Miracle-dz/UniFAR-FTUs huggingface dataset:
Informed Choice of Composite End Points in Cardiovascular Trials

A composite end point is often used as the primary end point to assess the efficacy of a new treatment in randomized clinical trials. In cardiovascular trials, the often rare event of the relevant primary end point (individual or composite), such as cardiovascular death, myocardial infarction, or both, is combined with a more common secondary end point, such as target lesion revascularization, with the aim to increase the statistical power of the study. Gómez and Lagakos developed statistical methodology to be used at the design stage of a randomized clinical trial for deciding whether to expand a study-relevant primary end point to the composite of the relevant end point and a secondary end point. The method uses the asymptotic relative efficiency of the logrank test for comparing treatment groups based on the relevant end point versus the logrank test based on the composite end point. The method is used to assess, in the cardiovascular research area, the characteristics of the candidate individual end points that should govern the choice of using a composite end point as the primary end point in a clinical trial. A set of recommendations is provided based on the reported values of the frequencies of observing each candidate end point and on the magnitude of the effect of treatment as expressed by the hazard ratio, supported by cardiovascular randomized clinical trials published in 2008.
Network Analysis of Unfolding Trajectory of the SH3 Domain

It is important to understand how proteins consistently fold into their native-state structures and the relevance of structure to their function. In this work, we study the unfolding pathway of SH3 from the perspective of network. Our results show that the average clustering coefficient is less sensitive to the structural change and the average shortest path lengths can examine the larger structural changes. The betweenness values of the hydrophobic cores locate at the local maximum in the network of native state and that of the folding nucleus locate at the maximum in the network of transition state. It is easy for the betweenness of the transition state network to distinguish the folding nucleus from other residues and identify the hydrophobic core regions from the betweenness of the native state network. The hydrophobic core and folding nucleus all become derogated from native state to denature state. The hydrophobic collapse model and nucleation condensation model become reconciled in this finding.
Concept for zero-alignment micro-optical systems

In this paper we present the results of the first fabrication and micro-assembly experiments of a silicon- wafer based micro-optical table (MOT). Based on these experiments, estimates of position accuracy are reported. We also report on progress in fabrication of lens elements in a hybrid sol-gel material (HSGM). Diffractive optical elements have been patterned in a 13-micron thick HSGM layer on a 150-micron thick soda-lime glass substrate. The measured rms surface roughness was 20 nm. Finally, we describe modeling of MOT systems using non-sequential ray tracing.
The Hippo tumor-suppressor pathway regulates apical-domain size in parallel to tissue growth

The Hippo tumor-suppressor pathway controls tissue growth in Drosophila and mammals by regulating cell proliferation and apoptosis. The Hippo pathway includes the Fat cadherin, a transmembrane protein, which acts upstream of several other components that form a kinase cascade that culminates in the regulation of gene expression through the transcriptional coactivator Yorkie (Yki). Our previous work in Drosophila indicated that Merlin (Mer) and Expanded (Ex) are members of the Hippo pathway and act upstream of the Hippo kinase. In contrast to this model, it was suggested that Mer and Ex primarily regulate membrane dynamics and receptor trafficking, thereby affecting Hippo pathway activity only indirectly. Here, we examined the effects of Mer, Ex and the Hippo pathway on the size of the apical membrane and on apical-basal polarity complexes. We found that mer;ex double mutant imaginal disc cells have significantly increased levels of apical membrane determinants, such as Crb, aPKC and Patj. These phenotypes were shared with mutations in other Hippo pathway components and required Yki, indicating that Mer and Ex signal through the Hippo pathway. Interestingly, however, whereas Crb was required for the accumulation of other apical proteins and for the expansion of the apical domain observed in Hippo pathway mutants, its elimination did not significantly reverse the overgrowth phenotype of warts mutant cells. Therefore, Hippo signaling regulates cell polarity complexes in addition to and independently of its growth control function in imaginal disc cells.
The L18 Domain of Light-harvesting Chlorophyll Proteins Binds to Chloroplast Signal Recognition Particle 43*

Chloroplast signal recognition particle (cpSRP) is a novel type of SRP that contains a homolog of SRP54 and a 43-kDa subunit absent from all cytoplasmic SRPs but lacks RNA. It is also distinctive in its ability to post-translationally interact with light-harvesting chlorophyll proteins (LHCP), hydrophobic proteins synthesized in the cytoplasm and targeted to the thylakoid via the stroma. LHCP integration into thylakoid membranes requires the two subunits of cpSRP, cpFtsY, GTP, and the membrane protein ALB3. It had previously been shown that the L18 domain, an 18-amino acid peptide between the second and third transmembrane domains, and a hydrophobic domain are required for interaction with cpSRP. In the present study we used a pull-down assay, with cpSRP43 or cpSRP54 fused to glutathione-transferase, to study interactions between cpSRP43, cpSRP54, LHCP, and cpFtsY. cpFtsY was not observed to form significant interactions with any of the proteins even in the presence of nonhydrolyzable GTP analogs. Our data indicate that cpSRP43 binds to the L18 domain, that cpSRP54 binds to the hydrophobic domain, and that LHCP and cpSRP54 independently bind to cpSRP43. These data confirm that the novel post-translational interaction between LHCP and cpSRP is mediated through binding to cpSRP43.
Does Baum-Welch Re-estimation Help Taggers?

In part of speech tagging by Hidden Markov Model, a statistical model is used to assign grammatical categories to words in a text. Early work in the field relied on a corpus which had been tagged by a human annotator to train the model. More recently, Cutting et al. (1992) suggest that training can be achieved with a minimal lexicon and a limited amount of a priori information about probabilities, by using an Baum-Welch re-estimation to automatically refine the model. In this paper, I report two experiments designed to determine how much manual training information is needed. The first experiment suggests that initial biasing of either lexical or transition probabilities is essential to achieve a good accuracy. The second experiment reveals that there are three distinct patterns of Baum-Welch reestimation. In two of the patterns, the re-estimation ultimately reduces the accuracy of the tagging rather than improving it. The pattern which is applicable can be predicted from the quality of the initial model and the similarity between the tagged training corpus (if any) and the corpus to be tagged. Heuristics for deciding how to use re-estimation in an effective manner are given. The conclusions are broadly in agreement with those of Merialdo (1994), but give greater detail about the contributions of different parts of the model.
Trends in Short- and Long-Term Survival Among Out-of-Hospital Cardiac Arrest Patients Alive at Hospital Arrival

Background— Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and poses a significant burden to the healthcare system, but few studies have evaluated whether OHCA incidence and survival have changed over time. Methods and Results— A population-based cohort study was conducted, including 34 291 OHCA patients >20 years of age who were transported alive to the emergency department of an acute-care hospital from April 1, 2002, to March 31, 2012, in Ontario, Canada. Patients with life-threatening trauma and those who died before hospital arrival were excluded. The overall age- and sex-standardized incidence of OHCA patients who were transported alive was 36 cases per 100 000 persons and did not significantly change over the study period. Cardiac risk factor prevalence increased significantly, whereas the rate of most cardiovascular conditions decreased significantly. The 30-day survival improved from 9.4% in 2002 to 13.6% in 2011; 1-year survival improved from 7.7% to 11.8% (P<0.001). Patients hospitalized in 2011 were significantly more likely to survive 30 days (adjusted odds ratio, 1.47 [95% CI, 1.22–1.77]) and 1 year (adjusted odds ratio, 1.55 [95% CI, 1.27–1.91]) compared with 2002. A significant interaction between temporal trends in survival improvement and age group was observed in which the improvement in survival was largest in the youngest age groups. Conclusions— OHCA patients who were transported alive are increasingly likely to have cardiovascular risk factors but less likely to have previous cardiovascular conditions. The overall incidence of OHCA patients transported to hospital alive did not change over the past decade. Short- and longer-term survival after OHCA has substantially improved, with younger patients experiencing the greatest improvement.
Relativistically expanding cylindrical electromagnetic fields

We study relativistically expanding electromagnetic fields of cylindrical geometry. The fields emerge from the side surface of a cylinder and are invariant under translations parallel to the axis of the cylinder. The expansion velocity is in the radial direction and is parametrized by v = R/(ct). We consider force-free magnetic fields by setting the total force the electromagnetic field exerts on the charges and the currents equal to zero. Analytical and semi-analytical separable solutions are found for the relativistic problem. In the non-relativistic limit, the mathematical form of the equations is similar to equations that have already been studied in static systems of the same geometry.
Accurate and efficient replaying of file system traces

Replaying traces is a time-honored method for benchmarking, stress-testing, and debugging systems--and more recently--forensic analysis. One benefit to replaying traces is the reproducibility of the exact set of operations that were captured during a specific workload. Existing trace capture and replay systems operate at different levels: network packets, disk device drivers, network file systems, or system calls. System call replayers miss memory-mapped operations and cannot replay I/O-intensive workloads at original speeds. Traces captured at other levels miss vital information that is available only at the file system level. We designed and implemented Replayfs, the first system for replaying file system traces at the VFS level. The VFS is the most appropriate level for replaying file system traces because all operations are reproduced in a manner that is most relevant to file-system developers. Thanks to the uniform VFS API, traces can be replayed transparently onto any existing file system, even a different one than the one originally traced, without modifying existing file systems. Replayfs's user-level compiler prepares a trace to be replayed efficiently in the kernel where multiple kernel threads prefetch and schedule the replay of file system operations precisely and efficiently. These techniques allow us to replay I/O-intensive traces at different speeds, and even accelerate them on the same hardware that the trace was captured on originally.
Impact and factors associated with nighttime and early morning symptoms among patients with chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms. While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood. Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011. Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week. Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met. Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures. Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels. Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom. Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms. Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without. Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD.
Effects of Ochratoxin A on Livestock Production

Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain to humans. The aim of this paper is to review the available literature on: (1) the frequency and degree of occurrence of OTA in different feedstuffs; (2) the toxicological effects of OTA intake on the performance of the main livestock (i.e., poultry, swine, cattle, goats and sheep); and (3) the transfer of OTA, or its metabolites, from animal feed into animal products such as milk, meat and eggs.
Coordinate representation of order types requires exponential storage

We give doubly exponential upper and lower bounds on the size of the smallest grid on which we can embed every planar configuration of n points in general position up to order type. The lower bound is achieved by the construction of a widely dispersed “rigid” configuration which is then modified to one in general position by recent techniques of Sturmfels and White, while the upper bound uses recent results of Grigor'ev and Vorobjou on the solution of simultaneous inequalities. This provides a sharp answer to a question first posed by Chazelle.
Health economic impacts and cost-effectiveness of aflatoxin-reduction strategies in Africa: case studies in biocontrol and post-harvest interventions

Advances in health economics have proven useful in evaluating the cost-effectiveness of interventions, where the benefit usually takes the form of improved health outcomes rather than market outcomes. The paper performs health-based cost-effectiveness analyses of two potential aflatoxin control strategies in Africa: (1) pre-harvest biocontrol, using atoxigenic strains of Aspergillus flavus competitively to exclude toxigenic strains from colonizing maize in Nigeria; and (2) post-harvest interventions in a package to reduce aflatoxin accumulation in groundnuts in Guinea. It is described how health benefits gained from each intervention, in terms of fewer aflatoxin-induced hepatocellular carcinoma cases, can be compared with the costs of implementing the interventions. It is found that both interventions would be extremely cost-effective if applied widely in African agriculture. That is, the monetized value of lives saved and quality of life gained by reducing aflatoxin-induced hepatocellular carcinoma far exceeds the cost of either biocontrol or the post-harvest intervention package to achieve those health benefits. The estimated cost-effectiveness ratio (CER; gross domestic product multiplied by disability-adjusted life years saved per unit cost) for biocontrol in Nigerian maize ranged from 5.10 to 24.8; while the estimated CER for the post-harvest intervention package in Guinean groundnuts ranged from 0.21 to 2.08. Any intervention with a CER > 1 is considered by the World Health Organization (WHO) to be ‘very cost-effective’, while an intervention with a CER > 0.33 is considered ‘cost-effective’. Aside from cost-effectiveness, public health interventions must be readily accepted by the public, and must have financial and infrastructural support to be feasible in the parts of the world where they are most needed.
Distortion viewing techniques for 3-dimensional data

As the use of 3D information presentation becomes more prevalent, the need for effective viewing tools grows accordingly. Much work has been done in developing tools for 2D spaces which allow for detail in context views. We examine the extension of such 2D methods to 3D and explore the limitations encountered in accessing internal regions of the data with these methods. We then describe a novel solution to this problem of internal access with the introduction of a distortion function which creates a clear line of sight to the focus revealing sections previously obscured. The distortion is symmetric about the line of sight and is smoothly integrated back into the original 3D layout.
Regular expression pattern matching for XML

We propose regular expression pattern matching as a core feature for programming languages for manipulating XML (and similar tree-structured data formats). We extend conventional pattern-matching facilities with regular expression operators such as repetition (*), alternation (I), etc., that can match arbitrarily long sequences of subtrees, allowing a compact pattern to extract data from the middle of a complex sequence. We show how to check standard notions of exhaustiveness and redundancy for these patterns.Regular expression patterns are intended to be used in languages whose type systems are also based on the regular expression types. To avoid excessive type annotations, we develop a type inference scheme that propagates type constraints to pattern variables from the surrounding context. The type inference algorithm translates types and patterns into regular tree automata and then works in terms of standard closure operations (union, intersection, and difference) on tree automata. The main technical challenge is dealing with the interaction of repetition and alternation patterns with the first-match policy, which gives rise to subtleties concerning both the termination and the precision of the analysis. We address these issues by introducing a data structure representing closure operations lazily.
A manipulation planner for pick and place operations under continuous grasps and placements

This paper addresses the manipulation planning problem which deals with motion planning for robots manipulating movable objects among static obstacles. We propose a manipulation planner capable of handling continuous domains for modeling both the possible grasps and the stable placements of a single movable object, rather than discrete sets generally assumed by the existing planners. The algorithm relies on a topological property that characterizes the existence of solutions in the subspace of configurations where the robot grasps the object placed at a stable position. This property leads to reduce the problem by structuring the search-space. It allows us to devise a manipulation planner that directly captures in a probabilistic roadmap the connectivity of sub-dimensional manifolds of the composite configuration space. First experiments demonstrate the feasibility and the efficiency of the approach.
Cyclic Strain Inhibits Notch Receptor Signaling in Vascular Smooth Muscle Cells In Vitro

Notch signaling has been shown recently to regulate vascular cell fate in adult cells. By applying a uniform equibiaxial cyclic strain to vascular smooth muscle cells (SMCs), we investigated the role of strain in modulating Notch-mediated growth of SMCs in vitro. Rat SMCs cultured under conditions of defined equibiaxial cyclic strain (0% to 15% stretch; 60 cycles/min; 0 to 24 hours) exhibited a significant temporal and force-dependent reduction in Notch 3 receptor expression, concomitant with a significant reduction in Epstein Barr virus latency C promoter-binding factor-1/recombination signal-binding protein of the J&kgr; immunoglobulin gene–dependent Notch target gene promoter activity and mRNA levels when compared with unstrained controls. The decrease in Notch signaling was Gi-protein– and mitogen-activated protein kinase–dependent. In parallel cultures, cyclic strain inhibited SMC proliferation (cell number and proliferating cell nuclear antigen expression) while significantly promoting SMC apoptosis (annexin V binding, caspase-3 activity and bax/bcl-xL ratio). Notch 3 receptor overexpression significantly reversed the strain-induced changes in SMC proliferation and apoptosis to levels comparable to unstrained control cells, whereas Notch inhibition further potentiated the changes in SMC apoptosis and proliferation. These findings suggest that cyclic strain inhibits SMC growth while enhancing SMC apoptosis, in part, through regulation of Notch receptor and downstream target gene expression.
An Overview of Bayesian Methods for Neural Spike Train Analysis

Neural spike train analysis is an important task in computational neuroscience which aims to understand neural mechanisms and gain insights into neural circuits. With the advancement of multielectrode recording and imaging technologies, it has become increasingly demanding to develop statistical tools for analyzing large neuronal ensemble spike activity. Here we present a tutorial overview of Bayesian methods and their representative applications in neural spike train analysis, at both single neuron and population levels. On the theoretical side, we focus on various approximate Bayesian inference techniques as applied to latent state and parameter estimation. On the application side, the topics include spike sorting, tuning curve estimation, neural encoding and decoding, deconvolution of spike trains from calcium imaging signals, and inference of neuronal functional connectivity and synchrony. Some research challenges and opportunities for neural spike train analysis are discussed.