Miracle-dz/UniFAR-FTUs huggingface dataset:
KRAS mutant lung cancer cells are differentially responsive to MEK inhibitor due to AKT or STAT3 activation: Implication for combinatorial approach

KRAS is frequently mutated in nonsmall cell lung cancer (NSCLC), resulting in the activation of the MAPK/ERK kinase (MEK)/ERK pathway. High‐throughput mutation profile has shown that lung cancer frequently harbors comutation of cancer‐related genes. Therefore, given that cancer cells have multiple genetic alterations, combinatorial therapeutic strategy is demanded for effective cancer therapy. To address this, we first characterized MEK dependence in four NSCLC cells. Two cells (H358, A549) carried KRAS mutation only, and the other two (H23, H157) harbored comutation of KRAS/PTEN. H358 cells with KRAS mutation only were sensitive to MEK inhibition. However, the other KRAS mutant A549 cells were resistant to MEK inhibition. Previously, we have shown that dual inhibition of EGFR and MEK signaling shows a synergistic effect on KRAS mutant gastric cancer cells by suppressing compensatory activation of AKT. Here we also observed that this combination was effective in KRAS mutant A549 cells. However, the combination was ineffective in H23 and 157 cells with comutation of KRAS/PTEN. Compared to KRAS mutant/PTEN wild‐type cells, signal transducer and activator of transcription 3 (STAT3) was significantly activated following MEK inhibition in KRAS/PTEN comutant cells. Combined STAT3 inhibition by a JAK2 inhibitor or gene knockdown with MEK inhibition blocked STAT3 activation, synergistically suppressed cell growth, and induced apoptosis in comutant cells. Taken together, our study provides molecular insights that help explain the heterogeneous response to MEK inhibition in KRAS mutant lung cancers, and presents a rationale for the clinical investigation of combination of MEK and EGFR inhibitor or MEK and JAK2 inhibitor depending on PTEN status. © 2010 Wiley‐Liss, Inc.
Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates

Previous lineage analyses have shown that retinal progenitor cells (RPCs) are multipotent throughout development, and expression-profiling studies have shown a great deal of molecular heterogeneity among RPCs. To determine if the molecular heterogeneity predicts that an RPC will produce particular types of progeny, clonal lineage analysis was used to investigate the progeny of a subset of RPCs, those that express the basic helix–loop–helix transcription factor, Olig2. The embryonic Olig2+ RPCs underwent terminal divisions, producing small clones with primarily two of the five cell types being made by the pool of RPCs at that time. The later, postnatal Olig2+ RPCs also made terminal divisions, which were biased toward production of rod photoreceptors and amacrine cell interneurons. These data indicate that the multipotent progenitor pool is made up of distinctive types of RPCs, which have biases toward producing subsets of retinal neurons in a terminal division, with the types of neurons produced varying over time. This strategy is similar to that of the developing Drosophila melanogaster ventral nerve cord, with the Olig2+ cells behaving as ganglion mother cells.
CBRAIN: a web-based, distributed computing platform for collaborative neuroimaging research

The Canadian Brain Imaging Research Platform (CBRAIN) is a web-based collaborative research platform developed in response to the challenges raised by data-heavy, compute-intensive neuroimaging research. CBRAIN offers transparent access to remote data sources, distributed computing sites, and an array of processing and visualization tools within a controlled, secure environment. Its web interface is accessible through any modern browser and uses graphical interface idioms to reduce the technical expertise required to perform large-scale computational analyses. CBRAIN's flexible meta-scheduling has allowed the incorporation of a wide range of heterogeneous computing sites, currently including nine national research High Performance Computing (HPC) centers in Canada, one in Korea, one in Germany, and several local research servers. CBRAIN leverages remote computing cycles and facilitates resource-interoperability in a transparent manner for the end-user. Compared with typical grid solutions available, our architecture was designed to be easily extendable and deployed on existing remote computing sites with no tool modification, administrative intervention, or special software/hardware configuration. As October 2013, CBRAIN serves over 200 users spread across 53 cities in 17 countries. The platform is built as a generic framework that can accept data and analysis tools from any discipline. However, its current focus is primarily on neuroimaging research and studies of neurological diseases such as Autism, Parkinson's and Alzheimer's diseases, Multiple Sclerosis as well as on normal brain structure and development. This technical report presents the CBRAIN Platform, its current deployment and usage and future direction.
Square-extensional mode single-crystal silicon micromechanical resonator for low-phase-noise oscillator applications

A micromechanical 13.1-MHz bulk acoustic mode silicon resonator having a high quality factor (Q=130 000) and high maximum drive level (P= 0.12 mW at the hysteresis limit) is demonstrated. The prototype resonator is fabricated of single-crystal silicon by reactive ion etching of a silicon-on-insulator wafer. A demonstration oscillator based on the new resonator shows single-sideband phase noise of -138 dBc/Hz at 1 kHz offset from the carrier.
Depression: An important factor associated with disability among patients with chronic low back pain.

OBJECTIVE The study aimed to compare the associations of pain indices, depression, anxiety, and somatic symptoms with disability among outpatients with chronic low back pain (CLBP). METHOD Consecutive orthopedics outpatients with CLBP in a medical center were enrolled. The Oswestry Disability Index and physical functioning and role limitations-physical of the Short-Form 36 were used as disability indices. The Hospital Anxiety and Depression Scale (HADS) and the Depression and Somatic Symptoms Scale were employed. Pain intensity was rated using a visual analogue scale. Multiple linear regressions were used to determine the impacts of these independent factors related to disability. RESULTS Among 225 participants (122 male, 103 female) with CLBP, patients with major depressive disorder and associated leg symptoms of CLBP had higher disability indices. A tendency was noted that depression (HADS-depression) had the highest correlation to the three disability indices, followed by pain intensity, anxiety, and somatic symptoms. After controlling for demographic variables, HADS-depression explained the highest variance of disability, followed by pain intensity. CONCLUSION Depression was the most powerful factor associated with disability of CLBP among depression, anxiety, and somatic symptoms. Depression should be evaluated when investigating disability among patients with CLBP.
Neuronal Effects of Sugammadex in combination with Rocuronium or Vecuronium

Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses steroidal NMB agents after anaesthesia. The present study was conducted in order to evaluate neuronal effects of SUG alone and in combination with both ROC and VEC. Using MTT, CASP-3 activity and Western-blot we determined the toxicity of SUG, ROC or VEC in neurons in primary culture. SUG induces apoptosis/necrosis in neurons in primary culture and increases cytochrome C (CytC), apoptosis-inducing factor (AIF), Smac/Diablo and Caspase 3 (CASP-3) protein expression. Our results also demonstrated that both ROC and VEC prevent these SUG effects. The protective role of both ROC and VEC could be explained by the fact that SUG encapsulates NMB drugs. In BBB impaired conditions it would be desirable to control SUG doses to prevent the excess of free SUG in plasma that may induce neuronal damage. A balance between SUG, ROC or VEC would be necessary to prevent the risk of cell damage.
Cardiotoxicity following Bupropion Overdose

OBJECTIVE: To determine whether bupropion overdose has been associated with cardiovascular toxicity. DATA SOURCES: MEDLINE (1966–January 2002), EMBASE (1980–January 2002), Current Contents (January 2002), and PubMed (January 2002) databases for English-language human reports. Search terms included bupropion, overdose (drug), intoxication, poisoning, and acute ingestion. DATA SYNTHESIS: Articles describing toxicity following bupropion overdose were evaluated independently by both authors to identify cases of cardiotoxicity. RESULTS: Thirteen articles describing bupropion overdose in 116 patients were identified. Only 3 patients exhibited cardiotoxicity following acute ingestion; 2 of these patients also ingested other medications. All 3 patients experienced tachycardia and conduction delays (widened QRS complex and/or prolonged QTc interval), but none of these delays progressed to a life-threatening arrhythmia. All patients recovered, with resolution of cardiotoxicity within 2–4 days following ingestion. CONCLUSIONS: We recommend that all patients with an overdose of bupropion should have an electrocardiogram performed on admission and should be monitored for the development of conduction delays and/or life-threatening arrhythmias.
Optimisations du chargement des instructions

Le coeur d'execution des processeurs actuels et a venir exploite le parallelisme entre instructions. Ils ne peuvent alors atteindre leurs performances maximales que s'ils sont alimentes par un debit d'instructions suffisant. Dans cet article, nous montrons que la bande passante d'acces au cache d'instructions est en general sous-exploitee. Nous proposons deux solutions pour optimiser les acces au cache d'instructions: l'une consiste a combiner plusieurs acces a une meme ligne de cache; l'autre prevoit de modifier l'ordre des acces pour limiter le nombre de conflits de bancs dans un cache multiport. Les resultats de simulation montrent que ces deux optimisations ameliorent sensiblement le debit de chargement des instructions. Par ailleurs, leur mise en oeuvre se fait au travers de sequences de controle du chargement qui tiennent egalement lieu de predicteur multiple de branchements.
A STUDY ON EGG QUALITY TRAITS IN JAPANESE QUAILS * (Coturnix coturnix japonica)

The data on egg quality traits of 607 Black and Brown strains of Japanese quails maintained at Poultry Experimental Station, College of Veterinary Science, Hyderabad were utilized for the present study and subjected to Least-squares analysis (Harvey, 1979) to resolve the effect of strains, generations and hatches on various egg quality traits. The birds were selected based on their body weight at 4 weeks age and their dams’ age at first egg (AFE) and egg production up to 16 weeks age (EP 16). The eggs laid by a bird (at 16 weeks of age) consecutively for three days were utilized for the measurement of external and internal egg quality traits. The weight of each egg, albumen, yolk and shell were recorded to the accuracy of 0.01g. The longer and wider diameter of the egg and the length and width of the thick albumen and yolk were measured by vernier calipers. The height of thick albumen and yolk were recorded with a spherometer. Yolk color was determined by using Roche yolk color fan. The Shape index, Albumen index (Heiman and Carver, 1936), Yolk index (Funk, 1948) and Haugh unit score (Kondaiah et al., 1983) were computed and the weights of albumen, yolk and shell were calculated in relation to egg weight
Neutrophil Elastase, Proteinase 3, and Cathepsin G as Therapeutic Targets in Human Diseases

Polymorphonuclear neutrophils are the first cells recruited to inflammatory sites and form the earliest line of defense against invading microorganisms. Neutrophil elastase, proteinase 3, and cathepsin G are three hematopoietic serine proteases stored in large quantities in neutrophil cytoplasmic azurophilic granules. They act in combination with reactive oxygen species to help degrade engulfed microorganisms inside phagolysosomes. These proteases are also externalized in an active form during neutrophil activation at inflammatory sites, thus contributing to the regulation of inflammatory and immune responses. As multifunctional proteases, they also play a regulatory role in noninfectious inflammatory diseases. Mutations in the ELA2/ELANE gene, encoding neutrophil elastase, are the cause of human congenital neutropenia. Neutrophil membrane-bound proteinase 3 serves as an autoantigen in Wegener granulomatosis, a systemic autoimmune vasculitis. All three proteases are affected by mutations of the gene (CTSC) encoding dipeptidyl peptidase I, a protease required for activation of their proform before storage in cytoplasmic granules. Mutations of CTSC cause Papillon-Lefèvre syndrome. Because of their roles in host defense and disease, elastase, proteinase 3, and cathepsin G are of interest as potential therapeutic targets. In this review, we describe the physicochemical functions of these proteases, toward a goal of better delineating their role in human diseases and identifying new therapeutic strategies based on the modulation of their bioavailability and activity. We also describe how nonhuman primate experimental models could assist with testing the efficacy of proposed therapeutic strategies.
Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations

How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncover the fitness landscape defined by gene expression levels. We found strong antagonism and sign epistasis between these beneficial mutations. Mutations with the largest individual benefit interacted the most antagonistically with other mutations, a trend we also uncovered through analyses of datasets from other model systems. However, these beneficial mutations interacted multiplicatively (i.e., no epistasis) at the level of enzyme expression. By generating a model that predicts fitness from enzyme levels we could explain the observed sign epistasis as a result of overshooting the optimum defined by a balance between enzyme catalysis benefits and fitness costs. Knowledge of the phenotypic landscape also illuminated that, although the fitness peak was phenotypically far from the ancestral state, it was not genetically distant. Single beneficial mutations jumped straight toward the global optimum rather than being constrained to change the expression phenotypes in the correlated fashion expected by the genetic architecture. Given that adaptation in nature often results from optimizing gene expression, these conclusions can be widely applicable to other organisms and selective conditions. Poor interactions between individually beneficial alleles affecting gene expression may thus compromise the benefit of sex during adaptation and promote genetic differentiation.
p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB

The tumor suppressor p53 is a transcription factor that controls cellular growth and proliferation. p53 targets include RNA polymerase (pol) III‐dependent genes encoding untranslated RNAs such as tRNA and 5S rRNA. These genes are repressed through interaction of p53 with TFIIIB, a TATA‐binding protein (TBP)‐containing factor. Although many studies have shown that p53 binds to TBP, the significance of this interaction has remained elusive. Here we demonstrate that the TBP–p53 interaction is of functional importance for regulating RNA pol III‐transcribed genes. Unlike RNA pol II‐dependent promoter repression, overexpressing TBP can reverse inhibition of tRNA gene transcription by p53. p53 does not disrupt the direct interaction between the TFIIIB subunits TBP and Brf1, but prevents the association of Brf1 complexes with TFIIIC2 and RNA pol III. Using chromatin immunoprecipitation assays, we found that TFIIIB occupancy on tRNA genes markedly decreases following p53 induction, whereas binding of TFIIIC2 to these genes is unaffected. Together our results support the idea that p53 represses RNA pol III transcription through direct interactions with TBP, preventing promoter occupancy by TFIIIB.
Spatiotemporal Variability of Dimethylsulphoniopropionate on a Fringing Coral Reef: The Role of Reefal Carbonate Chemistry and Environmental Variability

Oceanic pH is projected to decrease by up to 0.5 units by 2100 (a process known as ocean acidification, OA), reducing the calcium carbonate saturation state of the oceans. The coastal ocean is expected to experience periods of even lower carbonate saturation state because of the inherent natural variability of coastal habitats. Thus, in order to accurately project the impact of OA on the coastal ocean, we must first understand its natural variability. The production of dimethylsulphoniopropionate (DMSP) by marine algae and the release of DMSP’s breakdown product dimethylsulphide (DMS) are often related to environmental stress. This study investigated the spatiotemporal response of tropical macroalgae (Padina sp., Amphiroa sp. and Turbinaria sp.) and the overlying water column to natural changes in reefal carbonate chemistry. We compared macroalgal intracellular DMSP and water column DMSP+DMS concentrations between the environmentally stable reef crest and environmentally variable reef flat of the fringing Suleman Reef, Egypt, over 45-hour sampling periods. Similar diel patterns were observed throughout: maximum intracellular DMSP and water column DMS/P concentrations were observed at night, coinciding with the time of lowest carbonate saturation state. Spatially, water column DMS/P concentrations were highest over areas dominated by seagrass and macroalgae (dissolved DMS/P) and phytoplankton (particulate DMS/P) rather than corals. This research suggests that macroalgae may use DMSP to maintain metabolic function during periods of low carbonate saturation state. In the reef system, seagrass and macroalgae may be more important benthic producers of dissolved DMS/P than corals. An increase in DMS/P concentrations during periods of low carbonate saturation state may become ecologically important in the future under an OA regime, impacting larval settlement and increasing atmospheric emissions of DMS.
On the Relationship Between Bayes Risk and Word Error Rate in ASR

Recently, a number of (approximate) approaches emerged in speech processing, which try to overcome the known lack of match between symbol level evaluation measures (e.g., word error rate) and the standard string (symbol sequence) cost (e.g., sentence error)-based Bayes decision rule, by using symbol level cost functions for Bayes decision rule. Nevertheless, experiments show that for a majority of test samples both decision rules still give equal decisions, especially at lower error rates. In this paper, analytic evidence for these observations is provided. A set of conditions is presented, for which Bayes decision rule with symbol level and string level cost function leads to the same decisions. Furthermore, the case of word error cost represented by the Levenshtein (edit) distance is investigated, which upon others covers the important case of speech recognition. A Hamming distance-based upper bound to the Levenshtein cost function is discussed. This cost function relates to former, word-posterior based decision rules, and the corresponding efficient decision rule is shown to be strongly related to Bayes decision rule with the Levenshtein cost. The analytic results are verified experimentally, and their quantitative effect is studied by experiments on four different well-known large vocabulary automatic speech recognition tasks.
Apoptosis in the kidneys of rats that experienced intrauterine growth restriction

Intrauterine growth retardation (IUGR) can affect kidney development, leading to reduction in glomerular number. However, the associated cellular and molecular mechanisms have not been fully elucidated. This study investigated cell apoptosis and Bcl‐2 and Bax expression in the kidney of IUGR pups.
A catalog of inverse-kinematics planners for underactuated systems on matrix Lie groups

This paper presents motion planning algorithms for underactuated systems evolving on rigid rotation and displacement groups. Motion planning is transcribed into (low-dimensional) combinatorial selection and inverse-kinematics problems. We present a catalog of solutions for all underactuated systems on SE(2), SO(3) and SE(2) /spl times/ /spl Ropf/ classified according to their controllability properties.
Characteristics and physical mechanisms of positive bias and temperature stress-induced drain current degradation in HfSiON nMOSFETs

Drain current degradation in HfSiON gate dielectric nMOSFETs by positive gate bias and temperature stress is investigated by using a fast transient measurement technique. The degradation exhibits two stages, featuring a different degradation rate and stress temperature dependence. The first-stage degradation is attributed to the charging of preexisting high-k dielectric traps and has a log(t) dependence on stress time, whereas the second-stage degradation is mainly caused by new high-k trap creation. The high-k trap growth rate is characterized by two techniques, namely 1) a recovery transient technique and 2) a charge-pumping technique. Finally, the effect of processing on high-k trap growth is evaluated.
Auto-Immunity Dendritic Cell Algorithm

Security of information is of utmost importance to any organization or individual, which depend on computer system or internet for business transaction or source of information or research. Many viruses are able to recognize certain anti-virus software, and respond differently to such software than to programs designed for other purposes. Some viruses go after the databases stored by anti-virus products. Some viruses simply go after anti-virus products, trying to erase them. Immune systems also face this daunting control challenge. On the one hand, they need to minimize damage from pathogens, without wasting energy and resources, but on the other must avoid initiating or perpetuating autoimmune responses.
Controlling Listening-oriented Dialogue using Partially Observable Markov Decision Processes

This paper investigates how to automatically create a dialogue control component of a listening agent to reduce the current high cost of manually creating such components. We collected a large number of listening-oriented dialogues with their user satisfaction ratings and used them to create a dialogue control component using partially observable Markov decision processes (POMDPs), which can learn a policy to satisfy users by automatically finding a reasonable reward function. A comparison between our POMDP-based component and other similarly motivated systems using human subjects revealed that POMDPs can satisfactorily produce a dialogue control component that can achieve reasonable subjective assessment.