Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta‐analysis of genetic association studies and adjustment for multiple testing of correlated SNPs and traits

Meta‐analysis has become a key component of well‐designed genetic association studies due to the boost in statistical power achieved by combining results across multiple samples of individuals and the need to validate observed associations in independent studies. Meta‐analyses of genetic association studies based on multiple SNPs and traits are subject to the same multiple testing issues as single‐sample studies, but it is often difficult to adjust accurately for the multiple tests. Procedures such as Bonferroni may control the type‐I error rate but will generally provide an overly harsh correction if SNPs or traits are correlated. Depending on study design, availability of individual‐level data, and computational requirements, permutation testing may not be feasible in a meta‐analysis framework. In this article, we present methods for adjusting for multiple correlated tests under several study designs commonly employed in meta‐analyses of genetic association tests. Our methods are applicable to both prospective meta‐analyses in which several samples of individuals are analyzed with the intent to combine results, and retrospective meta‐analyses, in which results from published studies are combined, including situations in which (1) individual‐level data are unavailable, and (2) different sets of SNPs are genotyped in different studies due to random missingness or two‐stage design. We show through simulation that our methods accurately control the rate of type I error and achieve improved power over multiple testing adjustments that do not account for correlation between SNPs or traits. Genet. Epidemiol. 34: 739‐746, 2010. © 2010 Wiley‐Liss, Inc.
Detection of a Mixed Infection in a Culture-Negative Brain Abscess by Broad-Spectrum Bacterial 16S rRNA Gene PCR

ABSTRACT We describe the identification of two bacterial pathogens from a culture-negative brain abscess by the use of broad-spectrum 16S rRNA gene PCR. Simultaneous detection of Fusobacterium nucleatum and Porphyromonas endodontalis was possible due to a 24-bp length difference of their partially amplified 16S rRNA genes, which allowed separation by high-resolution polyacrylamide gel electrophoresis.
Reflex Sympathetic Dystrophy Associated with Antiepileptic Drugs

Summary: Reflex sympathetic dystrophy syndrome (RSDS) complicating antiepileptic drug (AED) therapy is not well acknowledged in the neurologic literature. We report 4 patients with reflex sympathetic dystrophy that occurred while they were receiving AEds. All patients had shoulder and hand involvement, which in 2 was bilateral, and 1 had ipsilateral foot involvement. Two patients did not respond to a change in AEDs, but all improved with a course of prednisone. One patient with phenobarbital (PB)‐associated RSDS relapsed on inadvertent rechallenge with secobarbital. A review of the literature showed that several other fibrosing disorders are associated with AED administration, including Du‐puytren's contractures, frozen shoulder, plantar and hand nodules, and Peyronie's disease. RSD associated with AEDs is important to recognize because it may result in permanent disability if treatment is delayed.
Precision measurements of absorption and refractive-index using an atomic candle

Across a broad range of disciplines, the accurate determination of an electromagnetic wave's amplitude (either absolute or relative) has considerable relevance. We demonstrate a novel and potentially very precise method for making intensity measurements based on the atomic stabilization of electromagnetic field-strength. For ease of reference, and by analogy to atomic clocks, we refer to this field-strength stabilization system as an atomic candle. While the candle's original purpose was to create a field with long-term intensity stability, its very nature makes it ideal for detecting subtle amplitude changes in strong electromagnetic fields, a problem that is fundamentally different from detecting weak signals in the presence of noise. In this paper, we discuss proof-of-principle experiments demonstrating the atomic candle's ability to make precise measurements of absorption coefficients and indices of refraction.
Detecting multiple copies in tampered images

Copy-move forgeries are parts of the image that are duplicated elsewhere into the same image, often after being modified by geometrical transformations. In this paper we present a method to detect these image alterations, using a SIFT-based approach. First we describe a state of the art SIFT-point matching method, which inspired our algorithm, then we compare it with our SIFT-based approach, which consists of three parts: keypoint clustering, cluster matching, and texture analysis. The goal is to find copies of the same object, i.e. clusters of points, rather than points that match. Cluster matching proves to give better results than single point matching, since it returns a complete and coherent comparison between copied objects. At last, textures of matching areas are analyzed and compared to validate results and to eliminate false positives.
Prognostic factors for perceived pain and function at one-year follow-up in primary care patients with neck pain

Purpose: To identify prognostic factors for perceived pain and function with focus at one-year follow-up in primary care patients treated for non-specific neck pain. Methods: A prospective study was performed including 193 neck pain patients. Before and after treatment period, and 12 months after the start date for treatment, patients completed a questionnaire including background data and aspects of pain, function and general health. Linear multiple regression analysis was used to identify prognostic factors with the dependent variables Oswestry score and pain intensity at 12-month follow-up. Response rate 81%. Results: At 12-month follow-up, Oswestry score identified four prognostic factors: pain intensity; well-being; expectations of treatment; and duration of current episode. Adjusted R2 for the model was 0.32, and 20% of the patients had three of the four prognostic factors at entry, indicating risk of poor outcome. The dependent variable pain intensity revealed three prognostic factors: Oswestry score; duration of current episode; and similar problem during the previous five years. Adjusted R2 was 0.24, and 60% of the patients had two of the three prognostic factors at entry, indicating risk of poor outcome. Conclusions: Different prognostic factors (with the exception of duration of current episode) were identified by the two outcome variables. Thus the results suggest that it should be taken into account whether an impairment or disability outcome is used.
Distributional Semantics for Answer Re-ranking in Question Answering

This paper investigates the role of Distributional Semantic Models (DSMs) into a Question Answering (QA) system. Our purpose is to exploit DSMs for answer re-ranking in QuestionCube, a framework for building QA systems. DSMs model words as points in a geometric space, also known as semantic space. Words are similar if they are close in that space. Our idea is that DSMs approaches can help to compute relatedness between users’ questions and candidate answers by exploiting paradigmatic relations between words, thus providing better answer reranking. Results of the evaluation, carried out on the CLEF2010 QA dataset, prove the effectiveness of the proposed approach.
Photoactivated [3+2] Addition of 6,7-seco-angustilobine B to Fullerene [C60]

A synthesis of a new alkaloid-fullerene conjugate (1) is reported. The reaction was carried out by photoinduced [3+2] cycloaddition of the Alstonia indole alkaloid, 6,7-seco-angustilobine B (2), to fullerene[C60] (3) under aerobic conditions. The major monoaddition photoadduct (1) was characterized unambiguously by UV, IR, MALDI-TOFMS and NMR experiments. A mechanism highlighted by sequential photoinduced electron transfer and radical recombination pathways is also proposed. No significant enhancement in inhibition against M. tuberculosis H37Rv was observed for 1 compared with its parent compounds 2 and 3.
Criteria to Assess In Vivo Performance and Bioequivalence of Generic Controlled‐Release Formulations of Carbamazepine

Summary: Purpose: Concern persists that the criteria used to establish bioequivalence of generic drugs may not adequately guarantee the interchangeability of antiepileptic medications (AEDs), particularly controlled‐release (CR) formulations. We examined the utilization of several new parameters, in addition to AUC, peak plasma concentration (Cmax), and time to reach Cmax (tmax), for the assessment of bioequivalence and in vivo performance of CBZ and other CR products. These new parameters may offer additional information for evaluation of CR products that yield a prominent plateau in the plasma time‐concentration curve. They include mean residence time (MRT), Cmax/AUC, plateau time or POT (the time span associated with the concentrations within 25% of Cmax), tapical, and Capical, (the arithmetic mean of the POT times and concentrations within 25% of Cmax respectively). Additional parameters for multiple‐dose studies include the percentage fluctuation and the flatness of the steady state‐concentration curve.
Sanitation in urban flood settings

People affected by floods in urban areas can be susceptible to illness and death from disease related to inadequate water supplies, sanitation and poor hygiene. The most significant diseases are infectious diseases transmitted by the faecal-oral route (such as diarrhoea). Other water and sanitation-related diseases include those carried by vectors associated with solid waste and water. The main objective of any WASH programmes in a urban flood setting is to reduce the transmission of faecal-oral and vector borne by promoting good hygiene practices, providing safe drinking water and by reducing environmental health risks through the provision of sanitation services.
How sensitive is processor customization to the workload's input datasets?

Hardware customization is an effective approach for meeting application performance requirements while achieving high levels of energy efficiency. Application-specific processors achieve high performance at low energy by tailoring their designs towards a specific workload, i.e., an application or application domain of interest. A fundamental question that has remained unanswered so far though is to what extent processor customization is sensitive to the training workload's input datasets. Current practice is to consider a single or only a few input datasets per workload during the processor design cycle — the reason being that simulation is prohibitively time-consuming which excludes considering a large number of datasets. This paper addresses this fundamental question, for the first time. In order to perform the large number of runs required to address this question in a reasonable amount of time, we first propose a mechanistic analytical model, built from first principles, that is accurate within 3.6% on average across a broad design space. The analytical model is at least 4 orders of magnitude faster than detailed cycle-accurate simulation for design space exploration. Using the model, we are able to study the sensitivity of a workload's input dataset on the optimum customized processor architecture. Considering MiBench benchmarks and 1000 datasets per benchmark, we conclude that processor customization is largely dataset-insensitive. This has an important implication in practice: a single or only a few datasets are sufficient for determining the optimum processor architecture when designing application-specific processors.
Capacity and Fairness Analysis of Heterogeneous Networks with Range Expansion and Interference Coordination

Range expansion and inter-cell interference coordination (ICIC) can improve the capacity and fairness of heterogeneous network (HetNet) deployments by off-loading macrocell users to low-power nodes. Due to difficulties in analytical treatment, current studies for range expansion and ICIC in HetNets rely mostly on simulations. In this letter, first, off-loading benefits of range expansion in HetNets are captured through cumulative distribution functions (CDFs) of the downlink signal to interference plus noise ratio (SINR) difference between the macrocell and strongest picocell signals. Then, these CDFs are used to investigate the system capacity and fairness as a continuous function of the range expansion bias, and benefits of using ICIC with range expansion are demonstrated through numerical results.
Dynamics in Prophage Content of Invasive and Noninvasive M1 and M28 Streptococcus pyogenes Isolates in The Netherlands from 1959 to 1996

ABSTRACT Invasive group A streptococcal (GAS) disease reemerged in The Netherlands in the late 1980s. To seek an explanation for this resurgence, the genetic compositions of 22 M1 and 19 M28 GAS strains isolated in The Netherlands between 1960s and the mid-1990s were analyzed by using a mixed-genome DNA microarray. During this four-decade period, M1 and especially M28 strains acquired prophages on at least eight occasions. All prophages carried a superantigen (speA2, speC, speK) or a streptodornase (sdaD2, sdn), both associated with invasive GAS disease. Invasive and noninvasive GAS strains did not differ in prophage acquisition, suggesting that there was an overall increase in the pathogenicity of M1 and M28 strains over the last four decades rather than emergence of hypervirulent subclones. The increased overall pathogenic potential may have contributed to the reemergence of invasive GAS disease in The Netherlands.
A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects

Background When chemical health hazards have been identified, probabilistic dose–response assessment (“hazard characterization”) quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. Objectives We developed a unified framework for probabilistic dose–response assessment. Methods We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose–response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, “effect metrics” can be specified to define “toxicologically equivalent” sizes for this underlying individual response; and d) dose–response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose–response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Results Probabilistically derived exposure limits are based on estimating a “target human dose” (HDMI), which requires risk management–informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%–10% effect sizes. Conclusions Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions. Citation Chiu WA, Slob W. 2015. A unified probabilistic framework for dose–response assessment of human health effects. Environ Health Perspect 123:1241–1254; http://dx.doi. org/10.1289/ehp.1409385
Domain Interaction Studies of Herpes Simplex Virus 1 Tegument Protein UL16 Reveal Its Interaction with Mitochondria

ABSTRACT The UL16 tegument protein of herpes simplex virus 1 (HSV-1) is conserved among all herpesviruses and plays many roles during replication. This protein has an N-terminal domain (NTD) that has been shown to bind to several viral proteins, including UL11, VP22, and glycoprotein E, and these interactions are negatively regulated by a C-terminal domain (CTD). Thus, in pairwise transfections, UL16 binding is enabled only when the CTD is absent or altered. Based on these results, we hypothesized that direct interactions occur between the NTD and the CTD. Here we report that the separated and coexpressed functional domains of UL16 are mutually responsive to each other in transfected cells and form complexes that are stable enough to be captured in coimmunoprecipitation assays. Moreover, we found that the CTD can associate with itself. To our surprise, the CTD was also found to contain a novel and intrinsic ability to localize to specific spots on mitochondria in transfected cells. Subsequent analyses of HSV-infected cells by immunogold electron microscopy and live-cell confocal imaging revealed a population of UL16 that does not merely accumulate on mitochondria but in fact makes dynamic contacts with these organelles in a time-dependent manner. These findings suggest that the domain interactions of UL16 serve to regulate not just the interaction of this tegument protein with its viral binding partners but also its interactions with mitochondria. The purpose of this novel interaction remains to be determined. IMPORTANCE The HSV-1-encoded tegument protein UL16 is involved in multiple events of the virus replication cycle, ranging from virus assembly to cell-cell spread of the virus, and hence it can serve as an important drug target. Unfortunately, a lack of both structural and functional information limits our understanding of this protein. The discovery of domain interactions within UL16 and the novel ability of UL16 to interact with mitochondria in HSV-infected cells lays a foundational framework for future investigations aimed at deciphering the structure and function of not just UL16 of HSV-1 but also its homologs in other herpesviruses.
The Circadian System Contributes to Apnea Lengthening across the Night in Obstructive Sleep Apnea.

STUDY OBJECTIVE To test the hypothesis that respiratory event duration exhibits an endogenous circadian rhythm. DESIGN Within-subject and between-subjects. SETTINGS Inpatient intensive physiologic monitoring unit at the Brigham and Women's Hospital. PARTICIPANTS Seven subjects with moderate/severe sleep apnea and four controls, age 48 (SD = 12) years, 7 males. INTERVENTIONS Subjects completed a 5-day inpatient protocol in dim light. Polysomnography was recorded during an initial control 8-h night scheduled at the usual sleep time, then through 10 recurrent cycles of 2 h 40 min sleep and 2 h 40 min wake evenly distributed across all circadian phases, and finally during another 8-h control sleep period. MEASUREMENTS AND RESULTS Event durations, desaturations, and apnea-hypopnea index for each sleep opportunity were assessed according to circadian phase (derived from salivary melatonin), time into sleep, and sleep stage. Average respiratory event durations in NREM sleep significantly lengthened across both control nights (21.9 to 28.2 sec and 23.7 to 30.2 sec, respectively). During the circadian protocol, event duration in NREM increased across the circadian phases that corresponded to the usual sleep period, accounting for > 50% of the increase across normal 8-h control nights. AHI and desaturations were also rhythmic: AHI was highest in the biological day while desaturations were greatest in the biological night. CONCLUSIONS The endogenous circadian system plays an important role in the prolongation of respiratory events across the night, and might provide a novel therapeutic target for modulating sleep apnea.
Local Cell Mediated Immune Reaction in Primary Obstructive Male Infertility

Increased intra-epididymal pressure due to obstruction causes a breach in the epididymal lining exposing the highly antigenic sperms to the interstitium. When the exposure is small and intermittent, it is likely to induce a local humoral response which may affect sperm maturation and also react with the epididymal epithelium producing irreversible histological changes. The present study on 30 patients of primary obstructive infertility found direct and indirect evidence of the production of antisperm antibodies locally. ELISA for antisperm antibodies was positive in the epididymal fluid in 16/30 (53%) of the patients. Indirect evidence of the role of local antigen-antibody reaction in the epididymis is apparent in 22/30 (73%) patients who had a lymphocytic infiltrate. The local presence of antisperm antibodies in the epididymal fluid correlated well with the presence of lymphocytic infiltration in the interstitium (p < 0.05). In our study 16/30 patients had a positive ELISA for antisperm antibody and all these patients had interstitial lymphocytic infiltration. In addition eight patients with a negative ELISA also showed interstitial lymphocytic infiltration. Thus 22/30 (73%) patients had an evidence of a local immune reaction directly in the form of a positive ELISA for antisperm antibodies in the epididymal fluid and / or indirect evidence in the form of lymphocytic infiltrate in the interstitium. None of the five controls had either a positive ELISA or lymphocytic infiltrate, this difference was found to be statistically significant (p < 0.005).
An improved algorithm to find the length of the longest common subsequence of two strings

Let <i>A</i> and <i>B</i> be strings of common length <i>n. </i> Define <i>LLCS</i>(<i>A, B</i>) to be the length of the longest common subsequence of <i>A</i> and <i>B. </i> Hunt and Szymanski presented an algorithm for finding <i>LLCS</i>(<i>A, B</i>) with time complexity <i>O</i>((<i>r</i> + <i>n</i>)<i>logn</i>), where <i>r</i> is the number of elements in the set {(<i>i, j</i>)|<i>A</i>[<i>i</i>] = <i>B</i>[<i>j</i>]}. In the worst case the algorithm has running time of <i>O</i>(<i>n</i><sup>2</sup><i>logn</i>). We present an improvement to this algorithm which changes the time complexity to <i>O</i>(<i>r</i> + <i>n</i>(<i>LLCS</i>(<i>A, B</i>) + <i>logn</i>)). Some experimental results show dramatic improvements for large <i>n. </i>
DVM-MAC: A Mandatory Access Control System in Distributed Virtual Computing Environment

We design and implement a Mandatory Access Control (MAC) system in distributed virtual computing environment, named DVM-MAC, aiming to provide distributed trust through enforcing MAC policies. In DVM-MAC, Prioritized Chinese Wall (PCW) model is implemented to control potential covert channels between VMs in both single node and distributed environment. A policy enforcement module locates inside Xen VMM for better enforcing MAC locally rather than outside the VMM. DVM-MAC adopts centralized architecture for multi-level management and secure transmission of inter-node policy information. For performance consideration, a specific policy decision and enforcement module for controlling inter-node behaviors is moved out of Xen VMM and up to user space. DVM-MAC authorizes a specific center node named Central Security Server (CSS) to be responsible for the decision making between the nodes as well as leaves the inter-node policy enforcement module in each node. Through our experiments and data analysis, we verify the correctness, effectiveness, and efficiency in our prototype when implementing PCW model.