Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal Structure of the Formin mDia1 in Autoinhibited Conformation

Background Formin proteins utilize a conserved formin homology 2 (FH2) domain to nucleate new actin filaments. In mammalian diaphanous-related formins (DRFs) the FH2 domain is inhibited through an unknown mechanism by intramolecular binding of the diaphanous autoinhibitory domain (DAD) and the diaphanous inhibitory domain (DID). Methodology/Principal Findings Here we report the crystal structure of a complex between DID and FH2-DAD fragments of the mammalian DRF, mDia1 (mammalian diaphanous 1 also called Drf1 or p140mDia). The structure shows a tetrameric configuration (4 FH2 + 4 DID) in which the actin-binding sites on the FH2 domain are sterically occluded. However biochemical data suggest the full-length mDia1 is a dimer in solution (2 FH2 + 2 DID). Based on the crystal structure, we have generated possible dimer models and found that architectures of all of these models are incompatible with binding to actin filament but not to actin monomer. Furthermore, we show that the minimal functional monomeric unit in the FH2 domain, termed the bridge element, can be inhibited by isolated monomeric DID. NMR data on the bridge-DID system revealed that at least one of the two actin-binding sites on the bridge element is accessible to actin monomer in the inhibited state. Conclusions/Significance Our findings suggest that autoinhibition in the native DRF dimer involves steric hindrance with the actin filament. Although the structure of a full-length DRF would be required for clarification of the presented models, our work here provides the first structural insights into the mechanism of the DRF autoinhibition.
A study of the propagation of Alfvén waves in the auroral density cavities

From the Viking and, more recently, the FAST spacecraft observations, it is known that the auroral acceleration regions correspond to relatively small-scale density cavities (a few kilometers to a few tens of kilometers in a direction perpendicular to the magnetic field). In order to study how Alfven waves can contribute to the auroral acceleration, we analyze their propagation in the presence of the sharp density gradients that characterize the edges of these cavities. It is shown that an Alfven wave packet entering into the cavity quickly develops short perpendicular length scales in the region of density inhomogeneity. Transverse scales of the order of c/ω pe are reached after a propagation of a few tenths of second, which corresponds to ∼ 2000 km in the cavity. This contributes to the creation of significant parallel electric field in the region of density gradient. Its amplitude is enhanced by the formation, on the gradients, of strong space charges due to the ion polarization drift. As the auroral cavities are known to be strong current regions, the density gradients would thus be the sites of particularly powerful wave/particle energy transfer and consequently, if the incident flux of Alfven waves coming from the magnetosphere is high enough, of the strongest particle acceleration.
A Hybrid Ant Colony Algorithm with a Local Search for the Strongly Correlated Knapsack Problem

Large combinatorial optimization problems may be overly complex to be processed by a single type of algorithm. This explains the growing interest of researchers in the hybrid resolution. The hybridization of algorithms aims to take advantage of each one benefits, thereby achieving better results.In this paper, a hybrid metaheuristic is proposed to solve one of the most complex variants of the knapsack problem which is the Strongly Correlated Knapsack Problem (SCKP). The proposed approach combines a proposed Ant Colony Optimization algorithm (ACO) with a 2-opt algorithm. The proposed ACO scheme used combines two ant algorithms: the MAX-MIN Ant System and the Ant Colony System.At a first stage, our proposed ACO aims to solve the SCKP to optimality. In case an optimal solution is not found, a proposed 2-opt algorithm is used. Even if the 2-opt heuristic fails to find the optimal solution, it would hopefully improve the solution quality by reducing the gap between the found solution and the optimum.The proposed algorithm was tested on a set of instances and compared with classical and recent methods reported in the literature.
Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection

Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV‐positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β‐globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P < 0.001). The viral mean load was 4.81 ± 1.98 log10 copies/1000 cells for patients under the age of 4‐year‐old (P < 0.001). The viral mean loads were 4.51 ± 2.04 cells in patients with low respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression.
XYLANASES FROM THE FUNGAL TOMATO PATHOGEN FUSARIUM

We purified four xylan-degrading enzymes (endo-xylanases: EC 3.2.1.8) produced in vitro by the fungal pathogen Fusarium oxysporum f.sp. lycopersici (Fol). The xylanases were resolved by a combination of ion exchange and hydrophobic interaction chromatography, and preparative native-PAGE electrophoresis. They had molecular masses of 38, 34, 22 and 19 kDa, pI higher than 9.3, endo-cleavage mechanism and maximal activity at pH 6.0 and 45°C. Comparison of the reaction products showed differences in the cleavage mechanism of two of the xylanases. In addition their role as possible elicitors of stress and defence responses was examined in preliminary assays. Xylanases from a variety of pathogenic and nonpathogenic fungi have been described as inducers of plant stress and defence responses. A role as elicitors of active defence mechanisms was suggested for the ethylene biosynthesis-inducing xylanase from T. viride (EIX) and EIX-like enzymes from a variety of pathogenic fungi. In spite of the homologies with the EIX from T. viride none of the Fol xylanases examined by us were antigenically related to it. Furthermore, they showed no EIX-like eliciting activity on cell culture suspensions or intact tomato leaflets in our tests. Therefore their role as recognition factors is not established in our experimental model.
Optimization Beyond the Convolution: Generalizing Spatial Relations with End-to-End Metric Learning

To operate intelligently in domestic environments, robots require the ability to understand arbitrary spatial relations between objects and to generalize them to objects of varying sizes and shapes. In this work, we present a novel end-to-end approach to generalize spatial relations based on distance metric learning. We train a neural network to transform 3D point clouds of objects to a metric space that captures the similarity of the depicted spatial relations, using only geometric models of the objects. Our approach employs gradient-based optimization to compute object poses in order to imitate an arbitrary target relation by reducing the distance to it under the learned metric. Our results based on simulated and real-world experiments show that the proposed method enables robots to generalize spatial relations to unknown objects over a continuous spectrum.
Population Modeling of Tumor Kinetics and Overall Survival to Identify Prognostic and Predictive Biomarkers of Efficacy for Durvalumab in Patients With Urothelial Carcinoma

Durvalumab is an anti‐PD‐L1 monoclonal antibody approved for patients with locally advanced or metastatic urothelial carcinoma (UC) that has progressed after platinum‐containing chemotherapy. A population tumor kinetic model, coupled with dropout and survival models, was developed to describe longitudinal tumor size data and predict overall survival in UC patients treated with durvalumab (NCT01693562) and to identify prognostic and predictive biomarkers of clinical outcomes. Model‐based covariate analysis identified liver metastasis as the most influential factor for tumor growth and immune‐cell PD‐L1 expression and baseline tumor burden as predictive factors for tumor killing. Tumor or immune‐cell PD‐L1 expression, liver metastasis, baseline hemoglobin, and albumin levels were identified as significant covariates for overall survival. These model simulations provided further insights into the impact of PD‐L1 cutoff values on treatment outcomes. The modeling framework can be a useful tool to guide patient selection and enrichment strategies for immunotherapies across various cancer indications.
Origin of Conductivity Threshold in the Solid Electrolyte Glass System: Ag S As S

The electrical conductivity of Ag S As S glasses increases to display a step-like jump of nearly five orders of magnitude in the narrow composition range, range. To elucidate the origin of this threshold behavior, we have now examined the molecular structure of these glasses in modulated-differential scanning calorimetry (MDSC) and Raman scattering experiments. Our MDSC results reveal bimodal glass transition temperatures (T s), a low-T and a high-T in the range but unimodal ones outside this range. The low-T phase bears a similarity to that of the stoichiometric glass at , or AgAsS , and we identify it with a Ag-rich phase formed in these glasses once . The Ag-rich phase is thought to percolate near , and to contribute to the large jump in conductivity of the glasses. The high-T phase represents a semiconducting As S glass phase alloyed with a few mole percent of Ag S, and it displays a reversibility window in the range. The semiconducting phase becomes elastically flexible once . Softening of the high-T phase lowers Ag ion migration energies and also contributes to the conductivity threshold.
Functional Characterization of Glycoprotein H Chimeras Composed of Conserved Domains of the Pseudorabies Virus and Herpes Simplex Virus 1 Homologs

ABSTRACT Membrane fusion is indispensable for entry of enveloped viruses into host cells. The conserved core fusion machinery of the Herpesviridae consists of glycoprotein B (gB) and the gH/gL complex. Recently, crystal structures of gH/gL of herpes simplex virus 2 (HSV-2) and Epstein-Barr virus and of a core fragment of pseudorabies virus (PrV) gH identified four structurally conserved gH domains. To investigate functional conservation, chimeric genes encoding combinations of individual domains of PrV and herpes simplex virus 1 (HSV-1) gH were expressed in rabbit kidney cells, and their processing and transport to the cell surface, as well as activity in fusion assays including gB, gD, and gL of PrV or HSV-1, were analyzed. Chimeric gH containing domain I of HSV-1 and domains II to IV of PrV exhibited limited fusion activity in the presence of PrV gB and gD and HSV-1 gL, but not of PrV gL. More strikingly, chimeric gH consisting of PrV domains I to III and HSV-1 domain IV exhibited considerable fusion activity together with PrV gB, gD, and gL. Replacing PrV gB with the HSV-1 protein significantly enhanced this activity. A cell line stably expressing this chimeric gH supported replication of gH-deleted PrV. Our results confirm the specificity of domain I for gL binding, demonstrate functional conservation of domain IV in two alphaherpesviruses from different genera, and indicate species-specific interactions of this domain with gB. They also suggest that gH domains II and III might form a structural and functional unit which does not tolerate major substitutions. IMPORTANCE Envelope glycoprotein H (gH) is essential for herpesvirus-induced membrane fusion, which is required for host cell entry and viral spread. Although gH is structurally conserved within the Herpesviridae, its precise role and its interactions with other components of the viral fusion machinery are not fully understood. Chimeric proteins containing domains of gH proteins from different herpesviruses can serve as tools to elucidate the molecular basis of gH function. The present study shows that the C-terminal part of human herpesvirus 1 (herpes simplex virus 1) gH can functionally substitute for the corresponding part of suid herpesvirus 1 (pseudorabies virus) gH, whereas other tested combinations proved to be nonfunctional. Interestingly, the exchangeable fragment included the membrane-proximal end of the gH ectodomain (domain IV), which is most conserved in sequence and structure and might be capable of transient membrane interaction during fusion.
Effectiveness of interventions for co‐residing family caregivers of people with dementia: Systematic review and meta‐analysis

BACKGROUND/AIM Occupational therapists and health practitioners commonly provide interventions to family caregivers of people with dementia with the aim of relieving burden, depression, and disruptions in health and social support. To date, the effects of multicomponent interventions specifically targeting these four important outcomes has not been established. The aim of this study was to evaluate the effectiveness of multicomponent interventions on four outcomes for co-residing family caregivers of people with dementia. METHODS A comprehensive database search of the literature was performed using CINAHL, MEDLINE, PubMed, PsycINFO, OTseeker, EMBASE and the Cochrane library. Randomised control trials (RCTs) that included multicomponent interventions for co-residing family caregivers addressing burden, depression, health and social support were selected. Relevant articles were critically reviewed and study results were synthesised. Meta-analysis was conducted separately. RESULTS Twenty-two of 358 retrieved studies were selected, with 15 studies being included in the meta-analyses. The multicomponent interventions identified were comprised of a range of different individual strategies. Significant effective results were found for all four specified outcomes. CONCLUSIONS Many types of multicomponent interventions appear beneficial on all of the four specified outcomes. The literature presents a trend that multicomponent interventions consisting of a combination of counselling, support groups, education, stress and mood management or telephone support are important strategies within an effective multicomponent intervention.
Performance studies of Wire Electro Discharge Machining (WEDM) of Inconel 718

This paper describes the development of mathematical models and multi response optimisation to predict and select the best cutting parameters for Wire Electro Discharge Machining (WEDM) process. Inconel 718 was selected as work material for experimentation. A brass wire of 0.25 mm diameter was applied as a tool electrode to cut the specimen. The responses were optimised concurrently using Multi Response Signal to Noise (MRSN) ratio. ANOVA was employed to identify the level of importance of the machining parameters. Finally, experimental confirmations were carried out to identify the effectiveness of this proposed method.
Characterization and properties of low-linear-density polyethylene/Typha latifolia composites

ABSTRACT The characterization of the effects of different sizes and loadings of Typha latifolia on the tensile, thermal, and morphological properties of linear-low-density polyethylene (LLDPE)/T. latifolia composites were evaluated using tensile test, Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy analyses. Results indicated the tensile strength and elongation at break decreased as T. latifolia loading increased. However, T. latifolia fine size (fs) exhibited better tensile properties than coarse size at the same loading in the composite. T. latifolia (15%, fs) recorded higher thermal stability than LLDPE control and other T. latifolia loadings and sizes due to the strong interaction of T. latifolia (15%, fs) in LLDPE matrix as shown in morphology.
Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung

Chronic inflammation containing CD8+ lymphocytes, neutrophils, and macrophages, and pulmonary emphysema coexist in lungs from patients with chronic obstructive pulmonary disease. Although this inflammatory response is believed to cause the remodeling that is seen in these tissues, the mechanism(s) by which inflammation causes emphysema have not been defined. Here we demonstrate that interferon γ (IFN-γ), a prominent product of CD8+ cells, causes emphysema with alveolar enlargement, enhanced lung volumes, enhanced pulmonary compliance, and macrophage- and neutrophil-rich inflammation when inducibly targeted, in a transgenic fashion, to the adult murine lung. Prominent protease and antiprotease alterations were also noted in these mice. They included the induction and activation of matrix metalloproteinase (MMP)-12 and cathepsins B, H, D, S, and L, the elaboration of MMP-9, and the selective inhibition of secretory leukocyte proteinase inhibitor. IFN-γ causes emphysema and alterations in pulmonary protease/antiprotease balance when expressed in pulmonary tissues.
Surgeon Influence on Variation in Receipt of Contralateral Prophylactic Mastectomy for Women With Breast Cancer

Importance Rates of contralateral prophylactic mastectomy (CPM) have markedly increased but we know little about the influence of surgeons on variability of the procedure in the community. Objective To quantify the influence of the attending surgeon on rates of CPM and clinician attitudes that explained it. Design, Setting, and Participants In this population-based survey study, we identified 7810 women with stages 0 to II breast cancer treated in 2013 to 2015 through the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County. Surveys were sent approximately 2 months after surgery. Surveys were also sent to 488 attending surgeons identified by the patients. Main Outcomes and Measures We conducted multilevel analyses to examine the impact of surgeon influence on variations in patient receipt of CPM using information from patient and surgeon surveys merged to Surveillance, Epidemiology, and End Results data. Results A total of 5080 women responded to the survey (70% response rate), and 377 surgeons responded (77% response rate). The mean (SD) age of responding women was 61.9 (11) years; 28% had an increased risk of second primary cancer, and 16% received CPM. Half of surgeons (52%) practiced for more than 20 years and 30% treated more than 50 new patients with breast cancer annually. Attending surgeon explained a large amount (20%) of the variation in CPM, controlling for patient factors. The odds of a patient receiving CPM increased almost 3-fold (odds ratio, 2.8; 95% CI, 2.1-3.4) if she saw a surgeon with a practice approach 1 SD above a surgeon with the mean CPM rate (independent of age, diagnosis date, BRCA status, and risk of second primary). One-quarter (25%) of the surgeon influence was explained by attending attitudes about initial recommendations for surgery and responses to patient requests for CPM. The estimated rate of CPM was 34% for surgeons who least favored initial breast conservation and were least reluctant to perform CPM vs 4% for surgeons who most favored initial breast conservation and were most reluctant to perform CPM. Conclusions and Relevance In this study, attending surgeons exerted influence on the likelihood of receipt of CPM after a breast cancer diagnosis. Variations in surgeon attitudes about recommendations for surgery and response to patient requests for CPM explain a substantial amount of this influence.
Longer Food Chains in Pelagic Ecosystems: Trophic Energetics of Animal Body Size and Metabolic Efficiency

Factors constraining the structure of food webs can be investigated by comparing classes of ecosystems. We find that pelagic ecosystems, those based on one-celled primary producers, have longer food chains than terrestrial ecosystems. Yet pelagic ecosystems have lower primary productivity, contrary to the hypothesis that greater energy flows permit higher trophic levels. We hypothesize that longer food chain length in pelagic ecosystems, compared with terrestrial ecosystems, is associated with smaller pelagic animal body size permitting more rapid trophic energy transfer. Assuming negative allometric dependence of biomass production rate on body mass at each trophic level, the lowest three pelagic animal trophic levels are estimated to add biomass more rapidly than their terrestrial counterparts by factors of 12, 4.8, and 2.6. Pelagic animals consequently transport primary production to a fifth trophic level 50–190 times more rapidly than animals in terrestrial webs. This difference overcomes the approximately fivefold slower pelagic basal productivity, energetically explaining longer pelagic food chains. In addition, ectotherms, dominant at lower pelagic animal trophic levels, have high metabolic efficiency, also favoring higher rates of trophic energy transfer in pelagic ecosystems. These two animal trophic flow mechanisms imply longer pelagic food chains, reestablishing an important role for energetics in food web structure.
Antihypertensive medication adherence and blood pressure control among central Alabama veterans

Medication nonadherence is associated with adverse outcomes. To evaluate antihypertensive medication adherence and its association with blood pressure (BP) control, the authors described population adherence to prescribed antihypertensive medication (proportion of days covered ≥80%) and BP control (mean BP <140/90 mm Hg) among central Alabama veterans during the fiscal year 2015. Overall, 75.1% of patients receiving antihypertensive medication were considered adherent, and 66.1% had adequate BP control. Patients adherent to antihypertensive medication were more likely to have adequate BP control compared with patients classified as nonadherent (67.4% vs 62.0%; adjusted odds ratio 1.33; 95% confidence interval, 1.22–1.44 [P<.0001]). Among patients who had uncontrolled BP, 73.6% were considered adherent to medication. Adherence to antihypertensive medication was associated with adequate BP control; however, a substantial proportion of patients with inadequate BP control were also considered adherent. Interventions to increase BP control could address more aggressive medication management to achieve BP goals.