Miracle-dz/UniFAR-FTUs huggingface dataset:
The TGB1 Movement Protein of Potato virus X Reorganizes Actin and Endomembranes into the X-Body, a Viral Replication Factory1[W]

Potato virus X (PVX) requires three virally encoded proteins, the triple gene block (TGB), for movement between cells. TGB1 is a multifunctional protein that suppresses host gene silencing and moves from cell to cell through plasmodesmata, while TGB2 and TGB3 are membrane-spanning proteins associated with endoplasmic reticulum-derived granular vesicles. Here, we show that TGB1 organizes the PVX “X-body,” a virally induced inclusion structure, by remodeling host actin and endomembranes (endoplasmic reticulum and Golgi). Within the X-body, TGB1 forms helically arranged aggregates surrounded by a reservoir of the recruited host endomembranes. The TGB2/3 proteins reside in granular vesicles within this reservoir, in the same region as nonencapsidated viral RNA, while encapsidated virions accumulate at the outer (cytoplasmic) face of the X-body, which comprises a highly organized virus “factory. ” TGB1 is both necessary and sufficient to remodel host actin and endomembranes and to recruit TGB2/3 to the X-body, thus emerging as the central orchestrator of the X-body. Our results indicate that the actin/endomembrane-reorganizing properties of TGB1 function to compartmentalize the viral gene products of PVX infection.
FIVE-YEAR OUTCOMES OF INTRAVITREAL INJECTION OF RANIBIZUMAB FOR THE TREATMENT OF MYOPIC CHOROIDAL NEOVASCULARIZATION

Purpose: To evaluate the 5-year outcomes, efficacy, and safety of intravitreal ranibizumab injections for the treatment of myopic choroidal neovascularization. Methods: The medical records of 18 consecutive eyes of 14 patients who received intravitreal injections of ranibizumab for myopic choroidal neovascularization with a follow-up of 5 years were retrospectively reviewed. Outcomes included best-corrected visual acuity, total number of treatments, and complications. Results: The average number of injections over 5 years was 4.56 ± 3.52. Ten eyes (55.56%) had no need for treatment after the first year. Mean best-corrected visual acuity improved from 0.59 ± 0.47 logarithm of the minimum angle of resolution (Snellen equivalent, 6/24) at baseline to 0.32 ± 0.35 logarithm of the minimum angle of resolution (Snellen equivalent, 6/13) at 1 year, and to 0.38 ± 0.42 logarithm of the minimum angle of resolution (Snellen equivalent, 6/15) at 2 years (P = 0.001 and 0.020, respectively; paired t-test). After 2 years, although mean best-corrected visual acuity remained better than baseline, the difference was not statistically significant. At 5 years, vision improved by at least 1 line for 61.11% of eyes and by more than 3 lines for 33.33%. The final visual acuity of 2 eyes was worse than baseline because of disease activity and profound chorioretinal atrophy, which increased in six eyes. No complications were noted. Conclusion: Intravitreal ranibizumab was safe and effective for treating myopic choroidal neovascularization. Only 44% of eyes required retreatment after the first year, and vision improved in more than 60% of eyes over 5 years.
Adherence to preventive medications in asthmatic children at a tertiary care teaching hospital in Malaysia

Purpose Asthma affects an estimated 300 million people worldwide. Poor adherence to prescribed preventive medications, especially among children with asthma, leads to increased mortality and morbidity. The purpose of this study was to assess the adherence and persistence levels of asthmatic children at the Universiti Kebangsaan Malaysia Medical Center (UKMMC), a tertiary care teaching hospital, and to determine the factors that influence adherence to prescribed preventive medications. Patients and methods Participants were asthmatic patients aged 18 years and younger with at least one prescription for a preventive medication refilled between January and December 2011. Refill records from the pharmacy dispensing database were used to determine the medication possession ratio (MPR) and continuous measure of gaps (CMG), measures of adherence and persistence levels, respectively. Results The sample consisted of 218 children with asthma from the General and Respiratory pediatric clinics at UKMMC. The overall adherence level was 38% (n=83; MPR ≥80%), and the persistence level was 27.5% (n=60; CMG ≤20%). We found a significant association between the adherence and persistence levels (r=0.483, P<0.01). The presence of comorbidities significantly predicted the adherence (odds ratio [OR] =16.21, 95% confidence interval [CI]: 7.76–33.84, P<0.01) and persistence level (OR =2.63, 95% CI: 0.13–52.79, P<0.01). Other factors, including age, sex, ethnicity, duration of asthma diagnosis, and number of prescribed preventive medications did not significantly affect adherence or persistence (P>0.05). Conclusion In conclusion, the adherence level among children with asthma at UKMMC was low. The presence of comorbidities was found to influence adherence towards preventive medications in asthmatic children.
Private Paternalism, the Commitment Puzzle, and Model-Free Equilibrium†

Paternalism is a policy that advances an individual's interests by restricting his or her freedom. In a setting with present-biased agents, I characterize the scope of private paternalism—paternalism implemented by private institutions. Private paternalism arises from two channels: (i) agents who seek commitment because they hold sophisticated beliefs about their present bias, and (ii) agents (naive or sophisticated) who use model-free forecasts to choose organizations that have a history of generating high experienced utility flows for their members (O'Donoghue and Rabin 1999b). When naive consumers are common, private paternalism will be shrouded, explaining why commitment mechanisms are typically shrouded in the labor market (the commitment puzzle). Private paternalism has greater traction when production occurs in the formal sector instead of the informal (household) sector, where monitors are not always present, able, or willing to implement socially efficient forcing mechanisms.
Demonstration of nuclear 3H-estradiol binding in hypothalamus and amygdala of female, androgenized-female, and male rats.

The subcellular distribution of radioactivity in female, androgenized female, and male rats 1 hour after the iv administration of tritiated estradiol was examined. High regional specificity among nucle ar fractions of brain areas was seen with the preoptic-anterior hypothal amic area (POA-AH), median eminence-basal hypothalamus (ME-BH), and amygdala having much higher nuclear binding than other brain areas. Nuc lear binding was receptor-mediated in POA-AH, ME-BH, amygdala, dorsal hypothalamus, and the prehypothalamic area in all groups, as demonstrate d by competetive inhibition with diethylstilbestrol (DES). At this time period no differences between male and female rats in DES-blockable radioactivity levels of either nuclear or supernatant fractions in any brain area or pituitary were observed. Androgenized females had lower DES-blockable, nuclear radioactivity levels in POA-AH, ME-BH, and uteri but the % of total tissue radioactivity in the nuclei did not differ between groups for any tissue. These results demonstrate that males and females have similar estradiol uptake systems that are capable of high levels of nuclear binding in various brain areas.
The Actual Intrinsic Excitability of Granular Cells Determines the Ruling Neurovascular Coupling Mechanism in the Rat Dentate Gyrus

Paired-pulse stimulation of the perforant pathway was used to study the relation between granular cell activity and the resultant fMRI response in the rat dentate gyrus. By varying the interpulse interval (IPI), paired-pulse stimulations caused: a depression (20 ms IPI), a facilitation (100 ms IPI), a mixture of depression and facilitation (30 ms IPI), or no change (500 ms IPS) in the second response. Eight identical paired pulses were applied during one stimulation train and the evoked field potentials and generated fMRI responses were measured simultaneously. Application of consecutive stimulation trains caused time-dependent variations in electrophysiological and fMRI responses, which were characteristic for each stimulus protocol. Depending on the IPI, the magnitude of the fMRI response either correlated strongly with or was apparently unrelated to the spiking or postsynaptic activity of the granular cells. A strong relation between spiking activity and resultant fMRI response was only found when the stimulation protocol caused an increase in the recorded population spike latency. If the latency was decreased, the fMRI response was more closely related to the applied input activity. Perforant pathway fibers monosynaptically activate granular cells, so variations in population spike latencies reflect changes in their intrinsic excitability. Therefore, during increased intrinsic excitability, signaling cascades upstream of the granular cells determine the fMRI response, whereas granular cell activity-related mechanisms control the fMRI response during decreased intrinsic excitability.
A Proposed System for Real Time Adaptive N Version Programming

N-version programming is a fault tolerance technique that depends on a generic decision algorithm to determine a consensus result from the results delivered by two or more member versions of the software. In N-version programming, N teams of developers work independently on N unique but equivalent implementations of the same program. The major objectives of the NVP process are to maximize the independence of version development and to employ design diversity in order to minimize the probability that two or more member versions will produce similar erroneous results that coincide in time for a decision (consensus) action. But this fault-tolerance technique has been criticized for its statistical assumptions and high cost. A solution is proposed in which there are N versions of the software out of which t versions implement only a subset of the entire functionality which is highly critical while (N – t) versions implement the entire functionality. One of the biggest hurdles in using N version programming for fault tolerance is its high implementation cost. This proposed technique minimizes the cost of implementation while improving the efficiency and reliability of the system.
Robust Continuous Co-Clustering

Clustering consists of grouping together samples giving their similar properties. The problem of modeling simultaneously groups of samples and features is known as Co-Clustering. This paper introduces ROCCO - a Robust Continuous Co-Clustering algorithm. ROCCO is a scalable, hyperparameter-free, easy and ready to use algorithm to address Co-Clustering problems in practice over massive cross-domain datasets. It operates by learning a graph-based two-sided representation of the input matrix. The underlying proposed optimization problem is non-convex, which assures a flexible pool of solutions. Moreover, we prove that it can be solved with a near linear time complexity on the input size. An exhaustive large-scale experimental testbed conducted with both synthetic and real-world datasets demonstrates ROCCO's properties in practice: (i) State-of-the-art performance in cross-domain real-world problems including Biomedicine and Text Mining; (ii) very low sensitivity to hyperparameter settings; (iii) robustness to noise and (iv) a linear empirical scalability in practice. These results highlight ROCCO as a powerful general-purpose co-clustering algorithm for cross-domain practitioners, regardless of their technical background.
Identify Susceptible Locations in Medical Records via Adversarial Attacks on Deep Predictive Models

The surging availability of electronic medical records (EHR) leads to increased research interests in medical predictive modeling. Recently many deep learning based predicted models are also developed for EHR data and demonstrated impressive performance. However, a series of recent studies showed that these deep models are not safe: they suffer from certain vulnerabilities. In short, a well-trained deep network can be extremely sensitive to inputs with negligible changes. These inputs are referred to as adversarial examples. In the context of medical informatics, such attacks could alter the result of a high performance deep predictive model by slightly perturbing a patient's medical records. Such instability not only reflects the weakness of deep architectures, more importantly, it offers a guide on detecting susceptible parts on the inputs. In this paper, we propose an efficient and effective framework that learns a time-preferential minimum attack targeting the LSTM model with EHR inputs, and we leverage this attack strategy to screen medical records of patients and identify susceptible events and measurements. The efficient screening procedure can assist decision makers to pay extra attentions to the locations that can cause severe consequence if not measured correctly. We conduct extensive empirical studies on a real-world urgent care cohort and demonstrate the effectiveness of the proposed screening.
Surface tension/thermal mismatch in a self-assembly process

Surface tension is increasingly used for the self-assembly of 3D microstructures. This paper studies the use of a benzocyclobutene (BCB) photo-resist material for the out-of-plane rotation via self-assembly behavior of a silicon micro-part. The literature discusses both surface-tension self-assembly and thermal-mismatch self-assembly, but these two topics are treated separately. Due to its relatively large thermal expansion coefficient, the BCB photo-resist material exhibits both surface-tension and thermal-mismatch effects during self-assembly. Therefore, the residual stresses induced by the self-assembly process on the interface between the melting pad and the microstructure are an issue that needs clarification. In order to quantify the shear stress on the interface, a micro-cantilever test specimen is designed and fabricated by a two-mask self-assembly process using a BSOI wafer and DRIE etching. Two cantilever designs are compared, one having a single section of photo-resist coverage and the other having two sections of photo-resist coverage. The MSC/NASTRAN finite-element method with an interfacial shear-lag model is used to estimate the deflection of the cantilever beam due to residual stresses from surface tension and thermal shrinkage. A clamped-edge-body-rotation model is proposed in order to calibrate measurement results by confocal optical microscopy with numerical results. The interfacial shear between the BCB photo-resist and the silicon structure is found to range from 0.4 to 1.0 MPa due to thermal shrinkage (after soft bake and structure release). The residual stress from surface tension (after material reflow and self-assembly) depends on the thickness of the PR layer and in some cases is twice the residual stress from material mismatch. Finally, a micro-mirror design employing BCB melting pads is presented to verify a self-assembly process powered by both surface tension and thermal mismatch.
A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac alternans dynamics

In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1.2 (e.g. cooperative gating). Here, mathematical analysis and computational models were used to determine how changes in the strength of cooperative gating between LTCCs may impact membrane voltage and intracellular Ca2+ dynamics in the heart. We found that increasing the degree of coupling between LTCCs increases the amplitude of Ca2+ currents (ICaL) and prolongs AP duration (APD). Increased AP duration is known to promote cardiac alternans, a potentially arrhythmogenic substrate. In addition, our analysis shows that increasing the strength of cooperative activation of LTCCs makes the coupling of Ca2+ on the membrane voltage (Cai→Vm coupling) more positive and destabilizes the Vm-Cai dynamics for Vm-driven alternans and Cai-driven alternans, but not for quasiperiodic oscillation. These results suggest that cooperative gating of LTCCs may have a major impact on cardiac excitation-contraction coupling, not only by prolonging APD, but also by altering Cai→Vm coupling and potentially promoting cardiac arrhythmias.
Progression of Coronary Artery Calcium and Incident Heart Failure: The Multi‐Ethnic Study of Atherosclerosis

Background Although the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi‐Ethnic Study of Atherosclerosis. Methods and Results The Multi‐Ethnic Study of Atherosclerosis is a population‐based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi‐Ethnic Study of Atherosclerosis participants who had baseline and follow‐up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2 years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow‐up of 9.6 (interquartile range: 8.8–10.6) years, 182 participants developed incident HF. CAC progression of 10 units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease (P=0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (β=0.16; P=0.03) and LV end systolic volume (β=0.12; P=0.006) after excluding participants with any coronary heart disease. Conclusions CAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow‐up exam independent of overt coronary heart disease.
Accurate estimation of f0 and aperiodicity based on periodicity detector residuals and deviations of phase derivatives

We introduce a new fundamental frequency (f0) and aperiodicity estimation method with its certified calibration data on estimation accuracy. The proposed method is based on two independent representations. The first representation is a set of band-wise residuals of a self-tuning process to suppress the prominent periodic component in the band-pass filtered output. The second representation is a set of band-wise deviation measure of the instantaneous frequency of the band-pass filtered output. The combined measure of these representations provides accurate estimates of SNR of each filtered band. This combination significantly reduces the distribution spread from 0.5% to 99.5% probability. The reduction is about 5 dB (for example, 21 dB to 16 dB). A wavelet-based configuration provides the initial estimate of f0. A short term Fourier transform-based configuration provides refinement of f0 and accurate estimate of aperiodicity. A MATLAB implementation of the procedure will be available as an open-source package.
Secrecy Performance of Finite-Sized Cooperative Full-Duplex Relay Systems With Unreliable Backhauls

This paper investigates secrecy performance of finite-sized cooperative full-duplex relay (FDR) systems with unreliable wireless backhaul connections across multiple transmitters under Nakagami- $m$ fading. Closed-form expressions for the secrecy outage probability and probability of nonzero achievable secrecy rate are derived in terms of self-interference (SI), transmitter cooperation, and backhaul reliability. It is shown that transmitter cooperation can effectively enhance the secrecy performance, while the asymptotic limits on the secrecy outage probability and probability of nonzero achievable secrecy rate are exclusively determined by backhaul reliability. With the aid of transmitter cooperation, the burden of SI cancelation can be alleviated for the FDR system in achieving the smallest allowed secrecy outage probability. Compared to that of a half-duplex relay (HDR) system, the FDR system achieves a lower secrecy outage probability with well suppressed SI. The analysis shows that the secrecy outage probability achieved by the FDR system converges to that of the HDR system under perfect backhaul as the target secrecy rate becomes small. The secrecy performance metrics of the considered system are verified by simulations for various backhaul scenarios.
An event-triggered dynamic scheduling method for randomly arriving tasks in cloud manufacturing

ABSTRACT Cloud manufacturing (CMfg) is a service-oriented manufacturing mode and provides customers with on-demand manufacturing services via network. To solve the task scheduling problem in the dynamic CMfg environment with randomly arriving tasks, this article presents an event-triggered dynamic task scheduling (EDS) method. The event-triggered strategy is designed by considering arrival of new tasks and completion of first or middle subtasks in the subtask sequences to improve the timeliness of the service scheduler. The subtask-oriented strategy is applied to avoid service pre-emption so that the timely and effective task schedules can be obtained. The service time, logistic time and earliest available time of the candidate services are combined to choose the optimal services for triggered subtasks. Based on a case study of numerical control machining, the experimental results demonstrate that the average task execution time of the task schedules obtained through EDS was shorter than the other three task scheduling methods as tasks arrive randomly over time, and the total amount of occupied services during the scheduling period was not high.
Target Identification and Mode of Action of Four Chemically Divergent Drugs against Ebolavirus Infection

Here, we show that four chemically divergent approved drugs reported to inhibit Ebolavirus infection, benztropine, bepridil, paroxetine and sertraline, directly interact with the Ebolavirus glycoprotein. Binding of these drugs destabilizes the protein, suggesting that this may be the mechanism of inhibition, as reported for the anticancer drug toremifene and the painkiller ibuprofen, which bind in the same large cavity on the glycoprotein. Crystal structures show that the position of binding and the mode of interaction within the pocket vary significantly between these compounds. The binding constants (Kd) determined by thermal shift assay correlate with the protein–inhibitor interactions as well as with the antiviral activities determined by virus cell entry assays, supporting the hypothesis that these drugs inhibit viral entry by binding the glycoprotein and destabilizing the prefusion conformation. Details of the protein–inhibitor interactions of these complexes and their relation with binding affinity may facilitate the design of more potent inhibitors.