Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced contractility and myosin phosphorylation induced by Ca(2+)-independent MLCK activity in hypertensive rats.

AIMS The role of Ca(2+) sensitization induced by a Ca(2+)-independent myosin light chain kinase (MLCK) in hypertension has not been determined. The aim of this study was to clarify the role of possible Ca(2+)-independent MLCK activity in hypertension. METHODS AND RESULTS We compared increases in contractile force and phosphorylation of myosin light chain (MLC) evoked by calyculin A, a phosphatase inhibitor, in β-escin-permeabilized mesenteric arteries at pCa 9.0 between spontaneously hypertensive rat (SHR) and Wistar Kyoto rat (WKY). We found that there was no detectable phosphorylation of MLC at pCa 9.0, but that the administration of 1 μM calyculin A gradually increased force and mono- and di-phosphorylation of MLC. This contraction was inhibited by staurosporine but not by wortmannin, Y-27632, or calphostin-C. The calyculin A-induced contraction was significantly greater in the SHR than in the WKY and was associated with an increase in mono- and di-phosphorylation of MLC. SM-1, a zipper-interacting protein kinase (ZIPK)-inhibiting peptide, significantly inhibited the amplitude of the calyculin A-induced contraction and di-phosphorylation. Total ZIPK expression (54 + 32 kDa) was greater in the SHR than in the WKY. Phosphorylation of myosin phosphatase target subunit at Thr(697), but not at Thr(855), was consistently stronger in the SHR than in the WKY in calyculin A-treated tissues at pCa 9.0. CONCLUSIONS Our results suggest that Ca(2+)-independent MLCK activity is enhanced in the SHR, and that ZIPK plays, at least in part, an important role as a candidate for this kinase in rat mesenteric arteries.
Seismic Analyses of Soil Pressure against Embedded Mat Foundation and Pile Displacements for a Building in Moderate Seismic Area

Seismic analyses of a pile under a large rigid basement foundation embedded in the homogeneous soil layer were performed practically by a response displacement method assuming a sinusoidal wave form. However, it is hard to take into account the characteristics of a large mat foundation and a heterogeneous soil layer with the response displacement method. The response displacement method is relevant to the 2D problems for longitudinal structures such as tunnel, underground cave structure, etc., but might not be relevant with isolated foundations for building structures. In this study, seismic pile analysis by a pseudo 3D finite element method was carried out to compare numerical results with results of the response displacement method considering 3D characteristics of a foundation-soil system which is important for the building foundation analyses. Study results show that seismic analyses results of a response displacement method are similar to those of a pseudo 3D numerical method for stiff and dense soil layers, but they are too conservative for a soft soil layer inducing large soil pressures on the foundation wall and large pile displacements due to ignored foundation rigidity and resistance.
Emissions from forest fires near Mexico City

The emissions of NO_x (defined as NO (nitric oxide) + NO_2 (nitrogen dioxide)) and hydrogen cyanide (HCN), per unit amount of fuel burned, from fires in the pine forests that dominate the mountains surrounding Mexico City (MC) are about 2 times higher than normally observed for forest burning. The ammonia (NH_3) emissions are about average for forest burning. The upper limit for the mass ratio of NO_x to volatile organic compounds (VOC) for these MC-area mountain fires was ~0.38, which is similar to the NO_x/VOC ratio in the MC urban area emissions inventory of 0.34, but much larger than the NO_x/VOC ratio for tropical forest fires in Brazil (~0.068). The nitrogen enrichment in the fire emissions may be due to deposition of nitrogen-containing pollutants in the outflow from the MC urban area. This effect may occur worldwide wherever biomass burning coexists with large urban areas (e.g. the tropics, southeastern US, Los Angeles Basin). The molar emission ratio of HCN to carbon monoxide (CO) for the mountain fires was 0.012±0.007, which is 2–9 times higher than widely used literature values for biomass burning. The ambient molar ratio HCN/CO in the MC-area outflow is about 0.003±0.0003. Thus, if only mountain fires emit significant amounts of HCN, these fires may be contributing about 25% of the CO production in the MC-area (~98–100 W and 19–20 N). Comparing the PM_(10)/CO and PM_(2.5)/CO mass ratios in the MC Metropolitan Area emission inventory (0.0115 and 0.0037) to the PM1/CO mass ratio for the mountain fires (0.133) then suggests that these fires could produce as much as ~79–92% of the primary fine particle mass generated in the MC-area. Considering both the uncertainty in the HCN/CO ratios and secondary aerosol formation in the urban and fire emissions implies that about 50±30% of the "aged" fine particle mass in the March 2006 MC-area outflow could be from these fires.
Arabidopsis OST1 Protein Kinase Mediates the Regulation of Stomatal Aperture by Abscisic Acid and Acts Upstream of Reactive Oxygen Species Production Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.007906.

During drought, the plant hormone abscisic acid (ABA) triggers stomatal closure, thus reducing water loss. Using infrared thermography, we isolated two allelic Arabidopsis mutants (ost1-1 and ost1-2) impaired in the ability to limit their transpiration upon drought. These recessive ost1 mutations disrupted ABA induction of stomatal closure as well as ABA inhibition of light-induced stomatal opening. By contrast, the ost1 mutations did not affect stomatal regulation by light or CO2, suggesting that OST1 is involved specifically in ABA signaling. The OST1 gene was isolated by positional cloning and was found to be expressed in stomatal guard cells and vascular tissue. In-gel assays indicated that OST1 is an ABA-activated protein kinase related to the Vicia faba ABA-activated protein kinase (AAPK). Reactive oxygen species (ROS) were shown recently to be an essential intermediate in guard cell ABA signaling. ABA-induced ROS production was disrupted in ost1 guard cells, whereas applied H2O2 or calcium elicited the same degree of stomatal closure in ost1 as in the wild type. These results suggest that OST1 acts in the interval between ABA perception and ROS production. The relative positions of ost1 and the other ABA-insensitive mutations in the ABA signaling network (abi1-1, abi2-1, and gca2) are discussed.
FOXM1 is overexpressed in B-acute lymphoblastic leukemia (B-ALL) and its inhibition sensitizes B-ALL cells to chemotherapeutic drugs

The Forkhead box protein M1 (FOXM1) is a transcription factor that plays a central role in the regulation of cell cycle, proliferation, DNA repair, and apoptosis. FOXM1 is overexpressed in many human tumors and its upregulation has been linked to high proliferation rates and poor prognosis. We therefore studied the role of FOXM1 in B-lymphoblastic leukemia (B-ALL) in order to understand whether FOXM1 could be a key target for leukemia therapy. RT-PCR and western blot analysis were carried out in a small cohort of pediatric B-ALL patients to evaluate FOXM1 levels. To assess its biological relevance, its expression was down-modulated by transient RNA interference in B-ALL cell lines (REH and NALM-6). Our results show that FOXM1 expression is higher in both B-ALL patients and cell lines when compared to PBMC or normal B-cells (CD19+) from healthy donors. Furthermore, blocking FOXM1 activity in two B-ALL cell lines, by either knockdown or treatment with the FOXM1 inhibitor thiostrepton, causes significant decrease in their cell proliferation. This decrease in cell proliferation was coupled with both an induction of the G2/M cell cycle arrest and with a reduction in the S phase population. Finally, we noted how thiostrepton synergises with chemotherapeutic agents commonly used in B-ALL therapy, thus increasing their efficiency. Therefore our results suggest that FOXM1 is highly expressed in both patients and B-ALL cell lines, and that targeting FOXM1 could be an attractive strategy for leukemia therapy and for overcoming drug resistance.
The relative impact of cognitive anxiety and self-confidence upon sport performance: a meta-analysis

This meta-analysis (k = 48) investigated two relationships in competitive sport: (1) state cognitive anxiety with performance and (2) state self-confidence with performance. The cognitive anxiety mean effect size was r = −0.10 (P <0.05). The self-confidence mean effect size was r = 0.24 (P <0.001). A paired-samples t-test revealed that the magnitude of the self-confidence mean effect size was significantly greater than that of the cognitive anxiety mean effect size. The moderator variables for the cognitive anxiety-performance relationship were sex and standard of competition. The mean effect size for men (r = −0.22) was significantly greater than the mean effect size for women (r = −0.03). The mean effect size for high-standard competition (r = −0.27) was significantly greater than that for comparatively low-standard competition (r = −0.06). The significant moderator variables for the self-confidence-performance relationship were sex, standard of competition and measurement. The mean effect size for men (r = 0.29) was significantly greater than that for women (r = 0.04) and the mean effect size for high-standard competition (r = 0.33) was significantly greater than that for low-standard competition (r = 0.16). The mean effect size derived from studies employing the Competitive State Anxiety Inventory-2 (r = 0.19) was significantly smaller than the mean effect size derived from studies using other measures of self-confidence (r = 0.38). Measurement issues are discussed and future research directions are offered in light of the results.
An Alternative Model for Mixtures of Experts

We propose an alternative model for mixtures of experts which uses a different parametric form for the gating network. The modified model is trained by the EM algorithm. In comparison with earlier models--trained by either EM or gradient ascent--there is no need to select a learning stepsize. We report simulation experiments which show that the new architecture yields faster convergence. We also apply the new model to two problem domains: piecewise nonlinear function approximation and the combination of multiple previously trained classifiers.
Oxygen-Induced Retinopathy in Mice: Amplification by Neonatal IGF-I Deficit and Attenuation by IGF-I Administration

In preterms, low serum levels of IGF (IGF-I) correlate with retinopathy of prematurity (ROP). In mice, IGF-I is a prerequisite for normal retinal development. We further explored the link between IGF-I and oxygen-induced retinopathy (OIR). To assess the role of endogenous IGF-I, pups were redistributed into smaller versus larger litters at birth; in one subgroup, we measured body weight and circulating IGF-I; in another, we applied hyperoxia and assessed retinal neovascularization (NV). To screen for the potential role of exogenous IGF-I, we administered a single bolus of rhIGF-I on postnatal day (P) 4 to pups in normal litters, and applied hyperoxia; body weight and IGF-I were measured; maturation and NV were assessed. Neonatal mice in larger litters had a lower body weight than mice in smaller litters; they had lower levels of circulating IGF-I, and developed more OIR (p = 0.002). Mice who had received rhIGF-I, weighed more and had higher endogenous IGF-I levels; they matured faster and developed less OIR (p = 0.00001). These findings in mice are the first to support the notion that higher availability of endogenous or exogenous IGF-I reduces OIR risk, and thus sharpen the perspective that ROP may be preventable by briefly up-regulating IGF-I after birth.
Epigenetic dysregulation by nickel through repressive chromatin domain disruption

Significance Histone modifications associated with gene silencing typically mark large contiguous regions of the genome forming repressive chromatin domain structures. Since the repressive domains exist in close proximity to active regions, maintenance of domain structure is critically important. This study shows that nickel, a nonmutagenic carcinogen, can disrupt histone H3 lysine 9 dimethylation (H3K9me2) domain structures genome-wide, resulting in spreading of H3K9me2 marks into the active regions, which is associated with gene silencing. Our results suggest inhibition of DNA binding of the insulator protein CCCTC-binding factor (CTCF) at the H3K9me2 domain boundaries as a potential reason for H3K9me2 domain disruption. These findings have major implications in understanding chromatin dynamics and the consequences of chromatin domain disruption during pathogenesis. Investigations into the genomic landscape of histone modifications in heterochromatic regions have revealed histone H3 lysine 9 dimethylation (H3K9me2) to be important for differentiation and maintaining cell identity. H3K9me2 is associated with gene silencing and is organized into large repressive domains that exist in close proximity to active genes, indicating the importance of maintenance of proper domain structure. Here we show that nickel, a nonmutagenic environmental carcinogen, disrupted H3K9me2 domains, resulting in the spreading of H3K9me2 into active regions, which was associated with gene silencing. We found weak CCCTC-binding factor (CTCF)-binding sites and reduced CTCF binding at the Ni-disrupted H3K9me2 domain boundaries, suggesting a loss of CTCF-mediated insulation function as a potential reason for domain disruption and spreading. We furthermore show that euchromatin islands, local regions of active chromatin within large H3K9me2 domains, can protect genes from H3K9me2-spreading–associated gene silencing. These results have major implications in understanding H3K9me2 dynamics and the consequences of chromatin domain disruption during pathogenesis.
EFFECT OF GROWTH HORMONE ON THE METABOLISM OF THYMUS AND ON THE IMMUNE RESPONSE AGAINST SHEEP ERYTHROCYTES

The effect of pituitary growth hormone on the biosynthesis of DNA in the thymus and other lymphoid organs, as well as the ability of the rat to respond immunologically to sheep red blood cells, has been evaluated. There is a marked reduction in plaque-forming cells, hemagglutination titers, and DNA synthesis in animals when examined at 15 wk after hypophysectomy. Administration of bovine growth hormone (BGH) leads to the enhancement of DNA synthesis in lymphoid organs and recovery of the immune response. Similar effects of the hormone are observed in plateaued rats. Injection of rabbit anti-BGH globulins, in contrast to normal rabbit globulins, over 5 days causes a drop in the weight of the thymus and in the rate of DNA synthesis in this organ. The thymus is also the organ in which stimulation of DNA synthesis is observed at a time period earlier than the spleen and lymph nodes after a single injection of BGH. The hormone stimulates not only the incorporation of thymidine-3H into DNA in the cortical cells, but also the incorporation of sodium sulfate-35S into TCA-insoluble biopolymers reported to be elaborated in the medullary area of the thymus. An in vitro system for the action of BGH on the thymus has been described. There is an obligatory requirement for calcium, but not for fetal calf serum in the medium for the hormone effect. An early action of the hormone is the enhanced incorporation of uridine-G-3H into RNA in thymocytes which is followed by a stimulation of the synthesis of proteins and DNA. The stimulatory action of growth hormone on RNA synthesis is not because of a facilitated uptake of the radioactive uridine by the cells under hormonal influence, a mechanism by which insulin is observed to increase RNA synthesis in thymocytes in vitro. The action of growth hormone on thymocytes is specific, since thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and heat-inactivated growth hormone are not effective. BGH has also a beneficial action on the regeneration of the thymus and spleen in starved rats.
Rotting Bandits

The Multi-Armed Bandits (MAB) framework highlights the trade-off between acquiring new knowledge (Exploration) and leveraging available knowledge (Exploitation). In the classical MAB problem, a decision maker must choose an arm at each time step, upon which she receives a reward. The decision maker's objective is to maximize her cumulative expected reward over the time horizon. The MAB problem has been studied extensively, specifically under the assumption of the arms' rewards distributions being stationary, or quasi-stationary, over time. We consider a variant of the MAB framework, which we termed Rotting Bandits, where each arm's expected reward decays as a function of the number of times it has been pulled. We are motivated by many real-world scenarios such as online advertising, content recommendation, crowdsourcing, and more. We present algorithms, accompanied by simulations, and derive theoretical guarantees.
Activation of ERK/CREB pathway in spinal cord contributes to chronic constrictive injury-induced neuropathic pain in rats

AbstractAim:To investigate whether activation and translocation of extracellular signal-regulated kinase (ERK) is involved in the induction and maintenance of neuropathic pain, and effects of activation and translocation of ERK on expression of pCREB and Fos in the chronic neuropathic pain.Methods:Lumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats. The left sciatic nerve was loosely ligated proximal to the sciatica's trifurcation at approximately 1.0 mm intervals with 4-0 silk sutures. The mitogen-activated protein kinase kinase (MEK) inhibitor U0126 or phosphorothioate-modified antisense oligonucleotides (ODN) were intrathecally administered every 12 h, 1 d pre-chronic constriction injury (CCI) and 3 d post-CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal latency (PWL) to radiant heat and von Frey filaments. The expression of pERK, pCREB, and Fos were assessed by both Western blotting and immunohistochemical analysis.Results:Intrathecal injection of U0126 or ERK antisense ODN significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia. CCI significantly increased the expression of p-ERK-IR neurons in the ipsilateral spinal dorsal horn to injury, not in the contralateral spinal dorsal horn. The time courses of pERK expression showed that the levels of both cytosol and nuclear pERK, but not total ERK, were increased at all points after CCI and reached a peak level on postoperative d 5. CCI also significantly increased the expression of pCREB and Fos. Phospho-CREB-positive neurons were distributed in all laminae of the bilateral spinal cord and Fos was expressed in laminae I and II of the ipsilateral spinal dorsal horn. Intrathecal injection of U0126 or ERK antisense ODN markedly suppressed the increase of CCI-induced pERK, pCREB and c-Fos expression in the spinal cord.Conclusion:The activation of ERK pathways contributes to neuropathic pain in CCI rats, and the function of pERK may partly be accomplished via the cAMP response element binding protein (CREB)-dependent gene expression.
Communication optimization and code generation for distributed memory machines

This paper presents several algorithms to solve code generation and optimization problems specific to machines with distributed address spaces. Given a description of how the computation is to be partitioned across the processors in a machine, our algorithms produce an SPMD (single program multiple data) program to be run on each processor. Our compiler generated the necessary receive and send instructions, optimizes the communication by eliminating redundant communication and aggregating small messages into large messages, allocates space locally on each processor, and translates global data addresses to local addresses. Our techniques are based on an exact data-flow analysis on individual array element accesses. Unlike data dependence analysis, this analysis determines if two dynamic instances refer to the same value, and not just to the same location. Using this information, our compiler can handle more flexible data decompositions and find more opportunities for communication optimization than systems based on data dependence analysis. Our technique is based on a uniform framework, where data decompositions, computation decompositions and the data flow information are all represented as systems of linear inequalities. We show that the problems of communication code generation, local memory management, message aggregation and redundant data communication elimination can all be solved by projecting polyhedra represented by sets of inequalities onto lower dimensional spaces.
Cre/lox System and PCR-Based Genome Engineering in Bacillus subtilis

ABSTRACT We have developed a fast and accurate method to engineer the Bacillus subtilis genome that involves fusing by PCR two flanking homology regions with an antibiotic resistance gene cassette bordered by two mutant lox sites (lox71 and lox66). The resulting PCR products were used directly to transform B. subtilis, and then transient Cre recombinase expression in the transformants was used to recombine lox71 and lox66 into a double-mutant lox72 site, thereby excising the marker gene. The mutation process could also be accomplished in 2 days by using a strain containing a cre isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible expression cassette in the chromosome as the recipient or using the lox site-flanked cassette containing both the cre IPTG-inducible expression cassette and resistance marker. The in vivo recombination efficiencies of different lox pairs were compared; the lox72 site that remains in the chromosome after Cre recombination had a low affinity for Cre and did not interfere with subsequent rounds of Cre/lox mutagenesis. We used this method to inactivate a specific gene, to delete a long fragment, to realize the in-frame deletion of a target gene, to introduce a gene of interest, and to carry out multiple manipulations in the same background. Furthermore, it should also be applicable to large genome rearrangement.