Miracle-dz/UniFAR-FTUs huggingface dataset:
Function of immunoglobulin A in immunity

Immunoglobulin A (IgA) is by far the most abundant immunoglobulin in humans.1 It is also the most heterogeneous. Serum IgA is mainly monomeric. It is produced by B lymphocytes in the bone marrow and in some lymphoid organs. Humans produce as much serum IgA as they do IgG. Most of the IgA in mammals is, however, found in mucosal secretions. Secretory IgA is dimeric or polymeric IgA associated with J chain and with secretory component, a part of the receptor involved in the secretion process. Recent research2 has suggested that secretory IgA in the gut comes from two sources. Approximately 75% is from B2 lymphocytes in organised germinal centres of mucosal lymphoid tissues such as Peyer's patches. This IgA production is T lymphocyte dependent. A second source, possibly contributing around 25% of the secretory IgA, is produced by B1 lymphocytes that develop in the peritoneal cavity and are distributed diffusely in the intestinal lamina propria. This IgA may represent a primitive T lymphocyte independent source of IgA recognising commensal bacteria. Given the abundance and complexity of IgA, it is difficult to envisage that it does not perform important functions in health and disease. Identification and characterisation of a leucocyte Fc receptor for IgA (FcαR, CD89) present on neutrophils, eosinophils, and monocytes demonstrated an active role for IgA in …
Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence

Purpose To identify the barriers to, and facilitators of, the implementation of physiological track and trigger systems (PTTSs), perceived by healthcare workers, through a systematic review of the extant qualitative literature. Data sources Searches were performed in PUBMED, CINAHL, PsycInfo, Embase and Web of Science. The reference lists of included studies were also screened. Study selection The electronic searches yielded 2727 papers. After removing duplicates, and further screening, a total of 10 papers were determined to meet the inclusion criteria and were reviewed. Data extraction A deductive content analysis approach was taken to organizing and analysing the data. A framework consisting of two overarching dimensions ('User-related changes required to implement PTTSs effectively' and 'Factors that affect user-related changes'), 5 themes (staff perceptions of PTTSs and patient safety, workflow adjustment, PTTS, implementation process and local context) and 14 sub themes was used to classify the barriers and facilitators to the implementation of PTTSs. Results of data synthesis Successful implementation of a PTTS must address the social context in which it is to be implemented by ensuring that the users believe that the system is effective and benefits patient care. The users must feel invested in the PTTS and its use must be supported by training to ensure that all healthcare workers, senior and junior, understand their role in using the system. Conclusion PTTSs can improve patient safety and quality of care. However, there is a need for a robust implementation strategy or the benefits of PTTSs will not be realized.
Activation of cJUN N-Terminal Kinase by Herpes Simplex Virus Type 1 Enhances Viral Replication

ABSTRACT Signal transduction pathways convey signals generated at the cell surface into the cell nucleus in order to initiate a program of gene expression that is characteristic for particular stimuli. Here we present evidence that infection by herpes simplex virus type 1 activated the two terminal kinases, cJUN N-terminal kinase (JNK) and p38, of stress-activated signal transduction kinase cascades. By using a solid-phase kinase assay, a phospho-specific antibody, and extracts prepared from a variety of infected cell types, we determined that activation of both kinases began 3 to 4 h postinfection (p.i.) and remained elevated out to 14 h p.i. Through the use of UV-irradiated or antibody-neutralized wild-type virus and the temperature-sensitive mutant tsB7, the high level of JNK activation was shown to be dependent on viral gene expression. Activation of JNK following infection by vi13, an ICP4 mutant virus that does not express early or late genes, suggested that only virus entry and immediate-early gene expression were necessary for JNK activation. The activation of JNK and p38 correlated with increased chloramphenicol acetyltransferase (CAT) activity in reporter assays dependent upon the activity of cJUN and ATF2trans-activation domains. Increased CAT activity dependent on TRE and CRE promoter sites was also observed in response to herpes simplex virus infection. The activities of ERK and ERK-dependent transcription factors were unchanged or depressed following infection, showing that activation of JNK and p38 was a specific event. Finally, the activation of JNK was important for the efficiency of viral replication. The yield of virus in NIH 3T3 cells stably expressing JIP-1, an inhibitor of JNK translocation to the nucleus, was reduced 70% compared to that of control cells, in single-step growth experiments.
The Situational Eight DIAMONDS : A Taxonomy of Major Dimensions of Situation Characteristics

Taxonomies of person characteristics are well developed, whereas taxonomies of psychologically important situation characteristics are underdeveloped. A working model of situation perception implies the existence of taxonomizable dimensions of psychologically meaningful, important, and consequential situation characteristics tied to situation cues, goal affordances, and behavior. Such dimensions are developed and demonstrated in a multi-method set of 6 studies. First, the “Situational Eight DIAMONDS” dimensions Duty, Intellect, Adversity, Mating, pOsitivity, Negativity, Deception, and Sociality (Study 1) are established from the Riverside Situational Q-Sort (Sherman, Nave, & Funder, 2010, 2012, 2013; Wagerman & Funder, 2009). Second, their rater agreement (Study 2) and associations with situation cues and goal/trait affordances (Studies 3 and 4) are examined. Finally, the usefulness of these dimensions is demonstrated by examining their predictive power of behavior (Study 5), particularly vis-à-vis measures of personality and situations (Study 6). Together, we provide extensive and compelling evidence that the DIAMONDS taxonomy is useful for organizing major dimensions of situation characteristics. We discuss the DIAMONDS taxonomy in the context of previous taxonomic approaches and sketch future research directions.
Mild-to-moderate functional tricuspid regurgitation in patients undergoing valve replacement for rheumatic mitral disease: the influence of tricuspid valve repair on clinical and echocardiographic outcomes

To the Editor We read with great interest the article by Kim and colleagues.1 First, we would like to congratulate the authors for their study investigating relatively underestimated or neglected valvular disease; mild to moderate functional tricuspid regurgitation (FTR). Although the latest guidelines do not recommend any intervention to this patient population,2 numerous …
A Novel Probabilistic Flooding Strategy for Unstructured Peer-to-Peer Networks

In this work we propose a novel probabilistic flooding strategy for unstructured p2p networks. Our strategy takes into account the popularity of resources and the hop distance from the node that initiated the query. The latter is used to estimate the number of nodes reached by the query message. Based on the above parameters we adjust the forwarding probability at the time a node receives the query message so as to reduce the duplicate message overhead while maintaining a high probability of query success. The primary goal of our approach is to minimize the cost of search associated with excessive message transmissions. The experimental results support our claims and provide insights into the effect of the above parameters to search performance.
Interleukin 10 blocks matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase synthesis in primary human prostate tumor lines.

Insulin-like growth factor (IGF) I has been shown previously to up-regulate matrix metalloproteinase-2 (MMP-2) production, whereas the interleukin (IL) 10/IL-10 receptor axis has been found to down-regulate MMP-2 synthesis in tumor cells. In this paper, we showed that IL-10 activation of the IL-10 receptor blocked MMP-2 and membrane type 1 (MT1) -MMP transcription and protein synthesis in nonimmortalized primary human prostate cell strains (i.e., HPCA-10a and HPCA-10c) derived from high-grade cancer. Northern blots, Western blots, and ELISAs showed that IL-10 suppressed IGF-I induction of MMP-2 and MT1-MMP mRNA synthesis in these cell strains (P < 0.001). Inhibition studies with IL-10 and IGF-I receptor antibodies plus transfections experiments with IL-10 sense, and IGF-I receptor antisense constructs confirmed these results. Finally, transient transfection experiments and chloramphenicol acetyltransferase assays with different regions of the 5' promoter region of the MMP-2 gene (-1659 to -555 bp) additionally showed that IGF-I stimulated p53-dependent plasmid catecholamine acetyltransferase activity and that IL-10 blocked IGF-I-induced plasmid catecholamine acetyltransferase activity. Electrophoretic mobility shift assays revealed that IL-10 induced protein(s) binding to a putative "silencer element" (-1309 to -555 fragment) downstream of the p53 binding site (-1649 to -1640). The data show that IL-10 blocks IGF-I activation of MMP-2 and MT1-MMP mRNA expression and protein synthesis in primary prostate cell strains.
Identifying Common Genetic Variants in Blood Pressure Due to Polygenic Pleiotropy With Associated Phenotypes

Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affected by environmental factors, but has a strong heritable component. Despite recent large genome-wide association studies, few genetic risk factors for blood pressure have been identified. Epidemiological studies suggest associations between blood pressure and several diseases and traits, which may partly arise from a shared genetic basis (genetic pleiotropy). Using genome-wide association studies summary statistics and a genetic pleiotropy-informed conditional false discovery rate method, we systematically investigated genetic overlap between systolic blood pressure (SBP) and 12 comorbid traits and diseases. We found significant enrichment of single nucleotide polymorphisms associated with SBP as a function of their association with body mass index, low-density lipoprotein, waist/hip ratio, schizophrenia, bone mineral density, type 1 diabetes mellitus, and celiac disease. In contrast, the magnitude of enrichment due to shared polygenic effects was smaller with the other phenotypes (triglycerides, high-density lipoproteins, type 2 diabetes mellitus, rheumatoid arthritis, and height). Applying the conditional false discovery rate method to the enriched phenotypes, we identified 62 loci associated with SBP (false discovery rate <0.01), including 42 novel loci. The observed polygenic overlap between SBP and several related disorders indicates that the epidemiological associations are not mediated solely via lifestyle factors but also reflect an etiologic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to lipid biology and the immune system in SBP.
Pheophorbide a Is a Specific Probe for ABCG2 Function and Inhibition

Pheophorbide a (PhA), a chlorophyll catabolite, was shown to be an ABCG2 substrate based on Abcg2−/− knockout mouse studies (J. W. Jonker et al., Proc. Natl. Acad. Sci. USA, 99: 15649–15654, 2002). We developed a functional assay for ABCG2 using PhA and the ABCG2 inhibitor fumitremorgin C. In selected cell lines expressing high levels of P-glycoprotein, multidrug resistance-associated protein 1, or ABCG2, PhA transport was observed only in cells expressing ABCG2. Fumitremorgin C-inhibitable PhA transport was found to correlate with cell surface ABCG2 expression as measured by the anti-ABCG2 antibody 5D3. We found that 100 μm of the cyclin-dependent kinase inhibitor UCN-01 or 1 μm of the P-glycoprotein inhibitor tariquidar inhibited ABCG2-mediated PhA transport. In 4-day cytotoxicity assays, ABCG2-mediated resistance to SN-38 and topotecan was abrogated in ABCG2-transfected HEK-293 cells treated with 1 μm tariquidar, and ABCG2-transfected cells were 6–7-fold resistant to UCN-01. PhA is an ABCG2-specific substrate with potential value in measuring ABCG2 function and expression in clinical samples.
Functionally important glycosyltransferase gain and loss during catarrhine primate emergence

A glycosyltransferase, α1,3galactosyltransferase, catalyzes the terminal step in biosynthesis of Galα1,3Galβ1–4GlcNAc-R (αGal), an oligosaccharide cell surface epitope. This epitope or antigenically similar epitopes are widely distributed among the different forms of life. Although abundant in most mammals, αGal is not normally found in catarrhine primates (Old World monkeys and apes, including humans), all of which produce anti-αGal antibodies from infancy onward. Natural selection favoring enhanced resistance to αGal-positive pathogens has been the primary reason offered to account for the loss of αGal in catarrhines. Here, we question the primacy of this immune defense hypothesis with results that elucidate the evolutionary history of GGTA1 gene and pseudogene loci. One such locus, GGTA1P, a processed (intronless) pseudogene (PPG), is present in platyrrhines, i.e., New World monkeys, and catarrhines but not in prosimians. PPG arose in an early ancestor of anthropoids (catarrhines and platyrrhines), and GGTA1 itself became an unprocessed pseudogene in the late catarrhine stem lineage. Strong purifying selection, denoted by low nonsynonymous substitutions per nonsynonymous site/synonymous substitutions per synonymous site values, preserved GGTA1 in noncatarrhine mammals, indicating that the functional gene product is subjected to considerable physiological constraint. Thus, we propose that a pattern of alternative and/or more beneficial glycosyltransferase activity had to first evolve in the stem catarrhines before GGTA1 inactivation could occur. Enhanced defense against αGal-positive pathogens could then have accelerated the replacement of αGal-positive catarrhines by αGal-negative catarrhines. However, we emphasize that positively selected regulatory changes in sugar chain metabolism might well have contributed in a major way to catarrhine origins.
Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics

Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, “RCaMPs,” engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca2+-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors in vitro and in vivo in Caenorhabditis elegans, Drosophila larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca2+]) and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation via channelrhodopsin-2 (ChR2) or a red-shifted variant, and activity imaging via RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in vivo in crawling C. elegans. We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca2+ affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan, and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics.
Dependence of cloud fraction and cloud top height on surface temperature derived from spectrally resolved UV/vis satellite observations

Cloud climate feedback constitutes the most important uncertainty in climate modelling, and currently even its sign is still unknown. In the recently published report of the intergovernmental panel on climate change (IPCC), from 20 climate models 6 showed a positive and 14 a negative cloud radiative feedback in a doubled CO2 scenario. The radiative budget of clouds has also been investigated by experimental methods, especially by studying the relation of satellite observed broad band shortwave and longwave radiation to sea surface temperature. Here we present a new method for the investigation of the dependence of cloud properties on temperature changes, derived from spectrally resolved UV/vis satellite observations. Our study differs from previous investigations in three important ways: first, we directly extract cloud properties (amount and altitude) and relate them to surface temperature. Second, we retrieve the cloud altitude from the atmospheric O2 absorption instead from thermal IR radiation. Third, our correlation analysis is performed using 7.5 years of global monthly anomalies (with respect to the average of the same month for all years). For most parts of the globe (except the tropics) we find a negative correlation of cloud fraction versus surface-near temperature. In contrast, for the cloud top height a positive correlation is found for almost the whole globe. Both findings might serve as an indicator for an overall positive cloud climate feedback. Another peculiarity of our study is that the cloud-temperature relationships are determined for fixed locations (instead to spatial variations over selected areas) and are based on the "natural" variability over several years (instead the anomaly for a strong El-Nino event). Thus our results might be especially representative for the extrapolation to long term climate changes. Climate models should aim to reproduce our findings: if substantial differences are found, this might indicate that important details are not yet well captured by these models. If good agreement is found, from the models reliable information on the magnitude and the detail mechanisms of cloud climate feedback could be gained.
Assessing learning outcomes and cost effectiveness of an online sleep curriculum for medical students.

OBJECTIVE Sleep disorders are highly prevalent across all age groups but often remain undiagnosed and untreated, resulting in significant health consequences. To overcome an inadequacy of available curricula and learner and instructor time constraints, this study sought to determine if an online sleep medicine curriculum would achieve equivalent learner outcomes when compared with traditional, classroom-based, face-to-face instruction at equivalent costs. METHOD Medical students rotating on a required clinical clerkship received instruction in 4 core clinical sleep-medicine competency domains in 1 of 2 delivery formats: a single 2.5-hour face-to-face workshop or 4 asynchronous e-learning modules. Immediate learning outcomes were assessed in a subsequent clerkship using a multiple-choice examination and standardized patient station, with long-term outcomes assessed through analysis of students' patient write-ups for inclusion of sleep complaints and diagnoses before and after the intervention. Instructional costs by delivery format were tracked. Descriptive and inferential statistical analyses compared learning outcomes and costs by instructional delivery method (face-to-face versus e-learning). RESULTS Face-to-face learners, compared with online learners, were more satisfied with instruction. Learning outcomes (i.e., multiple-choice examination, standardized patient encounter, patient write-up), as measured by short-term and long-term assessments, were roughly equivalent. Design, delivery, and learner-assessment costs by format were equivalent at the end of 1 year, due to higher ongoing teaching costs associated with face-to-face learning offsetting online development and delivery costs. CONCLUSIONS Because short-term and long-term learner performance outcomes were roughly equivalent, based on delivery method, the cost effectiveness of online learning is an economically and educationally viable instruction platform for clinical clerkships.
The Effect of Material Strength on Segment Penetration Behavior

Abstract : The effects of penetrator material strength on the terminal ballistic behavior of tungsten alloy segments fired into armor plate was determined by a series of impact experiments. Three different strength tungsten alloys were machined into cylinders with an aspect ratio of 4 and were subsequently impacted into rolled homogeneous armor at 1.5 km/s. The depth of penetration and the shape of the penetrator material remaining in the penetration cavity were recorded and compared. Decreasing the penetrator material strength was observed to slightly decrease the length of residual material and the depth of penetration. The diameter of the plastically deformed residual material was observed to increase with decreasing penetrator material strength.
On the Correctness Criteria of Fine-Grained Access Control in Relational Databases

Databases are increasingly being used to store information covered by heterogeneous policies, which require support for access control with great flexibility. This has led to increasing interest in using fine-grained access control, where different cells in a relation may be governed by different access control rules. Although several proposals have been made to support fine-grained access control, there currently does not exist a formal notion of correctness regarding the query answering procedure. In this paper, we propose such a formal notion of correctness in fine-grained database access control, and discuss why existing approaches fall short in some circumstances. We then propose a labeling approach for masking unauthorized information and a query evaluation algorithm which better supports fine-grained access control. Finally, we implement our algorithm using query modification and evaluate its performance.