $T=0$. We explicitly extract a length scale proportional to the Kondo length scale, $\xi_K$. The numerical results are in good agreement with the proposed scaling form and confirm the existence of the Kondo screening cloud.
Identification of Novel Equine (Equus caballus) Tendon Markers Using RNA Sequencing

Although several tendon-selective genes exist, they are also expressed in other musculoskeletal tissues. As cell and tissue engineering is reliant on specific molecular markers to discriminate between cell types, tendon-specific genes need to be identified. In order to accomplish this, we have used RNA sequencing (RNA-seq) to compare gene expression between tendon, bone, cartilage and ligament from horses. We identified several tendon-selective gene markers, and established eyes absent homolog 2 (EYA2) and a G-protein regulated inducer of neurite outgrowth 3 (GPRIN3) as specific tendon markers using RT-qPCR. Equine tendon cells cultured as three-dimensional spheroids expressed significantly greater levels of EYA2 than GPRIN3, and stained positively for EYA2 using immunohistochemistry. EYA2 was also found in fibroblast-like cells within the tendon tissue matrix and in cells localized to the vascular endothelium. In summary, we have identified EYA2 and GPRIN3 as specific molecular markers of equine tendon as compared to bone, cartilage and ligament, and provide evidence for the use of EYA2 as an additional marker for tendon cells in vitro.
Interval Estimation for Small Area Proportions with Small True Proportions from Stratified Random Sampling Survey Data y

Consider interval estimation ofm small area proportionsPi (i = 1; ;m), where we assume a stratified random sampling design with equal number of observationsn in each stratum, and where the domains of interest are the strata. A 100(1 )% confidence interval for Pi that has appeared repeatedly in the literature and is used in application is given by ^ P EB i z= 2 p msei; where ^
Interface design for older adults

As computers become available in more places and situations, particularly with increased use of the Web to disseminate information, it becomes increasingly necessary for older adults, and by this I mean people over 70, to gain access.This paper investigates the factors that seem to inhibit Web use by older adults, and explores aspects of human-computer interface design, which accommodate older users with age-associated disabilities. These disabilities typically include memory impairment, and cognitive and visual impairment, all of which vary from day to day and over longer time periods within an individual. Memory and good sight are crucial for using today's Graphical User Interfaces (GUIs) with small buttons, multitasking windows and the requirement to build strategies at the interface in order to complete tasks.This paper draws upon the author's experience in designing a Web browser for visually impaired user's called BrookesTalk, which was subsequently customised for older adults with memory loss. It also shows the need for Design for Dynamic Diversity (DDD), an interface design approach, which accommodates design issues which come about as a result of changing user requirements related to older users' changing abilities.
Bounding the Hubble flow in terms of the w parameter

The last decade has seen increasing efforts to circumscribe and bound the cosmological Hubble flow in terms of model-independent constraints on the cosmological fluid—for instance, the classical energy conditions of general relativity. Quite a bit can certainly be said in this regard, but much more refined bounds can be obtained by placing more precise constraints (either theoretical or observational) on the cosmological fluid. In particular, the use of the w parameter (w = p/ρ) has become increasingly common as a surrogate for trying to say something about the cosmological equation of state. Herein we explore the extent to which a constraint on the w parameter leads to useful and non-trivial constraints on the Hubble flow, in terms of constraints on density ρ(z), Hubble parameter H(z), density parameter Ω(z), cosmological distances d(z), and lookback time T(z). In contrast to the case for other partial results in the literature, the computations here are carried out for arbitrary values of the space curvature , or equivalently for arbitrary .
The Distribution and the Fibrotic Role of Elevated Inflammatory Th17 Cells in Patients With Primary Biliary Cirrhosis

AbstractT helper (Th) 17 cells were reported to have the property of proinflammation and profibrosis. We first investigate the levels of Th17 cells in primary biliary cirrhosis (PBC) patients, and then explore their distribution and fibrotic role in the disease.We compared the circulating Th17 and hepatic interleukin (IL)-17-positive cells between patients and healthy controls (HCs) at different disease stages by flow cytometry and immunohistochemistry, respectively. The levels of chemokine (c-c motif) ligand (CCL) 20 were then measured. For exploration of the reason why Th17 cells increased, CD4+CD161+ populations were sorted and cultured with IL-23 and IL-1&bgr; to analyze their proliferation and IL-17 secretions. The serum IL-23 and IL-1&bgr; were tested by enzyme-linked immunosorbent assay. The proliferation and expressions of &agr;-smooth muscle actin and IL-8 of hepatic stellate cells (HSCs) were identified after stimulated by different concentrations of IL-17.Circulating and hepatic Th17 cells were elevated in PBC patients compared with HCs. Early PBC patients presented with more Th17 cells in periphery blood and less in the liver than advanced PBC patients. Accordingly, the levels of both serum and hepatic CCL20 for Th17 cells were higher, especially in those with advanced disease. The progenitor of Th17, CD4+CD161+ cell was increased in PBC. Moreover, the percentage of Th17 cells was positively related with CD4+CD161+ cell. After stimulation with IL-23 and IL-1&bgr; which were improved in PBC patients, CD4+CD161+ cells from PBC patients expressed more IL-17, although their proliferation were not different between 2 groups. IL-17 can promote the proliferation of HSCs at a dose-dependent method, and also increase the IL-8 expression in a dose/time-dependent way. Anti-IL-17 can neutralize the above reactions.CD4+CD161+ cells are a source of increased Th17 in PBC patients. With disease progression, Th17 population decreased in the circulation, accompanied by greater accumulation in the liver, which is regulated by CCL20 in advanced patients. IL-17 may be involved in the process of PBC fibrosis.
Efficient multiplierless channel filters for multi-standard SDR

This paper investigates the design of very low complexity multiplierless linear phase FIR filters for use in the channelizer of multi-standard software defined radios. A technique for reducing the hardware complexity of linear phase FIR digital filters which minimizes the adder depth and the number of adders in the multiplier block is introduced and is used to implement a multistage, multi-standard decimating filter. The design reuses components for different communications standards and is thus ideal for use in systems which support dynamic reconfiguration.
Ethnic diversity and attitudes towards refugees

ABSTRACT The recent surge in refugee arrivals to Europe has underscored the importance of identity concerns, with politicians and ordinary citizens alike expressing fear that admitting foreigners may result in unacceptable demographic and cultural change. However, scholars have not systematically examined the impact of ethnic diversity on attitudes towards refugees. Group threat theory and the contact hypothesis offer competing predictions: The former would expect diversity to be associated with opposition to refugees, while the latter would expect diversity to generate support for them. We explore individual-level attitudes in nineteen countries using the 2014 wave of the European Social Survey, combined with country-level data from the World Bank’s World Development Indicators, the Manifesto Project Dataset, and five different databases of ethnic diversity measures. Crucially, we employ multiple approaches to measuring diversity, including various measures of ethnic fractionalisation, linguistic heterogeneity, polarisation, and other relevant constructs. We find that greater ethnic diversity is associated with decreased support for refugees, but this relationship is not consistent across all measures of diversity. Since the relationship between ethnic diversity and support for refugees is highly dependent on the measure of diversity used, scholars should be wary of drawing strong conclusions about the effects of ethnic diversity without comparing different measures.
BOND BEHAVIOUR OF RIBBED BARS AT INELASTIC STEEL STRAINS

A method for electrically interconnecting a laminated printed circuit structure comprises the steps of inserting a solder-plated connecting conductor pin into a through hole bored through overlying interconnecting sections of the respective printed circuit sheets, applying pressure to both ends of the pin to compress and thicken the pin, and passing an electric current through the pin to solder the pin and the respective interconnecting sections to one another at the inner peripheral surface of the through hole.
What is up? Parental Whatsapp discussion groups in diverse educational settings in Israel

ABSTRACT We explore and characterize the use of WhatsApp group instant messaging as part of the social media trend in the context of parental engagement and participation in public schooling. We reveal how this platform is utilized within public school parental interactions, emphasizing the possible benefits as well as obstacles for such technologies in promoting parental engagement in diverse settings in Israel. Given the abundance of literature dealing with parental involvement in education in various cultural and socio-economic contexts, we propose a fresh outlook regarding one specific kind of such involvement through a social media platform, offering a novel methodology and proposing a new avenue of study for additional research in other contexts.
Triatoma maculata colonises urban domicilies in Boa Vista, Roraima, Brazil

During a medical entomology course in Boa Vista, Roraima, colonies of Triatoma maculata closely associated with pigeon nests were observed in concrete air-conditioner box located on the external plastered and cemented walls of a modern brick-built apartment block. In only one eight-hole ceramic brick, located inside one air-conditioner box, 127 specimens of T. maculata were collected. T. maculata is a recognised vector of Trypanosoma cruzi in the surrounding area and its domiciliation increases the risk of Chagas disease transmission.
An Extension of XQuery for Graph Analysis of Biological Pathways

The vast quantity of scientific data produced in life sciences demands the use of sophisticated storage and analysis techniques. In particular, for biological pathways graph analysis plays an important role and data is commonly available in XML-based formats. Thus, there is a growing need to make analysis capabilities available through query languages for XML. This paper presents an approach to extend XQuery for graph analysis with focus on data for biological pathways. A graph model is introduced within the XQuery environment. New built-in functions define the available operations on the graph model. XQuery expressions can be utilized to populate graphs with data and execute graph algorithms. Graph data and results of algorithms can be accessed in an XML representation for further processing. In addition, a reference mechanism can be used to preserve associations from graph data to the original XML data. The approach has been implemented as an extension to exist. First evaluations of the implementation show that the introduced approach is practical and efficient for reaction networks with several thousand vertices and edges.
Bilirubin, Renal Hemodynamics, and Blood Pressure

Bilirubin is generated from the breakdown of heme by heme oxygenase and the reduction of biliverdin by the enzyme biliverdin reductase. Several large population studies have reported a significant inverse correlation between plasma bilirubin levels and the incidence of cardiovascular disease. Protection from cardiovascular disease is also observed in patients with Gilbert’s syndrome which is a disease characterized by mutations in hepatic UGT1A1, the enzyme responsible for the conjugation of bilirubin into the bile. Despite the strong correlation between plasma bilirubin levels and the protection from cardiovascular disease, the mechanism by which increases in plasma bilirubin acts to protect against cardiovascular disease is unknown. Since the chronic antihypertensive actions of bilirubin are likely due to its renal actions, the effects of moderate increases in plasma bilirubin on renal hemodynamics as well as bilirubin’s potential effects on renal tubule function will be discussed in this review. Mechanisms of action as well as the potential for antihypertensive therapies targeting moderate increases in plasma bilirubin levels will also be highlighted.
Anemia in Heart Failure Patients

Heart failure is a very common disease, with severe morbidity and mortality, and a frequent reason of hospitalization. Anemia and a concurrent renal impairment are two major risk factors contributing to the severity of the outcome and consist of the cardio renal anemia syndrome. Anemia in heart failure is complex and multifactorial. Hemodilution, absolute or functional iron deficiency, activation of the inflammatory cascade, and impaired erythropoietin production and activity are some pathophysiological mechanisms involved in anemia of the heart failure. Furthermore other concomitant causes of anemia, such as myelodysplastic syndrome and chemotherapy, may worsen the outcome. Based on the pathophysiology of cardiac anemia, there are several therapeutic options that may improve hemoglobin levels, tissues' oxygenation, and probably the outcome. These include administration of iron, erythropoiesis-stimulating agents, and blood transfusions but still the evidence provided for their use remains limited.