Miracle-dz/UniFAR-FTUs huggingface dataset:
A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure

During a heart failure, an increased content and activity of nucleoside diphosphate kinase (NDPK) in the sarcolemmal membrane is responsible for suppressing the formation of the second messenger cyclic adenosine monophosphate (cAMP)—a key component required for calcium ion homeostasis for the proper systolic and diastolic functions. Typically, this increased NDPK content lets the surplus NDPK react with a mutated G protein in the beta-adrenergic signal transduction pathway, thereby inhibiting cAMP synthesis. Thus, it is thus that inhibition of NDPK may cause a substantial increase in adenylate cyclase activity, which in turn may be a potential therapy for end-stage heart failure patients. However, there is little information available about the molecular events at the interface of NDPK and any prospective molecule that may potentially influence its reactive site (His118). Here we report a novel computational approach for understanding the interactions between graphene oxide (GO) and NDPK. Using molecular dynamics, it is found that GO interacts favorably with the His118 residue of NDPK to potentially prevent its binding with adenosine triphosphate (ATP), which otherwise would trigger the phosphorylation of the mutated G protein. Therefore, this will result in an increase in cAMP levels during heart failure.
Interleukin-6 and Interferon-α Signaling via JAK1–STAT Differentially Regulate Oncolytic versus Cytoprotective Antiviral States

Malignancy-induced alterations to cytokine signaling in tumor cells differentially regulate their interactions with the immune system and oncolytic viruses. The abundance of inflammatory cytokines in the tumor microenvironment suggests that such signaling plays key roles in tumor development and therapy efficacy. The JAK–STAT axis transduces signals of interleukin-6 (IL-6) and interferons (IFNs), mediates antiviral responses, and is frequently altered in prostate cancer (PCa) cells. However, how activation of JAK–STAT signaling with different cytokines regulates interactions between oncolytic viruses and PCa cells is not known. Here, we employ LNCaP PCa cells, expressing (or not) JAK1, activated (or not) with IFNs (α or γ) or IL-6, and infected with RNA viruses of different oncolytic potential (EHDV-TAU, hMPV-GFP, or HIV-GFP) to address this matter. We show that in JAK1-expressing cells, IL-6 sensitized PCa cells to viral cell death in the presence or absence of productive infection, with dependence on virus employed. Contrastingly, IFNα induced a cytoprotective antiviral state. Biochemical and genetic (knockout) analyses revealed dependency of antiviral state or cytoprotection on STAT1 or STAT2 activation, respectively. In IL-6-treated cells, STAT3 expression was required for anti-proliferative signaling. Quantitative proteomics (SILAC) revealed a core repertoire of antiviral IFN-stimulated genes, induced by IL-6 or IFNs. Oncolysis in the absence of productive infection, induced by IL-6, correlated with reduction in regulators of cell cycle and metabolism. These results call for matching the viral features of the oncolytic agent, the malignancy-induced genetic-epigenetic alterations to JAK/STAT signaling and the cytokine composition of the tumor microenvironment for efficient oncolytic virotherapy.
Improvement of the Mechanical Properties of Nano-TiO2/Poly(Vinyl Alcohol) Composites by Enhanced Interaction Between Nanofiller and Matrix

Surface-carboxylated nano-TiO2 was used to prepare poly (vinyl alcohol) (PVA) nanocomposites to improve the dispersity of nano-TiO2 particles in PVA and to enhance the interaction between nanofiller and matrix. The effects of the extents of carboxylation and carboxylated nano-TiO2 loading on mechanical properties of the nanocomposites were investigated. The results show that the tensile strength of the nanocomposites was greatly improved, both by increasing the carboxylated nano-TiO2 loading and by the extent of carboxylation of the nanoparticles, compared with unmodified nano-TiO2. The storage modulus within the rubbery state increased and the loss tangent decreased with increasing COOH content on the TiO2 surface and with increasing carboxylated nano-TiO2 loading. These observations were attributed to a high dispersion of modified nano-TiO2 in the PVA matrix and to crosslinking between OH groups in PVA chains and COOH moieties on inorganic nanoparticle surfaces. POLYM. COMPOS. , 31:1184–1193, 2010. © 2009 Society of Plastics Engineers
MAST/Orbit has a role in microtubule–kinetochore attachment and is essential for chromosome alignment and maintenance of spindle bipolarity

Multiple asters (MAST)/Orbit is a member of a new family of nonmotor microtubule-associated proteins that has been previously shown to be required for the organization of the mitotic spindle. Here we provide evidence that MAST/Orbit is required for functional kinetochore attachment, chromosome congression, and the maintenance of spindle bipolarity. In vivo analysis of Drosophila mast mutant embryos undergoing early mitotic divisions revealed that chromosomes are unable to reach a stable metaphase alignment and that bipolar spindles collapse as centrosomes move progressively closer toward the cell center and eventually organize into a monopolar configuration. Similarly, soon after depletion of MAST/Orbit in Drosophila S2 cells by double-stranded RNA interference, cells are unable to form a metaphase plate and instead assemble monopolar spindles with chromosomes localized close to the center of the aster. In these cells, kinetochores either fail to achieve end-on attachment or are associated with short microtubules. Remarkably, when microtubule dynamics is suppressed in MAST-depleted cells, chromosomes localize at the periphery of the monopolar aster associated with the plus ends of well-defined microtubule bundles. Furthermore, in these cells, dynein and ZW10 accumulate at kinetochores and fail to transfer to microtubules. However, loss of MAST/Orbit does not affect the kinetochore localization of D-CLIP-190. Together, these results strongly support the conclusion that MAST/Orbit is required for microtubules to form functional attachments to kinetochores and to maintain spindle bipolarity.
Interactive effects of water limitation and elevated temperature on the physiology, development and fitness of diverse accessions of Brachypodium distachyon.

An enduring question in plant physiology and evolution is how single genotypes of plants optimize performance in diverse, often highly variable, environments. We grew 35 natural accessions of the grass Brachypodium distachyon in four environments in the glasshouse, contrasting soil water deficit, elevated temperature and their interaction. We modeled treatment, genotype and interactive effects on leaf-level and whole-plant traits, including fecundity. We also assessed the relationship between glasshouse-measured traits and parameters related to climate at the place of origin. We found abundant genetic variation in both constitutive and induced traits related to plant-water relations. Most traits showed strong interaction between temperature and water availability, and we observed genotype-by-environment interaction for several traits. Notably, leaf free proline abundance showed a strong effect of genotype × temperature × water. We found strong associations between phenology, biomass and water use efficiency (WUE) with parameters describing climate of origin. Plants respond to multiple stressors in ways not directly predictable from single stressors, underscoring the complex and trait-specific mechanisms of environmental response. Climate-trait correlations support a role for WUE and phenology in local adaptation to climate in B. distachyon.
Distinct risk factors for obsessive and compulsive symptoms in chronic schizophrenia

Abstract Background Obsessive-compulsive disorder (OCD) is common in clozapine-treated patients although the actual prevalence, phenomenology and risk factors remain unclear. The aim of the present study was to address the three aforementioned questions. Methods The electronic records of a large cohort of clozapine-medicated schizophrenia patients routinely screened for OCD were used. The Obsessive Compulsive Inventory Revised version (OCI-R) was available from 118 cases and a 21 points cut-off threshold for OCD was defined. Results OCD prevalence was 47%, higher in patients on poly-pharmacy than on monotherapy (64% vs 31%; p = 0.001). Two OCI-R factors had significantly higher scores and distinct risk factors: checking behaviour (mean = 5.1; SD = 3.6) correlated with length of clozapine treatment (r = 0.21; p = 0.026), and obsessing factor (mean = 4.8; SD = 3.6) correlated with psychosis severity (r = 0.59; p = 0.001). These factors along with total OCI-R, did not correlate with either clozapine dose or plasma levels, after correcting for psychosis severity. Conclusions Screening for OCD in clozapine patients, and probably in those treated with structurally similar drugs with potent antiserotoninergic properties, should be widely adopted by clinicians. Further research is needed to understand the pathophysiology underlying repetitive behavior onset in clozapine-treated patients.
Sleep Quality Associated With Different Work Schedules: A Longitudinal Study of Nursing Staff

Purpose: To explore the differences in sleep parameters between nurses working a slow, forward rotating shift and those working a fixed day shift. Method: A longitudinal parallel-group comparison design was used in this prospective study. Participants (female) were randomly assigned to a rotating shift or a fixed day shift group. Participants in the rotating shift group worked day shift for the first 4 weeks, followed by evening shift for the second and night shift the third. Those in the day shift group worked day shift for all 12 weeks. Each kept a sleep diary and wore an actigraph (actigraph data were used to calculate total sleep time [TST], sleep onset latency [SOL], wake after sleep onset [WASO], and sleep efficiency [SE]) for 12 days, from Workday 1–4 in each of Weeks 4, 8, and 12. Results: TST in nurses working evening rotating shift was higher than that for those working the day or night rotating shift and fixed day shift. WASO was significantly longer on Day 2 for rotating shift participants working evening versus day shift. SOL and SE were significantly shorter and lower in rotating shift nurses working night versus both day and evening shifts. Conclusions: A comprehensive understanding of the sleep patterns and quality of nurses with different work shifts may lead to better management of work shifts that reduces the influence of shift work on sleep quality.
Laboratory Evaluation of Warm Stone Matrix Asphalt Mixture

Two kinds of warm additives, Sasobit and Evotherm DAT, were used to develop warm stone mastic asphalt (SMA) mixture. The test results showed that compaction temperature of SMA can be decreased by 30-40°C when using Sasobit or Evotherm DAT. Then, to compare the mechanical performance properties of SMA and warm SMAs, mechanical properties of pavement mixture, including Marshall stability, retained Marshall stability, tensile strength ratio, Cantabro loss, rutting dynamic stability and low temperature flexural strength, were tested in laboratory. The results indicated that Sasobit can decrease obviously the moisture resistance ability and low temperature cracking resistance ability of SMA. Therefore, the pavement performance properties of Sasobit warm SMA are inferior to those of Evotherm DAT warm SMA, which has the nearly same performance properties as hot SMA.
Subcortical hyperintensities in the cholinergic system are associated with improvements in executive function in older adults with coronary artery disease undergoing cardiac rehabilitation

Coronary artery disease (CAD) is frequently accompanied by white matter hyperintensities and executive dysfunction. Because acetylcholine is important in executive function, these symptoms may be exacerbated by subcortical hyperintensities (SH) located in cholinergic (CH) tracts. This study investigated the effects of SH on cognitive changes in CAD patients undergoing a 48‐week cardiac rehabilitation program.
Effect of PCB surface finish on creep properties of lead‐free solder joints

Purpose – To provide further knowledge of the effect of solder composition and PCB surface finish on the creep properties of lead‐free SnAgCu solder joints.Design/methodology/approach – Single‐overlap shear specimens were prepared for the creep testing. The test matrix included three different SnAgCu pastes with hypoeutectic, eutectic, and hypereutectic compositions. An Sn63Pb37 solder paste was used as a reference. The PCB finishes used were NiAu, organic solderability preservative (OSP) and immersion tin. The creep tests were performed at 85 and 105°C using a dead‐weight system.Findings – According to the results, the SnAgCu solder with eutectic or near‐eutectic composition is the safest choice when the creep behaviour of solder joints is considered. Of the three different PCB surface finishes, immersion tin is the most favourable choice for use with SnAgCu joints when creep is the predominant deformation mechanism in the joints. On the NiAu finish the creep properties of SnAgCu solder joints were signi.
Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection

Elderly people are at high risk for influenza-related morbidity and mortality due to progressive immunosenescence. While toll-like receptor (TLR) agonist containing adjuvants, and other adjuvants, have been shown to enhance influenza vaccine-induced protective responses, the mechanisms underlying how these adjuvanted vaccines could benefit the elderly remain elusive. Here, we show that a split H1N1 influenza vaccine (sH1N1) combined with a TLR4 agonist, glucopyranosyl lipid adjuvant formulated in a stable oil-in-water emulsion (GLA-SE), boosts IgG2c:IgG1 ratios, enhances hemagglutination inhibition (HAI) titers, and increases protection in aged mice. We find that all adjuvanted sH1N1 vaccines tested were able to protect both young and aged mice from lethal A/H1N1/California/4/2009 virus challenge after two immunizations compared to vaccine alone. We show that GLA-SE combined with sH1N1, however, also provides enhanced protection from morbidity in aged mice given one immunization (based on change in weight percentage). While the GLA-SE-adjuvanted sH1N1 vaccine promotes the generation of cytokine-producing T helper 1 cells, germinal center B cells, and long-lived bone marrow plasma cells in young mice, these responses were muted in aged mice. Differential in vitro responses, dependent on age, were also observed from mouse-derived bone marrow-derived dendritic cells and lung homogenates following stimulation with adjuvants, including GLA-SE. Besides enhanced HAI titers, additional protective factors elicited with sH1N1 + GLA-SE in young mice were observed, including (a) rapid reduction of viral titers in the lung, (b) prevention of excessive lung inflammation, and (c) homeostatic maintenance of alveolar macrophages (AMs) following H1N1 infection. Collectively, our results provide insight into mechanisms of adjuvant-mediated immune protection in the young and elderly.
Effectiveness and Safety of LMWH Treatment in Patients With Cancer Diagnosed With Non-High-Risk Venous Thromboembolism: Turkish Observational Study (TREBECA)

We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in patients with cancer who are at low risk of venous thromboembolism (VTE). Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed up for a period of 12 months. Due to the study design, there was no specific treatment protocol for LMWH. Primary end points were efficacy and the time to change in VTE status. Of the included 250 patients, 239 (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month 3, month 6, and month 12 visits, respectively. Number of patients treated with enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively. Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients using enoxaparin and bemiparin, respectively (P = .004). Thrombus resolution was observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87 and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third visit, respectively (P = .038). Thrombus resolution was observed in 21 more patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64 patients administered enoxaparin and bemiparin at the fourth visit, respectively (P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal bleeding. This pioneering study shows bemiparin is more effective than enoxaparin in thrombosis resolution and has a similar tolerability profile.
Investigating camera calibration for eye tracking of the physically challenged

This paper tries to address a problem faced by a proportion of community - the paralysed people, and investigates a solution in calibrating a camera used for the purpose of eye detection. The eye tracking is later used to read characters from a partner-assisted keyboard. As such, this keyboard solves the problem of immobility. In order to calibrate camera for the purpose of eye detection, two approaches are implemented-Artificial Neural Networks and Support Vector Machines in context of paralysed people, and are discussed in detail in this paper. The results of both approaches are compared in order to select the best approach to be used in keyboard that operates on eye tracking.
Epicenters of dynamic connectivity in the adaptation of the ventral visual system

Objectives and design: Neuronal responses adapt to familiar and repeated sensory stimuli. Enhanced synchrony across wide brain systems has been postulated as a potential mechanism for this adaptation phenomenon. Here, we used recently developed graph theory methods to investigate hidden connectivity features of dynamic synchrony changes during a visual repetition paradigm. Particularly, we focused on strength connectivity changes occurring at local and distant brain neighborhoods. Principal observations: We found that connectivity reorganization in visual modal cortex—such as local suppressed connectivity in primary visual areas and distant suppressed connectivity in fusiform areas—is accompanied by enhanced local and distant connectivity in higher cognitive processing areas in multimodal and association cortex. Moreover, we found a shift of the dynamic functional connections from primary‐visual‐fusiform to primary‐multimodal/association cortex. Conclusions: These findings suggest that repetition‐suppression is made possible by reorganization of functional connectivity that enables communication between low‐ and high‐order areas. Hum Brain Mapp 38:1965–1976, 2017. © 2017 Wiley Periodicals, Inc.
Interphysician agreement on subclassification of myocardial infarction

Objective The universal definition of myocardial infarction (MI) differentiates MI due to oxygen supply/demand mismatch (type 2) from MI due to plaque rupture (type 1) as well as from myocardial injuries of non-ischaemic or multifactorial nature. The purpose of this study was to investigate how often physicians agree in this classification and what factors lead to agreement or disagreement. Methods A total of 1328 patients diagnosed with MI at eight different Swedish hospitals 2011 were included. All patients were retrospectively reclassified into different MI or myocardial injury subtypes by two independent specially trained physicians, strictly adhering to the third universal definition of MI. Results Overall, there was a moderate interobserver agreement with a kappa coefficient (κ) of 0.55 in this classification. There was substantial agreement when distinguishing type 1 MI (κ: 0.61), compared with moderate agreement when distinguishing type 2 MI (κ: 0.54). In multivariate logistic regression analyses, ST elevation MI (P<0.001), performed coronary angiography (P<0.001) and larger changes in troponin levels (P=0.023) independently made the physicians agree significantly more often, while they disagreed more often with symptoms of dyspnoea (P<0.001), higher systolic blood pressure (P=0.001) and higher C reactive protein levels on admission (P=0.016). Conclusion Distinguishing MI types is challenging also for trained adjudicators. Although strictly adhering to the third universal definition of MI, differentiation between type 1 MI, type 2 MI and myocardial injury only gave a moderate rate of interobserver agreement. More precise and clinically applicable criteria for the current classification, particularly for type 2 MI diagnosis, are urgently needed.
Dynamics of putative raft-associated proteins at the cell surface

Lipid rafts are conceptualized as membrane microdomains enriched in cholesterol and glycosphingolipid that serve as platforms for protein segregation and signaling. The properties of these domains in vivo are unclear. Here, we use fluorescence recovery after photobleaching to test if raft association affects a protein's ability to laterally diffuse large distances across the cell surface. The diffusion coefficients (D) of several types of putative raft and nonraft proteins were systematically measured under steady-state conditions and in response to raft perturbations. Raft proteins diffused freely over large distances (>4 μm), exhibiting Ds that varied 10-fold. This finding indicates that raft proteins do not undergo long-range diffusion as part of discrete, stable raft domains. Perturbations reported to affect lipid rafts in model membrane systems or by biochemical fractionation (cholesterol depletion, decreased temperature, and cholesterol loading) had similar effects on the diffusional mobility of raft and nonraft proteins. Thus, raft association is not the dominant factor in determining long-range protein mobility at the cell surface.
Discovering shakers from evolving entities via cascading graph inference

In an interconnected and dynamic world, the evolution of one entity may cause a series of significant value changes for some others. For example, the currency inflation of Thailand caused the currency slump of other Asian countries, which eventually led to the financial crisis of 1997. We call such high impact entities shakers. To discover shakers, we first introduce the concept of a cascading graph to capture the causality relationships among evolving entities over some period of time, and then infer shakers from the graph. In a cascading graph, nodes represent entities and weighted links represent the causality effects. In order to find hidden shakers in such a graph, two scoring functions are proposed, each of which estimates how much the target entity can affect the values of some others. The idea is to artificially inject a significant change on the target entity, and estimate its direct and indirect influence on the others, by following an inference rule under the Markovian assumption. Both scoring functions are proven to be only dependent on the structure of a cascading graph and can be calculated in polynomial time. Experiments included three datasets in social sciences. Without directly applicable previous methods, we modified three graphical models as baselines. The two proposed scoring functions can effectively capture those high impact entities. For example, in the experiment to discover stock market shakers, the proposed models outperform the three baselines by as much as 50% in accuracy with the ground truth obtained from Yahoo! ~Finance.