Miracle-dz/UniFAR-FTUs huggingface dataset:
Platinum Sensitivity–Related Germline Polymorphism Discovered via a Cell-Based Approach and Analysis of Its Association with Outcome in Ovarian Cancer Patients

Purpose: Cell-based approaches were used to identify genetic markers predictive of patients' risk for poor response prior to chemotherapy. Experimental Design: We conducted genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNP) associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCL) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression-free survival (PFS) in patients. Phase 1 validation was based on 377 ovarian cancer patients receiving at least four cycles of carboplatin and paclitaxel from the Australian Ovarian Cancer Study (AOCS). Positive associations were then assessed in phase 2 validation analysis of 1,326 patients from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas. Results: In the initial GWAS, 342 SNPs were associated with carboplatin-induced cytotoxicity, of which 18 unique SNPs were retained after assessing their association with gene expression. One SNP (rs1649942) was replicated in an independent LCL set (Bonferroni adjusted P < 0.05). It was found to be significantly associated with decreased PFS in phase 1 AOCS patients (Pper-allele = 2 × 10−2), with a stronger effect in the subset of women with optimally debulked tumors (Pper-allele = 4 × 10−3). rs1649942 was also associated with poorer overall survival in women with optimally debulked tumors (Pper-allele = 9 × 10−3). However, this SNP was not significant in phase 2 validation analysis with patients from numerous cohorts. Conclusion: This study shows the potential of cell-based, genome-wide approaches to identify germline predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect. Clin Cancer Res; 17(16); 5490–500. ©2011 AACR.
Memory security management for reconfigurable embedded systems

The constrained operating environments of many FPGA-based embedded systems require flexible security that can be configured to minimize the impact on FPGA area and power consumption. In this paper, a security approach for external memory in FPGA-based embedded systems that exploits FPGA configurability is presented. Our FPGA-based security core provides both confidentiality and integrity for data stored externally to an FPGA which is accessed by a processor on the FPGA chip. The benefits of our security core are demonstrated using four embedded applications implemented on a Stratix II device. Each application requires a collection of tasks with varying memory security requirements. Our security core is used in conjunction with a NIOS II soft processor running the MicroC/OS II operating system. An average memory and energy savings of about 64%and 16%, respectively, is achieved for the four applications versus a non-configurable, uniform security approach.
Immunotherapy and Targeted Therapies in the Treatment of Non-small Cell Lung Cancer

I n the last decade, the emergence of targeted therapies has changed the treatment paradigm for non-small cell lung cancer (NSCLC). The growing availability of therapies targeting specific genetic alterations, such as epidermal growth factor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, have led to changes in the guidelines to reflect the need for molecular profiling. More recently, immunotherapeutic approaches have been investigated in the treatment setting of NSCLC, and these may provide superior outcomes and have substantially better tolerability compared to chemotherapy. Immunotherapies currently available for NSCLC include the checkpoint inhibitors anti-PD-1 antibodies nivolumab and pembrolizumab. Several other anti-PD-L1 compounds such as atezolizumab, durvalumab and avelumab are also very advanced in clinical investigation, in monotherapy as well as in combination with immune priming phase activators anti-CTLA4 ipilimumab and tremelimumab, across all treatment lines. The challenge facing oncologists is identifying which therapy is best suited to the individual patient.
Analysis of chain reaction between two stock indices fluctuations by statistical physics systems

In this paper, we consider the statistical properties of chain reaction of stock indices. The theory of interacting systems and statistical physics are applied to describe and study the fluctuations of two stock indices in a stock market, and the properties of the interacting reaction of the two indices are investigated in the present paper. In this work, stochastic analysis and the two random paths model are used to study the probability distribution for the chain reaction of stock indices, further we show the asymptotical behavior of probability measures of the fluctuations for the two stock indices model. In the last part, we discuss the convergence of the finite dimensional probability distributions for the financial model.
Calculation of the Maximum Mechanical Stress on the Rotor of Interior Permanent-Magnet Synchronous Motors

This paper proposes a novel analytical method to calculate the maximum mechanical stress (MMS) on the rotor of the interior permanent-magnet synchronous motor with V-shaped rotor structure. Based on the traditional equivalent ring method, an improved method, which draws on the principle of equivalent centroid, is proposed to calculate the mechanical stress on the bilateral magnetic bridge. A rotor model with spokes is also built to calculate the mechanical stress on the central magnetic bridge. The stress concentration factor, together with its selection method, is also defined to calculate the MMS on the junctions. Then, the changing trends of the mechanical stress on the bilateral and central bridges are obtained along with the change in the V-shaped angle. The rotor faults of the two IPMSMs are analyzed based on the research results, and the optimized prototype is designed and fabricated. Experimental results of the optimized prototype show that the proposed equivalent methods have great applicability. Finally, the suggestion to design the V-shaped rotor structure is presented to determine the design rapidly and accurately.
Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs.
Species delimitation and phylogeographic analyses in the Ectocarpus subgroup siliculosi (Ectocarpales, Phaeophyceae)

The genus Ectocarpus (Ectocarpales, Phaeophyceae) contains filamentous algae widely distributed in marine and estuarine habitats of temperate regions in both hemispheres. While E. siliculosus has become a model organism for genomics and genetics of the brown macroalgae, accurate species delineation, distribution patterns and diversity for the genus Ectocarpus remain problematic. In this study, we used three independent species delimitation approaches to generate a robust species hypothesis for 729 Ectocarpus specimens collected mainly along the European and Chilean coasts. These approaches comprised phylogenetic reconstructions and two bioinformatics tools developed to objectively define species boundaries (General Mixed Yule Coalescence Method and Automatic Barcode Gap Discovery). Our analyses were based on DNA sequences of two loci: the mitochondrial cytochrome oxidase subunit 1 and the nuclear internal transcribed spacer 1 of the ribosomal DNA. Our analyses showed the presence of at least 15 cryptic species and suggest the existence of incomplete lineage sorting or introgression between five of them. These results suggested the possible existence of different levels of reproductive barriers within this species complex. We also detected differences among species in their phylogeographic patterns, range and depth distributions, which may suggest different biogeographic histories (e.g., endemic species or recent introductions).
Spectrum of Lateral Medullary Syndrome: Correlation Between Clinical Findings and Magnetic Resonance Imaging in 33 Subjects

Background and Purpose Computed tomography is insufficient in evaluation of medullary lesions. Although lateral medullary infarction is a relatively common type of cerebrovascular disease, detailed correlation between clinical findings and magnetic resonance imaging (MRI) has not yet been reported. Methods We studied 33 consecutive patients with lateral medullary infarction who showed appropriate MRI lesions and correlated their clinical findings with the MRI results. Results Gait ataxia (88%), vertigo/dizziness (91%), nausea/vomiting (73%), dysphagia (61%), hoarseness (55%), Horner sign (73%), and facial (85%) and hemibody (94%) sensory changes were frequent clinical findings. MRI results showed that the lesions located in the rostral part of the medulla were usually diagonal band‐shaped and were associated with more severe dysphagia, hoarseness, and the presence of facial paresis, whereas the caudal lesions, situated usually in the lateral surface of the medulla, appeared to correlate with more marked vertigo, nystagmus, and gait ataxia. Nausea/vomiting and Horner sign were common regardless of the lesion location, and lesions extending ventromedially correlated with facial sensory change on the contralateral side of the lesion. Conclusions Analysis of MRI findings in rostrocaudal and dorsoventral aspects allows us, although not unequivocally, to make anatomicoclinical correlations in the evaluation of patients with lateral medullary stroke syndrome. (Stroke. 1994;25:1405‐1410.)
In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum

ABSTRACT The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.
Glucose Intolerance Due to Insulin Resistance in Patients with Spinal Cord Injuries

SUMMARY Glucose intolerance occurs frequently in patients with spinal cord injury (SCI). To characterize this better, 45 patients with spinal cord injuries received oral glucose tolerance tests (OGTT). The subjects with glucose intolerance had significantly higher insulin levels than either the glucose-tolerant or normal control subjects. Since hyperinsulinism in the presence of glucose intolerance suggests insulin resistance, the peripheral insulin activity (A) was calculated from the OGTT data. The glucose-intolerant SCI patients had significantly lower A values than the other groups. The most resistant SCI subjects (A<0.3) also had resistance to exogenous insulin. In 18 subjects receiving insulin tolerance tests, the A value calculated from the OGTT was 100% accurate in predicting the presence of sensitivity or resistance to exogenous insulin. In spite of the presence of insulin resistance, however, 125I-insulin binding to SCI patients' circulating monocytes was not significantly different from that in control subjects.
Hearing loss impacts neural alpha oscillations under adverse listening conditions

Degradations in external, acoustic stimulation have long been suspected to increase the load on working memory (WM). One neural signature of WM load is enhanced power of alpha oscillations (6–12 Hz). However, it is unknown to what extent common internal, auditory degradation, that is, hearing impairment, affects the neural mechanisms of WM when audibility has been ensured via amplification. Using an adapted auditory Sternberg paradigm, we varied the orthogonal factors memory load and background noise level, while the electroencephalogram was recorded. In each trial, participants were presented with 2, 4, or 6 spoken digits embedded in one of three different levels of background noise. After a stimulus-free delay interval, participants indicated whether a probe digit had appeared in the sequence of digits. Participants were healthy older adults (62–86 years), with normal to moderately impaired hearing. Importantly, the background noise levels were individually adjusted and participants were wearing hearing aids to equalize audibility across participants. Irrespective of hearing loss (HL), behavioral performance improved with lower memory load and also with lower levels of background noise. Interestingly, the alpha power in the stimulus-free delay interval was dependent on the interplay between task demands (memory load and noise level) and HL; while alpha power increased with HL during low and intermediate levels of memory load and background noise, it dropped for participants with the relatively most severe HL under the highest memory load and background noise level. These findings suggest that adaptive neural mechanisms for coping with adverse listening conditions break down for higher degrees of HL, even when adequate hearing aid amplification is in place.
An Etiological Model of Posttraumatic Stress Disorder in Female OEF/OIF/OND Veterans: Adding Military Sexual Trauma as a Risk Factor

AN ETIOLOGICAL MODEL OF POSTTRAUMATIC STRESS DISORDER IN FEMALE OEF/OIF/OND VETERANS: ADDING MILITARY SEXUAL TRAUMA AS A RISK FACTOR Erin Doty Kurtz Virginia Consortium Program in Clinical Psychology, 2016 Director: Dr. Michelle L. Kelley Studies on posttraumatic stress disorder (PTSD) in returning Iraq and Afghanistan veterans have involved limited focus on the specific risk and protective factors for female veterans and how these may differ from factors identified for male veterans. Additionally, models incorporating risk and protective factors for PTSD in female veterans have yet to include military sexual trauma (MST) as a risk factor. Given the prevalence of MST among female service members, this study examined whether MST predicts PTSD diagnosis in addition to other frequently examined variables (premilitary trauma exposure, combat exposure, postmilitary trauma, and perceived social support). In addition, the degree to which social support mediated any identified relationship between MST and PTSD diagnosis was explored, as well as whether MST moderated the relationship between combat exposure and PTSD diagnosis. An etiological model for PTSD was proposed and was explored for model fit with female veterans to determine pathways among risk and protective factors for women. Data were examined from 202 female veterans and active duty service members who took part in a multi-site research study conducted through the Department of Veterans Affairs (VA) VISN 6 Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC). Results indicate that MST is a key risk factor to include in models of PTSD in female veterans returning from Iraq and Afghanistan. It was found that social support mediated the relationship between MST and PTSD symptoms, and partially mediated the relationship between aftermath of battle and PTSD symptoms, but did not mediate the relationship between combat trauma and PTSD symptoms; rather, combat experiences had a direct effect on PTSD symptoms. Additionally, results suggest that experiences of premilitary trauma may increase female service members’ vulnerability to MST and that social support mediated the relationship between premilitary trauma and PTSD symptoms, but only through an increased vulnerability to MST. Postmilitary trauma was also found to mediate the relationship between premilitary trauma and PTSD symptoms. Results may provide key information for developing training programs and therapeutic interventions to reduce both MST and PTSD in female veterans.
Fracture characteristics of wood under mode I, mode II and mode III loading

Abstract Wood is a highly optimized cellular orthotropic material. Its structural properties have major influence on the fracture mechanics behaviour of the material. The aim of the presented study is the evaluation and analysis of differences in the fracture process of wood subjected to fundamental fracture modes. The results of fracture mechanics experiments for mode I, mode II and mode III in two crack propagation systems were evaluated. The fracture process is discussed by means of the load-displacement diagrams recorded under stable crack propagation and the calculation of the specific fracture energy. It was found that the typical specific fracture energy is much higher for the mode II and mode III cases than for mode I loading. The differences for wood are explained by different energy-dissipating processes such as the development of larger damage zones for mode II and mode III loading than for mode I loading. The influence of the chosen orientation and its relation to structural parameters of the material are also discussed. The findings are supported by microscopic images of typical fracture surfaces.
Comparative Analysis of Proliferation and Differentiation Potentials of Stem Cells from Inflamed Pulp of Deciduous Teeth and Stem Cells from Exfoliated Deciduous Teeth

Stem cells isolated from exfoliated deciduous teeth (SHEDs) are highly capable of proliferation and differentiation, and they represent good cell sources for mesenchymal stem cell- (MSC-) mediated dental tissue regeneration, but the supply of SHEDs is limited. A previous study found that stem cells could be isolated from inflamed tissues, but it is unknown whether primary dental pulp diagnosed with irreversible pulpitis might contain stem cells with appropriate tissue regeneration capacity. In this study, we aimed to isolate stem cells from both inflamed pulps of deciduous teeth (SCIDs) and SHEDs from Chinese children and to compare their proliferation and differentiation potentials. Our results showed that SCIDs were positive for cell surface markers, including CD105, CD90, and CD146, and they had high proliferation ability and osteogenic, adipogenic, and chondrogenic differentiation potentials. There was no significant difference in proliferation and differentiation potentials between SCIDs and SHEDs. The mRNA of inflammatory factors, including IL-1β, IL-6, and TNF-α, was expressed at similar levels in SCIDs and SHEDs, but SCIDs secreted more TNF-α protein. In conclusion, our in vitro results showed that SCIDs have proliferation and differentiation potentials similar to those of SHEDs. Thus, SCIDs represent a new potentially applicable source for MSC mediated tissue regeneration.
Socioeconomic Disparities and Prevalence of Autism Spectrum Disorders and Intellectual Disability

Background and Objectives Study of the impact of socioeconomic status on autism spectrum disorders (ASD) and severe intellectual disabilities (ID) has yielded conflicting results. Recent European studies suggested that, unlike reports from the United States, low socioeconomic status is associated with an increased risk of ASD. For intellectual disabilities, the links with socioeconomic status vary according to the severity. We wished to clarify the links between socioeconomic status and the prevalence of ASD (with or without ID) and isolated severe ID. Methods 500 children with ASD and 245 children with severe ID (IQ <50) aged 8 years, born 1995 to 2004, were recruited from a French population-based registry. Inclusions were based on clinical diagnoses reported in medical records according to the International Classification of Diseases, 10th Revision. Socioeconomic status was measured by indicators available at block census level which characterize the population of the child’s area of residence. Measures of deprivation, employment, occupation, education, immigration and family structure were used. Prevalences were compared between groups of census units defined by the tertiles of socioeconomic level in the general population. Results Prevalence of ASD with associated ID was higher in areas with the highest level of deprivation and the highest percentage of unemployed adults, persons with no diploma, immigrants and single-parent families. No association was found when using occupational class. Regarding ASD without associated ID, a higher prevalence was found in areas with the highest percentage of immigrants. No association was found for other socioeconomic indicators. The prevalence of isolated severe ID was likely to be higher in the most disadvantaged groups defined by all indicators. Conclusion The prevalence of ASD with associated ID and of severe isolated ID is more likely to be higher in areas with the highest level of deprivation.
Outage diversity of MIMO block-fading channels with causal channel state information

We study the outage diversity of the multiple-input multiple-output (MIMO) Rayleigh block-fading channel when causal channel state information (CSI) is available at the transmitter (CSIT). Within this setting, we consider the optimal power allocation for blocks b = 1, …, B given perfect CSIT for blocks 1, …, b–u only, subject to a long-term power constraint. The parameter 0 ≤ u ≤ B is a fixed arbitrary integer that determines the delay in acquiring perfect knowledge of the CSI at the transmitter. Without explicitly solving the optimal power allocation problem, we derive the outage diversity of the system. For general 0 ≤ u ≤ B, we derive a simple recursive expression for computing the outage diversity. For the special case u = 0, it is shown that the outage diversity is infinite, coinciding with previously known results. For 1 ≤ u ≤ B, the outage diversity becomes finite and for the special case of u = 1, 2 it can be expressed in simple closed form.