Miracle-dz/UniFAR-FTUs huggingface dataset:
Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10−16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway.
A comparison of sperm RNA-seq methods

Abstract A significant challenge to the effective application of RNA-seq to the complete transcript analysis of low quantity and/or degraded samples is the amplification of minimal input RNA to enable sequencing library construction. Several strategies have been commercialized in order to facilitate this goal. However, each strategy has its own specific protocols and methodology, and each may introduce unique bias and in some cases show specific preference for a collection of sequences. Our wider investigation of human spermatozoal RNAs was able to reveal their complexity despite being generally characterized by low quantity and high fragmentation. In this study, the following four commercially available RNA-seq amplification and library protocols for the preparation of low quantity/highly fragmented samples, SMARTer™ Ultra Low RNA (SU) for Illumina® Sequencing, SeqPlex RNA Amplification (SP), Ovation® RNA-Seq System V2 (OR), and Ovation® RNA-Seq Formalin Fixed Paraffin Embedded System (FFPES) were assessed using human sperm RNAs. Further investigation analyzed the effects on the end results of two different library preparation methods, Encore NGS Multiplex System I (Enc) and Ovation Ultralow Library Systems (UL), that appeared best suited to this type of RNA, along with other potential confounding factors such as FFPE preservation. Our results indicate that for each library preparation protocol, the differences in the initial amount of input RNA and choice of RNA purification step do not generate marked differences in terms of RNA profiling. However, substantial disparity is introduced by individual amplification methods prior to library construction. These significant differences may be caused by the different priming methods or amplification strategies used in each of the four different protocols examined. The observation of intra-sample variation introduced by the choice of protocol highlights the role that external factors play in planning and subsequent reliable interpretation of results of any RNA-seq experiment.
Modélisation des facteurs abiotiques de l'écosystème fluvial du lac Saint-françois, fleuve Saint-Laurent.

Le lac Saint-Francois est un troncon du fleuve Saint-Laurent qui presente une grande complexite tant au niveau de sa topographie que de son hydrologie. Depuis 150 ans, ce lac fluvial a subi de nombreuses transformations qui ont modifie son ecosysteme. Les changements dans les facteurs abiotiques tels que les debits, les vagues ou la composition de la masse d'eau, ont une influence sur la sedimentation, la chimie et sur l'ensemble du biota. Dans la these, les facteurs abiotiques sont analyses de facon 1) unidimensionnelle, c'est-a-dire liee a l'analyse des series temporelles des debits et des niveaux, ou encore 2) bidimensionnelle permettant ainsi de tenir compte des variations spatiales des composantes physiques du systeme. L'analyse des series temporelles et de l'historique des ouvrages a permis de decrire l’impact des transformations du milieu sur l'evolution de l'hydrologie. La principal effet a ete le relevement puis la stabilisation du niveau d'eau qui a entraine l'augmentation de la biomasse des plantes submergees et la modification des milieux humides. Les simulations numeriques bidimensionnelles ont permis de decrire plusieurs facteurs abiotiques, dont l'hydrodynamique sur l'ensemble du lac Saint-Francois. Ces simulations se basent sur l'elaboration d'un modele de terrain constitue de cartes de la topometrie du substrat et des plantes aquatiques. La caracterisation des plantes aquatiques est une donnee difficile a obtenir ; la methode utilisee a permis, entre autres, de cartographier la distribution spatiale des especes, leur hauteur et leur proportion dans les assemblages. Les donnees decrivant le terrain ont servi a modeliser l'hydrodynamique actuelle a des conditions de 5000, 7500 et 10 000 m³/s, correspondant respectivement aux debits moyen, minimum et maximum. L'influence des plantes aquatiques a ete integree aux simulations afin de representer l'ecoulement en periode estivale. Deux series de mesures de vitesse ont ete utilisees pour valider les simulations. L'hydrodynamique de la periode preindustrielle a ete simulee a l'aide de la reconstruction des donnees sur l'hydrologie ancienne. La comparaison avec les conditions actuelles de debit a ete effectuee. Cette analyse montre des changements significatifs dans le patron d'ecoulement. Une base de donnees d'habitat a ete constitue a partir d'un maillage de calcul raffine a un diametre moyen de 50 m. Cette base de donnees contient l'information sur la pente du terrain, les courants, la profondeur, les vagues pour plusieurs conditions saisonnieres, la lumiere au fond et la sedimentation des particules fines. Les observations de la presence des especes de macrophytes submerges ont ete associees a cette base de donnees d'habitat a l'aide de modeles de regression logistique. L'habitat des plantes permet de predire la distribution des especes de plantes avec une exactitude de 81 a 92%, permettant d'envisager a court terme l'evaluation de l'impact de changements futurs dans les conditions abiotiques sur cet aspect du vivant.
On Dynamic Effects Influencing IGBT Losses in Soft-Switching Converters

Two different dynamic effects influencing the insulated gate bipolar transistor (IGBT) losses in soft-switching converters are demonstrated. The first one, the Dynamic tail-charge effect shows that the tail charge is dependent not only on the absolute value of the current at turn-off, but also on the dynamics of the current. This effect may have a significant impact on the optimization of zero-current-switching converters. The Dynamic conduction losses originate from the conductivity modulation lag of the IGBT. It is shown by experiments that the on-state losses depend on the operating frequency. Different methods to accurately determine the on-state losses are evaluated. It was found that the best method is an indirect measurement, where the stray inductance is identified by the use of an oscillating circuit. The experiments are performed under a sinusoidal current excitation at a fixed amplitude (150 A) for different frequencies (up to 104 kHz). The switching devices used are IGBT modules rated 300-400 A/1200 V in a bridge-leg configuration. From the experiments performed, it is found that IGBTs of a modern punch-though (PT) designs have the lowest losses in the series-loaded resonant converters studied in this paper.
Making sense of large volumes of unstructured email responses

Unstructured textual data has increased to unprecedented levels with the rapid spread of user generated content via social media. Handling large volumes of unstructured text data is a challenging task that is increasingly becoming needed in a variety of situations. Reading and extracting important information from large collections of text manually is impractical and often impossible. This research concerns making sense of 500,000 email submissions received in response to a debate on Net Neutrality in India. The large volume of HTML format data was preprocessed using natural language processing (NLP) before analyzing it. Topic modeling and sentiment analysis were used to explore the nature and scope of the submissions so received, and provided a framework for dealing with this increasingly recurring problem. Interesting topics were identified from the submissions by using the Latent Dirichlet Allocation (LDA) topic model, which included themes such as the speed of internet, security, privacy and internet traffic among others. Word clouds were then generated to visualize key concepts within these email responses. A lexicon-based approach was used to classify the sentiment polarity of responses as positive, negative and neutral. Two methods were used to classify polarity of responses. In the first method, negative and positive word lists were used to classify polarity. There was considerable accuracy in the classification results. In the second method, the SentiWordNet lexical resource was used for classification and resulted in improved performance.
Bevacizumab for recurrent ependymoma.

2060 Background: Ependymoma is a rare type of glioma, representing less than 5% of brain tumors in adults. Radiotherapy (RT) is commonly administered, but there is no standard chemotherapy. At recurrence ependymoma is notoriously refractory to therapy and the prognosis is poor. In recurrent glioblastoma, encouraging responses with bevacizumab have been observed. Therefore, we treated patients with recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. METHODS We retrospectively identified adults treated for recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. We determined radiographic response (Macdonald criteria) and estimated median time to progression (TTP) and overall survival (OS) by the Kaplan-Meier method. RESULTS There were six patients, four women and two men, with a median age of 29 years (range, 20-65). Prior treatment included RT in all and temozolomide in four. Bevacizumab (5-10 mg/kg) every other week was combined with cytotoxic agents: irinotecan (3), carboplatin (2), or temozolomide (1). Five patients achieved a partial response (83%); in one patient the disease was stable. Median TTP and OS were 6.5 (95% CI: 2.7-10.2) and 9.4 (95% CI: 6.3-12.6) months, respectively, with a median follow up of 18.7 months for the two surviving patients. One additional patient is initiating bevacizumab monotherapy (not included in this analysis). CONCLUSIONS Bevacizuamb has efficacy in the treatment of recurrent ependymoma. Prospective study is warranted. [Table: see text].
Angular-Dependent Axial-Shift Correction for Pinhole SPECT

Compensation for pinhole-SPECT calibration parameters has been previously shown to be important for achieving good resolution. It has also been shown that angular-dependent (AD) compensations for the variation of radius of rotation can reduce reconstruction artifacts. In this study, we evaluate the effect of AD compensation of axial mechanical shifts (AMS) on the axial resolution of reconstructions. Measuring the AD AMS was accomplished using point-source scans. The centroids of the scans were fitted to their expected values in the transverse and axial directions. The differences in the axial direction between the data and fit were used to calculate the AD AMS under the assumption that the differences were due only to this shift. The effect on reconstruction was evaluated using a cold-disk phantom with 1.6 mm thick disks. Triple-head acquisitions using circular and helical paths were performed. The data were reconstructed with and without the calculated correction. The results show that the amplitude of the axial shift is approximately 0.5-1.0 mm for our system. The angular dependence of the heads is similar and suggests that the paths of the heads are distorted by gravitational effects. The circular and helical reconstructions show substantial improvement with compensation. In conclusion, AD compensation for AMS has a large impact on reconstruction quality. It is likely that the further development of other AD compensations may also have a large impact on resolution
Grouping Pursuit Through a Regularization Solution Surface

Extracting grouping structure or identifying homogenous subgroups of predictors in regression is crucial for high-dimensional data analysis. A low-dimensional structure in particular—grouping, when captured in a regression model—enables to enhance predictive performance and to facilitate a model’s interpretability. Grouping pursuit extracts homogenous subgroups of predictors most responsible for outcomes of a response. This is the case in gene network analysis, where grouping reveals gene functionalities with regard to progression of a disease. To address challenges in grouping pursuit, we introduce a novel homotopy method for computing an entire solution surface through regularization involving a piecewise linear penalty. This nonconvex and overcomplete penalty permits adaptive grouping and nearly unbiased estimation, which is treated with a novel concept of grouped subdifferentials and difference convex programming for efficient computation. Finally, the proposed method not only achieves high performance as suggested by numerical analysis, but also has the desired optimality with regard to grouping pursuit and prediction as showed by our theoretical results.
Low Levels of STRP Variability Are Not Universal in American Indians

AbstractData related to 15 short tandem repeat polymorphisms (STRPs) are reported for five Brazilian Indian populations, and a set of them compared with results previously reported for Asian, neo-Brazilian, North American, Iberian, and African populations. The low variability observed for these markers among the Suruí Indians is confirmed, but the other populations show variability levels that are similar to those found elsewhere. Previous suggestions of population bottlenecks in the prehistorical colonization of the New World were not confirmed. On the other hand, STRPs again showed to be good markers for the establishment of population relationships.
Autophagy flux inhibition, G2/M cell cycle arrest and apoptosis induction by ubenimex in glioma cell lines

This study aimed to investigate whether ubenimex could work as an anti-tumor drug alone in glioma cells and figure out the underlying potential mechanisms. Ubenimex is widely used as an adjunct therapy in multiple solid cancers. However, it is rarely used to treat glioblastoma. The function of ubenimex in enhancing JQ1 treatment sensitivity of glioma cells by blocking autophagic degradation of HEXIM1 was previously studied. However, the detailed mechanism of autophagy regulation by ubenimex remains unclear. The U87 and U251 cell lines were treated with different doses of ubenimex. Cell viability was measured by using the WST-8 assay. Cell death was assessed using trypan blue staining and flow cytometry. The migration and invasive ability of glioma cells were examined by transwell migration/invasion assay. LC3-GFP-RFP was used to measure autophagic flux. Protein expression was assessed by Western blot analysis. Autophagosomes were evaluated using the transmission electron microscopy. Moreover, cell cycle arrest (PI Staining) was measured by flow cytometry. Results revealed that ubenimex inhibited cell proliferation as well as migration/invasion in glioma cells. Besides, ubenimex increased glioma cell death via autophagic flux inhibition. Meanwhile, ubenimex induced G2/M phase arrest and apoptosis, and this effect was accompanied by the decreased levels of p-Akt, indicating the role of ubenimex in the regulation of glioma cell proliferation and metastasis. To sum up, this study concluded that ubenimex could work as an anti-tumor drug alone in the glioma cells via inhibiting autophagic flux and inducing G2/M arrest as well as apoptosis.
Microwave absorption characteristics of composites with tungsten coated filler particles

This study compares the dielectric relaxation, measured at microwave frequencies, of composites made with four distinct types of filler particles. The particles studied are 3Mtrade glass bubbles, with diameter approximately 60 mum, sputter coated with tungsten. Prior to sputter coating, one batch of glass bubbles was dried at 150degC and another at 350degC. The drying process removes bound water from the de-aggregating agent (Volanreg) used to coat the glass bubbles. Of these two batches, some particles were further coated with aluminum oxide (AlOx) to prevent conduction between the particles when in contact. To measure the permittivity, the particles were dispersed in a matrix of paraffin wax at various volume fractions. The electromagnetic properties were measured in the frequency range 2 to 18 GHz using a 7 mm coaxial reflection/transmission line method. Dielectric loss was observed in this frequency range for all four types of filler particle. The composites containing the particles coated with AlOx were observed to have a higher real and imaginary relative permittivity than those containing non-AlOx-coated particles. For AlOx-coated particles, the drying temperature of 150degC yielded stronger relaxation than that of 350degC. This behavior is attributed to traces of bound water remaining in the particles dried at 150degC and its effect on the morphology of the tungsten layer in these particles.
Soapstone (steatite) cookware as a source of minerals

Steatite or soapstone, is a soft metamorphic rock composed mainly of talc, dolomite and actinolite, which is abundantly found and used for the manufacture of cookware in south-east Brazil. The study estimates its usage for cookware among dwellers of Ouro Preto, and assesses the possible toxicological or nutritional impact on food preparation. Pans made of steatite were purchased both in the crude (n = 6) and ‘cured’ forms (n = 6). Migration of Ca, Fe, Mg, Mn, Co, Al, Cr, Ni, Pb and Cd was determined for 20 sequential cooking trials, using 3 and 5% acetic acid as a food simulant. Analytical determinations were carried out by inductively coupled plasma atomic-emission spectrometry and the data treated by an individual model of random effects, simple linear regression and Pearson's correlation. About 81% of Ouro Preto's native population own soapstone cookware and, of these, 79% use the pans regularly. Mineral migration followed the general solubility of the crystalline components of the rock. Therefore, Ca, Mg, Fe and Mn were, in that order, the elements that exhibited highest migration, whereas the remaining were seen in negligible levels, except for Ni in the crude pans. The 5% solution favoured migration, whereas curing tended to restrict migration and extend durability of the pan. It is concluded that while cured soapstone pans do not offer mineral toxicity, they may contribute to the mineral nutrition of human beings.
Suppression of an Hsp70 Mutant Phenotype in Saccharomyces cerevisiae through Loss of Function of the Chromatin Component Sin1p/Spt2p

ABSTRACT The Ssa subfamily of Hsp70 molecular chaperones in the budding yeast Saccharomyces cerevisiae has four members, encoded bySSA1, SSA2, SSA3, andSSA4. Deletion of the two constitutively expressed genes,SSA1 and SSA2, results in cells which are slow growing and temperature sensitive. In this study, we demonstrate that an extragenic suppressor of the temperature sensitivity of ssa1 ssa2 strains, EXA1-1, is a loss-of-function mutation in SIN1/SPT2, which encodes a nonhistone component of chromatin. Loss of function of Sin1p leads to overexpression ofSSA3 in the ssa1 ssa2 mutant background, at a level which is sufficient to mediate suppression. In a strain which is wild type for SSA genes, we detected no effect of Sin1p on Ssa3p expression except under conditions of heat shock. Existing data indicate that expression of SSA3 in thessa1 ssa2 mutant background as well as in heat-shocked wild-type strains is mediated by the heat shock transcription factor HSF. Our findings suggest that it is HSF-mediated induction of SSA3 which is modulated by Sin1p. TheEXA1-1 suppressor mutation thus improves the growth ofssa1 ssa2 strains by selectively increasing HSF-mediated expression of SSA3.
Autonomic modulation analysis in active and sedentary kidney transplanted recipients

Modulation of the autonomic nervous system on heart rate can be compromised in chronic kidney disease and may result in changes in the frequency and duration of the cardiac cycle. The aim of this study was to evaluate autonomic modulation in active and sedentary renal transplant recipients. Twenty renal‐transplanted individuals were analyzed at the Centro de Prevenção de Doenças Renais (Kidney Disease Education Centre), in the academic hospital of Universidade Federal do Maranhão, and were divided into the active group (AG) and the sedentary group (SG). The AG comprised of six men and four women (age 43.10 ± 13.02) and was in regular concurrent training intervention for 8 weeks, while the SG was composed of three men and seven women (age 36.8 ± 9.26). Analysis of heart rate (HR) variability in time and frequency domain demonstrated that HR mean values in the SG and AG were 787.32 ± 79.60 and 870 ± 106.66 ms, respectively. Differences were observed in the time domain and frequency domain. The total index of low frequency and high frequency showed no differences between the SG and AG. Biochemical variables presented significantly lower levels after 8 weeks of training. Higher heart rate variability in the time domain and greater vagal modulation was observed in the AG. The AG ad greater vagal modulation when compared to the SG, with removal of the sympathetic and increased parasympathetic in the behaviour was confirmed by sympatho‐vagal balance. The AG also presented significant improvements in the frequency domain.
Vitamin C supplementation does not protect L‐gulono‐γ‐lactone oxidase‐deficient mice from Helicobacter pylori‐induced gastritis and gastric premalignancy

In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C‐deficient B6.129P2‐Gulotm1Umc/mmcd (gulo−/−) mice lacking L‐gulono‐γ‐lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori‐infected gulo−/− mice supplemented with low (33 mg/L) or high (3,300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo−/− mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo−/− mice supplemented with high vitamin C, but lesions were less severe in gulo−/− mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo−/− mice supplemented with low vitamin C correlated with reduced Th1‐associated IgG2c, gastric IFN‐γ and TNF‐α mRNA and higher H. pylori colonization levels. These results in the H. pylori‐infected gulo−/− mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo−/− mice from H. pylori‐induced premalignant gastric lesions. In addition, less severe gastric lesions in H.pylori infected gulo−/− mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response. © 2007 Wiley‐Liss, Inc.