Miracle-dz/UniFAR-FTUs huggingface dataset:
Up-Regulation of P-TEFb by the MEK1-Extracellular Signal-Regulated Kinase Signaling Pathway Contributes to Stimulated Transcription Elongation of Immediate Early Genes in Neuroendocrine Cells

ABSTRACT The positive elongation factor P-TEFb appears to function as a crucial C-terminal-domain (CTD) kinase for RNA polymerase II (Pol II) transcribing immediate early genes (IEGs) in neuroendocrine GH4C1 cells. Chromatin immunoprecipitation indicated that in resting cells Pol II occupied the promoter-proximal regions of the c-fos and junB genes, together with the negative elongation factors DSIF and NELF. Thyrotropin-releasing hormone (TRH)-induced recruitment of positive transcription elongation factor b (P-TEFb) abolished the pausing of Pol II and enhanced phosphorylation of CTD serine 2, resulting in transcription elongation. In addition, P-TEFb was essential for splicing and 3′-end processing of IEG transcripts. Importantly, the MEK1-extracellular signal-regulated kinase (ERK) signaling pathway activated by TRH up-regulated nuclear CDK9 and CDK9/cyclinT1 dimers (i.e., P-TEFb), facilitating the recruitment of P-TEFb to c-fos and other IEGs. Thus, in addition to established gene transcription control via promoter response elements, the MEK1-ERK signaling pathway controls transcription elongation by Pol II via the up-regulation of nuclear CDK9 integrated into P-TEFb.
Basal body and flagellum mutants reveal a rotational constraint of the central pair microtubules in the axonemes of trypanosomes

Productive beating of eukaryotic flagella and cilia requires a strict regulation of axonemal dynein activation. Fundamental to any description of axonemal beating is an understanding of the significance of the central pair microtubules and the degree to which central pair rotation has a role. However, for the majority of organisms, it is unclear whether the central pair actually rotates. Using an extra-axonemal structure as a fixed reference, we analysed the orientation of the central pair in African trypanosomes and other kinetoplastid protozoa. A geometric correction allowed the superposition of data from many cross-sections, demonstrating that the axis of the central pair is invariant and that there is no central pair rotation in these organisms. Analysis of mutants depleted in particular flagellar and basal body proteins [γ-tubulin, δ-tubulin, Parkin co-regulated gene product (PACRG) or the paraflagellar rod protein PFR2] allowed a dissection of the mechanisms for central pair constraint. This demonstrated that orientation is independent of flagellum attachment and beating, but is influenced by constraints along its length and is entirely dependent on correct positioning at the basal plate.
When multiplicative noise stymies control

We consider the stabilization of an unstable discrete-time linear system that is observed over a channel corrupted by continuous multiplicative noise. Our main result shows that if the system growth is large enough, then the system cannot be stabilized in a second-moment sense. This is done by showing that the probability that the state magnitude remains bounded must go to zero with time. Our proof technique recursively bounds the conditional density of the system state (instead of focusing on the second moment) to bound the progress the controller can make. This sidesteps the difficulty encountered in using the standard data-rate theorem style approach; that approach does not work because the mutual information per round between the system state and the observation is potentially unbounded. It was known that a system with multiplicative observation noise can be stabilized using a simple memoryless linear strategy if the system growth is suitably bounded. In this paper, we show that while memory cannot improve the performance of a linear scheme, a simple non-linear scheme that uses one-step memory can do better than the best linear scheme.
Analysis of the filtered-X LMS algorithm

The presence of a transfer function in the error path, as in the case of active noise control requires a filtered update of the LMS (least mean square) algorithm. To ensure convergence of the algorithm, the input to the error correlator has to be filtered by a copy of the error path transfer function. The author presents an analysis of the filtered-X LMS algorithm in the presence of spherically invariant input process. Some theoretical results and simulated behavior are shown to agree very well. <<ETX>>
Requirement for the Lymphocyte Semaphorin, CD100, in the Induction of Antigen-Specific T Cells and the Maturation of Dendritic Cells1

CD100 belongs to the semaphorin family, several members of which are known to act as repulsive axonal guidance factors during neuronal development. We have previously demonstrated that CD100 plays a crucial role in humoral immunity. In this study, we show that CD100 is also important for cellular immunity through the maturation of dendritic cells (DCs). CD100−/− mice fail to develop experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide, because myelin oligodendrocyte glycoprotein-specific T cells are not generated in the absence of CD100. In vitro studies with T cells from OVA-specific TCR-transgenic mice demonstrate that Ag-specific T cells lacking CD100 fail to differentiate into cells producing either IL-4 or IFN-γ in the presence of APCs and OVA peptide. In addition, DCs from CD100−/− mice display poor allostimulatory capabilities and defects in costimulatory molecule expression and IL-12 production. The addition of exogenous soluble rCD100 restores normal functions in CD100−/− DCs and further enhances functions of normal DCs. Furthermore, treatment of Ag-pulsed DCs with both soluble CD100 and anti-CD40 before immunization significantly enhances their immunogenicity. This treatment elicits improved T cell priming in vivo, enhancing both primary and memory T cell responses. Collectively, these results demonstrate that CD100, which enhances the maturation of DCs, is essential in the activation and differentiation of Ag-specific T cells.
The Role of Text Pre-processing in Opinion Mining on a Social Media Language Dataset

This work describes an opinion mining application over a dataset extracted from the web and composed of reviews with several Internet slangs, abbreviations and typo errors. Opinion mining is a study field that tries to identify and classify subjectivity, such as opinions, emotions or sentiments in natural language. In this research, 759.176 Portuguese reviews were extracted from the app store Google Play. Due to the large amount of reviews, large-scale processing techniques were needed, involving powerful frameworks such as Hadoop and Mahout. Based on tests conducted it was concluded that pre-processing has an insignificant role in opinion mining task for the specific domain of reviews of mobile apps. The work also contributed to the creation of a corpus consisting of 759 thousand reviews and a dictionary of slangs and abbreviations commonly used in the Internet.
Searching the Web by Voice

Spoken queries are a natural medium for searching the Web in settings where typing on a keyboard is not practical. This paper describes a speech interface to the Google search engine. We present experiments with various statistical language models, concluding that a unigram model with collocations provides the best combination of broad coverage, predictive power, and real-time performance. We also report accuracy results of the prototype system.
Diagnostics for schistosomiasis in Africa and Arabia: a review of present options in control and future needs for elimination

SUMMARY Within the World Health Organization 2012–2020 roadmap for control and elimination of schistosomiasis, the scale-up of mass drug administration with praziquantel is set to change the epidemiological landscape across Africa and Arabia. Central in measuring progress is renewed emphasis upon diagnostics which operate at individual, community and environmental levels by assessing reductions in disease, infections and parasite transmission. However, a fundamental tension is revealed between levels for present diagnostic tools, and methods applied in control settings are not necessarily adequate for application in elimination scenarios. Indeed navigating the transition from control to elimination needs careful consideration and planning. In the present context of control, we review current options for diagnosis of schistosomiasis at different levels, highlighting several strengths and weaknesses therein. Future challenges in elimination are raised and we propose that more cost-effective diagnostics and clinical staging algorithms are needed. Using the Kingdom of Saudi Arabia as a contemporary example, embedding new diagnostic methods within the primary care health system is discussed with reference to both urogenital and intestinal schistosomiasis.
PRIDE: Quality control in a proteomics data repository

The PRoteomics IDEntifications (PRIDE) database is a large public proteomics data repository, containing over 270 million mass spectra (by November 2011). PRIDE is an archival database, providing the proteomics data supporting specific scientific publications in a computationally accessible manner. While PRIDE faces rapid increases in data deposition size as well as number of depositions, the major challenge is to ensure a high quality of data depositions in the context of highly diverse proteomics work flows and data representations. Here, we describe the PRIDE curation pipeline and its practical application in quality control of complex data depositions. Database URL: http://www.ebi. ac.uk/pride/.
election bias in college admissions test scores

Data from college admissions tests can provide a valuable measure of student achievement, but the non-representativeness of test-takers is an important concern. We examine selectivity bias in both state-level and school-level SAT and ACT averages. The degree of selectivity may differ importantly across and within schools, and across and within states. To identify within-state selectivity, we use a control function approach that conditions on scores from a representative test. Estimates indicate strong selectivity of test-takers in “ACT states,” where most college-bound students take the ACT, and much less selectivity in SAT states. To identify withinand between-school selectivity, we take advantage of a policy reform in Illinois that made taking the ACT a graduation requirement. Estimates based on ollege admissions test
How hallucinations may arise from brain mechanisms of learning, attention, and volition

This article suggests how brain mechanisms of learning, attention, and volition may give rise to hallucinations during schizophrenia and other mental disorders. The article suggests that normal learning and memory are stabilized through the use of learned top-down expectations. These expectations learn prototypes that are capable of focusing attention upon the combinations of features that comprise conscious perceptual experiences. When top-down expectations are active in a priming situation, they can modulate or sensitize their target cells to respond more effectively to matched bottom-up information. They cannot, however, fully activate these target cells. These matching properties are shown to be essential towards stabilizing the memory of learned representations. The modulatory property of top-down expectations is achieved through a balance between top-down excitation and inhibition. The learned prototype is the excitatory on-center in this top-down network. Phasic volitional signals can shift the balance between excitation and inhibition to favor net excitatory activation. Such a volitionally mediated shift enables top-down expectations, in the absence of supportive bottom-up inputs, to cause conscious experiences of imagery and inner speech and thereby to enable fantasy and planning activities to occur. If these volitional signals become tonically hyperactive during a mental disorder, the top-down expectations can give rise to conscious experiences in the absence of bottom-up inputs and volition. These events are compared with data about hallucinations. The article predicts where these top-down expectations and volitional signals may act in the laminar circuits of visual cortex and, by extension, in other sensory and cognitive neocortical areas, and how the level of abstractness of learned prototypes may covary with the abstractness of hallucinatory content. A similar breakdown of volition may lead to delusions of control in the motor system. (JINS, 2000, 6, 583–592.)
Structure-sensitive Noise Inference: Comprehenders Expect Exchange Errors

Previous research has found that comprehenders are willing to adopt non-literal interpretations of sentences whose literal reading is unlikely. Several studies found evidence that comprehenders decide whether or not a given utterance should be taken at face value in accordance with principles of Bayesian rationality, by weighing the prior probability of potential interpretations against the degree to which they are (in)consistent with the literal form of the utterance. While all of these results are consistent with string-edit noise models, many error processes are known to be sensitive to the underlying linguistic structure of the intended utterance. Here, we explore the case of exchange errors and provide experimental evidence that comprehenders’ noise model is structure-sensitive. Our results add further support to the noisy-channel theory of language comprehension, extend the set of known noise operations to include positional exchanges, and show that comprehenders’ noise models are well-adapted to structure-sensitive sources of signal corruption during communication.
Melody extraction by means of a source-filter model and pitch contour characterization (MIREX 2015)

This abstract presents our submission to the MIREX 2015 melody extraction task, whose goal is the identification of the melody pitch sequence from polyphonic musical audio. Our approach combines a source-filter model with the characterisation and analysis of pitch contours. The proposed method obtained the highest overall accuracy on several datasets among the algorithms participating in this year’s competition.
Mechanisms of adenosine-induced epicardial coronary artery dilatation.

BACKGROUND In order to ascertain whether human adenosine-induced dilatation of epicardial arteries is direct or flow-mediated, we compared the effects of intracoronary adenosine infusion on epicardial coronary arteries with those produced by dipiridamole, a selective arteriolar vasodilator. METHODS AND RESULTS In 24 patients with angiographically normal coronary arteries, coronary blood flow velocity was measured by a Doppler wire during intracoronary infusion of adenosine or dipyridamole, which is known to increase intramyocardial adenosine concentration. Coronary angiograms were obtained at baseline and immediately after the end of each infusion period; coronary diameters 5 mm distal to the wire tip were measured by computer-assisted quantitative coronary angiography. Peak coronary blood flow velocities during adenosine or dipyridamole infusions were similar (52.0 +/- 15.5 and 47.9 +/- 24.2 cm.s-1, P = ns). Coronary diameters immediately after adenosine and dipyridamole infusions were similar and both higher than that at baseline (2.80 +/- 0.63 and 2.86 +/- 0.64 vs 2.44 +/- 0.69 mm, P < 0.05). The absolute and percentage increases of coronary artery diameters in response to adenosine were highly correlated to coronary blood flow velocity (R = 0.622, intercept -0.10 +/- 0.14, P = 0.002 and R = 0.617, intercept -15.2 +/- 9.9, P = 0.001, respectively); similar correlations were found in response to dipyridamole (R = 0.708, intercept -0.44 +/- 0.19, P < 0.001 and R = 0.649, intercept -13.5 +/- 8.7, P < 0.001, respectively). Finally the absolute and percentage changes of coronary artery diameters caused by adenosine were highly correlated to those caused by dipyridamole (R = 0.840 P < 0.001 and R = 0.836, P < 0.001 respectively). CONCLUSIONS A significant correlation exists between epicardial coronary vasodilation and coronary blood flow velocity during intracoronary adenosine infusion, thus suggesting that epicardial coronary vasodilation induced by adenosine is predominantly flow-mediated rather than direct. This conclusion is supported by the observation that similar findings were obtained using dipyridamole, which can only dilate epicardial coronary arteries indirectly, through the increase in coronary blood flow velocity caused by the inhibition of intramyocardial adenosine re-uptake.
Twenty-Four-Month-Olds’ Perception of Word-Medial Onsets and Codas

ABSTRACT Recent work has shown that children have detailed phonological representations of consonants at both word-initial and word-final edges. Nonetheless, it remains unclear whether onsets and codas are equally represented by young learners since word edges are isomorphic with syllable edges in this work. The current study sought to explore toddler’s sensitivity to onsets and codas without this overlap. This question is of theoretical interest since many theories of phonology suggest that onsets may be weighted more heavily than codas. We examined English-learning 24-month-olds’ sensitivity to mispronunciations in word-medial onset and coda positions in a word learning task. We predicted that if children’s sensitivity to onsets and codas is positionally constrained, then they should be more tolerant of Coda mispronunciations than onset ones. The results supported this prediction: children were less sensitive to coda mispronunciations than to onset mispronunciations in word-medial position, suggesting positionally driven biases in word processing.
Endothelin 1–Dependent Neurovascular Dysfunction in Chronic Intermittent Hypoxia

Obstructive sleep apnea, a condition resulting in chronic intermittent hypoxia (CIH), is an independent risk factor for stroke and dementia, but the mechanisms of the effect are unknown. We tested the hypothesis that CIH increases cerebrovascular risk by altering critical mechanisms regulating cerebral blood flow thereby lowering cerebrovascular reserves. Male C57Bl6/J mice were subjected to CIH (10% O2 for 90 seconds/room air for 90 seconds; during sleep hours) or sham treatment for 35 days. Somatosensory cortex blood flow was assessed by laser Doppler flowmetry in anesthetized mice equipped with a cranial window. CIH increased mean arterial pressure (from 74±2 to 83±3 mm Hg; P<0.05) and attenuated the blood flow increase produced by neural activity (whisker stimulation; −39±2%; P<0.05) or neocortical application of endothelium-dependent vasodilators (acetylcholine response: −41±3%; P<0.05). The cerebrovascular dysfunction was associated with oxidative stress in cerebral resistance arterioles and was abrogated by free radical scavenging or NADPH oxidase inhibition. Furthermore, cerebrovascular dysfunction and free radical increase were not observed in mice lacking the NOX2 subunit of NADPH oxidase. CIH markedly increased endothelin 1 in cerebral blood vessels, whereas cerebrovascular dysfunction and oxidative stress were abrogated by neocortical application of the endothelin type A receptor antagonist BQ123. These data demonstrate for the first time that CIH alters key regulatory mechanisms of the cerebral circulation through endothelin 1 and NADPH oxidase–derived radicals. The ensuing cerebrovascular dysfunction may increase stroke risk in patients with sleep apnea by reducing cerebrovascular reserves and increasing the brain's susceptibility to cerebral ischemia.
Lung adenocarcinoma harboring L858R and T790M mutations in epidermal growth factor receptor, with poor response to gefitinib: A case report

Lung cancer is the leading cause of mortality among malignant diseases in humans worldwide. During the last decade, molecular targeted therapies for non-small cell lung cancer using first-generation, reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib, have been shown to be a promising approach for patients harboring activating mutations in EGFR. The current study reports a 77-year-old patient diagnosed with adenocarcinoma harboring L858R and T790M point mutations in the EGFR gene. The patient was treated with gefitinib as the second-line therapy, but no clinical benefit was observed. As the majority of patients with lung cancer receiving EGFR-TKI therapy acquire resistance, repeated biopsies and detection of the EGFR mutation state are beneficial for selecting appropriate treatments.
The Acquisition of Musical Technological Pedagogical and Content Knowledge

Technological pedagogical and content knowledge (TPACK) is a conceptual framework for the teacher knowledge necessary to effectively integrate technology into teaching and learning. The purposes of this study were to (a) develop and administer an instrument to measure music educators’ TPACK, (b) examine how music teachers acquire their TPACK, and (c) determine if a relationship existed between those teachers’ TPACK and their reported integration of technology. Participants (N = 284) were music teachers who completed two questionnaires, one designed to measure their TPACK (Musical TPACK Questionnaire [MTPACK-Q]) and another to describe the level of technology integration in their classroom (Concerns-Based Adoption Model–Levels of Use [CBAM-LoU] instrument). Scores on the technology-related domains of the TPACK model were lower than content, pedagogical, or pedagogical content domains. A moderate, significant, positive correlation (r = .51, p ≤ .01) was found between the participants’ MTPACK-Q score and the level of technology integration in their classroom as reported by the CBAM-LoU.
The relevance of using the Childhood Health Assessment Questionnaire (CHAQ) in revised versions for the assessment of juvenile idiopathic arthritis

Objectives: The Childhood Health Assessment Questionnaire (CHAQ) is widely used to measure functional impairment in juvenile idiopathic arthritis (JIA). However, the original version (CHAQ30) has reduced overall validity in terms of an increasing ceiling effect and decreasing discriminative ability because of considerable improvements in functional ability of children with JIA. The aim of this study was to validate a revised CHAQ including eight new physically demanding questions (CHAQ38) with two categorical response and scoring models (CAT1 and CAT2) in Danish children with JIA and healthy controls of a comparable age and gender. The CHAQ versions with both response models were validated in relation to distribution of data, evaluation of the ceiling effect, sensitivity, and discriminative ability. Method: Four different version of the CHAQ were completed by 68 patients and 118 controls aged 10–16 years. Demographic data in both groups and disease-specific data among patients were obtained. Statistical analysis of all CHAQ versions was performed to evaluate score distribution and to test the ability to distinguish between patients and controls. Results: The use of the CHAQ38 broadened the range of scores and reduced the number of scores at zero. The ceiling effect, which was high in all versions, was best reduced using the CAT2 response model. Adding the new questions increased the sensitivity to discriminate between physically well-functioning JIA patients and healthy controls in either of the CAT models used. Overall, the CHAQ38 and to some extent the CAT2 had the best outcomes. Conclusions: The discriminative validity increased with the CHAQ38, though still not optimally.