Miracle-dz/UniFAR-FTUs huggingface dataset:
The Genetic Architecture of Intra-Species Hybrid Mito-Nuclear Epistasis

Genetic variants that are neutral within, but deleterious between, populations (Dobzhansky-Muller Incompatibilities) are thought to initiate hybrid dysfunction and then to accumulate and complete the speciation process. To identify the types of genetic differences that might initiate speciation, it is useful to study inter-population (intra-species) hybrids that exhibit reduced fitness. In Caenorhabditis briggsae, a close relative of the nematode C. elegans, such minor genetic incompatibilities have been identified. One incompatibility between the mitochondrial and nuclear genomes reduces the fitness of some hybrids. To understand the nuclear genetic architecture of this epistatic interaction, we constructed two sets of recombinant inbred lines by hybridizing two genetically diverse wild populations. In such lines, selection is able to eliminate deleterious combinations of alleles derived from the two parental populations. The genotypes of surviving hybrid lines thus reveal favorable allele combinations at loci experiencing selection. Our genotype data from the resulting lines are consistent with the interpretation that the X alleles participate in epistatic interactions with autosomes and the mitochondrial genome. We evaluate this possibility given predictions that mitochondria-X epistasis should be more prevalent than between mitochondria and autosomes. Our empirical identification of inter-genomic linkage disequilibrium supports the body of literature indicating that the accumulation of mito-nuclear genetic incompatibilities might initiate the speciation process through the generation of less-fit inter-population hybrids.
Accurate Defect Detection in Thin-Wall Structures With Transducer Networks via Outlier Elimination

For the sake of structural health monitoring for defect detection in thin-wall structures, we present an outlier analysis approach by using robust principal component analysis (Robust PCA) for the Lamb wave signals generated by a transducer network. The signal matrix is decomposed into a low-rank matrix and a sparse matrix that contains outliers. By presenting a rank approximation function that matches the true rank more closely than does the nuclear norm and comparing a set of non-convex penalty functions to approximate the $\ell _{0}$ -norm, we derive an approximated non-convex Robust PCA (ANC-RPCA) algorithm to identify and even eliminate outliers in the data. This algorithm is able to find efficient defect detection methods under dimension-reduction conditions for high-dimensional measurement signals. The elimination of outliers is also evaluated by introducing the statistical Wasserstein distance, which provides a representation of the statistical distribution of the data. Experiments on wind turbine blade structures validate that the proposed ANC-RPCA is able to detect and eliminate outliers from three different situations that may occur in sensor systems. Therefore, the presented outlier analysis may perform as a promising preprocessing procedure to ensure that the data are in an acceptable statistical state for analysis.
Participation in software projects as professional communities of practice: A model

Cultivating communities of practice becomes an important goal in the workplaces to promote organizational and professional development. Software development communities, with the challenges that the vertiginous evolution of technologies and the new organizational forms of the software industry suppose, are failing to enable participation of newcomers. The lack of empirical and holistic experiences to guide managers to launch and maintain communities of practice in software development motivates this study. We are also concerned with the limited perspective with which participation is defined and measured in software development studies. The goal of the research is to design a model of participation in software development communities of practice. Specifically with this work, we aim to discuss the fundamentals sustaining the model and to present the methodology conducted to design and validate it. To obtain its first version, we conducted a methodology based on the theoretical analysis and synthesis of the related literature. In order to validate it, we designed a three-phase methodology comprising interview-based, expert-based and fuzz-cognitive-maps-based validations. By now, we have executed the interview-based study. The model that we already obtained includes contributions of other models, but it also achieves a multidimensional perspective of the phenomenon. The analysis of the interviews has enabled us to have an empirical notion of participation from different regions and workplace conditions.
An olive oil phenolic is a new chemotype of mutant isocitrate dehydrogenase 1 (IDH1) inhibitors

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene confer an oncogenic gain-of-function activity that allows the conversion of α-ketoglutarate (α-KG) to the oncometabolite R-2-hydroxyglutarate (2HG). The accumulation of 2HG inhibits α-KG-dependent histone and DNA demethylases, thereby generating genome-wide hypermethylation phenotypes with cancer-initiating properties. Several chemotypes of mutant IDH1/2-targeted inhibitors have been reported, and some of them are under evaluation in clinical trials. However, the recognition of acquired resistance to such inhibitors within a few years of clinical use raises an urgent need to discover new mutant IDH1 antagonists. Here, we report that a naturally occurring phenolic compound in extra-virgin olive oil (EVOO) selectively inhibits the production of 2HG by neomorphic IDH1 mutations. In silico docking, molecular dynamics, including steered simulations, predicted the ability of the oleoside decarboxymethyl oleuropein aglycone (DOA) to preferentially occupy the allosteric pocket of mutant IDH1. DOA inhibited the enzymatic activity of recombinant mutant IDH1 (R132H) protein in the low micromolar range, whereas >10-fold higher concentrations were required to inhibit the activity of wild-type (WT) IDH1. DOA suppressed 2HG overproduction in engineered human cells expressing a heterozygous IDH1-R132H mutation. DOA restored the 2HG-suppressed activity of histone demethylases as it fully reversed the hypermethylation of H3K9me3 in IDH1-mutant cells. DOA epigenetically restored the expression of PD-L1, an immunosuppressive gene silenced in IDH1 mutant cells via 2HG-driven DNA hypermethylation. DOA selectively blocked colony formation of IDH1 mutant cells while sparing WT IDH1 isogenic counterparts. In sum, the EVOO-derived oleoside DOA is a new, naturally occurring chemotype of mutant IDH1 inhibitors.
Glutamate, Glutamine and GABA Levels in Rat Brain Measured Using MRS, HPLC and NMR Methods in Study of Two Models of Autism

The disorders of the glutamatergic neurotransmission have been associated with pathogenesis of autism. In this study we evaluated the impact of the in vivo and ex vivo test methodology on measurements of levels of neurotransmitter amino acids in hippocampus of rats for valproic acid- (VPA) and thalidomide- (THAL) induced models of autism. The main goal was to compare the changes in concentrations of glutamate (Glu), glutamine (Gln) and GABA between both autistic groups and the control, measured in vivo and ex vivo in homogenates. The rat pups underwent three in vivo tests: ultrasonic vocalization (USV), magnetic resonance spectroscopy (MRS) and unilateral microdialysis of the hippocampus. Analyses of homogenates of rat hippocampus were performed using high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) spectroscopy. For the statistical analysis, we performed univariate and multivariate tests. USV test, which is considered in rodents as an indicator of pathology similar to autism, showed decreased USV in VPA and THAL groups. In vivo MRS studies demonstrated increases of Glu content in male rat’s hippocampus in VPA and THAL groups, while the microdialysis, which allows examination of the contents in the extracellular space, detected decreases in the basal level of Gln concentrations in VPA and THAL groups. Ex vivo HPLC studies showed that levels of Glu, Gln and GABA significantly increased in male rat’s hippocampus in the VPA and THAL groups, while NMR studies showed increased levels of Gln and GABA in the VPA group. Collectively, these results are consistent with the hypothesis suggesting the role of the glutamatergic disturbances on the pathogenesis of autism. For all methods used, the values of measured changes were in the same direction. The orthogonal partial least square discriminant analysis confirmed that both animal models of autism tested here can be used to trace neurochemical changes in the brain.
UWB Ranging for Rapid Movements

Ultra Wide Band (UWB) provides ranging capabilities much more precise than other radio communication technologies. This paper presents experimental measurement of ranging precision between two UWB tags when one of the tag is moving fast. The use of a specific electro-pneumatic actuator provides precise ground truth for real distance. This study will allow to improve ranging for human wearable tags as for example sportsmen positionning or interaction between dancers during live performances. We show in particular how the inherent noisy measurement has to be smoothed to obtain more acurate ranging.
Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication

The structure of a viral poly(ADP-ribose) polymerase 1 (PARP-1)-interacting protein from murine gammaherpesvirus 68 (MHV-68) is reported. Structure-based mutagenesis revealed residues that are critical for function and interaction with PARP-1, and a recombinant MHV-68 harboring mutations of these three residues showed severely attenuated viral replication in infected cells and mice. A homologous vPIP protein of Kaposi’s sarcoma-associated herpesvirus also interacted with PAPR-1 and disrupted its inhibitory function, suggesting the conserved molecular mechanism of vPIPs to facilitate viral replication among gammaherpesviruses.
A Preliminary Study of Compiler Transformations for Graph Applications on the Emu System

Unlike dense linear algebra applications, graph applications typically suffer from poor performance because of 1) inefficient utilization of memory systems through random memory accesses to graph data, and 2) overhead of executing atomic operations. Hence, there is a rapid growth in improving both software and hardware platforms to address the above challenges. One such improvement in the hardware platform is a realization of the Emu system, a thread migratory and near-memory processor. In the Emu system, a thread responsible for computation on a datum is automatically migrated over to a node where the data resides without any intervention from the programmer. The idea of thread migrations is very well suited to graph applications as memory accesses of the applications are irregular. However, thread migrations can hurt the performance of graph applications if overhead from the migrations dominates benefits achieved through the migrations. In this preliminary study, we explore two high-level compiler optimizations, i.e., loop fusion and edge flipping, and one low-level compiler transformation leveraging hardware support for remote atomic updates to address overheads arising from thread migration, creation, synchronization, and atomic operations. We performed a preliminary evaluation of these compiler transformations by manually applying them on three graph applications over a set of RMAT graphs from Graph500. ---Conductance, Bellman-Ford's algorithm for the single-source shortest path problem, and Triangle Counting. Our evaluation targeted a single node of the Emu hardware prototype, and has shown an overall geometric mean reduction of 22.08% in thread migrations.
Identification of Three Type II Toxin-Antitoxin Systems in Streptococcus suis Serotype 2

Type II toxin-antitoxin (TA) systems are highly prevalent in bacterial genomes and have been extensively studied. These modules involve in the formation of persistence cells, the biofilm formation, and stress resistance, which might play key roles in pathogen virulence. SezAT and yefM-yoeB TA modules in Streptococcus suis serotype 2 (S. suis 2) have been studied, although the other TA systems have not been identified. In this study, we investigated nine putative type II TA systems in the genome of S. suis 2 strain SC84 by bioinformatics analysis and identified three of them (two relBE loci and one parDE locus) that function as typical type II TA systems. Interestingly, we found that the introduction of the two RelBE TA systems into Escherichia coli or the induction of the ParE toxin led to cell filamentation. Promoter activity assays indicated that RelB1, RelB2, ParD, and ParDE negatively autoregulated the transcriptions of their respective TA operons, while RelBE2 positively autoregulated its TA operon transcription. Collectively, we identified three TA systems in S. suis 2, and our findings have laid an important foundation for further functional studies on these TA systems.
Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer

Purpose Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. Materials and Methods To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). Results Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). Conclusion We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.
Ethical Leadership as Antecedent of Job Satisfaction, Affective Organizational Commitment and Intention to Stay Among Volunteers of Non-profit Organizations

The aim of this paper is to investigate among a group of non-profit organizations: (a) the effect of ethical leadership (EL) on volunteers’ satisfaction, affective organizational commitment and intention to stay in the same organization; (b) the role played by job satisfaction as a mediator in the relationship between EL and volunteers’ intentions to stay in the same organization, as well as between EL and affective commitment. An anonymous questionnaire was individually administered to 198 Italian volunteers of different non-profit organizations. The questionnaire contained the Ethical Leadership Scale, the Volunteers Satisfaction Index, the Affective organization Scale, as well as questions regarding the participants’ age, sex, type of work, level of education, length of their volunteer works, intention to volunteer in the following months in the same organization. The construct as well the effects of EL on volunteers is approached in light of the Social Exchange Theory and the Social Learning Theory. Structural equation models were used to test hypothesized relationships. The results confirm the role of mediation of volunteer satisfaction in the relationships between the variables studied. In particular, EL was found to be positively associated both with volunteers’ intention of staying and with their affective commitment. In the first case this relationship is fully explained by the mediation of the volunteers’ satisfaction, while the latter is explained by both direct and indirect factors. To the authors’ knowledge, this the first attempt to understand the role played by EL on volunteers’ behavior and, more in general, in the management of non-profit organizations. Findings are relevant both for practitioners and managers of non-profit organization, since they suggest the relevance of the perception of EL by volunteers, as well as for scholars, since they further deepen the knowledge on EL and its effects on the followers. Limits of the study: the questionnaire was administered only among a group of non-statistical sample of volunteers. Furthermore, the study reached only volunteers from Italian non-profit organization.
Virtual Network Embedding Based on Computing, Network, and Storage Resource Constraints

Network virtualization can offer more flexibility and better maintainability for the current Internet through allowing multiple heterogeneous virtual networks (VNs) to share the network resource of a common infrastructure provider. The main challenge in this respect is the efficient embedding the virtual nodes and virtual links from the VN requests onto the limited substrate network resources. The notion of storage resource can exchange bandwidth resource to some extent gives us a hint that the efficient utilization of storage resource can relieve the bandwidth resource consumption. The existing VN embedding model does not consider the storage resource constraints on substrate nodes and virtual nodes, and does not keep up with the need of actual situation. In this paper, we propose a novel VN embedding model based on 3-D resource constraints including computing, network and storage, and devise two heuristic algorithms as the baseline algorithms to deal with the VN embedding problem. To our best of our knowledge, this is the first time to propose VN embedding problem based on 3-D resources including computing, network, and storage.
Cohort Profile: TWINS study of environment, lifestyle behaviours and health.

Cohort Profile: TWINS study of environment, lifestyle behaviours and health Glen E Duncan,* Ally Avery, Philip M Hurvitz, Anne Vernez Moudon, Siny Tsang and Eric Turkheimer Department of Nutrition and Exercise Physiology, Washington State University – Health Sciences Spokane, Spokane, WA, USA, Department of Urban Design and Planning, University of Washington, Seattle, WA, USA, Department of Epidemiology, Columbia University, New York, NY, USA and Department of Psychology, University of Virginia, Charlottesville, VA, USA
Complicaciones pulmonares asociadas a ventilación mecánica en el paciente neonatal

Se busco determinar la incidencia de complicaciones pulmonares asociadas a ventilacion mecanica en pacientes ingresados a un servicio de cuidados intensivos neonatales (UCIN) en un hospital de 2° nivel. Metodologia: Estudio analitico retrospectivo en expedientes de recien nacidos ingresados a una sala de UCIN y que recibieron ventilacion mecanica en un hospital de segundo nivel de atencion medica. Se recabaron datos demograficos, de la ventilacion mecanica, la intubacion y complicaciones reportadas en el expediente clinico y se analizaron en el programa estadistico SPSS 20. Resultados: De los 53 pacientes seleccionados se encontraron un total de 40 complicaciones. La incidencia anual de las complicaciones pulmonares asociadas a ventilacion mecanica en el area de UCIN del servicio de Neonatologia, en un hospital de segundo nivel en Sonora fue de 49.05% (IC 95% 0.35-0.62). Las complicaciones pulmonares mas frecuentes fueron: atelectasia 35%, neumonia 27.5%, neumotorax 15%, displasia broncopulmonar 15%, neumomediastino 15% y hemorragia pulmonar 2.5%. Conclusiones: La presentacion de complicaciones pulmonares secundarias a ventilacion mecanica en pacientes neonatales es similar a lo reportado en paises en desarrollo. La atelectasia es la complicacion pulmonar mas frecuente en los pacientes neonatales sometidos a ventilacion mecanica
Effectiveness of standard fasting guidelines as assessed by gastric ultrasound examination: A clinical audit

Background and Aims: An audit was conducted between July 2017 and November 2017 to assess the adequacy of American Society of Anesthesiologists (ASA) fasting guidelines on 246 patients by means of gastric ultrasonography (USG). The relevance of this audit is that many of our patients have one or more risk factors for aspiration such as diabetes mellitus, chronic kidney disease (CKD), gastro-oesophageal reflux disease (GERD), and obesity. Methods: This audit was a prospective observational study which included all patients posted for surgery within the audit period. Patients were fasted according to ASA fasting guidelines. Their gastric content was assessed preoperatively using USG. The residual gastric volume was calculated using a validated formula. Statistical correlation between gastric volumes and the risk factors were analysed. Results: Of 246 patients, 69 (28.04%) had high residual gastric volume. We found no correlation between hours of fasting and residual gastric volume (P = 0.47). We found a linear correlation between rising body mass index and residual gastric volume (P < 0.0001). Patients with GERD had 2.3 times higher risk. The CKD patient subgroup had 24 patients (30%) with high residual gastric volume. No incidents of aspiration were noted. Conclusion: In our audit, we found that risk factor association has a greater effect on residual gastric volume than hours of fasting. While the current fasting guidelines are adequate for healthy individuals, they are not conclusive in patients with risk factors. Ultrasound assessment of preoperative gastric volume is an effective screening tool in patients with risk factors.
Primary vs myocutaneous flap closure of perineal defects following abdominoperineal resection for colorectal disease: a systematic review and meta‐analysis

Perineal wound complications after abdominoperineal resection (APR) have become a major clinical challenge. Myocutaneous flap closure has been proposed in place of primary closure to improve wound healing. We conducted this comprehensive meta‐analysis to evaluate the current scientific evidence of primary closure vs myocutaneous flap closure of perineal defects following APR for colorectal disease.
Hybrid Memory Cube in Embedded Systems

This paper presents an evaluation of the Hybrid Memory Cube (HMC) usage in the Embedded Systems (ES) context. HMC can provide less use of energy and physical area — primary design goals for ES — and despite satisfying tight performance requirements. Our experiments' settings have used modest configurations of L1 and L2 caches in conjunction with the main memory of LPDDR3 or HMC types. gem5 was used to simulate four MiBench applications in a 4-CPU architecture. Estimations about time, energy, and area were made using CasHMC, CACTI, and a power calculator. The HMC memory allows improvements in execution time and consumed energy. In some situations, this memory type permits removing the L2 cache from the memory hierarchy. EDP (Energy Delay Product) and EDAP (Energy-Delay Area Product) metrics show that HMC provides both energy efficiency and improved density when compared to LPDDR3. In average, EDP and EDAP values for HMC settings were nearly 85% and 92% lower than LPDDR3 ones, respectively.