Miracle-dz/UniFAR-FTUs huggingface dataset:
Spliceman2: a computational web server that predicts defects in pre-mRNA splicing

Summary Most pre-mRNA transcripts in eukaryotic cells must undergo splicing to remove introns and join exons, and splicing elements present a large mutational target for disease-causing mutations. Splicing elements are strongly position dependent with respect to the transcript annotations. In 2012, we presented Spliceman, an online tool that used positional dependence to predict how likely distant mutations around annotated splice sites were to disrupt splicing. Here, we present an improved version of the previous tool that will be more useful for predicting the likelihood of splicing mutations. We have added industry-standard input options (i.e. Spliceman now accepts variant call format files), which allow much larger inputs than previously available. The tool also can visualize the locations-within exons and introns-of sequence variants to be analyzed and the predicted effects on splicing of the pre-mRNA transcript. In addition, Spliceman2 integrates with RNAcompete motif libraries to provide a prediction of which trans -acting factors binding sites are disrupted/created and links out to the UCSC genome browser. In summary, the new features in Spliceman2 will allow scientists and physicians to better understand the effects of single nucleotide variations on splicing. Availability and implementation Freely available on the web at http://fairbrother.biomed. brown.edu/spliceman2 . Website implemented in PHP framework-Laravel 5, PostgreSQL, Apache, and Perl, with all major browsers supported. Contact william_fairbrother@brown.edu. Supplementary information Supplementary data are available at Bioinformatics online.
Reward and Novelty Enhance Imagination of Future Events in a Motivational-Episodic Network

Thinking about personal future events is a fundamental cognitive process that helps us make choices in daily life. We investigated how the imagination of episodic future events is influenced by implicit motivational factors known to guide decision making. In a two-day functional magnetic resonance imaging (fMRI) study, we controlled learned reward association and stimulus novelty by pre-familiarizing participants with two sets of words in a reward learning task. Words were repeatedly presented and consistently followed by monetary reward or no monetary outcome. One day later, participants imagined personal future events based on previously rewarded, unrewarded and novel words. Reward association enhanced the perceived vividness of the imagined scenes. Reward and novelty-based construction of future events were associated with higher activation of the motivational system (striatum and substantia nigra/ ventral tegmental area) and hippocampus, and functional connectivity between these areas increased during imagination of events based on reward-associated and novel words. These data indicate that implicit past motivational experience contributes to our expectation of what the future holds in store.
Association of allergic diseases with children’s life satisfaction: population-based study in Finland

Objective To assess the impact of allergic diseases on the subjective well-being and life satisfaction of primary-school children. Design Population-based cohort. Setting Finnish sample of children ages 10 and 12 from the International Survey of Children’s Well-Being. Participants Nationally representative sample of 1947 school children. Main outcome measure Two different instruments to assess the child’s own perception of well-being, the short version of the Student Life Satisfaction Scale (SLSS) and the Brief Multidimensional Student Life Satisfaction Scale (BMSLSS). Results Altogether, 51.4% of children reported having at least one allergic condition (10.1% asthma, 23.8% eczema and 40.3% seasonal allergic rhinitis). A statistically significant distinction in life satisfaction emerged between non-allergic and allergic children (inferior in the latter). In particular, children with eczema were more likely to report a reduction in life satisfaction compared with non-allergic children (SLSS β=−128.220; BMSLSS β=−90.694; p<0.01). Apart from freedom from eczema, good life satisfaction was associated with a physically active lifestyle. Conclusions Active allergic disease reduces the child’s own perception of well-being. During clinical visits, more attention should be paid to the child’s psychosocial status and impairments, which may differ substantially from those of parents or medical authorities.
Evaluation of STT-MRAM L3 cache in 7nm FinFET process

The performance and power of the memory system cannot gradually follow the improving speed and power of the computational cores. To improve the memory performance, the L3 cache implemented with SRAM is generally used. However, the SRAM is not suitable for L3 cache, which has a low access rate (about 0.01%) and a large capacity (tens of MB) because the SRAM L3 cache has large area and consumes significant amount of leakage power. The STT-MRAM which is a next-generation memory, has a smaller cell area and very lower leakage power than that of SRAM. However, STT-MRAM is slower than SRAM in read and write operations, but it is fast enough to be used in the L3 cache. In this paper, we evaluate the STT-MRAM L3 cache by comparing with the SRAM L3 cache in 7nm FinFET process which maximizes the performance and integration of cores. Compared to the SRAM L3 cache, the STT-MRAM L3 cache has 50% smaller area, consumes 95% smaller leakage power. Although STT-MRAM has penalties in read/write latency and dynamic energies, these problems can be ignored because of low access rate of L3 cache. Therefore, it is attractive to replace the SRAM with ultra-low leakage STT-MRAM for L3 cache.
Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial

Importance Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Objective To examine the effects of sacubitril/valsartan on physical and social activities. Design, Setting, and Participants The PARADIGM-HF trial was a randomized, double-blind, active treatment–controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. Interventions Sacubitril/valsartan, 200 mg twice daily, or enalapril, 10 mg twice daily. Main Outcomes and Measures Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. Results At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95% CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95% CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95% CI, 0.78-2.60], P < .001; and 2.36 [95% CI, 1.01-3.71], P = .001, respectively). Conclusions and Relevance In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients. Trial Registration clinicaltrials.gov Identifier: NCT01035255
Much beyond Mantel: Bringing Procrustes Association Metric to the Plant and Soil Ecologist’s Toolbox

The correlation of multivariate data is a common task in investigations of soil biology and in ecology in general. Procrustes analysis and the Mantel test are two approaches that often meet this objective and are considered analogous in many situations especially when used as a statistical test to assess the statistical significance between multivariate data tables. Here we call the attention of ecologists to the advantages of a less familiar application of the Procrustean framework, namely the Procrustean association metric (a vector of Procrustean residuals). These residuals represent differences in fit between multivariate data tables regarding homologous observations (e.g., sampling sites) that can be used to estimate local levels of association (e.g., some groups of sites are more similar in their association between biotic and environmental features than other groups of sites). Given that in the Mantel framework, multivariate information is translated into a pairwise distance matrix, we lose the ability to contrast homologous data points across dimensions and data matrices after their fit. In this paper, we attempt to familiarize ecologists with the benefits of using these Procrustean residual differences to further gain insights about the processes underlying the association among multivariate data tables using real and hypothetical examples.
A study to investigate the reliability and validity of the Ten-Item Personality Inventory, when compared with two robust inventories, within a British sample

Personality inventories are commonly used instruments for the assessment of personality domains at various levels, whether it is the higher order factors or the facets underlying them. There are numerous inventories available for researchers to choose from, but a common disadvantage is the length of the inventory and consequently the completion time. The Ten-Item Personality Inventory (TIPI) aimed to address these issues. Short inventories are convenient and advantageous methodologically, but there are questions of reliability and validity, when compared with longer inventories. The aim of the current study is to investigate the validity and reliability of the TIPI, within a British sample (N = 81), when compared with the sixty item NEO-FFI and the forty-eight item EPQ-R short measure. The reliability indices of the TIPI closely corresponded to those found in the original literature. The convergent correlations indicated that the TIPI is valid within a British sample, a mean correlation of rs = . 61, compared with Furnham’s (2008) r = . 53. It is not recommended that the TIPI, or similar, supersede longer personality inventories, but the convenience of a short reliable and valid instrument is recognised for utilisation where time is limited or when personality is not the prime focus of research. Further psychometric investigation of the TIPI within various populations is warranted.
Genetic Analysis of Reemerging GII.P16-GII.2 Noroviruses in 2016–2017 in China

Background During 2016-2017, the previously rare GII.P16-GII.2 norovirus suddenly emerged as the predominant genotype causing gastroenteritis outbreaks in China and other countries. Its origin, phylodynamics, and mechanism behind the predominance remain unclear. Methods Bayesian phylogenetic analyses were performed on 180 full capsid and 150 polymerase sequences of 2016-2017 GII.P16-GII.2 noroviruses in China, and those for all publicly available GII.P16 and GII.2 sequences. Saliva-based histo-blood group antigen (HBGA) binding assays and crystal structural analysis were conducted by using the P proteins of 2016-2017 GII.P16-GII.2 noroviruses. Results The reemerging GII.P16-GII.2 norovirus showed a rapid genetic diversification after its emergence in 2012-2013. The antigenicity and HBGA binding profile of the early 2016-2017 and pre-2016 GII.2 noroviruses were similar. A further variant with a single Val256Ile mutation and the conventionally orientated Asp382 in the VP1 protein showed an expanded HBGA-binding spectrum. Mutations on the surface of polymerase that could alter its function were seen, which may help to accelerate the VP1 gene evolution to 5.5 × 10-3 substitutions per site per year. This virus can be traced back to Pearl River Delta, China. Conclusions Our findings provide new insights into GII.2 norovirus epidemics and highlight the necessity of enhanced global surveillance for potential epidemics of rare-genotype noroviruses.
Muscle Damage and Metabolic Responses to Repeated-Sprint Running With and Without Deceleration.

Minahan, CL, Poke, DP, Morrison, J, and Bellinger, PM. Muscle damage and metabolic responses to repeated-sprint running with and without deceleration. J Strength Cond Res XX(X): 000-000, 2017-This study aimed to determine whether repeated-sprint running with deceleration aggravates markers of muscle damage or delays the recovery of performance compared with repeated-sprint running without deceleration. Fourteen male team-sport athletes performed 2 randomly ordered testing sessions on a nonmotorized treadmill with one session requiring participants to decelerate (TMd) within 4 seconds before stopping or immediately step to the side of the treadmill belt at the completion of each sprint (TMa). Peak and mean velocities, speed decrement, blood lactate concentrations, and oxygen uptake were monitored during the repeated-sprint running protocols. Countermovement vertical jump (CMJ) performance, perceived muscle soreness, sit-and-reach flexibility, plasma creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb) concentrations were quantified immediately before and after and 45 minutes, 24 and 48 hours after repeated-sprint running protocols. Although muscle damage was indicated by increases in CK, LDH, and Mb (p ≤ 0.05) in both groups, there was no significant effect of condition (TMa vs. TMd) on any of the measured performance or physiological variables (p > 0.05). The present study indicated that the removal of deceleration from repeated-sprint running on a nonmotorized treadmill has no effect on metabolism or performance during or after repeated-sprint running or markers of muscle damage.
Intrinsic Brittlement of Mo3Si by First-Principle Calculations

First-principles method has been used to study the intrinsic brittlement of Mo3Si. The crystal constants, formation energy, cohesive energy, electronic structure, elastic constants of Mo3Si were calculated. The results were in good agreement with experiment data. Electronic structures showed that the strong covalent bonding between the nearest neighbour Mo atoms, which arrange perpendicularly each other, leads to embrittlement of Mo3Si.
Fuzzy Logic Enhanced Sensorless Alternative Energy Vehicular Drive System

This paper combines the best attributes of fuzzy logic and sliding mode intelligent controllers for enhancing the performance of an indirect field oriented induction motor drive system. A direct fuzzy controller (DFC) is designed for speed regulation which requires lesser tuning and gives robust speed tracking under external disturbances as compared to the traditional linear PI controller. The inputs of the designed fuzzy controller are speed error and change in error while the output is torque producing current. The performance of proposed drive system is further enhanced by incorporating a sliding mode current model flux observer which neither requires the rotor resistance information nor the rotor speed. The conventional current model observer is most sensitive to the rotor resistance and estimated speed information. Simulation program is developed for an indirect field oriented induction motor drive system with the proposed fuzzy controller for speed regulation and sliding mode current model observer for the flux and speed estimator. The effectiveness of proposed drive system is investigated and validated through intensive computer simulations.
Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B

Significance We describe the interaction between an intrinsically disordered protein (IDP), NUPR1, and the well-folded C-terminal region of RING1B protein of the Polycomb complex, involving residues Ala33 and Thr68 of the IDP. These observations are significant because they raise the possibility that NUPR1 aids the function of the members of the Polycomb complex, playing an active role in carcinogenesis. Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they are often associated with diseases in humans. The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and in the development and progression of pancreatic cancer; however, the details of such functions are unknown. Polycomb proteins are involved in specific transcriptional cascades and gene silencing. One of the proteins of the Polycomb complex is the Ring finger protein 1 (RING1). RING1 is related to aggressive tumor features in multiple cancer types. In this work we characterized the interaction between NUPR1 and the paralogue RING1B in vitro, in silico, and in cellulo. The interaction occurred through the C-terminal region of RING1B (C-RING1B), with an affinity in the low micromolar range (∼10 μM). The binding region of NUPR1, mapped by NMR, was a hydrophobic polypeptide patch at the 30s region of its sequence, as pinpointed by computational results and site-directed mutagenesis at Ala33. The association between C-RING1B and wild-type NUPR1 also occurred in cellulo as tested by protein ligation assays; this interaction is inhibited by trifluoperazine, a drug known to hamper binding of wild-type NUPR1 with other proteins. Furthermore, the Thr68Gln and Ala33Gln/Thr68Gln mutants had a reduction in the binding toward C-RING1B as shown by in vitro, in silico, and in cellulo studies. This is an example of a well-folded partner of NUPR1, because its other interacting proteins are also unfolded. We hypothesize that NUPR1 plays an active role in chromatin remodeling and carcinogenesis, together with Polycomb proteins.
Binary Feature-based Image Retrieval with Effective Indexing and Scoring

In this paper, we propose a stand-alone mobile visual search system based on binary features and bag of visual words framework. The contribution of this paper is two-fold: (1) a visual word-dependent substring extraction method is proposed; (2) a modified version of the local NBNN scoring method is proposed in the context of image retrieval. The proposed system improves retrieval accuracy by 11% compared with a conventional method without increasing the database size.
Web Service Recommendation With Reconstructed Profile From Mashup Descriptions

Web services are self-contained software components that support business process automation over the Internet, and mashup is a popular technique that creates value-added service compositions to fulfill complicated business requirements. For mashup developers, looking for desired component services from a sea of service candidates is often challenging. Therefore, web service recommendation has become a highly demanding technique. Traditional approaches, however, mostly rely on static and potentially subjectively described texts offered by service providers. In this paper, we propose a novel way of dynamically reconstructing objective service profiles based on mashup descriptions, which carry historical information of how services are used in mashups. Our key idea is to leverage mashup descriptions and structures to discover important word features of services and bridge the vocabulary gap between mashup developers and service providers. Specifically, we jointly model mashup descriptions and component service using author topic model in order to reconstruct service profiles. Exploiting word features derived from the reconstructed service profiles, a new service recommendation algorithm is developed. Experiments over a real-world data set from ProgrammableWeb.com demonstrate that our proposed service recommendation algorithm is effective and outperforms the state-of-the-art methods.Note to Practitioners—Service recommendation accuracy for mashup creation is often limited due to poor quality of service descriptions. Mashup descriptions contain valuable information about functions and features of its component services, which can be leveraged to enhance descriptive quality of original service profiles. Based on the assumption, this paper proposes a novel two-phase service recommendation framework to facilitate mashup creation. Specifically, our approach reconstructs service profiles by extracting appropriate words from historical mashup descriptions. Then, a novel service recommendation algorithm is developed by exploiting popularity and relevance measures hidden in the reconstructed profiles. Moreover, we propose the rules of dominant words discovery and employ it to further refine our algorithm.
Generation and biochemical characterization of glycoPEGylated factor VIIa derivatives

Summary Prophylaxis with 2–4 times weekly dosing of factor (F)VIII or FIX is established as an efficacious and safe treatment in haemophilia. Although prophylaxis is not readily available for the inhibitor patient,recent studies have demonstrated a reduction in bleeding episodes in inhibitor patients treated with daily infusions of FVIIa. In order to develop a treatment option comparable to prophylaxis with FVIII or FIX we looked to PEGylation which is an established method for prolonging the circulatory half-life of proteins. However, due to the numerous interactions of FVIIa with the cell surface,TF,FIX and FX there are limited options for unspecific chemical modification of FVIIa without loss of activity. Consequently, we explored the GlycoPEGylation™ technology for selective PEGylation of the two N-glycans in the FVIIa light chain and protease domain to generate seven specifically modified derivatives with PEG groups ranging from 2 to 40 kDa. These derivatives were evaluated in vitro for their ability to interact with small synthetic substrates as well as key molecules relevant to function in the coagulation pathway. The results demonstrate that modification of FVIIa using glycoPEGylation has only a very limited effect on the hydrolysis S-2288 and FX activation. However, the modification does to some extend alter the ability of FVIIa to interact with TF and more importantly, reduces the rate of ATIII inhibition by up to 50% which could allow for an extended active half-life in circulation.