Miracle-dz/UniFAR-FTUs huggingface dataset:
Runx1 Regulation of Pu.1 Corepressor/Coactivator Exchange Identifies Specific Molecular Targets for Leukemia Differentiation Therapy*

Background: Leukemia cells highly express master differentiation-driving transcription factors yet paradoxically, terminal differentiation genes are epigenetically repressed. Results: The hematopoietic transcription factors RUNX1 and PU.1 cooperated to exchange corepressors for coactivators, and deficiency of RUNX1, frequent in leukemia, caused aberrant recruitment of specific corepressors instead of coactivators to PU.1. Conclusion: This mechanism explains the paradox. Significance: Inhibition of the specific corepressors restored terminal differentiation. Gene activation requires cooperative assembly of multiprotein transcription factor-coregulator complexes. Disruption to cooperative assemblage could underlie repression of tumor suppressor genes in leukemia cells. Mechanisms of cooperation and its disruption were therefore examined for PU.1 and RUNX1, transcription factors that cooperate to activate hematopoietic differentiation genes. PU.1 is highly expressed in leukemia cells, whereas RUNX1 is frequently inactivated by mutation or translocation. Thus, coregulator interactions of Pu.1 were examined by immunoprecipitation coupled with tandem mass spectrometry/Western blot in wild-type and Runx1-deficient hematopoietic cells. In wild-type cells, the NuAT and Baf families of coactivators coimmunoprecipitated with Pu.1. Runx1 deficiency produced a striking switch to Pu.1 interaction with the Dnmt1, Sin3A, Nurd, CoRest, and B-Wich corepressor families. Corepressors of the Polycomb family, which are frequently inactivated by mutation or deletion in myeloid leukemia, did not interact with Pu.1. The most significant gene ontology association of Runx1-Pu.1 co-bound genes was with macrophages, therefore, functional consequences of altered corepressor/coactivator exchange were examined at Mcsfr, a key macrophage differentiation gene. In chromatin immunoprecipitation analyses, high level Pu.1 binding to the Mcsfr promoter was not decreased by Runx1 deficiency. However, the Pu.1-driven shift from histone repression to activation marks at this locus, and terminal macrophage differentiation, were substantially diminished. DNMT1 inhibition, but not Polycomb inhibition, in RUNX1-translocated leukemia cells induced terminal differentiation. Thus, RUNX1 and PU.1 cooperate to exchange corepressors for coactivators, and the specific corepressors recruited to PU.1 as a consequence of RUNX1 deficiency could be rational targets for leukemia differentiation therapy.
The Met Office Hadley Centre climate modelling capability: the competing requirements for improved resolution, complexity and dealing with uncertainty

Predictions of future climate change require complex computer models of the climate system to represent the full range of processes and interactions that influence climate. The Met Office Hadley Centre uses ‘families’ of models as part of the Met Office Unified Model Framework to address different classes of problems. The HadGEM family is a suite of state-of-the-art global environment models that are used to reduce uncertainty and represent and predict complex feedbacks. The HadCM3 family is a suite of well established but cheaper models that are used for multiple simulations, for example, to quantify uncertainty or to test the impact of multiple emissions scenarios.
Regular physical education class enhances sociality and physical fitness while reducing psychological problems in children of multicultural families

This study investigated the influence of physical education class (PEC) as an intervention method for aggression, sociality, stress, and physical fitness levels in children from multicultural families. The hypothesis was that participating in PEC would result in reduced aggression and stress and improved sociality and physical fitness in multicultural children. A three-item questionnaire, a body composition test, and physical fitness tests were given three times. Eighty-four subjects were divided into four groups: multicultural children who participated in PEC (multi-PEG, n=12), multicultural children who did not participate in PEC (multi-NPEG, n=13), single-cultural children who participated in PEC (sing-PEG, n=11), and single-cultural children who did not participate in PEC (sing-NPEG, n=12), respectively. Parametric and nonparametric statistical methods were conducted on the collected data with a significance level set a priori at P<0.05. After 8 weeks of PEC, fat mass (F=2.966, P=0.045) and body mass index (F=3.654, P=0.021) had significantly different interaction effects. In the aspect of interaction effects from physical fitness variables, cardiopulmonary endurance (F=21.961, P=0.001), flexibility (F=8.892, P=0.001), muscular endurance (F=31.996, P=0.001), muscular strength (F=4.570, P=0.008), and power (F=24.479, P=0.001) were significantly improved in the multi-PEG compared to those of the other three groups. Moreover, sociality (F=22.144, P=0.001) in the multi-PEG was enhanced, whereas aggression (F=6.745, P=0.001) and stress (F=3.242, P=0.033) levels were reduced. As conclusion, the PEC reduced aggression and stress levels, and improved sociality and physical fitness levels after 8 weeks. This study confirmed that PEC for children from multicultural families can improve psychosocial factors and physical health.
A New Method for Predicting Recovery After Stroke

Background and Purpose— Several prognostic factors have been identified for outcome after stroke. However, there is a need for empirically derived models that can predict outcome and assist in medical management during rehabilitation. To be useful, these models should take into account early changes in recovery and individual patient characteristics. We present such a model and demonstrate its clinical utility. Methods— Data on functional recovery (Barthel Index) at 0, 2, 4, 6, and 12 months after stroke were collected prospectively for 299 stroke patients at 2 London hospitals. Multilevel models were used to model recovery trajectories, allowing for day-to-day and between-patient variation. The predictive performance of the model was validated with an independent cohort of 710 stroke patients. Results— Urinary incontinence, sex, prestroke disability, and dysarthria affected the level of outcome after stroke; age, dysphasia, and limb deficit also affected the rate of recovery. Applying this to the validation cohort, the average difference between predicted and observed Barthel Index was −0.4, with 90% limits of agreement from −7 to 6. Predicted Barthel Index lay within 3 points of the observed Barthel Index on 49% of occasions and improved to 69% when patients’ recovery histories were taken into account. Conclusions— The model predicts recovery at various stages of rehabilitation in ways that could improve clinical decision making. Predictions can be altered in light of observed recovery. This model is a potentially useful tool for comparing individual patients with average recovery trajectories. Patients at elevated risk could be identified and interventions initiated.
Personal reputation in organizations: Two-study constructive replication and extension of antecedents and consequences

Personal reputation has been argued to demonstrate important influences on work outcomes. However, substantive research on personal reputation is relatively scarce. This two-study investigation empirically supports and extends existing theory regarding the temporal development of personal reputation (i.e., antecedents and consequences), and thus contributes to a more informed understanding of both the construct and criterion-related validity of this important construct. Study 1 is conducted longitudinally, in order to assess the development of personal reputation over time, which is undertaken to demonstrate the effects of human capital and social effectiveness as antecedents of reputation. Study 2 complements and extends the first study by conducting a field investigation examining the effects of time, human capital, and social effectiveness as antecedents of personal reputation, while also exploring the reputation consequences of autonomy, power, and career success. Our findings suggest that human capital, time, and social effectiveness play a part in the development of a reputation. Furthermore, career success, power, and autonomy were shown to be outcomes of the reputation construct. Contributions and strengths of this investigation, limitations, and directions for future research are discussed.
Analysis by synthesis of speech prosody: the Prozed environment

This paper presents ProZed, an environment for the multilingual analysis by synthesis of speech prosody. The analysis is based on the symbolic representation of prosodic form without reference to prosodic function. The parameters of the model are at present limited to fundamental frequency and duration but the same framework could be extended to accomodate other parameters such as spectral tilt or voice quality. Each parameter is defined with respect to specific domains and units for long-term and short-term phonetic interpretation with an abstract annotation system corresponding to a level of surface phonological representation. The environment is integrated with the Praat program for analysis and the Mbrola program for synthesis.
Papular Elastorrhexis: A Case and Differential Diagnosis

Papular elastorrhexis is a rare cutaneous disorder that occurs predominantly during adolescence. The disorder is characterized by asymptomatic indurated white or flesh papules showing decreased and fragmented elastic fibers in the dermis. We herein report on a 12-year-old girl with multiple asymptomatic white, nonfollicular, firm papules scattered on the extremities and trunk. Histological examination revealed focal areas showing increased layers of collagen fibers and decreased and fragmented elastic fibers in the upper dermis.
Text feature selection for sentiment classification of Chinese online reviews

In order to meet the requirement of customised services for online communities, sentiment classification of online reviews has been applied to study the unstructured reviews so as to identify users’ opinions on certain products. The purpose of this article is to select features for sentiment classification of Chinese online reviews with techniques well performed in traditional text classification. First, adjectives, adverbs and verbs are identified as the potential text features containing sentiment information. Then, four statistical feature selection methods, such as document frequency (DF), information gain (IG), chi-squared statistic (CHI) and mutual information (MI), are adopted to select features. After that, the Boolean weighting method is applied to set feature weights and construct a vector space model. Finally, a support vector machine (SVM) classifier is employed to predict the sentiment polarity of online reviews. Comparative experiments are conducted based on hotel online reviews in Chinese. The results indicate that the highest accuracy of the sentiment classification of Chinese online reviews is achieved by taking adjectives, adverbs and verbs together as the feature. Besides that, different feature selection methods make distinct performances on sentiment classification, as DF performs the best, CHI follows and IG ranks the last, whereas MI is not suitable for sentiment classification of Chinese online reviews. This conclusion will be helpful to improve the accuracy of sentiment classification and be useful for further research.
Tongue Abnormalities Are Associated to a Maternal Folic Acid Deficient Diet in Mice

It is widely accepted that maternal folic acid (FA) deficiency during pregnancy is a risk factor for abnormal development. The tongue, with multiple genes working together in a coordinated cascade in time and place, has emerged as a target organ for testing the effect of FA during development. A FA-deficient (FAD) diet was administered to eight-week-old C57/BL/6J mouse females for 2–16 weeks. Pregnant dams were sacrificed at gestational day 17 (E17). The tongues and heads of 15 control and 210 experimental fetuses were studied. In the tongues, the maximum width, base width, height and area were compared with width, height and area of the head. All measurements decreased from 10% to 38% with increasing number of weeks on maternal FAD diet. Decreased head and tongue areas showed a harmonic reduction (Spearman nonparametric correlation, Rho = 0.802) with respect to weeks on a maternal FAD diet. Tongue congenital abnormalities showed a 10.9% prevalence, divided in aglossia (3.3%) and microglossia (7.6%), always accompanied by agnathia (5.6%) or micrognathia (5.2%). This is the first time that tongue alterations have been related experimentally to maternal FAD diet in mice. We propose that the tongue should be included in the list of FA-sensitive birth defect organs due to its relevance in several key food and nutrition processes.
Beyond convex relaxation: A polynomial-time non-convex optimization approach to network localization

The successful deployment and operation of location-aware networks, which have recently found many applications, depends crucially on the accurate localization of the nodes. Currently, a powerful approach to localization is that of convex relaxation. In a typical application of this approach, the localization problem is first formulated as a rank-constrained semidefinite program (SDP), where the rank corresponds to the target dimension in which the nodes should be localized. Then, the non-convex rank constraint is either dropped or replaced by a convex surrogate, thus resulting in a convex optimization problem. In this paper, we explore the use of a non-convex surrogate of the rank function, namely the so-called Schatten quasi- norm, in network localization. Although the resulting optimization problem is non-convex, we show, for the first time, that a first- order critical point can be approximated to arbitrary accuracy in polynomial time by an interior-point algorithm. Moreover, we show that such a first-order point is already sufficient for recovering the node locations in the target dimension if the input instance satisfies certain established uniqueness properties in the literature. Finally, our simulation results show that in many cases, the proposed algorithm can achieve more accurate localization results than standard SDP relaxations of the problem.
Mixed DNA/oligo (ethylene glycol) functionalized gold surfaces improve DNA hybridization in complex media

Reliable, direct “sample-to-answer” capture of nucleic acid targets from complex media would greatly improve existing capabilities of DNA microarrays and biosensors. This goal has proven elusive for many current nucleic acid detection technologies attempting to produce assay results directly from complex real-world samples, including food, tissue, and environmental materials. In this study, we have investigated mixed self-assembled thiolated single-strand DNA (ssDNA) monolayers containing a short thiolated oligo (ethylene glycol) (OEG) surface diluent on gold surfaces to improve the specific capture of DNA targets from complex media. Both surface composition and orientation of these mixed DNA monolayers were characterized with x-ray photoelectron spectroscopy (XPS) and near-edge x-ray absorption fine structure (NEXAFS). XPS results from sequentially adsorbed ssDNA/OEG monolayers on gold indicate that thiolated OEG diluent molecules first incorporate into the thiolated ssDNA monolayer and, upon longer OEG exposures, competitively displace adsorbed ssDNA molecules from the gold surface. NEXAFS polarization dependence results #followed by monitoring the N 1s → π* transition) indicate that adsorbed thiolated ssDNA nucleotide base-ring structures in the mixed ssDNA monolayers are oriented more parallel to the gold surface compared to DNA bases in pure ssDNA monolayers. This supports ssDNA oligomer reorientation towards a more upright position upon OEG mixed adlayer incorporation. DNA target hybridization on mixed ssDNA probe/OEG monolayers was monitored by surface plasmon resonance (SPR). Improvements in specific target capture for these ssDNA probe surfaces due to incorporation of the OEG diluent were demonstrated using two model biosensing assays, DNA target capture from complete bovine serum and from salmon genomic DNA mixtures. SPR results demonstrate that OEG incorporation into the ssDNA adlayer improves surface resistance to both nonspecific DNA and protein adsorption, facilitating detection of small DNA target sequences from these undiluted, unpurified complex biological mixtures unachievable with previously reported, analogous ssDNA/11-mercapto-1-undecanol monolayer surfaces [P. Gong, C. -Y. Lee, L. J. Gamble, D. G. Castner, and D.W. Grainger, Anal. Chem. 78, 3326 (2006)].
An Assessment of the Effects of Serotonin 6 (5-HT6) Receptor Antagonists in Rodent Models of Learning

Antagonists of serotonin 6 (5-HT6) receptors have been reported to enhance cognition in animal models of learning, although this finding has not been universal. We have assessed the therapeutic potential of the specific 5-HT6 receptor antagonists 4-amino-N-(2,6-bis-methylamino-pyrimidin-4-yl)-benzenesulfonamide (Ro 04-6790) and 5-chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046) in rodent models of cognitive function. Although mice express the 5-HT6 receptor and the function of this receptor has been investigated in mice, all reports of activity with 5-HT6 receptor antagonists have used rat models. In the present study, receptor binding revealed that the pharmacological properties of the mouse receptor are different from the rat and human receptor: Ro 04-6790 does not bind to the mouse 5-HT6 receptor, so all in vivo testing included in the present report was conducted in rats. We replicated previous reports that 5-HT6 receptor antagonists produce a stretching syndrome previously shown to be mediated through cholinergic mechanisms, but Ro 04-6790 and SB-271046 failed to attenuate scopolamine-induced deficits in a test of contextual fear conditioning. We also failed to replicate the significant effects reported previously in both an autoshaping task and in a version of the Morris water maze. The results of our experiments are not consistent with previous reports that suggested that 5-HT6 antagonists might have therapeutic potential for cognitive disorders.
Sertraline increases the survival of retinoic acid induced neuronal cells but not glial cells from human mesenchymal stem cells

An increase in the number of viable in vitro differentiated neuronal cells is important for their use in clinics. A proportion of differentiated cells lose their viability before being used, and therefore we decided to use a pharmacological agent, sertraline, to increase neural cell differentiation and their survival. Purified endometrial stem cells (EnSCs) were examined for neuronal and glial cell specific markers after retinoic acid (RA) and sertraline treatment via RT‐PCR, immunocytochemistry and Western blot analysis. The survival of differentiated cells was measured by MTT assay and the frequency of apoptosis, demonstrated by caspase‐3‐like activity. EnSCs were differentiated into neuronal cells after RA induction. Sertraline increased neuronal cell differentiation by 1.2‐fold and their survival by 1.4‐fold, and decreased from glial cell differentiation significantly. The findings indicate that sertraline could be used to improve the in vitro differentiation process of stem cells into neuronal cells, and may be involved in regenerative pharmacology in future.
Effect of infusion of carnitine and glucose on blood glucose, ketones, and free fatty acids of ketotic cows.

Abstract Carnitine was infused into control (mid-lactation), feed-restricted ketotic and spontaneously ketotic cows. Blood glucose, aeetoacetate, β-hydroxybutyrate, and plasma free fatty acids were determined. DL-Carnitine infusion into control animals had no effect upon blood glucose or ketones nor did it affect milk yield or composition. DL-Carnitine infusion into spontaneously ketotic cows gave variable results. Infusion at 20 micromoles (3.9mg) dl-carnitine per kilogram per hour caused blood glucose to rise and ketones to fall in three cases; in a fourth case blood ketones rose and glucose fell. A single case treated with 145 μ moles l-carnitine (28.6mg) per hour per kilogram increased aeetoacetate accompanied by decreased plasma free fatty acids, whereas glucose showed only a transient elevation. l-Carnitine infusion into feed-restricted and spontaneously ketotic cows was consistent only in lowering plasma free fatty acids. Glucose infusion into feed-restricted ketotic cows increased blood glucose and decreased blood aeetoacetate; however, plasma free fatty acids were unaffected. Glucose infusion into a spontaneously ketotic cow immediately decreased plasma free fatty acids. Fatty acid metabolism in the ketotic cow did not function at peak efficiency and effects of carnitine infusion were the result of increased β-oxidation of long-chain fatty acids.
Translation Initiation Factors eIF3 and HCR1 Control Translation Termination and Stop Codon Read-Through in Yeast Cells

Translation is divided into initiation, elongation, termination and ribosome recycling. Earlier work implicated several eukaryotic initiation factors (eIFs) in ribosomal recycling in vitro. Here, we uncover roles for HCR1 and eIF3 in translation termination in vivo. A substantial proportion of eIF3, HCR1 and eukaryotic release factor 3 (eRF3) but not eIF5 (a well-defined “initiation-specific” binding partner of eIF3) specifically co-sediments with 80S couples isolated from RNase-treated heavy polysomes in an eRF1-dependent manner, indicating the presence of eIF3 and HCR1 on terminating ribosomes. eIF3 and HCR1 also occur in ribosome- and RNA-free complexes with both eRFs and the recycling factor ABCE1/RLI1. Several eIF3 mutations reduce rates of stop codon read-through and genetically interact with mutant eRFs. In contrast, a slow growing deletion of hcr1 increases read-through and accumulates eRF3 in heavy polysomes in a manner suppressible by overexpressed ABCE1/RLI1. Based on these and other findings we propose that upon stop codon recognition, HCR1 promotes eRF3·GDP ejection from the post-termination complexes to allow binding of its interacting partner ABCE1/RLI1. Furthermore, the fact that high dosage of ABCE1/RLI1 fully suppresses the slow growth phenotype of hcr1Δ as well as its termination but not initiation defects implies that the termination function of HCR1 is more critical for optimal proliferation than its function in translation initiation. Based on these and other observations we suggest that the assignment of HCR1 as a bona fide eIF3 subunit should be reconsidered. Together our work characterizes novel roles of eIF3 and HCR1 in stop codon recognition, defining a communication bridge between the initiation and termination/recycling phases of translation.