Miracle-dz/UniFAR-FTUs huggingface dataset:
The von Hippel‐Lindau tumor suppressor gene expression level has prognostic value in neuroblastoma

Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel‐Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the VHL syndrome, a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, including pheochromocytoma. Pheochromocytomas are, like NB, derived from neural crest cells, but, unlike NB, consist of more mature chromaffin cells instead of immature neuroblasts. Further arguments for a putative role of VHL in NB are its function as oxygen sensitizer and the reported relation between hypoxia and dedifferentiation of NB cells, leading to a more aggressive phenotype. To test the possible involvement of VHL in NB, we did mRNA expression analysis and sought evidence for VHL gene inactivation. Although no evidence for a classic tumor suppressor role for VHL in NB could be obtained, a strong correlation was observed between reduced levels of VHL mRNA and low patient survival probability (p = 0.013). Furthermore, VHL appears to have predictive power in NTRK1 (TRKA) positive tumor samples with presumed favorable prognosis, which makes it a potentially valuable marker for more accurate risk assessment in this subgroup of patients. The significance of the reduced VHL expression levels in relation to NB tumor biology remains unexplained, as functional analysis demonstrated no clear effect of the reduction in VHL mRNA expression on protein stability of its downstream target hypoxia‐inducible factor α. © 2006 Wiley‐Liss, Inc.
Comparison of QTL controlling seedling vigour under different temperature conditions using recombinant inbred lines in rice (Oryza sativa).

BACKGROUND AND AIMS Seedling vigour is one of the major determinants for stable stand establishment in rice (Oryza sativa), especially in a direct seeding cropping system. The objectives of this study were to identify superior alleles with consistent effects on seedling vigour across different temperature conditions and to investigate genotype x environmental temperature interactions for seedling vigour QTL. METHODS A set of 282 F13 recombinant inbred lines (RILs) derived from a rice cross were assessed for four seedling vigour traits at three temperatures (25 degrees C, 20 degrees C and 15 degrees C). Using a linkage map with 198 marker loci, the main-effect QTL for the traits were mapped by composite interval mapping. KEY RESULTS A total of 34 QTL for the four seedling vigour traits were identified. Of these QTL, the majority (82%) were clustered within five genomic regions, designated as QTL qSV-3-1, qSV-3-2, qSV-5, qSV-8-1 and qSV-8-2. All of these five QTL had small individual effects on the traits, explaining 3.1-15.8 % of the phenotypic variation with a mean of 7.3 %. QTL qSV-3-1, qSV-3-2 and qSV-8-1 showed almost consistent effects on the traits across all three temperatures while qSV-5 and qSV-8-2 had effects mainly at the 'normal' temperatures of 20 degrees C and 25 degrees C. Among the five QTL identified, all and four showed additive effects on shoot length and germination rate, respectively. The contributions of these five QTL to shoot length and germination rate were also much larger than those to the other two traits. CONCLUSIONS A few of genomic regions (or QTL) were identified as showing effects on seedling vigour. For these QTL, significant genotype x environmental temperature interactions were found and these interactions appeared to be QTL-specific. Among the four seedling vigour traits measured, shoot length and germination rate could be used as relatively good indicators to evaluate the level of seedling vigour in rice.
Exploiting Coherence for the Simultaneous Discovery of Latent Facets and associated Sentiments

Facet-based sentiment analysis involves discovering the latent facets, sentiments and their associations. Traditional facet-based sentiment analysis algorithms typically perform the various tasks in sequence, and fail to take advantage of the mutual reinforcement of the tasks. Additionally,inferring sentiment levels typically requires domain knowledge or human intervention. In this paper, we propose aseries of probabilistic models that jointly discover latent facets and sentiment topics, and also order the sentiment topics with respect to a multi-point scale, in a language and domain independent manner. This is achieved by simultaneously capturing both short-range syntactic structure and long range semantic dependencies between the sentiment and facet words. The models further incorporate coherence in reviews, where reviewers dwell on one facet or sentiment level before moving on, for more accurate facet and sentiment discovery. For reviews which are supplemented with ratings, our models automatically order the latent sentiment topics, without requiring seed-words or domain-knowledge. To the best of our knowledge, our work is the first attempt to combine the notions of syntactic and semantic dependencies in the domain of review mining. Further, the concept of facet and sentiment coherence has not been explored earlier either. Extensive experimental results on real world review data show that the proposed models outperform various state of the art baselines for facet-based sentiment analysis.
Intra-Arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model

Background—Recent clinical studies have demonstrated that hypothermia to 32° to 34°C provides significant clinical benefit when induced after resuscitation from cardiac arrest. However, cooling during the postresuscitation period was slow, requiring 4 to 8 hours to achieve target temperatures after return of spontaneous circulation (ROSC). Whether more rapid cooling would further improve survival remains unclear. We sought to determine whether cooling during cardiac arrest before ROSC (ie, “intra-arrest” hypothermia) has survival benefit over more delayed post-ROSC cooling, using a murine cardiac arrest model. Methods and Results—A model of potassium-induced cardiac arrest was established in C57BL/6 mice. After 8 minutes of untreated cardiac arrest, resuscitation was attempted with chest compression, ventilation, and intravenous fluid. Mice were randomized to 3 treatment groups (n=10 each): an intra-arrest hypothermia group, in which mice were cooled to 30°C just before attempted resuscitation, and then rewarmed after 1 hour; a post-ROSC hypothermia group, in which mice were kept at 37°C for 20 minutes after successful ROSC and then were cooled to 30°C for 1 hour; and a normothermic control group, in which mice were kept at 37°C. The intra-arrest hypothermia group demonstrated better 72-hour survival than delayed hypothermia and normothermia groups (6/10 versus 1/10 and 1/10 survivors, respectively, P <0.05), with similar differences seen at 6-hour survival and on neurological scoring. Conclusions—Timing of hypothermia is a crucial determinant of survival in the murine arrest model. Early intra-arrest cooling appears to be significantly better than delayed post-ROSC cooling or normothermic resuscitation.
Spectral-Spatial Classification of Hyperspectral Imagery with 3D Convolutional Neural Network

Recent research has shown that using spectral–spatial information can considerably improve the performance of hyperspectral image (HSI) classification. HSI data is typically presented in the format of 3D cubes. Thus, 3D spatial filtering naturally offers a simple and effective method for simultaneously extracting the spectral–spatial features within such images. In this paper, a 3D convolutional neural network (3D-CNN) framework is proposed for accurate HSI classification. The proposed method views the HSI cube data altogether without relying on any preprocessing or post-processing, extracting the deep spectral–spatial-combined features effectively. In addition, it requires fewer parameters than other deep learning-based methods. Thus, the model is lighter, less likely to over-fit, and easier to train. For comparison and validation, we test the proposed method along with three other deep learning-based HSI classification methods—namely, stacked autoencoder (SAE), deep brief network (DBN), and 2D-CNN-based methods—on three real-world HSI datasets captured by different sensors. Experimental results demonstrate that our 3D-CNN-based method outperforms these state-of-the-art methods and sets a new record.
Bayesian Methods for Genetic Association Studies

Bayesian Methods for Genetic Association Studies Lizhen Xu Doctor of Philosophy Graduate Department of Statistics University of Toronto 2012 We develop statistical methods for tackling two important problems in genetic association studies. First, we propose a Bayesian approach to overcome the winner’s curse in genetic studies. Second, we consider a Bayesian latent variable model for analyzing longitudinal family data with pleiotropic phenotypes. Winner’s curse in genetic association studies refers to the estimation bias of the reported odds ratios (OR) for an associated genetic variant from the initial discovery samples. It is a consequence of the sequential procedure in which the estimated effect of an associated genetic marker must first pass a stringent significance threshold. We propose a hierarchical Bayes method in which a spike-and-slab prior is used to account for the possibility that the significant test result may be due to chance. We examine the robustness of the method using different priors corresponding to different degrees of confidence in the testing results and propose a Bayesian model averaging procedure to combine estimates produced by different models. The Bayesian estimators yield smaller variance compared to the conditional likelihood estimator and outperform the latter in the low power studies. We investigate the performance of the method with simulations and applications to four real data examples. Pleiotropy occurs when a single genetic factor influences multiple quantitative or qualitative phenotypes, and it is present in many genetic studies of complex human traits. The longitudinal family studies combine the features of longitudinal studies in individuals and cross-sectional studies in families. Therefore, they provide more information about the genetic and environmental factors associated with the trait of interest. We propose a Bayesian latent variable modeling approach to model mul-
Electron Partitioning between the Two Branching Quinol-oxidizing Pathways in Acanthamoeba castellaniiMitochondria during Steady-state State 3 Respiration*

Amoeba mitochondria possess a respiratory chain with two quinol-oxidizing pathways: the cytochrome pathway and the cyanide-resistant alternative oxidase pathway. The ADP/O method, based on the non-phosphorylating property of alternative oxidase, was used to determine contributions of both pathways in overall state 3 respiration in the presence of GMP (an activator of the alternative oxidase in amoeba) and succinate as oxidizable substrate. This method involves pair measurements of ADP/O ratios plus and minus benzohydroxamate (an inhibitor of the alternative oxidase). The requirements of the method are listed and verified. When overall state 3 respiration was decreased by increasing concentrations of n-butyl malonate (a non-penetrating inhibitor of succinate uptake), the quinone reduction level declined. At the same time, the alternative pathway contribution decreased sharply and became negligible when quinone redox state was lower than 50%, whereas the cytochrome pathway contribution first increased and then passed through a maximum at a quinone redox state of 58% and sharply decreased at a lower level of quinone reduction. This study is the first attempt to examine the steady-state kinetics of the two quinol-oxidizing pathways when both are active and to describe electron partitioning between them when the steady-state rate of the quinone-reducing pathway is varied.
Convexity Rule for Shape Decomposition Based on Discrete Contour Evolution

We concentrate here on decomposition of 2D objects into meaningfulparts of visual form, orvisual parts. It is a simple observation that convex parts of objects determine visual parts. However, the problem is that many significant visual parts are not convex, since a visual part may have concavities. We solve this problem by identifying convex parts at different stages of a proposed contour evolution method in which significant visual parts will become convex object parts at higher stages of the evolution. We obtain a novel rule for decomposition of 2D objects into visual parts, called the hierarchical convexity rule, which states that visual parts are enclosed by maximal convex (with respect to the object) boundary arcs at different stages of the contour evolution. This rule determines not only parts of boundary curves but directly the visual parts of objects. Moreover, the stages of the evolution hierarchy induce a hierarchical structure of the visual parts. The more advanced the stage of contour evolution, the more significant is the shape contribution of the obtained visual parts.
Detection of Increased Plasma Interleukin-6 Levels and Prevalence of Prevotella copri and Bacteroides vulgatus in the Feces of Type 2 Diabetes Patients

Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D). The main goal of the present study was to evaluate the intestinal dysbiosis in Brazilian T2D patients and correlate these data with inflammatory cytokines and lipopolysaccharides (LPS) plasma concentrations. This study was approved by the Ethics Committees from Barretos Cancer Hospital and all individuals signed the informed consent form. Stool samples were required for DNA extraction, and the V3/V4 regions of bacterial 16S were sequenced using an Illumina platform. Peripheral blood was used to quantify inflammatory cytokines and plasma LPS concentrations, by CBA flex and ELISA, respectively. Statistical analyses were performed using Mann–Whitney and Spearman’s tests. Analysis of variance, diversity indexes, and analysis of alpha- and beta-diversity were conducted using an annotated Operational Taxonomic Unit table. This study included 20 patients and 22 controls. We observed significant differences (P < 0.01) in the microbiota composition (beta-diversity) between patients and controls, suggesting intestinal dysbiosis in Brazilian T2D patients. The prevalent species found in patients’ feces were the Gram-negatives Prevotella copri, Bacteroides vulgatus, Bacteroides rodentium, and Bacteroides xylanisolvens. The proinflammatory interleukin-6 (IL-6) was significantly increased (P < 0.05) in patients’ plasma and LPS levels were decreased. We find correlations between the proinflammatory interferon-gamma with Gram-negatives Bacteroides and Prevotella species, and a positive correlation between the LPS levels and P. copri reads. The P. copri and B. vulgatus species were associated with insulin resistance in previous studies. In this study, we suggested that the prevalence of Gram-negative species in the gut and the increased plasma IL-6 in patients could be linked to low-grade inflammation and insulin resistance. In conclusion, the P. copri and B. vulgatus species could represent an intestinal microbiota signature, associated with T2D development. Furthermore, the identification of these Gram-negative bacteria, and the detection of inflammatory markers, such as increased IL-6, could be used as diabetes predictive markers in overweight, obese and in genetically predisposed individuals to develop T2D.
Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

Background Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This study therefore aimed to identify and characterise the ‘bona fide’ MSC in human lungs and to investigate if the MSC numbers correlate with the development of bronchiolitis obliterans syndrome in lung-transplanted patients. Methods Primary lung MSC were directly isolated or culture-derived from central and peripheral transbronchial biopsies of lung-transplanted patients and evaluated using a comprehensive panel of in vitro and in vivo assays. Results Primary MSC were enriched in the CD90/CD105 mononuclear cell fraction with mesenchymal progenitor frequencies of up to four colony-forming units, fibroblast/100 cells. In situ staining of lung tissues revealed that CD90/CD105 MSCs were located perivascularly. MSC were tissue-resident and exclusively donor lung-derived even in biopsies obtained from patients as long as 16 years after transplantation. Culture-derived mesenchymal stromal cells showed typical in vitro MSC properties; however, xenotransplantation into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice showed that lung MSC readily differentiated into adipocytes and stromal tissues, but lacked significant in vivo bone formation. Conclusions These data clearly demonstrate that primary MSC in human lung tissues are not only tissue resident but also tissue-specific. The identification and phenotypic characterisation of primary lung MSC is an important first step in identifying the role of MSC in normal lung physiology and pulmonary diseases.
Possible functional links among brain- and skull-related genes selected in modern humans

The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language.
Patient and Implanting Physician Factors Associated With Mortality and Complications After Implantable Cardioverter-Defibrillator Implantation, 2002–2005

Background—Little is known about factors that influence survival and complications after implantable cardioverter-defibrillator (ICD) implantation in routine clinical practice. We examined patient and implanting physician factors associated with outcomes of ICD therapy in Medicare beneficiaries from 2002 through 2005. Methods and Results—We limited this analysis to patients aged ≥65 with Medicare fee-for-service coverage who received an ICD between January 2002 and September 2005. The main outcome measures are time to postprocedural complications within 90 days and 1-year mortality. During the study period, 8581 patients had an ICD implanted by 1959 physicians. The number of procedures increased from 1644 in 2002 to 2374 in the first 3 quarters of 2005. The overall complication rate declined from 18.8% in 2002 to 14.2% in 2005 (P<0.001). Factors independently associated with an increased hazard of complications include chronic lung disease, dementia, renal disease, implantation by a thoracic surgeon, and implantation with removal/replacement. History of congestive heart failure, outpatient implantation, and more recent years of ICD implantation were associated with a lower risk of complications (P<0.05 for all factors). From 2002 to 2005, we observed a decline in 1-year mortality (P<0.001). Conclusions—We observed an appreciable increase in the number of ICD implants, which was associated with a significant decrease in the rate of complications and 1-year mortality. We identified factors associated with an increased risk of mortality and postprocedural complications that may support more nuanced treatment decisions than are currently possible.
New perspectives concerning feedback influences on cardiorespiratory control during rhythmic exercise and on exercise performance

Abstract The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward ‘central command’ mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types of feedback afferents on the cardiorespiratory response to voluntary, rhythmic exercise by inhibiting their normal ‘tonic’ activity in healthy animals and humans and in chronic heart failure. Transient inhibition of the carotid chemoreceptors during moderate intensity exercise reduced muscle sympathetic nerve activity (MSNA) and increased limb vascular conductance and blood flow; and reducing the normal level of respiratory muscle work during heavier intensity exercise increased limb vascular conductance and blood flow. These cardiorespiratory effects were prevented via ganglionic blockade and were enhanced in chronic heart failure and in hypoxia. Blockade of μ opioid sensitive locomotor muscle afferents, with preservation of central motor output via intrathecal fentanyl: (a) reduced the mean arterial blood pressure (MAP), heart rate and ventilatory responses to all steady state exercise intensities; and (b) during sustained high intensity exercise, reduced O2 transport, increased central motor output and end‐exercise muscle fatigue and reduced endurance performance. We propose that these three afferent reflexes – probably acting in concert with feedforward central command – contribute significantly to preserving O2 transport to locomotor and to respiratory muscles during exercise. Locomotor muscle afferents also appear to provide feedback concerning the metabolic state of the muscle to influence central motor output, thereby limiting peripheral fatigue development.
Cultivation-dependent and cultivation-independent characterization of hydrocarbon-degrading bacteria in Guaymas Basin sediments

Marine hydrocarbon-degrading bacteria perform a fundamental role in the biodegradation of crude oil and its petrochemical derivatives in coastal and open ocean environments. However, there is a paucity of knowledge on the diversity and function of these organisms in deep-sea sediment. Here we used stable-isotope probing (SIP), a valuable tool to link the phylogeny and function of targeted microbial groups, to investigate polycyclic aromatic hydrocarbon (PAH)-degrading bacteria under aerobic conditions in sediments from Guaymas Basin with uniformly labeled [13C]-phenanthrene (PHE). The dominant sequences in clone libraries constructed from 13C-enriched bacterial DNA (from PHE enrichments) were identified to belong to the genus Cycloclasticus. We used quantitative PCR primers targeting the 16S rRNA gene of the SIP-identified Cycloclasticus to determine their abundance in sediment incubations amended with unlabeled PHE and showed substantial increases in gene abundance during the experiments. We also isolated a strain, BG-2, representing the SIP-identified Cycloclasticus sequence (99.9% 16S rRNA gene sequence identity), and used this strain to provide direct evidence of PHE degradation and mineralization. In addition, we isolated Halomonas, Thalassospira, and Lutibacterium sp. with demonstrable PHE-degrading capacity from Guaymas Basin sediment. This study demonstrates the value of coupling SIP with cultivation methods to identify and expand on the known diversity of PAH-degrading bacteria in the deep-sea.