Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving genetic diagnosis in Mendelian disease with transcriptome sequencing

Transcriptome sequencing improves the diagnostic rate for Mendelian disease in patients for whom genetic analysis has not returned a diagnosis. RNA analysis for patients Although genome and exome sequencing are becoming increasingly common and are often useful in diagnosing unexplained genetic disease, more than half of all patients remain undiagnosed by these methods. Cummings et al. have now gone one step further, using RNA sequencing to evaluate patients with undiagnosed muscle disorders. With this approach, the authors were able to provide a diagnosis for another 35% of their patients, suggesting its potential utility for clinical genetic evaluation. The authors also identified a new disease-causing mutation in collagen VI and validated it in an additional cohort of patients with undiagnosed collagen dystrophy, again successfully diagnosing a sizeable percentage of patients. Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples. We demonstrate the power of RNA-seq to validate candidate splice-disrupting mutations and to identify splice-altering variants in both exonic and deep intronic regions, yielding an overall diagnosis rate of 35%. We also report the discovery of a highly recurrent de novo intronic mutation in COL6A1 that results in a dominantly acting splice-gain event, disrupting the critical glycine repeat motif of the triple helical domain. We identify this pathogenic variant in a total of 27 genetically unsolved patients in an external collagen VI–like dystrophy cohort, thus explaining approximately 25% of patients clinically suggestive of having collagen VI dystrophy in whom prior genetic analysis is negative. Overall, this study represents a large systematic application of transcriptome sequencing to rare disease diagnosis and highlights its utility for the detection and interpretation of variants missed by current standard diagnostic approaches.
How Segregation Makes Us Fat: Food Behaviors and Food Environment as Mediators of the Relationship Between Residential Segregation and Individual Body Mass Index

Objectives Racial residential segregation affects food landscapes that dictate residents’ food environments and is associated with obesity risk factors, including individual dietary patterns and behaviors. We examine if food behaviors and environments mediate the association between segregation and body mass index (BMI). Methods Non-Hispanic Whites and Blacks living in the St. Louis and Kansas City metro regions from 2012 to 2013 were surveyed on dietary behaviors, food environment, and BMI (n = 1,412). These data were combined with the CDC’s modified retail food environment index and 2012 American Community Survey data to calculate racial segregation using various evenness and exposure indices. Multi-level mediation analyses were conducted to determine if dietary behavior and food environment mediate the association between racial residential segregation and individual BMI. Results The positive association between racial segregation and individual BMI is partially mediated by dietary behaviors and fully mediated by food environments. Conclusion Racial segregation (evenness and exposure) is associated with BMI, mediated by dietary behaviors and food environment. Elements of the food environment, which form the context for dietary behaviors, are potential targets for interventions to reduce obesity in residentially segregated areas.
Optimal Design of Sandwitch Composite Laminates for Minimum Cost and Maximum Frequency Using Simulated Annealing

Multi objective optimal design of sandwich composite laminates consisting of highstiffness and expensive surface and low-stiffness and inexpensive core layers with respect to cost and frequency is addressed in this paper. Discrete ply angles and number of low-stiffness core layers are considered as design variables and simulated annealing algorithm is used for simultaneous cost minimization and frequency maximization. The proposed model is applied to a graphite-epoxy/glassepoxy laminate and results are obtained for various aspect ratios and number of layers.
Image Set Classification for Low Resolution Surveillance

This paper proposes a novel image set classification technique based on the concept of linear regression. Unlike most other approaches, the proposed technique does not involve any training or feature extraction. The gallery image sets are represented as subspaces in a high dimensional space. Class specific gallery subspaces are used to estimate regression models for each image of the test image set. Images of the test set are then projected on the gallery subspaces. Residuals, calculated using the Euclidean distance between the original and the projected test images, are used as the distance metric. Three different strategies are devised to decide on the final class of the test image set. We performed extensive evaluations of the proposed technique under the challenges of low resolution, noise and less gallery data for the tasks of surveillance, video based face recognition and object recognition. Experiments show that the proposed technique achieves a better classification accuracy and a faster execution time under the challenging testing conditions.
Spark Plasma Sintering of Nb3Al Alloy Powder by MA and PMGA Method

We synthesized the Nb-Al alloy powder from Nb and Al elemental powders by Mechanical Alloying which provides the nanometer size crystals. Mixing ratio of Nb and Al was 7.5mass%Al corresponding to the Nb3Al composition. After 720 sec milling, the grain size of milled powder was about 3nm. Spark Plasma Sintering system was applied to sinter this MA powder. At the same time, the powder obtained by Plasma Melt Gas Atomize method (Nb-26.1at%Al) was sintered by SPS for comparison. Those SPSed compacts were investigated by SEM observation, EDX analysis, X-ray diffraction and Vickers hardness measurement at high temperature.The results obtained were as follows;(1) The MA powder, consisting of super saturated solid solution of Nb and Al, melted partially during SPS at 1773 K, however, the PMGA powder, consisting of mixed structure of Nb and Nb3Al, didn't melted at the same temperature. (2) The compact of MA powder by SPS had a mixed structure of Nb and Nb2Al, which was too fine to determine by SEM. On the other hand, the mixed structure consisting of Nb2Al grains and Nb3Al grains was formed in compact of PMGA powder. (3) Vickers hardness of SPSed compact of MA powder was higher than that of PMGA powder at R.T. -1 073K.
Modeling anisotropic surface reflectance with example-based microfacet synthesis

We present a new technique for the visual modeling of spatiallyvarying anisotropic reflectance using data captured from a single view. Reflectance is represented using a microfacet-based BRDF which tabulates the facets' normal distribution (NDF) as a function of surface location. Data from a single view provides a 2D slice of the 4D BRDF at each surface point from which we fit a partial NDF. The fitted NDF is partial because the single view direction coupled with the set of light directions covers only a portion of the "half-angle" hemisphere. We complete the NDF at each point by applying a novel variant of texture synthesis using similar, overlapping partial NDFs from other points. Our similarity measure allows azimuthal rotation of partial NDFs, under the assumption that reflectance is spatially redundant but the local frame may be arbitrarily oriented. Our system includes a simple acquisition device that collects images over a 2D set of light directions by scanning a linear array of LEDs over a flat sample. Results demonstrate that our approach preserves spatial and directional BRDF details and generates a visually compelling match to measured materials.
Effects of early motivational interviewing on post‐stroke depressive symptoms: A pilot randomized study of the Good Mood Intervention program

AIMS The aim of this pilot randomized study was to investigate the feasibility of early motivational interviewing, for reducing mood after acute stroke. BACKGROUND Depression is a frequent consequence of stroke that can adversely affect recovery. METHODS DESIGN: Pilot randomized study. Intervention group patients received 3, individual motivational interviewing sessions by nurses or social workers prior to hospital discharge. PARTICIPANTS Adult patients with acute stroke during 2013 to 2014. BLINDING Research assistant who collected data was blind to group assignment. OUTCOMES Data were collected at 3 time points: baseline, 1-month, and 3-month follow-up. Outcome measures (anxiety, depression, quality of life) were analysed by descriptive statistics. RESULTS Forty-eight patients were enrolled, and 79% retention was achieved at 3 months. Eight participants withdrew (16.7%), and 2 were unable to participate (death: 2.1% and new onset aphasia: 2.1%), leaving 38 participants in the final cohort (Intervention: N = 18, Control: N = 20). Anxiety, depression, and quality of life measures did not alter significantly in the study period. CONCLUSIONS Carefully designed studies are required to investigate the effectiveness of early motivational interviewing for improving mood after stroke. The therapy can be administered by nurses, but significant resources are required in terms of training and fidelity.
Taste Responses to Linoleic Acid: A Crowdsourced Population Study

Abstract Dietary fats serve multiple essential roles in human health but may also contribute to acute and chronic health complications. Thus, understanding mechanisms that influence fat ingestion are critical. All sensory systems may contribute relevant cues to fat detection, with the most recent evidence supporting a role for the sense of taste. Taste detection thresholds for fat vary markedly between individuals and responses are not normally distributed. Genetics may contribute to these observations. Using crowdsourced data obtained from families visiting the Denver Museum of Nature & Science, our objective was to estimate the heritability of fat taste (oleogustus). A pedigree analysis was conducted with 106 families (643 individuals) who rated the fat taste intensity of graded concentrations of linoleic acid (LA) embedded in taste strips. The findings estimate that 19% (P = 0.043) of the variability of taste response to LA relative to baseline is heritable at the highest concentration tested.
Dispersion relations for composite structures. Part I. Basic assumptions and realtionships for monoclinic lamina

Nowadays, the propagation of elastic waves, particularly Lamb waves, is very often used in detecting damages in different kinds of composite materials. These systems are known as structural health monitoring (SHM). However, the phenomenon of Lamb wave propagation is very complex, especially in the case of thin-walled composite structures. Generally, three types of Lamb waves are observed, namely: longitudinal or pressure waves (L), shear vertical (SV) and shear horizontal (SH). The phase and group velocities of the mentioned waves depend on the thickness of the structure and the frequency of the excited signal. This fact makes proper interpretation of the received dynamic response of the structure difficult or even impossible. Therefore, determining the appropriate dispersion curves for different materials is a very important issue. In the present review, the most commonly used analytical approaches for determining dispersion curves in the case of multilayered composite plates are presented. At the very beginning of this work the solution for single isotropic plates is presented. Next, the fundamental assumptions of the theoretical model, which describe the elastic wave propagation phenomenon in multilayered materials, are discussed. In the first part, the relationships describing the elastic wave propagation for single orthotropic lamina are presented. There are two studied cases: namely when the wave front of the elastic wave travels along the principal directions of the material and when the wave front of the elastic wave travels in any arbitrary direction.
Characterization and splice variants of neuronal nitric oxide synthase in rat small intestine.

The aim of this study was to characterize neuronal nitric oxide synthase (nNOS) activity and 5'-end splice variants in rat small intestine. nNOS was predominantly expressed in the longitudinal muscle layer, with attached myenteric plexus (LM-MP). The biochemical properties of NOS activity in enriched nerve terminals resemble those of nNOS isolated from the brain. Western blot analysis of purified NOS protein with an nNOS antibody showed a single band in the particulate fraction and three bands in the soluble fraction. Rapid amplification of 5' cDNA ends-PCR revealed the presence of three different 5'-end splice variants of nNOS. Two variants encode for nNOSα, which has a specific domain for membrane association. The third variant encodes for nNOSβ, which lacks the domain for membrane association and should therefore be soluble. nNOS is predominantly expressed in LM-MP and can be enriched in enteric nerve terminals. We present the first evidence that three 5'-end splice variants of nNOS encoding two different proteins are expressed in rat small intestine. These two nNOS enzymes exhibit different subcellular locations and might be implicated in different biological functions.
Population Parameters Underlying an Ongoing Soft Sweep in Southeast Asian Malaria Parasites

Multiple kelch13 alleles conferring artemisinin resistance (ART-R) are currently spreading through Southeast Asian malaria parasite populations, providing a unique opportunity to observe an ongoing soft selective sweep, investigate why resistance alleles have evolved multiple times and determine fundamental population genetic parameters for Plasmodium. We sequenced kelch13 (n = 1,876), genotyped 75 flanking SNPs, and measured clearance rate (n = 3,552) in parasite infections from Western Thailand (2001–2014). We describe 32 independent coding mutations including common mutations outside the kelch13 propeller associated with significant reductions in clearance rate. Mutations were first observed in 2003 and rose to 90% by 2014, consistent with a selection coefficient of ∼0.079. ART-R allele diversity rose until 2012 and then dropped as one allele (C580Y) spread to high frequency. The frequency with which adaptive alleles arise is determined by the rate of mutation and the population size. Two factors drive this soft sweep: (1) multiple kelch13 amino-acid mutations confer resistance providing a large mutational target—we estimate the target is 87–163 bp. (2) The population mutation parameter (&THgr; = 2Ne&mgr;) can be estimated from the frequency distribution of ART-R alleles and is ∼5.69, suggesting that short term effective population size is 88 thousand to 1.2 million. This is 52–705 times greater than Ne estimated from fluctuation in allele frequencies, suggesting that we have previously underestimated the capacity for adaptive evolution in Plasmodium. Our central conclusions are that retrospective studies may underestimate the complexity of selective events and the Ne relevant for adaptation for malaria is considerably higher than previously estimated.
Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling

The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress-mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.
A model describing diffusion in prostate cancer

Quantitative diffusion MRI has frequently been studied as a means of grading prostate cancer. Interpretation of results is complicated by the nature of prostate tissue, which consists of four distinct compartments: vascular, ductal lumen, epithelium, and stroma. Current diffusion measurements are an ill‐defined weighted average of these compartments. In this study, prostate diffusion is analyzed in terms of a model that takes explicit account of tissue compartmentalization, exchange effects, and the non‐Gaussian behavior of tissue diffusion.
Evaluation of different levels of hydration using a new physiological strain index.

A physiological strain index (PSI), based on rectal temperature (Tre) and heart rate (HR), was recently suggested for evaluating heat stress. The purpose of this study was to evaluate the PSI for different combinations of hydration level and exercise intensity. This index was applied to two databases. The first database was obtained from eight endurance-trained men dehydrated to four different levels (1.1, 2.3, 3.4, and 4.2% of body wt) during 120 min of cycling at a power output of 62-67% maximum O2 consumption (V˙o 2 max) in the heat [33°C and 50% relative humidity (RH)]. The second database was obtained from nine men performing exercise in the heat (30°C and 50% RH) for 50 min. These subjects completed a matrix of nine trials of exercise on a treadmill at three exercise intensities (25, 45, and 65%V˙o 2 max) and three hydration levels (euhydration and hypohydration at 3 and 5% of body wt). Tre, HR, esophageal temperature (Tes), and local sweating rate were measured. PSI (obtained from either Tre or Tes) significantly ( P < 0.05) differentiated among all exposures in both databases categorized by exercise intensity and hydration level, and we assessed the strain on a scale ranging from 0 to 10. Therefore, PSI applicability was extended for heat strain associated with hypohydration and continues to provide the potential to be universally accepted.
Overexpression of OsNAC14 Improves Drought Tolerance in Rice

Plants have evolved to have sophisticated adaptation mechanisms to cope with drought stress by reprograming transcriptional networks through drought responsive transcription factors. NAM, ATAF1-2, and CUC2 (NAC) transcription factors are known to be associated with various developmental processes and stress tolerance. In this study, we functionally characterized the rice drought responsive transcription factor OsNAC14. OsNAC14 was predominantly expressed at meiosis stage but is induced by drought, high salinity, ABA, and low temperature in leaves. Overexpression of OsNAC14 resulted in drought tolerance at the vegetative stage of growth. Field drought tests demonstrated that OsNAC14 overexpressing transgenic rice lines exhibited higher number of panicle and filling rate compared to non-transgenic plants under drought conditions. RNA-sequencing analysis revealed that OsNAC14 overexpression elevated the expression of genes for stress response, DNA damage repair, defense related, and strigolactone biosynthesis. In addition, chromatin immunoprecipitation analysis confirmed the direct interaction of OsNAC14 with the promoter of OsRAD51A1, a key component in homologous recombination in DNA repair system. Collectively, these results indicate that OsNAC14 mediates drought tolerance by recruiting factors involved in DNA damage repair and defense response resulting in improved tolerance to drought.
Lipid Target in Very High-Risk Cardiovascular Patients: Lesson from PCSK9 Monoclonal Antibodies

The role of low-density lipoproteins (LDLs) as a major risk factor for cardiovascular disease has been demonstrated by several epidemiological studies. The molecular basis for LDLs in atherosclerotic plaque formation and progression is not completely unraveled yet. Pharmacological modulation of plasma LDL-C concentrations and randomized clinical trials addressing the impact of lipid-lowering interventions on cardiovascular outcome have clearly shown that reducing plasma LDL-C concentrations results in a significant decrease in major cardiovascular events. For many years, statins have represented the most powerful pharmacological agents available to lower plasma LDL-C concentrations. In clinical trials, it has been shown that the greater the reduction in plasma LDL-C concentrations, the lower the rate of major cardiovascular events, especially in high-risk patients, because of multiple risk factors and recurrent events. However, in a substantial number of patients, the recommended LDL target is difficult to achieve because of different factors: genetic background (familial hypercholesterolemia), side effects (statin intolerance), or high baseline plasma LDL-C concentrations. In the last decade, our understanding of the molecular mechanisms involved in LDL metabolism has progressed significantly and the key role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged. This protein is an enzyme able to bind the LDL receptors (LDL-R) on hepatocytes, favoring their degradation. Blocking PCSK9 represents an intriguing new therapeutic approach to decrease plasma LDL-C concentrations, which in recent studies has been demonstrated to also result in a significant reduction in major cardiovascular events.
Immobilization of Laccase in Glycidoxypropyl-Functionalized Magnetic Mesoporous SiO2/Fe3O4 Hollow Microspheres

Glycidoxypropyl-functionalized magnetic mesoporous SiO2/Fe3O4 hollow microspheres (FMMS) with various amounts of terminally bonded groups in the pore channels were synthesized by the co-condensation of tetraethoxysilane (TEOS) and 3-glycidoxypropyltrimethoxylsilane (GPTMS) in the presence of cetyltrimethylammonium bromide (CTAB) and 1,3,5-triisoporpylbenzene (TMB), and utilized as supports for laccase immobilization. It is revealed that glycidoxypropyl groups have been successfully covalently attached to the pore wall of magnetic mesoporous SiO2/Fe3O4 hollow microspheres (MMS). The magnetic mesoporous SiO2/Fe3O4 microspheres (sample10%FMMS) have a saturation magnetization of 13.6 emu·g-1 and a low coercivity (50 Oe). The functional materials preserve a mesoscopic ordering at a concentration of GPTMS as high as 15%. The BET surface area and pore volume of the functionalized materials decrease with increasing amount of GPTMS, but a desirable pore structure remains when the GPTMS amount increases to 10%. The 10%FMMS material exhibits higher laccase immobilization and stability than pure MMS because of the covalent interaction between the amino groups of laccase and the epoxy groups of the functional MMS.