Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Mutation Analysis of Nonconserved Residues on the TIM-Barrel Surface of GH5_5 Cellulases for Catalytic Efficiency and Stability Improvement

A comprehensive understanding of the residues on the α-helices of the GH5_5 cellulases is important for catalytic efficiency and stability improvement. The main objective of this study was to use the evolutionary conservation and plasticity of the TIM-barrel fold to probe the relationship between nonconserved residues on the outer side of the α-helices and the catalytic efficiency of GH5_5 cellulases by conducting structure-guided protein engineering. ABSTRACT Exploring the potential functions of nonconserved residues on the outer side of α-helices and systematically optimizing them are pivotal for their application in protein engineering. Based on the evolutionary structural conservation analysis of GH5_5 cellulases, a practical molecular improvement strategy was developed. Highly variable sites on the outer side of the α-helices of the GH5_5 cellulase from Aspergillus niger (AnCel5A) were screened, and 14 out of the 34 highly variable sites were confirmed to exert a positive effect on the activity. After the modular combination of the positive mutations, the catalytic efficiency of the mutants was further improved. By using CMC-Na as the substrate, the catalytic efficiency and specific activity of variant AnCel5A_N193A/T300P/D307P were approximately 2.0-fold that of AnCel5A (227 ± 21 versus 451 ± 43 ml/s/mg and 1,726 ± 19 versus 3,472 ± 42 U/mg, respectively). The half-life (t1/2) of variant AnCel5A_N193A/T300P/D307P at 75°C was 2.36 times that of AnCel5A. The role of these sites was successfully validated in other GH5_5 cellulases. Computational analyses revealed that the flexibility of the loop 6-loop 7-loop 8 region was responsible for the increased catalytic performance. This work not only illustrated the important role of rapidly evolving positions on the outer side of the α-helices of GH5_5 cellulases but also revealed new insights into engineering the proteins that nature left as clues for us to find. IMPORTANCE A comprehensive understanding of the residues on the α-helices of the GH5_5 cellulases is important for catalytic efficiency and stability improvement. The main objective of this study was to use the evolutionary conservation and plasticity of the TIM-barrel fold to probe the relationship between nonconserved residues on the outer side of the α-helices and the catalytic efficiency of GH5_5 cellulases by conducting structure-guided protein engineering. By using a four-step nonconserved residue screening strategy, the functional role of nonconserved residues on the outer side of the α-helices was effectively identified, and a variant with superior performance and capability was constructed. Hence, this study proved the effectiveness of this strategy in engineering GH5_5 cellulases and provided a potential competitor for industrial applications. Furthermore, this study sheds new light on engineering TIM-barrel proteins.
A methodology for flexibility analysis of pipeline systems

Pipeline systems serve a crucial role in an effective transport of fluids to the designated location for medium to long span of distances. Owing to its paramount economic significance, pipeline design field have undergone extensive development over the past few years for enhancing the optimization and transport efficiency. This research paper attempts to propose a methodology for flexibility analysis of pipeline systems through employing contemporary computational tools and practices. A methodical procedure is developed, which involves modeling of the selected pipeline system in CAESAR II followed by the insertion of pipe supports and restraints. The specific location and selection of the inserted supports is based on the results derived from the displacement, stress, reaction, and nozzle analysis of the concerned pipeline system. Emphasis is laid on the compliance of the design features to the leading code of pipeline transportation systems for liquid and slurries, ASME B31.4. The discussed procedure and approach can be successfully adjusted for the analysis of various other types of pipeline system configuration. In addition to the provision of systematic flow in analysis, the method also improves efficient time-saving practices in the pipeline stress analysis.
A 0.8-μW and 74-dB High-Pass Sigma-Delta Modulator With OPAMP Sharing and Noise-Coupling Techniques for Biomedical Signal Acquisition

This work presents a third-order high-pass sigma-delta modulator (HPSDM) for biomedical signal acquisition. The operational amplifier (op-amp) sharing and noise-coupling techniques are adopted to reduce the required quantity of op-amps and add a noise-shaping order, which can achieve low power consumption and high resolution. A novel switched-capacitor architecture is proposed to suppress the increasing in-band noise and alleviate the circuit sensitivity to capacitor mismatch in the high-pass integrator. The proposed HPSDM was fabricated in a 0.18-μm standard CMOS process. Measurement results reveal that the proposed HPSDM has a signal-to-noise and distortion ratio (SNDR) of 75.26/74 dB in 200 Hz bandwidth and consumes 1.52/0.8 μW under 1.2/1 V supply voltage, which can achieve a peak Schreier Figure-of-Merit of 156.45/157.98 dB and a peak Walden FoM of 0.802/0.488 pJ/conv.
Computational Modeling of an Auditory Lexical Decision Experiment Using DIANA

We present an implementation of DIANA, a computational model of spoken word recognition, to model responses collected in the Massive Auditory Lexical Decision (MALD) project. DIANA is an end-to-end model, including an activation and decision component that takes the acoustic signal as input, activates internal word representations, and outputs lexicality judgments and estimated response latencies. Simulation 1 presents the process of creating acoustic models required by DIANA to analyze novel speech input. Simulation 2 investigates DIANA’s performance in determining whether the input signal is a word present in the lexicon or a pseudoword. In Simulation 3, we generate estimates of response latency and correlate them with general tendencies in participant responses in MALD data. We find that DIANA performs fairly well in free word recognition and lexical decision. However, the current approach for estimating response latency provides estimates opposite to those found in behavioral data. We discuss these findings and offer suggestions as to what a contemporary model of spoken word recognition should be able to do.
Multi-way relation-enhanced hypergraph representation learning for anti-cancer drug synergy prediction

MOTIVATION Drug combinations have exhibited promise in treating cancers with less toxicity and fewer adverse reactions. However, in vitro screening of synergistic drug combinations is time-consuming and labour-intensive because of the combinatorial explosion. Although a number of computational methods have been developed for predicting synergistic drug combinations, the multi-way relations between drug combinations and cell lines existing in drug synergy data have not been well exploited. RESULTS We propose a multi-way relation-enhanced hypergraph representation learning method to predict anti-cancer drug synergy, named HypergraphSynergy. HypergraphSynergy formulates synergistic drug combinations over cancer cell lines as a hypergraph, in which drugs and cell lines are represented by nodes and synergistic drug-drug-cell line triplets are represented by hyperedges, and leverages the biochemical features of drugs and cell lines as node attributes. Then, a hypergraph neural network is designed to learn the embeddings of drugs and cell lines from the hypergraph and predict drug synergy. Moreover, the auxiliary task of reconstructing the similarity networks of drugs and cell lines is considered to enhance the generalization ability of the model. In the computational experiments, HypergraphSynergy outperforms other state-of-the-art synergy prediction methods on two benchmark datasets for both classification and regression tasks, and is applicable to unseen drug combinations or cell lines. The studies revealed that the hypergraph formulation allows us to capture and explain complex multi-way relations of drug combinations and cell lines, and also provides a flexible framework to make the best use of diverse information. AVAILABILITY AND IMPLEMENTATION The source data and codes of HypergraphSynergy can be freely downloaded from https://github.com/liuxuan666/HypergraphSynergy. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
The Performance Quality Rating Scale for Somatosensation After Stroke: A Pilot Study

To our knowledge, no measure of observed performance in self-selected activities has been specifically tested for use with stroke survivors with somatosensory deficits. The objective of this study is to modify the Performance Quality Rating Scale (PQRS) for use with stroke survivors with somatosensory deficits and report the interrater reliability. Videos of stroke survivors (N = 22) with somatosensory deficits performing self-selected activities on two separate occasions (76 video clips; 38 activities) were viewed by two clinicians who rated performance using the modified PQRS. Reported properties of the modified PQRS included the interclass correlation coefficient (ICC2,1), Spearman’s rho and standard error of measurement (SEM). Interrater reliability was good (ICC2,1 = 0.81). Raters’ scores correlated highly (Spearman’s rho = 0.81), and the SEM (1.07) was acceptable. The modified PQRS demonstrated good interrater reliability. Further modifications such as developing common operational definitions that are applicable across a wide range of activities may improve the clinical usability of the scale.
Plasmid-Borne AFM Alleles in Pseudomonas aeruginosa Clinical Isolates from China

Acquiring metallo-β-lactamase genes is one of the important carbapenem resistance mechanisms of P. aeruginosa. Alcaligenes faecalis metallo-β-lactamase is a newly identified metallo-β-lactamase, the prevalence and genetic context of which need to be explored. In this study, we identified AFM-producing P. aeruginosa strains among clinical isolates and found a new mutant of AFM, AFM-4. ABSTRACT Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a pathogen of global concern due to the fact that therapeutic drugs are limited. Metallo-β-lactamase (MBL)-producing P. aeruginosa has become a critical part of CRPA. Alcaligenes faecalis metallo-β-lactamase (AFM) is a newly identified subclass B1b MBL. In this study, 487 P. aeruginosa strains isolated from patients and the environment in an intensive care unit were screened for AFM alleles. Five AFM-producing strains were identified, including four AFM-2-producing strains (ST262) and one AFM-4-producing strain (ST671). AFM-2-producing strains were isolated from rectal and throat swabs, and AFM-4-producing strains were isolated from the water sink. The blaAFM-2 carrying plasmids belonged to the IncP-2 type, while the blaAFM-4 carrying plasmid pAR19438 was a pSTY-like megaplasmid. Plasmid pAR19438 was acquired blaAFM-4 by the integration of the Tn1403-like transposon. All blaAFM genes were embedded in an ISCR29-blaAFM unit core module flanked by class 1 integrons. The core module of blaAFM-2 was ISCR29-ΔgroL-blaAFM-2-bleMBL-ΔtrpF-ΔISCR, while the core module of blaAFM-4 was ISCR29-ΔgroL-blaAFM-2-bleMBL-ΔtrpF-ISCR-msrB-msrA-yfcG-corA-ΔISCR. The flanking sequences of ISCR29-blaAFM units also differed. The expression of AFM-2 and AFM-4 in DH5α and PAO1 illustrated the same effect for the evaluation of the MICs of β-lactams, except for aztreonam. Identification of AFM-4 underscores that the quick spread and emerging development of mutants of MBLs require continuous surveillance in P. aeruginosa. IMPORTANCE Acquiring metallo-β-lactamase genes is one of the important carbapenem resistance mechanisms of P. aeruginosa. Alcaligenes faecalis metallo-β-lactamase is a newly identified metallo-β-lactamase, the prevalence and genetic context of which need to be explored. In this study, we identified AFM-producing P. aeruginosa strains among clinical isolates and found a new mutant of AFM, AFM-4. The blaAFM-4 carrying plasmid pAR19438 was a pSTY-like megaplasmid, unlike the plasmids encoding other blaAFM alleles. The genetic context of blaAFM-4 was also different. However, AFM-2 and AFM-4 had the same impacts on antibiotic susceptibility. The presence and transmission of AFM alleles in P. aeruginosa pose a challenge to clinical practice.
Uterine fibroid: a socially malignant illness in Haiti

Abstract This qualitative study documented the effects of uterine fibroids on the suffering of women in Haiti. It makes a unique contribution by re-socializing this disease, by making visible the social inequalities and what is at stake for the women, for their families, and for healthcare delivery. Uterine fibroid is a benign tumor of the uterus, common in gynecology, but profoundly malignant in how it affects women’s lives. Little has been reported on their lived experiences. Haiti has historical, social, and economic factors that hinder the search for treatment. The study explores how and why patients seek surgical care for uterine fibroids at Mirebalais University Hospital. Seventeen in-depth interviews with patients and seven accompanying family members were conducted and recorded in Creole and translated into English, along with participant observations in two patients’ homes. Content and narrative analysis were done iteratively, and the processual ethnographic method was used to relate our findings to Haitian history, to the context of the study, and to future implications. The women’s experience of accompaniment, their suffering in their pèlerinage (care-seeking journey), and the troubling social impact of uterine fibroids make it a socially malignant illness. The study shows that it is critical to address the suffering of women afflicted with uterine fibroids by strengthening the Haitian health system, improving economic advantages, and establishing ways for them to gain access to social goods and participate in community activities.
Tuberculosis screening among newly arrived asylum seekers in Denmark

Abstract Background Tuberculosis (TB) screening programmes among asylum seekers tend to focus on chest radiography (CXR) for early diagnosis, whereas knowledge on sputum examination is limited. We evaluated active TB screening using CXR and sputum culture among asylum seekers arriving in Denmark. In addition, we assessed the coverage of a voluntary health assessment. Methods Between 1 February 2017 and 31 March 2019, all newly arrived asylum seekers in Denmark ≥ 18 years from TB high-incidence countries or risk groups, who attended a voluntary general health assessment, were offered active TB screening with CXR and spot sputum examination. Sputum samples were examined by culture and smear microscopy. Results Coverage of the general health assessment was 65.1%. Among 1,154 referred for active TB screening, 923 (80.0%) attended. Of these, 854 were screened by CXR and one case of active TB was identified equivalent to a yield of 0.12%. Sputum samples were collected from 758 and one M. tuberculosis culture-positive TB case (also identified by CXR) was identified, equivalent to a yield of 0.13%. No cases were found by sputum culture screening only. In addition, screening found three cases of malignant disease. Conclusion We suggest that TB screening should focus on asylum seekers from TB high-incidence countries. Furthermore, early health assessments should be of high priority to ensure migrant health.
Mapping early tumor response to radiotherapy using diffusion kurtosis imaging**

Purpose In this pilot study, DKI measures of diffusivity and kurtosis were compared in active tumor regions and correlated to radiologic response to radiotherapy after completion of 2 weeks of treatment to derive potential early measures of tumor response. Methods MRI and Magnetic Resonance Spectroscopic Imaging (MRSI) data were acquired before the beginning of RT (pre-RT) and 2 weeks after the initiation of treatment (during-RT) in 14 glioblastoma patients. The active tumor region was outlined as the union of the residual contrast-enhancing region and metabolically active tumor region. Average and standard deviation of mean, axial, and radial diffusivity (MD, AD, RD) and mean, axial, and radial kurtosis (MK, AK, RK) values were calculated for the active tumor VOI from images acquired pre-RT and during-RT and paired t-tests were executed to estimate pairwise differences. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive capabilities of changes in diffusion metrics for progression-free survival (PFS). Results Analysis showed significant pairwise differences for AD (p = 0.035; Cohen’s d of 0.659) and AK (p = 0.019; Cohen’s d of 0.753) in diffusion measures after 2 weeks of RT. ROC curve analysis showed that percentage change differences in AD and AK between pre-RT and during-RT scans provided an Area Under the Curve (AUC) of 0.524 and 0.762, respectively, in discriminating responders (PFS>180 days) and non-responders (PFS<180 days). Conclusion This pilot study, although preliminary in nature, showed significant changes in AD and AK maps, with kurtosis derived AK maps showing an increased sensitivity in mapping early changes in the active tumor regions.
Atlas of Crystal Structure Types for Intermetallic Phases

The Atlas of Crystal Structure Types for Intermetallic Phases offers you pictorial detail, clearly illustratedThe Atlas is the perfect reference to keep on your shelf beside the Second Edition of Pearson's Handbook. For each structure type, you can quickly find for all atoms (point sets): A list of all coordination atoms with corresponding coordinates, the distance to its central atom, its coordination number and its polyhedron code. A histogram of the number of surrounding atoms (n) versus interatomic distances between the central atom and surrounding atoms, the interatomic distances are given relative to the shortest distance and nearest in the coordination polyhedron (dn/dnearest). The standard setting of all structure types is analagous to Pearson's Second Edition data. All point sets are numbered consistently throughout a structure type, so you can easily trace each atom in all drawings and tables. For accuracy, all drawings and tables are computer-generated directly from the database. All structure types have been checked for consistency. Published: 1991 Format: 4 Volume Set
Adaptive algorithm for dependent infrastructure network restoration in an imperfect information sharing environment

Critical infrastructure networks are vital for a functioning society and their failure can have widespread consequences. Decision-making for critical infrastructure resilience can suffer based on several characteristics exhibited by these networks, including (i) that there exist interdependencies with other networks, (ii) that several decision-makers represent potentially competing interests among the interdependent networks, and (iii) that information about other decision-makers’ actions are uncertain and potentially unknown. To address these concerns, we propose an adaptive algorithm using machine learning to integrate predictions about other decision-makers’ behavior into an interdependent network restoration planning problem considering an imperfect information sharing environment. We examined our algorithm against the optimal solution for various types, sizes, and dependencies of networks, resulting in insignificant differences. To assess the proposed algorithm’s efficiency, we compared its results with a proposed heuristic method that prioritizes, and schedules components restoration based on centrality-based importance measures. The proposed algorithm provides a solution sufficiently close to the optimal solution showing the algorithm performs well in situations where the information sharing environment is incomplete.
Sex differences in In‐hospital outcomes of catheter ablation for atrial fibrillation

There is limited data on in-hospital outcomes of catheter ablation (CA) for atrial fibrillation (AF) compared between men and women. We investigated National Inpatient Sample database to examine gender differences on in-hospital outcomes of CA for AF. A total of 30,365 hospitalizations were identified and included in the final analysis. Multivariate analysis showed that women had lower in-hospital all-cause mortality (aOR 0.57, 95% CI 0.41-0.80, p=0.001) and acute HF (aOR 0.90, 95% CI 0.83-0.96, p=0.005) compared to men. While our study has limitations, future randomized trials are necessary to evaluate benefits of early CA for AF in females. This article is protected by copyright. All rights reserved.
Changes in postural sway during upright stance after short-term lower limb physical inactivity: A prospective study

Previous studies have reported that motor behavior is affected by short-term physical inactivity using cast immobilization; however, the effects of inactivity on postural sway are not well-understood. This study aimed to investigate the effects of short-term lower limb disuse on postural sway in the upright position after cast removal. Twenty-two healthy young adults were enrolled, and each participant’s lower limb on one side was fixed with a soft bandage and medical splint made from metal and soft urethane for 10 h. Fluctuations in the center of pressure (COP) were measured before and after immobilization; the total trajectory length, mean velocity, COP root mean square (RMS) area, mean medial-lateral (M-L) COP, and mean anterior-posterior (A-P) COP were selected as evaluation parameters. Compared with the postural sway before cast application, we noted an increase and shift (from the fixed to the nonfixed side) in the postural sway after cast removal. Our results therefore suggest that short-term disuse may cause acute changes in COP movements during quiet standing. Moreover, patients may maintain their standing posture by adopting a compensatory strategy involving lateral control, similar to individuals with stroke and patients who have undergone total knee arthroplasty.
Bayesian modeling and test planning for multiphase reliability assessment

We propose a Bayesian hierarchical model to assess the reliability of a family of vehicles, based on the development of the joint light tactical vehicle (JLTV). The proposed model effectively combines information across three phases of testing and across common vehicle components. The analysis yields estimates of failure rates for specific failure modes and vehicles as well as an overall estimate of the failure rate for the family of vehicles. We are also able to obtain estimates of how well vehicle modifications between test phases improve failure rates. In addition to using all data to improve on current assessments of reliability and reliability growth, we illustrate how to leverage the information learned from the three phases to determine appropriate specifications for subsequent testing that will demonstrate if the reliability meets a given reliability threshold.