Miracle-dz/UniFAR-FTUs huggingface dataset:
RPEL Motifs Link the Serum Response Factor Cofactor MAL but Not Myocardin to Rho Signaling via Actin Binding

ABSTRACT Myocardin (MC) family proteins are transcriptional coactivators for serum response factor (SRF). Each family member possesses a conserved N-terminal region containing three RPEL motifs (the “RPEL domain”). MAL/MKL1/myocardin-related transcription factor A is cytoplasmic, accumulating in the nucleus upon activation of Rho GTPase signaling, which alters interactions between G-actin and the RPEL domain. We demonstrate that MC, which is nuclear, does not shuttle through the cytoplasm and that the contrasting nucleocytoplasmic shuttling properties of MAL and MC are defined by their RPEL domains. We show that the MAL RPEL domain binds actin more avidly than that of MC and that the RPEL motif itself is an actin-binding element. RPEL1 and RPEL2 of MC bind actin weakly compared with those of MAL, while RPEL3 is of comparable and low affinity in the two proteins. Actin binding by all three motifs is required for MAL regulation. The differing behaviors of MAL and MC are specified by the RPEL1-RPEL2 unit, while RPEL3 can be exchanged between them. We propose that differential actin occupancy of multiple RPEL motifs regulates nucleocytoplasmic transport and activity of MAL.
The flavonoid kaempferol sensitizes human glioma cells to TRAIL-mediated apoptosis by proteasomal degradation of survivin

Resistance to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2L) limits its potential as a drug for cancer therapy. Here, we report that kaempferol, a bioactive plant flavonoid, sensitizes U251 and U87 glioma cells to TRAIL-mediated apoptosis. In contrast, U373 cells are not affected by kaempferol treatment. Treatment of kaempferol alone for 24 h did not induce apoptosis in the cell lines. We provide evidence that TRAIL-induced apoptosis is partially driven by kaempferol-mediated reduction of survivin protein levels. On kaempferol treatment, proteasomal degradation of survivin was observed. Inhibition of proteasomal degradation with MG132 in kaempferol-treated cells restored survivin protein levels in both glial cell lines. Consequently, overexpression of survivin attenuated TRAIL-kaempferol–induced apoptosis. In addition, we show that kaempferol mediates down-regulation of phosphorylated Akt, thereby further reducing survivin protein level. Furthermore, the blockage of the serine/threonine kinase Akt activity by kaempferol is important for inhibition of survivin because active phosphorylated Akt enhances the stability of survivin. However, we also show that the combined treatment of TRAIL and kaempferol induces cleavage (activation) of caspase-8, thereby exerting a proapoptotic effect independent of survivin known not to inhibit caspase-8 activation. Other effects induced by kaempferol were suppression of X-linked inhibitor of apoptosis proteins as the antiapoptotic members of the Bcl-2 family, Bcl-2, Bcl-xL, and Mcl-1 in a concentration-dependent manner. In summary, we showed that suppression of survivin is an essential mechanism in TRAIL-kaempferol–mediated apoptosis. [Mol Cancer Ther 2008;7(11):3566–74]
Transcatheter Ablation of Ectopic Atrial Tachycardia in Young Patients Using Radiofrequency Current

BackgroundEctopic atrial tachycardia (EAT) is a reversible cause of cardiomyopathy but may be quite difficult to control with conventional therapy. Transcatheter ablation with radiofrequency current was tested as an alternative to medical or surgical treatment of this condition Methods and ResultsTwelve young patients (aged 10 months to 19 years) with drug-resistant EAT were treated with direct transcatheter ablation of the ectopic focus using radiofrequency (RF) energy. All had depressed left ventricular contractility by echocardiographic criteria, involving shortening fractions of 10–26% (median, 20%; normal, 28–35%). The EAT was mapped to the left atrium in seven cases and to the right atrium in five. Local atrial activation at the ectopic site preceded the onset of the surface P wave by 20–60 msec (median, 42 msec). Tachycardia terminated 0.5–13.0 seconds (median, 2.0 seconds) into a successful RF application. The ablation effectively eliminated EAT in 11 of 12 patients (92%), all of whom were discharged in sinus rhythm without medications after a median hospital stay of 48 hours. Ablation was unsuccessful in one patient with diffuse dysplasia of the anterior right atrium, who eventually did well after surgical resection of abnormal atrial tissue. Transient depression of sinus node function was noted in one patient who had successful ablation of an EAT focus in close proximity to the sinus node, although normal sinus node function returned within 72 hours. No other complications were encountered. During follow-up (3–21 months; median, 13 months), one patient had recurrence of a slower and less-sustained EAT that was successfully eliminated at a second ablation session. All others remained in sinus rhythm, and all 12 subjects recovered normal ventricular function ConclusionsRF ablation appears to be a safe and effective therapeutic option for drug-resistant ectopic atrial tachycardia and may be the preferred first-line therapy for those patients with depressed ventricular function.
Geographic distribution of vestibular schwannomas in West Scotland between 2000-2015

BACKGROUND Although the natural history of vestibular schwannomas (VS) has been previously studied, few studies have investigated associated epidemiological factors, primarily because of the lack of large available cohorts. OBJECTIVE The objective of this study was to perform a multi-scale geographical analysis of the period prevalence of VS in West Scotland from 2000 to 2015. METHODS Adults diagnosed with sporadic VS were identified through the National Health Services of West Scotland database and geocoded to the unit postcode. To assess whether the cohort of VS cases could be pooled into a period prevalence measure, the locations of VS cases were analyzed by sex using Cross-L and Difference-K functions. VS period prevalence was examined at two aggregate spatial scales: the postcode district and a coarser scale of NHS Health Boards. The spatial structure of period prevalence within each level of spatial aggregation was measured using univariate global and local Moran's I. Bivariate local Moran's I was used to examine the between-scale variability in period prevalence from the postcode district level to the NHS Health Boards levels. Prior to spatial autocorrelation analyses, the period prevalence at the postcode district was tested for stratified spatial heterogeneity within the NHS Health Boards using Wang's q-Statistic. RESULTS A total of 512 sporadic VS were identified in a population of over 3.1 million. Between 2000 and 2015, VS period prevalence was highest within the NHS Health Boards of Greater Glasgow and Clyde, Ayrshire and Arran and the Western Isles. However, at the NHS scale, period prevalence exhibited no spatial autocorrelation globally or locally. At the district scale, Highland exhibited the most unusual local spatial autocorrelation. Bivariate local Moran's I results indicated general stability of period prevalence across the postcode district to Health Boards scales. However, locally, some postcode districts in Greater Glasgow and Clyde, Ayrshire and Arran exhibited unusually low district to zone spatial autocorrelation in period prevalence, as did the southern parts of the Western Isles. Some unusually high period prevalence values between the postcode district to Health Board scale were found in Tayside, Forth Valley and Dumfries and Galloway. CONCLUSION Geographic variability in VS in West Scotland was identified in this patient population, showing that there are areas, even remote, with unusually high or low period prevalence. This can be partially attributed to links between primary and tertiary care. Potential genetic or environmental risk factors that may contribute to geographic variation in this disease within Scotland are also a possibility but require further investigation.
Experimental Investigations on Viscoelastic Properties of a Shape Memory Polymer

The shape memory polymers (SMPs) are polymeric smart materials which have the remarkable ability to recover their primary shape from a temporary one under an external stimulus. The study deals with the synthesis and the thermo-mechanical characterization of a thermally-actuated SMP, the tBA/PEGDMA, with a special focus on viscoelastic properties. The mechanical characterization is performed using three kinds of tests: quasi-static tensile tests, dynamic mechanical analysis (DMA) and modal tests. The first one allows the identification of the Youngs modulus and the Poisson’s ratio at ambient temperature. Modal analyses are done for various temperature values, and resonance frequencies are measured. In order to validate the time-temperature equivalence on this SMP, a DMA is performed under harmonic loading for different temperatures and a master curve highlights a complementarity of the results. Finally a suitable model for the viscoelastic behavior of the SMP is identified.Copyright © 2014 by ASME
Infant Milk Formulas: Effect of Storage Conditions on the Stability of Powdered Products towards Autoxidation

Thirty samples of powdered infant milk formulas containing polyunsaturated fatty acids (PUFAs) have been stored at four different temperatures (20, 28, 40 and 55 °C) and periodically monitored for their malondialdehyde (MDA) content up to one year. MDA levels ranged between 250 and 350 ng/kg in sealed samples with a maximum of 566 ng/kg in samples stored at 28 °C for three weeks after opening of their original packages, previously maintained for ten months at 20 °C. Sample stored at 40° and 55 °C were also submitted to CIE (Commission Internationale de l’Eclairage) colorimetric analysis, since color is the first sensorial property that consumers may evaluate. Overall, the results demonstrated a good stability of PUFA-enriched infant milk formulas in terms of MDA content. However, some care has to be paid when these products are not promptly consumed and stored for a long time after first opening.
Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression.

OBJECTIVE Family and twin studies indicate substantial overlap of genetic influences on psychotic and mood disorders. Linkage and candidate gene studies have also suggested overlap across schizophrenia, bipolar disorder, and major depressive disorder. The purpose of this study was to apply genomewide association study (GWAS) analysis to address the specificity of genetic effects on these disorders. METHOD The authors combined GWAS data from three large effectiveness studies of schizophrenia (CATIE, genotyped: N=741), bipolar disorder (STEP-BD, geno-typed: N=1,575), and major depressive disorder (STAR*D, genotyped: N=1,938) as well as from psychiatrically screened control subjects (NIMH-Genetics Repository: N=1,204). A two-stage analytic procedure involving an omnibus test of allele frequency differences among case and control groups was applied, followed by a model selection step to identify the best-fitting model of allelic effects across disorders. RESULTS The strongest result was seen for a single nucleotide polymorphism near the adrenomedullin (ADM) gene (rs6484218), with the best-fitting model indicating that the effect was specific to bipolar II disorder. Findings also revealed evidence suggesting that several genes may have effects that transcend clinical diagnostic boundaries, including variants in NPAS3 that showed pleiotropic effects across schizophrenia, bipolar disorder, and major depressive disorder. CONCLUSIONS This study provides the first genomewide significant evidence implicating variants near the ADM gene on chromosome 11p15 in psychopathology, with effects that appear to be specific to bipolar II disorder. Although genomewide significant evidence of cross-disorder effects was not detected, the results provide evidence that there are both pleiotropic and disorder-specific effects on major mental illness and illustrate an approach to dissecting the genetic basis of mood and psychotic disorders that can inform future large-scale cross-disorder GWAS analyses.
Flatness and motion planning : the car with n trailers.

A solution of the motion planning without obstacles for the nonholonomic system describing a car with n trailers is proposed. This solution relies basically on the fact that the system is flat with the cartesian coordinates of the last trailer as linearizing output. The Frnet formulas are used to simplify the calculation. The 2-trailers case is treated in details and illustrated through parking simulations.
Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner

Intrinsic activity in the brain is organized into networks. Although constrained by their anatomical connections, functional correlations between nodes of these networks reorganize dynamically. Dynamic organization implies that couplings between network nodes can be reconfigured to support processing demands. To explore such reconfigurations, we combined repetitive transcranial magnetic stimulation (rTMS) and functional connectivity MRI (fcMRI) to modulate cortical activity in one node of the default network, and assessed the effect of this upon functional correlations throughout the network. Two different frequencies of rTMS to the same default network node (the left posterior inferior parietal lobule, lpIPL) induced two topographically distinct changes in functional connectivity. High-frequency rTMS to lpIPL decreased functional correlations between cortical default network nodes, but not between these nodes and the hippocampal formation. In contrast, low frequency rTMS to lpIPL did not alter connectivity between cortical default network nodes, but increased functional correlations between lpIPL and the hippocampal formation. These results suggest that the default network is composed of (at least) two subsystems. More broadly, the finding that two rTMS stimulation regimens to the same default network node have distinct effects reveals that this node is embedded within a network that possesses multiple, functionally distinct relationships among its distributed partners.
Epigenetic regulation of NK cell differentiation and effector functions

Upon maturation, natural killer (NK) cells acquire effector functions and regulatory receptors. New insights suggest a considerable functional heterogeneity and dynamic regulation of receptor expression in mature human NK cell subsets based on different developmental axes. Such processes include acquisition of lytic granules as well as regulation of cytokine production in response to exogenous cytokine stimulation or target cell interactions. One axis is regulated by expression of inhibitory receptors for self-MHC class I molecules, whereas other axes are less well defined but likely are driven by different activating receptor engagements or cytokines. Moreover, the recent identification of long-lived NK cell subsets in mice that are able to expand and respond rapidly following a secondary viral challenge suggest previously unappreciated plasticity in the programming of NK cell differentiation. Here, we review advances in our understanding of mature NK cell development and plasticity with regards to regulation of cellular function. Furthermore, we highlight some of the major questions that remain pertaining to the epigenetic changes that underlie the differentiation and functional specialization of NK cells and the regulation of their responses.
An Incremental Adaptive Life Long Learning Approach for Type-2 Fuzzy Embedded Agents in Ambient Intelligent Environments

In this paper, we present a novel type-2 fuzzy systems based adaptive architecture for agents embedded in ambient intelligent environments (AIEs). Type-2 fuzzy systems are able to handle the different sources of uncertainty and imprecision encountered in AIEs to give a very good response. The presented agent architecture uses a one pass method to learn in a nonintrusive manner the user's particular behaviors and preferences for controlling the AIE. The agent learns the user's behavior by learning his particular rules and interval type-2 Membership Functions (MFs), these rules and MFs can then be adapted online incrementally in a lifelong learning mode to suit the changing environmental conditions and user preferences. We will show that the type-2 agents generated by our one pass learning technique outperforms those generated by genetic algorithms (GAs). We will present unique experiments carried out by different users over the course of the year in the Essex Intelligent Dormitory (iDorm), which is a real AIE test bed. We will show how the type-2 agents learnt and adapted to the occupant's behavior whilst handling the encountered short term and long term uncertainties to give a very good performance that outperformed the type-1 agents while using smaller rule bases
Effect of phosphoric acid etching on the shear bond strength of two self-etch adhesives

Objective: To evaluate the effect of optional phosphoric acid etching on the shear bond strength (SBS) of two self-etch adhesives to enamel and dentin. Material and Methods: Ninety-six bovine mandibular incisors were ground flat to obtain enamel and dentin substrates. A two-step self-etch adhesive (FL-Bond II) and a one-step self-etch adhesive (BeautiBond) were applied with and without a preliminary acid etching to both the enamel and dentin. The specimens were equally and randomly assigned to 4 groups per substrate (n=12) as follows: FL-Bond II etched; FL-Bond II un-etched; BeautiBond etched; BeautiBond un-etched. Composite cylinders (Filtek Z100) were bonded onto the treated tooth structure. The shear bond strength was evaluated after 24 hours of storage (37ºC, 100% humidity) with a testing machine (Ultra-tester) at a speed of 1 mm/min. The data was analyzed using a two-way ANOVA and post-hoc Tukey's test with a significance level of p<0.05. A field emission scanning electron microscope was used for the failure mode analysis. Results: Both adhesives evidenced a significant decrease in the dentin SBS with the use of an optional phosphoric acid-etching step (p<0.05). Preliminary phosphoric acid etching yielded significantly higher enamel SBS for FL-Bond II (p<0.05) only, but not for BeautiBond. FL-Bond II applied to un-etched dentin demonstrated the highest mean bond strength (37.7±3.2 MPa) and BeautiBond applied to etched dentin showed the lowest mean bond strength (18.3±6.7 MPa) among all tested groups (p<0.05). Conclusion: The use of a preliminary acid-etching step with 37.5% phosphoric acid had a significant adverse effect on the dentin bond strength of the self-etch adhesives evaluated while providing improvement on the enamel bond strength only for FL-Bond II. This suggests that the potential benefit that may be derived from an additional etching step with phosphoric acid does not justify the risk of adversely affecting the bond strength to dentin.
5‐HT2A receptor blockade and 5‐HT2C receptor activation interact to reduce cocaine hyperlocomotion and fos protein expression in the caudate‐putamen

Both the 5‐HT2A receptor (R) antagonist M100907 and the 5‐HT2CR agonist MK212 attenuate cocaine‐induced dopamine release and hyperlocomotion. This study examined whether these drugs interact to reduce cocaine hyperlocomotion and Fos expression in the striatum and prefrontal cortex. We first determined from dose‐effect functions a low dose of both M100907 and MK212 that failed to alter cocaine (15 mg/kg, i.p.) hyperlocomotion. Subsequently, we examined whether these subthreshold doses given together would attenuate cocaine hyperlocomotion, consistent with a 5‐HT2A/5‐HT2CR interaction. Separate groups of rats received two sequential drug injections 5 min apart immediately before a 1‐h locomotion test as follows: (1) saline + saline, (2) saline + cocaine, (3) 0.025 mg/kg M100907 + cocaine, (4) 0.125 mg/kg MK212 + cocaine, or (5) cocktail combination of 0.025 mg/kg M100907 and 0.125 mg/kg MK212 + cocaine. Brains were extracted for Fos immunohistochemistry 90 min after the second injection. We next examined the effects of 0.025 mg/kg M100907 and 0.125 mg/kg MK212, alone and in combination, on spontaneous locomotor activity. While neither drug given alone produced any effects, the M100907/MK212 cocktail attenuated cocaine hyperlocomotion as well as cocaine‐induced Fos expression in the dorsolateral caudate‐putamen (CPu), but had no effect on spontaneous locomotion. The findings suggest that 5‐HT2ARs and 5‐HT2CRs interact to attenuate cocaine hyperlocomotion and Fos expression in the CPu, and that the CPu is a potential locus of the interactive effects between these 5‐HT2R subtypes on behavior. Further research investigating combined 5‐HT2AR antagonism and 5‐HT2CR agonism as a treatment for cocaine dependence is warranted. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
A Granular Computing Approach to Machine Learning

The key to granular computing is to make use of granules in problem solving. Classification is one of the well studied problems in machine learning and data mining as it involves of discovery knowledge from large databases. We presents a granular computing view to classification problems and propose a granular computing approach to classification in this paper. The ID3 [8] and PRISM [2] algorithma are studied and extended to granular computing algorithm.
A Survey on the use of Alternative Drugs During Pregnancy

Objective. To describe the use of alternative drugs during pregnancy. Design. A trial including 3 surveys on drug use during pregnancy in maternity centers in one area of Finland in 1985–86 (study 1), and a retrospective survey in 2 maternity hospitals in Finland in 1988 (study 2). Patients and methods. Study 1: 2912 pregnant women (about 94% of pregnant women in the area during the study period); 97–88% returned questionnaires. Study 2: 180 out of 181 consecutive women giving birth. In study 1, drug use (including drug-like products) in the last two weeks was asked by questionnaires around 12th, 28th, and 36th gestation weeks. In study 2, women were interviewed 2–3 days after birth asking about any drugs used during pregnancy. Due to the method of asking, our studies underestimate the level of using alternative drugs. Results. In study 1, a total of 97 (3.6%) pregnant women reported use of alternative drugs. Most drugs were dietary supplements, and by current knowledge harmless. But a few women had used (potentially) dangerous drugs. The users were from the higher social class and they had also used pharmaceutical specialties more often than non-users. In study 2, 14% had used alternative drugs at some time during pregnancy. Conclusion. Because our surveys showed that alternative drugs are used, possibly with increasing frequency, during pregnancy, further studies on safety are needed.
Requirement of Hos2 Histone Deacetylase for Gene Activity in Yeast

Histone deacetylases, typified by class I Rpd3 in the yeastSaccharomyces cerevisiae, have historically been associated with gene repression. We now demonstrate that Hos2, another member of the class I family, binds to the coding regions of genes primarily during gene activation, when it specifically deacetylates the lysines in H3 and H4 histone tails. Moreover, Hos2 is preferentially associated with genes of high activity genome-wide. We also show that Hos2 and an associated factor, Set3, are necessary for efficient transcription. Therefore, our data indicate that, in contrast to other class I histone deacetylases, Hos2 is directly required for gene activation.