Miracle-dz/UniFAR-FTUs huggingface dataset:
3D expression patterns of cell cycle genes in the developing chick wing and comparison with expression patterns of genes implicated in digit specification

Sonic hedgehog (Shh) signalling controls integrated specification of digit pattern and growth in the chick wing but downstream gene networks remain to be unravelled. We analysed 3D expression patterns of genes encoding cell cycle regulators using Optical Projection Tomography. Hierarchical clustering of spatial matrices of gene expression revealed a dorsal layer of the wing bud, in which almost all genes were expressed, and that genes encoding positive cell cycle regulators had similar expression patterns while those of N‐myc and CyclinD2 were distinct but closely related. We compared these patterns computationally with those of genes implicated in digit specification and Ptch1, 50 genes in total. Nineteen genes have similar posterior expression to Ptch1, including Hoxd13, Sall1, Hoxd11, and Bmp2, all likely Gli targets in mouse limb, and cell cycle genes, N‐myc, CyclinD2. We suggest that these genes contribute to a network integrating digit specification and growth in response to Shh. Developmental Dynamics 240:1278–1288, 2011. © 2011 Wiley‐Liss, Inc.
Potentials Differential Effects of Neuromuscular Electrical Stimulation Parameters on Submental Motor-Evoked

Background. Neuromuscular electrical stimulation (NMES) of the muscles underlying the pharynx and faucial pillars affects the excitability of corticobulbar projections in a frequencyand duration-specific manner. The anterior hyomandibular (submental) muscles are primary targets for the clinical application of NMES to improve disordered swallowing, but the optimal NMES parameters for this application are unknown. Objective. To determine the influence of NMES parameters on the excitability of corticobulbar projections to the submental musculature. Methods. Transcranial magnetic stimulation (TMS) was used in event-related protocols, triggered by either volitional contraction of the submental muscles or pharyngeal swallowing, to assess corticobulbar excitability prior to, immediately following, and 30, 60, and 90 minutes post-NMES in 25 healthy volunteers. In the first 2 experiments, 4 stimulus frequencies (5, 20, 40, and 80 Hz) and 3 NMES dosages, manipulated through stimulus train durations or number of repetitions, were evaluated. The optimal excitatory NMES triggered by volitional swallowing (event-related NMES) was then replicated in a new sample and contrasted with nonevent-related NMES (either discrete events or continuously for 1 hour). Results. It was found that 80Hz NMES increased motor-evoked potential (MEP) amplitude at 30 minutes and 60 minutes poststimulation only after 60 repetitions of 4-s event-related NMES trains. Non-event-related and continuous NMES did not affect MEP amplitudes. No changes in MEP onset latencies were observed. Conclusions. Changes in corticobulbar excitability induced by NMES of the submental muscle group are frequency and dose dependent and only occur after NMES triggered by volitional swallowing. Underlying neural mechanisms are discussed.
Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages

Summary Thrombocytopenia is an important clinical manifestation of dengue disease. The hypotheses concerning the pathogenesis of thrombocytopenia include decreased production and increased destruction or consumption of platelets. We previously suggested a mechanism of molecular mimicry in which antibodies (Abs) directed against dengue virus (DENV) nonstructural protein 1 (NS1) cross-react with platelets. Furthermore, several lines of evidence show activation of endothelial cells (ECs) and macrophages are related to dengue disease severity. Previous studies also suggested that Ab-opsonised platelets facilitate the engulfment of platelets by macrophages. Here we show that TNF-α-activated ECs upregulate adhesion molecule expression to enhance the binding of platelets and macrophages and lead to anti-DENV NS1 Ab-mediated platelet phagocytosis. We further demonstrate that the interaction between macrophages and TNF-α-activated ECs requires binding of FcγR with the Fc region of platelet-bound anti-DENV NS1 Abs. Importantly, the binding of anti-DENV NS1 Abs to platelets did not interfere with platelet adhesion to ECs. The adhesion molecules ICAM-1 and β3 integrin expressed on ECs as well as the FcγR expressed on macrophages were critical in anti-DENV NS1 Ab-mediated platelet phagocytosis on activated ECs. Moreover, anti-DENV NS1 Abs dramatically enhanced platelet engulfment by macrophages in a murine model of DENV infection. Our study provides evidence for a novel role for anti-DENV NS1 Abs in the pathogenesis of thrombocytopenia in dengue disease by enhancing platelet phagocytosis by macrophages.
Which Psychosocial Factors Best Predict Cognitive Performance in Older Adults?

Abstract Negative affect (e.g., depression) is associated with accelerated age-related cognitive decline and heightened dementia risk. Fewer studies examine positive psychosocial factors (e.g., emotional support, self-efficacy) in cognitive aging. Preliminary reports suggest that these variables predict slower cognitive decline independent of negative affect. No reports have examined these factors in a single model to determine which best relate to cognition. Data from 482 individuals 55 and older came from the normative sample for the NIH Toolbox for the Assessment of Neurological and Behavioral Function. Negative and positive psychosocial factors, executive functioning, working memory, processing speed, and episodic memory were measured with the NIH Toolbox Emotion and Cognition modules. Confirmatory factor analysis and structural equation modeling characterized independent relations between psychosocial factors and cognition. Psychosocial variables loaded onto negative and positive factors. Independent of education, negative affect and health status, greater emotional support was associated with better task-switching and processing speed. Greater self-efficacy was associated with better working memory. Negative affect was not independently associated with any cognitive variables. Findings support the conceptual distinctness of negative and positive psychosocial factors in older adults. Emotional support and self-efficacy may be more closely tied to cognition than other psychosocial variables. (JINS, 2014, 20, 1–9)
Probing the interactive effects of career commitment and emotional intelligence on perceived objective/subjective career success

Purpose – The purpose of this paper is to find out the moderating role of emotional intelligence (EI) in the relationship between career commitment and career success of the bank employees working in Pakistan. Design/methodology/approach – The study used ex post facto method where 200 middle-level managerial bank employees were surveyed by means of a close-ended questionnaire. Moderated multiple regression was run to test the hypotheses. Findings – As expected, the research findings confirmed the expectation of significant relationship between career commitment and objective/subjective career success. Further, the research findings bolstered one of the research postulates that EI will moderate career commitment-objective career success relationship. However the argument of EI’s moderation between career commitment-subjective career success relationship was not supported by the findings. Originality/value – This paper adds value to the existing body of knowledge by augmenting the need of understanding the .
Curriculum policy reform in an era of technical accountability: ‘fixing’ curriculum, teachers and students in English schools

Abstract Drawing on a Levinasian ethical perspective, the argument driving this paper is that the technical accountability movement currently dominating the educational system in England is less than adequate because it overlooks educators’ responsibility for ethical relations in responding to difference in respect of the other. Curriculum policy makes a significant contribution to the technical accountability culture through complicity in performativity, high-stakes testing and datafication, at the same time as constituting student and teacher subjectivities. I present two different conceptualizations of subjectivity and education, before engaging these in the analysis of data arising from an empirical study which investigated teachers’ and stakeholders’ experiences of curriculum policy reform in ‘disadvantaged’ English schools. The study’s findings demonstrate how a prescribed programme of technical curriculum regulation attempts to ‘fix’ or mend educational problems by ‘fixing’ or prescribing educational solutions. This not only denies ethical professional relations between students, teachers and parents, but also deflects responsibility for educational success from government to teachers and hastens the move from public to private educational provision. Complying with prescribed curriculum policy requirements shifts attention from broad philosophical and ethical questions about educational purpose as well as conferring a violence by assuming control over student and teacher subjectivities.
ADHD and Giftedness: A Neurocognitive Consideration of Twice Exceptionality

Current models of cognition and behavioral diagnosis emphasize categorical classification over continuous considerations of function and promote the “differential diagnosis” of various conditions according to observational criteria. However, an overemphasis on a purely behavioral, categorical approach to understanding human function fails to address the comorbidity of different disorders and does not include a consideration of overlapping levels of function, from “pathological” through “normal,” to “gifted” or exceptional. The frequent co-occurrence of “gifted” and “pathological” function is thus difficult to understand from a corticocentric and purely behavioral and observational point of view. This article reviews “giftedness” in relation to the diagnosis of attention-deficit hyperactivity disorder, coexistence of which is termed “twice exceptional. ” It additionally considers problems in assessing these functions using current neuropsychological tests and methodologies that are presumably based upon a corticocentric model of cognition.
Investigation of Maximum Entropy Hybrid Language Models for Open Vocabulary German and Polish LVCSR

For languages like German and Polish, higher numbers of word inflections lead to high out-of-vocabulary (OOV) rates and high language model (LM) perplexities. Thus, one of the main challenges in large vocabulary continuous speech recognition (LVCSR) is recognizing an open vocabulary. In this paper, we investigate the use of mixed type of sub-word units in the same recognition lexicon. Namely, morphemic or syllabic units combined with pronunciations called graphones, normal graphemic morphemes or syllables, along with full-words. In addition, we investigate the suitability of hybrid mixed-unit Ngrams as features for Maximum Entropy LM along with adaptation. We achieve significant improvements in recognizing OOVs and word error rate reductions for German and Polish LVCSR compared to the conventional full-word approach and state-of-the-art N-gram mixed type hybrid LM.
Equalization Transfers and Dynamic Fiscal Adjustment: Results for German Municipalities and a US-German Comparison

A large panel of German municipalities is employed in order to investigate the dynamic fiscal policy adjustment of local jurisdictions using a VEC model which explicitly takes account of the intertemporal budget constraint. The results confirm that a substantial part of adjustment takes place by offsetting changes in intergovernmental transfers, in particular, in ‘fiscal equalization’ transfers: in present value terms about 34 cents of a one euro decrease in own revenue is compensated by subsequent changes in equalization transfers. The contribution of intergovernmental transfers to restoring fiscal balance, therefore, is about two to three times higher, compared to the case of US municipalities investigated by Buettner and Wildasin (2006). Nevertheless, budget components such as own revenues and general expenditures display larger fluctuations in the German case. This is consistent with the view that fiscal equalization transfers create a moral-hazard problem.
BRAF mutation in papillary thyroid cancer : a meta-analysis

Background: The role of the BRAF V600E mutation as an independent prognostic factors in papillary thyroid cancer (PTC) has not been fully quantified. To address this controversy, a meta-analysis was performed to determine the strength of associations between BRAF mutation status and PTC prognosis, focusing on the recurrence or persistence of the PTC. Review Methods: PubMed, Web of Knowledge, Ovid’s database were searched from January 2000 to August 2015. 236 relevant studies were hand-searched. We selected 30 studies that included 5873 PTC patients and calculated the pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each study. Results: In 30 studies, compared with the patients who had the wild-type BRAF genes, the PTC patients with the BRAF V600E mutation had increased ORs of an older age (≥45 years) (OR, 1.51; 95% CI, 1.17-1.94), an extrathyroidal invasion (OR, 2.03; 95% CI, 1.76-2.34), a lymph node metastasis (OR, 1.59; 95% CI, 1.40-1.81), an advanced TNM stage (OR, 1.77; 95% CI, 1.56-2.01). The BRAF mutation in PTC was not associated with multiplicity (OR, 1.06; 95% CI, 0.91-1.23) or distant metastasis (OR, 0.88; 95% CI, 0.55-1.42). In 8 studies, patients with the mutation had 3.34fold increased risk of recurrent and persistent disease (95% CI, 2.36-4.73). The associations were generally consistent across the different study populations. Conclusion: This meta-analysis demonstrates that the BRAF V600E mutation in PTC was significantly associated with PTC older age, extrathyroidal extension, lymph node metastasis, advanced stage AJCC III/IV and recurrence. We recommend that patients with a suspected malignant thyroid nodule undergo preoperative BRAF V600E testing to guide the initial surgical treatment in PTC.
Ethnic struggle, coexistence, and democratization in Eastern Europe

1. Ethnic protest, moderation, and democratization 2. Time, process, and events in democratization 3. Ethnic contention in context 4. Local violence and uncertainty in Targu Mures, 1990 5. The power of symbols: Romanians, Hungarians, and King Mathias in Cluj 6. Forging language laws: schools and sign wars 7. Debating local governance: autonomy, local control, and minority enclaves 8. Implications of group interaction.
Adaptive Monostatic System for Measuring Microwave Reflections from the Breast

A second-generation monostatic radar system to measure microwave reflections from the human breast is presented and analyzed. The present system can measure the outline of the breast with an accuracy of ±1 mm and precisely place the microwave sensor in an adaptive matter such that microwaves are normally incident on the skin. Microwave reflections are measured between 10 MHz to 12 GHz with sensitivity of 65 to 75 dB below the input power and a total scan time of 30 min for 140 locations. The time domain reflections measured from a volunteer show fidelity above 0.98 for signals in a single scan. Finally, multiple scans of a breast phantoms demonstrate the consistency of the system in terms of recorded reflection, outline measurement, and image reconstruction.
Development of interfirm network management activities: The impact of industry, firm age and size

Abstract This article investigates the structural characteristics of firms that promote activities involving partners who coordinate with each other to achieve common or individual goals. The article also aims to verify empirically whether these activities generate advantages for companies embedded in relationships by examining the effects of industry, age and size on interfirm network management activities in a sample of Spanish companies operating in several industries and belonging to networks. The results show differences according to the life cycle stage: growth or maturity. Only the relation between interfirm network management activity and performance has been confirmed in both samples. The findings point to the need to consider the industrial environment when analysing firms’ networking decisions because the situations they face differ in mature or growing industries.
Efficient and versatile CRISPR engineering of human neurons in culture to model neurological disorders

The recent identification of multiple new genetic causes of neurological disorders highlights the need for model systems that give experimental access to the underlying biology. In particular, the ability to couple disease-causing mutations with human neuronal differentiation systems would be beneficial. Gene targeting is a well-known approach for dissecting gene function, but low rates of homologous recombination in somatic cells (including neuronal cells) have traditionally impeded the development of robust cellular models of neurological disorders. Recently, however, CRISPR/Cas9 gene editing technologies have expanded the number of systems within which gene targeting is possible. Here we adopt as a model system LUHMES cells, a commercially available diploid human female mesencephalic cell line that differentiates into homogeneous mature neurons in 1-2 weeks. We describe optimised methods for transfection and selection of neuronal progenitor cells carrying targeted genomic alterations using CRISPR/Cas9 technology. By targeting the endogenous X-linked MECP2 locus, we introduced four independent missense mutations that cause the autism spectrum disorder Rett syndrome and observed the desired genetic structure in 3-26% of selected clones, including gene targeting of the inactive X chromosome. Similar efficiencies were achieved by introducing neurodevelopmental disorder-causing mutations at the autosomal EEF1A2 locus on chromosome 20. Our results indicate that efficiency of genetic “knock-in” is determined by the location of the mutation within the donor DNA molecule. Furthermore, we successfully introduced an mCherry tag at the MECP2 locus to yield a fusion protein, demonstrating that larger insertions are also straightforward in this system. We suggest that our optimised methods for altering the genome of LUHMES cells make them an attractive model for the study of neurogenetic disorders.
Title Integrative network analysis reveals molecular mechanisms of blood pressure regulation Permalink

Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expressionrelated SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3 / mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3 / mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.
ROUNDING-OFF ERRORS IN MATRIX PROCESSES

A number of methods of solving sets of linear equations and inverting matrices are discussed. The theory of the rounding-off errors involved is investigated for some of the methods. In all cases examined, including the well-known 'Gauss elimination process', it is found that the errors are normally quite moderate: no exponential build-up need occur. Included amongst the methods considered is a generalization of Choleski's method which appears to have advantages over other known methods both as regards accuracy and convenience. This method may also be regarded as a rearrangement of the elimination process.
Genome-Wide Expression of Azoospermia Testes Demonstrates a Specific Profile and Implicates ART3 in Genetic Susceptibility

Infertility affects about one in six couples attempting pregnancy, with the man responsible in approximately half of the cases. Because the pathophysiology underlying azoospermia is not elucidated, most male infertility is diagnosed as idiopathic. Genome-wide gene expression analyses with microarray on testis specimens from 47 non-obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) patients were performed, and 2,611 transcripts that preferentially included genes relevant to gametogenesis and reproduction according to Gene Ontology classification were found to be differentially expressed. Using a set of 945 of the 2,611 transcripts without missing data, NOA was further categorized into three classes using the non-negative matrix factorization method. Two of the three subclasses were different from the OA group in Johnsen's score, FSH level, and/or LH level, while there were no significant differences between the other subclass and the OA group. In addition, the 52 genes showing high statistical difference between NOA subclasses (p < 0.01 with Tukey's post hoc test) were subjected to allelic association analyses to identify genetic susceptibilities. After two rounds of screening, SNPs of the ADP-ribosyltransferase 3 gene (ART3) were associated with NOA with highest significance with ART3-SNP25 (rs6836703; p = 0.0025) in 442 NOA patients and 475 fertile men. Haplotypes with five SNPs were constructed, and the most common haplotype was found to be under-represented in patients (NOA 26.6% versus control 35.3%, p = 0.000073). Individuals having the most common haplotype showed an elevated level of testosterone, suggesting a protective effect of the haplotype on spermatogenesis. Thus, genome-wide gene expression analyses were used to identify genes involved in the pathogenesis of NOA, and ART3 was subsequently identified as a susceptibility gene for NOA. These findings clarify the molecular pathophysiology of NOA and suggest a novel therapeutic target in the treatment of NOA.
When Bad Emotions Seem Better

Evaluations of objects change as a function of our experience with them. We suggest that this also applies to the evaluation of emotions. In three studies, we show that the evaluation of anger changes as a function of direct experience with anger. We found that the experience of anger in a context in which it could be beneficial (i.e., an aggressive computer game) led people to perceive anger as more useful (Study 1). Moreover, people came to evaluate anger less negatively after experiencing anger in a context in which it could be beneficial. These changes did not result from the mere experience of anger or from exposure to an aggressive context (Study 2). Rather, the more anger improved their performance, the less negatively participants came to evaluate anger (Study 3). These findings suggest that how bad anger seems may depend on our direct experience with it.