Miracle-dz/UniFAR-FTUs huggingface dataset:
Embolisation of pulmonary arteriovenous malformations: results and follow up in 32 patients.

BACKGROUND--Pulmonary arteriovenous malformations may cause a number of complications when left untreated. Embolisation of the feeding vessels is a relatively new approach and information concerning its efficacy and long term results is scarce. METHODS--Pulmonary arteriovenous malformations with feeding arteries of > 3 mm were treated by embolisation. Right to left shunt fraction and arterial oxygen pressure breathing air (PaO2) were measured before and after treatment. Six monthly measurement of shunt fraction was used for follow up. RESULTS--In 32 patients 92 pulmonary arteriovenous malformations were treated by coil embolisation. Mean shunt fraction decreased from 16.6% to 7.4% and PaO2 increased from 9.6 kPa to 11.5 kPa. Treatment was incomplete in two patients, one of whom was subsequently treated surgically. Serious complications occurred in one patient. Recanalisation of embolised vessels occurred in two cases after 22 and 28 months, respectively. Mean period of follow up was 25 months. CONCLUSIONS--Embolisation is a safe and efficacious treatment for most pulmonary arteriovenous malformations. Long term studies are necessary to determine the risk of recanalisation.
Molecular Mechanism for Divergent Regulation of Cav1.2 Ca2+ Channels by Calmodulin and Ca2+-binding Protein-1*

Ca2+-binding protein-1 (CaBP1) and calmodulin (CaM) are highly related Ca2+-binding proteins that directly interact with, and yet differentially regulate, voltage-gated Ca2+ channels. Whereas CaM enhances inactivation of Ca2+ currents through Cav1.2 (L-type) Ca2+ channels, CaBP1 completely prevents this process. How CaBP1 and CaM mediate such opposing effects on Cav1.2 inactivation is unknown. Here, we identified molecular determinants in the α1-subunit of Cav1.2 (α11.2) that distinguish the effects of CaBP1 and CaM on inactivation. Although both proteins bind to a well characterized IQ-domain in the cytoplasmic C-terminal domain of α11. 2, mutations of the IQ-domain that significantly weakened CaM and CaBP1 binding abolished the functional effects of CaM, but not CaBP1. Pulldown binding assays revealed Ca2+-independent binding of CaBP1 to the N-terminal domain (NT) of α11. 2, which was in contrast to Ca2+-dependent binding of CaM to this region. Deletion of the NT abolished the effects of CaBP1 in prolonging Cav1.2 Ca2+ currents, but spared Ca2+-dependent inactivation due to CaM. We conclude that the NT and IQ-domains of α11. 2 mediate functionally distinct interactions with CaBP1 and CaM that promote conformational alterations that either stabilize or inhibit inactivation of Cav1.2.
PERSONALITY PROCESSES AND INDIVIDUAL DIFFERENCES Double Dissociation Between Implicit and Explicit Personality Self-Concept: The Case of Shy Behavior

Using the trait of shyness as an example, the authors showed that (a) it is possible to reliably assess individual differences in the implicitly measured self-concept of personality that (b) are not accessible through traditional explicit self-ratings and (c) increase significantly the prediction of spontaneous behavior in realistic social situations. A total of 139 participants were observed in a shyness-inducing laboratory situation, and they completed an Implicit Association Test (IAT) and explicit self-ratings of shyness. The IAT correlated moderately with the explicit self-ratings and uniquely predicted spontaneous (but not controlled) shy behavior, whereas the explicit ratings uniquely predicted controlled (but not spontaneous) shy behavior (double dissociation). The distinction between spontaneous and controlled behavior was validated in a 2nd study.
Combining Cationic Liposomal Delivery with MPL-TDM for Cysteine Protease Cocktail Vaccination against Leishmania donovani : Evidence for Antigen Synergy and Protection

Background With the paucity of new drugs and HIV co-infection, vaccination remains an unmet research priority to combat visceral leishmaniasis (VL) requiring strong cellular immunity. Protein vaccination often suffers from low immunogenicity and poor generation of memory T cells for long-lasting protection. Cysteine proteases (CPs) are immunogenic proteins and key mediators of cellular functions in Leishmania. Here, we evaluated the vaccine efficacies of CPs against VL, using cationic liposomes with Toll like receptor agonists for stimulating host immunity against L. donovani in a hamster model. Methodology/Principal Findings Recombinant CPs type I (cpb), II (cpa) and III (cpc) of L. donovani were tested singly and in combination as a triple antigen cocktail for antileishmanial vaccination in hamsters. We found the antigens to be highly immunoreactive and persistent anti-CPA, anti-CPB and anti-CPC antibodies were detected in VL patients even after cure. The liposome-entrapped CPs with monophosphoryl lipid A-Trehalose dicorynomycolate (MPL-TDM) induced significantly high nitric oxide (up to 4 fold higher than controls) mediated antileishmanial activity in vitro, and resulted in strong in vivo protection. Among the three CPs, CPC emerged as the most potent vaccine candidate in combating the disease. Interestingly, a synergistic increase in protection was observed with liposomal CPA, CPB and CPC antigenic cocktail which reduced the organ parasite burden by 1013–1016 folds, and increased the disease-free survival of >80% animals at least up to 6 months post infection. Robust secretion of IFN-γ and IL-12, along with concomitant downregulation of Th2 cytokines, was observed in cocktail vaccinates, even after 3 months post infection. Conclusion/Significance The present study is the first report of a comparative efficacy of leishmanial CPs and their cocktail using liposomal formulation with MPL-TDM against L. donovani. The level of protection attained has not been reported for any other subcutaneous single or polyprotein vaccination against VL.
Molecular Recognition of H3/H4 Histone Tails by the Tudor Domains of JMJD2A: A Comparative Molecular Dynamics Simulations Study

Background Histone demethylase, JMJD2A, specifically recognizes and binds to methylated lysine residues at histone H3 and H4 tails (especially trimethylated H3K4 (H3K4me3), trimethylated H3K9 (H3K9me3) and di,trimethylated H4K20 (H4K20me2, H4K20me3)) via its tandem tudor domains. Crystal structures of JMJD2A-tudor binding to H3K4me3 and H4K20me3 peptides are available whereas the others are not. Complete picture of the recognition of the four histone peptides by the tandem tudor domains yet remains to be clarified. Methodology/Principal Findings We report a detailed molecular dynamics simulation and binding energy analysis of the recognition of JMJD2A-tudor with four different histone tails. 25 ns fully unrestrained molecular dynamics simulations are carried out for each of the bound and free structures. We investigate the important hydrogen bonds and electrostatic interactions between the tudor domains and the peptide molecules and identify the critical residues that stabilize the complexes. Our binding free energy calculations show that H4K20me2 and H3K9me3 peptides have the highest and lowest affinity to JMJD2A-tudor, respectively. We also show that H4K20me2 peptide adopts the same binding mode with H4K20me3 peptide, and H3K9me3 peptide adopts the same binding mode with H3K4me3 peptide. Decomposition of the enthalpic and the entropic contributions to the binding free energies indicate that the recognition of the histone peptides is mainly driven by favourable van der Waals interactions. Residue decomposition of the binding free energies with backbone and side chain contributions as well as their energetic constituents identify the hotspots in the binding interface of the structures. Conclusion Energetic investigations of the four complexes suggest that many of the residues involved in the interactions are common. However, we found two receptor residues that were related to selective binding of the H3 and H4 ligands. Modifications or mutations on one of these residues can selectively alter the recognition of the H3 tails or the H4 tails.
Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study

Objective To determine the comparative effectiveness of exercise versus drug interventions on mortality outcomes. Design Metaepidemiological study. Eligibility criteria Meta-analyses of randomised controlled trials with mortality outcomes comparing the effectiveness of exercise and drug interventions with each other or with control (placebo or usual care). Data sources Medline and Cochrane Database of Systematic Reviews, May 2013. Main outcome measure Mortality. Data synthesis We combined study level death outcomes from exercise and drug trials using random effects network meta-analysis. Results We included 16 (four exercise and 12 drug) meta-analyses. Incorporating an additional three recent exercise trials, our review collectively included 305 randomised controlled trials with 339 274 participants. Across all four conditions with evidence on the effectiveness of exercise on mortality outcomes (secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure, prevention of diabetes), 14 716 participants were randomised to physical activity interventions in 57 trials. No statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. Physical activity interventions were more effective than drug treatment among patients with stroke (odds ratios, exercise v anticoagulants 0.09, 95% credible intervals 0.01 to 0.70 and exercise v antiplatelets 0.10, 0.01 to 0.62). Diuretics were more effective than exercise in heart failure (exercise v diuretics 4.11, 1.17 to 24.76). Inconsistency between direct and indirect comparisons was not significant. Conclusions Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.
Long-Distance Time-Event Relation Extraction

This paper proposes state-of-the-art models for time-event relation extraction (TERE). The models are specifically designed to work effectively with relations that span multiple sentences and paragraphs, i.e., inter-sentence TERE. Our main idea is: (i) to build a computational representation of the context of the two target relation arguments, and (ii) to encode it as structural features in Support Vector Machines using tree kernels. Results on two data sets – Machine Reading and TimeBank – with 3-fold crossvalidation show that the combination of traditional feature vectors and the new structural features improves on the state of the art for inter-sentence TERE by about 20%, achieving a 30.2 F1 score on intersentence TERE alone, and 47.2 F1 for all TERE (inter and intra sentence combined).
Mountain Terrain Atmospheric Modeling and Observations (MATERHORN) Program

Abstract : The prediction of weather in complex terrain is a difficult challenge due to a host of physical and thermodynamic processes and numerical issues involved. While many theoretical and observational studies have been conducted on flow over gradually varying low slopes (hills), flow over high mountains with steep slopes of practical consequence under diurnal forcing still remains an understudied topic. The atmospheric boundary layer therein is forced by diurnal thermal forcing(valley and slope flows), large-scale synoptic influence or a combination thereof, and in all cases the boundary layer is replete With interesting sub-grid scale phenomena that are paramount for mesoscale modeling.
Consistency of Brief Psychiatric Rating Scale Factor Structure across a Broad Spectrum of Schizophrenia Patients

Background: The Brief Psychiatric Rating Scale (BPRS) has been the workhorse of psychopathology assessment in studies of schizophrenia and related psychotic disorders for over 40 years. Our goal was to evaluate the discriminant validity of the BPRS across the broad spectrum of persons with schizophrenia. Sampling and Methods: The total sample of 565 subjects with schizophrenia (84%) or schizoaffective disorder (16%) came from eight separate studies conducted under the aegis of the UCLA Clinical Research Center for Schizophrenia and Psychiatric Rehabilitation over a period of 15 years. The total sample could be divided into three subsamples based on illness chronicity and degree of refractoriness to treatment: Recent-onset patients had been ill for less than 2 years (n = 178), stable chronic patients between 2 and 19 years (n = 243) and treatment-refractory patients for more than 19 years (n = 144). Exploratory principal components analysis and varimax rotation were performed on the total sample. The results of each of the three subsamples were compared to the total sample using a correlation matrix and by calculating a coefficient of congruence. Results: A 4-factor solution was considered the most interpretable for each subsample, reflecting the same 4 components identified in the total sample: positive symptoms, negative symptoms, agitation-mania and depression-anxiety. Correlation coefficients and coefficient of congruence were very high, ranging from 0.91 to 0.98. Conclusions: The consistency of the 4-factor solution of the 24-item BPRS across the range of subjects, from first psychotic episode to long-stay, institutionalized patients, supports the use of these factors and this instrument as a whole to track changes over time and with treatment in research and clinical samples.
What are the Problem Makers: Ranking Activities According to their Relevance for Process Changes

Recently, a new generation of adaptive process management technology has emerged, which enables dynamic changes of composite services and process models respectively. This, in turn, results in a large number of process variants derived from the same process model, but differing in structure due to the applied changes. Since such process variants are expensive to maintain, the process model should be evolved accordingly. In this context, we need to know which activities have been more often involved in process adaptations than others, such that we can focus on them when reconfiguring the process model. This paper provides two approaches for ranking activities according to their involvement in process adaptations. The first one allows to precisely rank the activities, but is expensive to perform since the algorithm is at NP level. We therefore provide as alternative an approximation ranking algorithm which computes in polynomial time. The performance of the approximation algorithm is evaluated and compared through a simulation of 3600 process models. Statistical significance tests indicate that the performance of the approximation ranking algorithm does not depend on the size of process models, i.e., our algorithm can scale up.
Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner

Th17 cells and Foxp3+ regulatory T cells (Tregs) are thought to promote and suppress inflammatory responses, respectively. However, whether they counteract each other or synergize in regulating immune reactions remains controversial. To determine their interactions, we describe the results of experiments employing mouse models of intestinal inflammation by transferring antigen-specific Th cells (Th1, Th2, and Th17) differentiated in vitro followed by the administration of the cognate antigen via enema. We show that cotransfer of induced Tregs (iTregs) suppressed Th1- and Th2-mediated colon inflammation. In contrast, colon inflammation induced by transfer of Th17 cells, was augmented by the cotransfer of iTregs. Furthermore, oral delivery of antigen potentiated Th17-mediated colon inflammation. Administration of a blocking antibody against cytotoxic T lymphocyte-associated antigen 4 (CTLA4) abrogated the effects of cotransfer of iTregs, while the injection of a soluble recombinant immunoglobulin (Ig) fusion protein, CTLA4-Ig substituted for the cotransfer of iTregs. These results suggest that antigen-specific activation of iTregs in a local environment stimulates the Th17-mediated inflammatory response in a CTLA4-dependent manner.
SNPeffect 4.0: on-line prediction of molecular and structural effects of protein-coding variants

Single nucleotide variants (SNVs) are, together with copy number variation, the primary source of variation in the human genome and are associated with phenotypic variation such as altered response to drug treatment and susceptibility to disease. Linking structural effects of non-synonymous SNVs to functional outcomes is a major issue in structural bioinformatics. The SNPeffect database (http://snpeffect.switchlab.org) uses sequence- and structure-based bioinformatics tools to predict the effect of protein-coding SNVs on the structural phenotype of proteins. It integrates aggregation prediction (TANGO), amyloid prediction (WALTZ), chaperone-binding prediction (LIMBO) and protein stability analysis (FoldX) for structural phenotyping. Additionally, SNPeffect holds information on affected catalytic sites and a number of post-translational modifications. The database contains all known human protein variants from UniProt, but users can now also submit custom protein variants for a SNPeffect analysis, including automated structure modeling. The new meta-analysis application allows plotting correlations between phenotypic features for a user-selected set of variants.
Hypopharyngeal Squamous Cell Carcinoma: Treatment Results in 138 Consecutively Admitted Patients

The aim of this study was to evaluate the results of the initial and salvage treatment for hypopharyngeal carcinoma. The study was conducted in 1963 to 1991and included 138 patients (38 females (28%) and 100 males (73%)). Most of the tumours originated in the piriform sinus (86%). Tumour stage distribution was T1: 20%, T2: 27%, T3: 37% and T4: 17% and nodal stage distribution was N0: 45%, N1: 25%, N2: 10%, and N3: 20%. Primary treatment was delivered with curative intent in 124 out of 138 cases (90%). Treatment failure was noted in 98 patients, with 55% recurrence in T-position, 39% in N-position, and 14% at distant metastases sites. Salvage surgery was successful in 9 out of 32 patients. The overall 5-year locoregional tumour control, cause-specific and overall survival rates were 20%, 25% and 19%, respectively. Univariate actuarial analysis showed that T- and N-stage, clinical stage, tumour size and well-differentiated tumours were significant prognostic parameters. A Cox multivariate analysis showed that only the T- and N-stages were independent prognostic factors. In conclusion, the prognosis for advanced hypopharyngeal carcinoma is extremely poor and the meagre results with conventional radiotherapy alone indicate that other treatment modalities should be introduced in the management of this disease.
A Path Model of Effective Technology-Intensive Inquiry-Based Learning

Individual aptitude, attitudes, and behavior in inquiry-based learning (IBL) settings may affect work and learning performance outcomes during activities using different technologies. To encourage multifaceted learning, factors in IBL settings must be statistically significant and effective, and not cognitively or psychomotor intensive. We addressed these questions in a study of 421 students from 11 Slovenian middle schools using an experimental design. Learning achievements were measured by pre- and post-test, while IBL experiences and perceptions were surveyed in a one-shot study. IBL and its effects were successfully measured with a reliable technological literacy test. We designed a path model to capture the effects from multiple interferers. Course content was the most decisive influential factor, with strong impacts on learning achievements, satisfaction, and perceived course intensity. Prior knowledge and capacity, which affects IBL and decreases its psychomotor intensity, was a surprisingly strong influence. IBL had a large, positive effect on technological knowledge and the development of problem solving, critical thinking, and decision-making abilities. The study findings showed that the proposed IBL model is an effective teaching approach in technology-intensive education.
Tidal marshes as a source of optically and chemically distinctive colored dissolved organic matter in the Chesapeake Bay

The role of tidal marshes as a source of dissolved organic carbon (DOC) and colored dissolved organic matter (CDOM) for adjacent estuarine waters was studied in the Rhode River subestuary of the Chesapeake Bay. Water in a tidal creek draining brackish, high‐elevation marshes was sampled every hour during several semidiurnal tidal cycles in order to examine the tidal exchange of dissolved organic matter (DOM). Water leaving the marsh during ebbing tide was consistently enriched in DOC compared to water entering the marsh during flooding tide. There was a net DOC export from the marsh to the estuary during seasons of both low and high marsh plant biomass. Optical analysis demonstrated that, in addition to contributing to the carbon budgets, the marsh had a strong influence on the estuary’s CDOM dynamics. Marsh‐exported CDOM had optical properties that were consistently and markedly different from those of CDOM in the adjacent estuary. Specifically, marsh CDOM had: (1) considerably stronger absorption, (2) larger DOC‐specific absorption, (3) lower exponential spectral slope, (4) larger fluorescence signal, (5) lower fluorescence per unit absorbance, and (6) higher fluorescence at wavelengths >400 nm. These optical characteristics are indicative of relatively complex, high‐molecular‐weight, aromatic‐rich DOM, and this was confirmed by results of molecular‐weight‐distribution analysis. Our findings illustrate the importance of tidal marshes as sources of optically and chemically distinctive dissolved organic compounds, and their influence on CDOM dynamics, DOC budgets, and, thus, photochemical and biogeochemical processes, in adjacent estuarine ecosystems.
Highest Trees of Random Mappings

We prove the exact asymptotic $1-\left({\frac{2\pi}{3}-\frac{827}{288\pi}}+o(1)\right)/{\sqrt{n}}$ for the probability that the underlying graph of a random mapping of $n$ elements possesses a unique highest tree. The property of having a unique highest tree turned out to be crucial in the solution of the famous Road Coloring Problem as well as the generalization of this property in the proof of the author's result about the probability of being synchronizable for a random automaton.