Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel G-Protein Complex Whose Requirement Is Linked to the Translational Status of the Cell

ABSTRACT G proteins, which bind and hydrolyze GTP, are involved in regulating a variety of critical cellular processes, including the process of protein synthesis. Many members of the subfamily of elongation factor class G proteins interact with the ribosome and function to regulate discrete steps during the process of protein synthesis. Despite sequence similarity to factors involved in translation, a role for the yeast Hbs1 protein has not been defined. In this work we have identified a genetic relationship between genes encoding components of the translational apparatus and HBS1. HBS1, while not essential for viability, is important for efficient growth and protein synthesis under conditions of limiting translation initiation. The identification of an Hbs1p-interacting factor, Dom34p, which shares a similar genetic relationship with components of the translational apparatus, suggests that Hbs1p and Dom34p may function as part of a complex that facilitates gene expression. Dom34p contains an RNA binding motif present in several ribosomal proteins and factors that regulate translation of specific mRNAs. Thus, Hbs1p and Dom34p may function together to help directly or indirectly facilitate the expression either of specific mRNAs or under certain cellular conditions.
Effect of Bifidobacterium breve M-16V supplementation on faecal bifidobacteria in growth restricted very preterm infants – analysis from a randomised trial

Abstract Background: Gut development, function and colonisation are impaired in animal models of prematurity with intrauterine growth restriction (IUGR). The effect of Bifidobacterium breve (B. breve) supplementation on faecal bifidobacteria in small for gestational age (SGA: birth weight <10th centile due to IUGR) preterm infants is not known. Objective: We compared B. breve M-16V supplementation effect on faecal bifidobacteria in preterm (<33 weeks) SGA versus non-SGA infants in the two arms of our randomised controlled trial. Results: There were no baseline differences in the proportion of detectable B. breve counts between SGA versus non-SGA infants [probiotic: 7 (33%) versus 22 (42%), p = 0.603; placebo: 1 (6%) versus 1 (2%), p = 0.429]. B. breve counts did not differ between SGA and non-SGA infants in response to treatment (p = 0.589), after adjusting for baseline count (p < 0.001) and treatment allocation (p < 0.001). An interaction term between growth status and treatment showed negligible change (p = 0.938). Probiotic treated SGA infants reached full feeds earlier than SGA controls (HR 2.00, 95% CI 1.05–3.82, p = 0.035): Median (IQR): 16 (12–26) versus 19 (11–25) days, after adjustment for age at starting feeds and gestation <28 weeks. Conclusion: Response to B. breve M-16V supplementation was not significantly different in preterm (<33 weeks) SGA versus non-SGA infants.
Applying Molecular Dynamics Simulations to Identify Rarely Sampled Ligand-bound Conformational States of Undecaprenyl Pyrophosphate Synthase, an Antibacterial Target

Undecaprenyl pyrophosphate synthase is a cis‐prenyltransferase enzyme, which is required for cell wall biosynthesis in bacteria. Undecaprenyl pyrophosphate synthase is an attractive target for antimicrobial therapy. We performed long molecular dynamics simulations and docking studies on undecaprenyl pyrophosphate synthase to investigate its dynamic behavior and the influence of protein flexibility on the design of undecaprenyl pyrophosphate synthase inhibitors. We also describe the first X‐ray crystallographic structure of Escherichia coli apo‐undecaprenyl pyrophosphate synthase. The molecular dynamics simulations indicate that undecaprenyl pyrophosphate synthase is a highly flexible protein, with mobile binding pockets in the active site. By carrying out docking studies with experimentally validated undecaprenyl pyrophosphate synthase inhibitors using high‐ and low‐populated conformational states extracted from the molecular dynamics simulations, we show that structurally dissimilar compounds can bind preferentially to different and rarely sampled conformational states. By performing structural analyses on the newly obtained apo‐undecaprenyl pyrophosphate synthase and other crystal structures previously published, we show that the changes observed during the molecular dynamics simulation are very similar to those seen in the crystal structures obtained in the presence or absence of ligands. We believe that this is the first time that a rare ‘expanded pocket’ state, key to drug design and verified by crystallography, has been extracted from a molecular dynamics simulation.
Cellular and Viral Factors Regulate the Varicella-Zoster Virus gE Promoter during Viral Replication

ABSTRACT Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for viral replication and is involved in cell-to-cell spread, secondary envelopment, and entry. We created a set of mutations in the gE promoter to investigate the role of viral and cellular transcriptional factors in regulation of the gE promoter. Deletion or point mutation of the two Sp1 sites in the gE promoter abolished Sp1 binding and IE62-mediated transactivation of the gE promoter in vitro. Incorporation of the deletion or the point mutations disrupting both of the Sp1 binding sites into the VZV genome was not compatible with viral replication. A point mutation altering the atypical Sp1 binding site was lethal, while altering the second site impaired VZV replication significantly, indicating functional differences between the two Sp1 binding sites. Deletions in the gE promoter that abolished putative binding sites for cellular transcriptional factors other than Sp1, identified by bioinformatics analysis, were inserted in the VZV genome. Replication of the viruses with mutations of the gE promoter did not differ from control recombinants in melanoma cells or primary human tonsil T cells in vitro. These deletions did not affect infection of human skin xenografts in SCIDhu mice. These results indicate that Sp1 is required for IE62-mediated transactivation of the gE promoter and that this transcriptional factor appears to be the only cellular factor essential for regulation of the gE promoter.
Multiple-Layer Adaptation of HUT Snow Emission Model: Comparison With Experimental Data

Modeling of snow emission at microwave frequencies is necessary in order to understand the complex relations between the emitted brightness temperature and snowpack characteristics such as density, grain size, moisture content, and vertical structure. Several empirical, semiempirical, and purely theoretical models for the prediction of snow emission properties have been developed in recent years. In this paper, we investigate the capability of one such model to simulate snow emission during the peak snow season-a new multilayer version of the Helsinki University of Technology (HUT) snow model. Developed with a single layer, the original HUT model was easily applied over large geographic areas for the estimation of snow cover characteristics by model inversion. A single homogenous layer, however, may not accurately allow the simulation of vertically structured natural snowpacks. The new modification to the model allows the simulation of emission from a snowpack with several snow or ice layers, with the individual component layers treated as in the original HUT model. The results of modeled snowpack emission, using both the original model and the new multilayer modification, are compared with reference measurements made using ground-based radiometers deployed in Finland and Canada. Detailed in situ measurements of the snowpack are used to set the model inputs. We show that, in most cases, use of the multiple-layer model improves estimates for the higher frequencies tested, with up to 38% improvement in rms error. In some cases, however, the use of the multiple-layer model weakens model performance particularly at lower frequencies.
QUANTUM MANY-BODY THEORY OF LOW ENERGY NUCLEAR REACTION INDUCED BY ACOUSTIC CAVITATION IN DEUTERATED LIQUID

There have been a number of reports of observation of nuclear fusion events in acoustic cavitation experiments with deuterated liquid. Some of the reported results have been interpreted as a result of achieving thermonuclear fusion temperatures (~a few keV) during acoustic bubble cavitation (ABC). We propose an alternative theoretical model for the ABC fusion based on Bose-Einstein condensation (BEC) mechanism. Our theoretical model yields two main predictions. The first prediction is that the Coulomb interaction between two charged bosons is suppressed for the case in which number N of charged bosons is large, and hence the conventional Gamow factor is absent. The second prediction is that the fusion rate depends on the probability of the BEC ground state occupation instead of the conventional Gamow factor. This implies that the fusion rate will increase as the temperature of the system is lowered since the probability of the BEC state is larger at lower temperatures. These predictions imply that the ABC fusion may be achievable at lower temperatures. A number of key improvement to acoustic cavitation experiments are proposed to check these predictions as well as the results of other experiments.
Self-Controlled Feedback Facilitates Motor Learning in Both High and Low Activity Individuals

The purpose of this study was to determine if high and low activity individuals differed in terms of the effects of self-controlled feedback on the performance and learning of a movement skill. The task consisted of a blindfolded beanbag toss using the non-preferred arm. Participants were pre-screened according to their physical activity level using the International Physical Activity Questionnaire. An equal number of high activity (HA) and low activity (LA) participants were assigned to self-control (SC) and yoked (YK) feedback conditions, creating four groups: Self-Control-High Activity; Self-Control-Low Activity; Yoked-High Activity; and Yoked-Low Activity. SC condition participants were provided feedback whenever they requested it, while YK condition participants received feedback according to a schedule created by their SC counterpart. Results indicated that the SC condition was more accurate than the YK condition during acquisition and transfer phases, and the HA condition was more accurate than the LA condition during all phases of the experiment. A post-training questionnaire indicated that participants in the SC condition asked for feedback mostly after what they perceived to be “good” trials; those in the YK condition indicated that they would have preferred to receive feedback after “good” trials. This study provided further support for the advantages of self-controlled feedback when learning motor skills, additionally showing benefits for both active and less active individuals. The results suggested that the provision of self-controlled feedback to less active learners may be a potential avenue to teaching motor skills necessary to engage in greater amounts of physical activity.
Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women

Truncated telomeres are among the defining characteristics of most carcinomas. Given the role of telomeres in tumorigenesis, we reasoned that constitutionally short telomeres might be associated with an increased risk of bladder cancer. Using quantitative real-time PCR, we measured relative telomere length in bladder cancer cases and healthy controls and evaluated the association between telomere length, cigarette smoking, and bladder cancer risk in a case-control study nested within the Health Professionals Follow-up Study and a case-control study nested within the Nurses' Health Study. Telomeres were significantly shorter in bladder cancer cases (n = 184) than in controls (n = 192). The mean relative telomere length in cases was 0.23 (SD, 0.16) versus 0.27 (SD, 0.15) in controls (P = 0.001). The adjusted odds ratio for bladder cancer was 1.88 (95% confidence interval, 1.05, 3.36) for individuals in the quartile with the shortest telomeres as compared with individuals in the quartile with the longest telomeres (Ptrend = 0.006). We observed a statistically significant difference in telomere length among men and women (P < 0.001); however, the interaction between gender, telomere length, and bladder cancer risk was not significant. We also observed a significant difference in telomere length across categories of pack-years of smoking (P = 0.01). These findings suggest that truncated telomeres are associated with an increased risk of bladder cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(4):815–9)
The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes.

BACKGROUND During ICSI, we occasionally observe pronucleus sized translucent vacuoles. We investigated why these vacuoles occur and determined the effect on pregnancy outcome. METHODS Translucent vacuole-positive oocytes and the corresponding cohort were examined by transmission electron microscopy (TEM) and histochemical staining with DiI and ER-Tracker. Stimulation methods, hormonal levels, patients' condition and grade of transferred embryos were compared between vacuole-positive and vacuole-negative cycles. RESULTS By TEM, we confirmed that the vacuoles were tubular-type smooth endoplasmic reticulum clusters (sERCs). Numerous small sERCs were also observed in the oocytes from the same cohort. Veeck's grades of transferred embryos were higher in sERC-positive cycles and fertilization rate was similar to those of sERC-negative cycles. However, in sERC-positive cycles, significantly lower pregnancy and higher biochemical pregnancy rates were shown. Serum estradiol levels on the day of hCG administration were significantly higher in sERC-positive cycles. CONCLUSIONS The presence of sERCs is associated with lower chances of successful pregnancy, even in sERC-negative oocytes from the same cohort that are transferred along with the sERC-positive oocytes. High estradiol levels could be one of the causes of sERC formation.
Down-Regulation of Treg Cells and Up-Regulation of Th1/Th2 Cytokine Ratio Were Induced by Polysaccharide from Radix Glycyrrhizae in H22 Hepatocarcinoma Bearing Mice

Radix Glycyrrhizae polysaccharide (GP) possesses multiple pharmacological activities. However, the effect of GP on CD4+CD25+ regulatory T (Treg) cells has not been elucidated. This study aimed to investigate the effects of GP on Treg cells and Th1/Th2 cytokines in H22 hepatocarcinoma tumor-bearing mice. The results demonstrated that GP inhibits tumor progression. In the lymph nodes of the tumor microenvironment and spleen, the proportion of Treg cells was significantly higher in the tumor-bearing mice. GP administration down-regulated the population of Treg cells (P < 0.01) and decreased lymph node Foxp3 and IL-10 mRNA expression (P < 0.01). In addition, GP treatment decreased IL-10 and TGF-β level (P < 0.01) and increased IL-2 and IL-12p70 level in serum (P < 0.01). In conclusion, GP reduced the proportion of Treg cells and Foxp3 lowered expression in Treg cells, and up-regulated Th1/Th2 cytokine ratio in serum in the tumor bearing mice, which might partially cause the inhibition of tumor growth.
Optimising Energy Consumption of Design Patterns

Software design patterns are widely used in software engineering to enhance productivity and maintainability.However, recent empirical studies revealed the high energy overhead in these patterns. Our vision is to automatically detect and transform design patterns during compilation for better energy efficiency without impacting existing coding practices. In this paper, we propose compiler transformations for two design patterns, Observer and Decorator, and perform an initial evaluation of their energy efficiency.
Synthesis and characterization of silver nanowires as a transparent conductive electrode

Silver nanowire meshes have been proven to show a high electrical conductivity with high optical transmittance. This special characteristic is desirable in transparent conductive electrodes in optoelectronic applications, such as solar cells, light emitting diodes, liquid crystal displays, and touch screens, among others. In this document, we report the synthesis of silver nanowires by the polyol process and the characterization of their morphology. We also prepared uniform thin films of commercially available silver nanowires on glass substrate using a dip-coating technique. The samples were further treated with heat to improve their electrical conductivity. Additionally, we characterized the optical and electrical properties of the samples analyzing the influence of the nanowire length in the overall performance of the film as a transparent conductive electrode. Two figures of merit were used to measure the quality of the films and to compare the silver nanowire networks with metal oxides.
Econometric Measures of Connectedness and Systemic Risk in the Finance and Insurance Sectors

We propose several econometric measures of connectedness based on principal-components analysis and Granger-causality networks, and apply them to the monthly returns of hedge funds, banks, broker/dealers, and insurance companies. We find that all four sectors have become highly interrelated over the past decade, likely increasing the level of systemic risk in the finance and insurance industries through a complex and time-varying network of relationships. These measures can also identify and quantify financial crisis periods, and seem to contain predictive power in out-of-sample tests. Our results show an asymmetry in the degree of connectedness among the four sectors, with banks playing a much more important role in transmitting shocks than other financial institutions.
Homeostasis in the vertebrate lens: mechanisms of solute exchange

The eye lens is avascular, deriving nutrients from the aqueous and vitreous humours. It is, however, unclear which mechanisms mediate the transfer of solutes between these humours and the lens' fibre cells (FCs). In this review, we integrate the published data with the previously unpublished ultrastructural, dye loading and magnetic resonance imaging results. The picture emerging is that solute transfer between the humours and the fibre mass is determined by four processes: (i) paracellular transport of ions, water and small molecules along the intercellular spaces between epithelial and FCs, driven by Na+-leak conductance; (ii) membrane transport of such solutes from the intercellular spaces into the fibre cytoplasm by specific carriers and transporters; (iii) gap-junctional coupling mediating solute flux between superficial and deeper fibres, Na+/K+-ATPase-driven efflux of waste products in the equator, and electrical coupling of fibres; and (iv) transcellular transfer via caveoli and coated vesicles for the uptake of macromolecules and cholesterol. There is evidence that the Na+-driven influx of solutes occurs via paracellular and membrane transport and the Na+/K+-ATPase-driven efflux of waste products via gap junctions. This micro-circulation is likely restricted to the superficial cortex and nearly absent beyond the zone of organelle loss, forming a solute exchange barrier in the lens.
Slow recovery of impaired phrenic responses to hypoxia following perinatal hyperoxia in rats

1 Previous studies demonstrated that both ventilatory and phrenic nerve responses to acute hypoxia are greatly attenuated in adult rats (3–5 months old) previously exposed to 1 month of perinatal hyperoxia (60 % O2; perinatal treated rats). The present study tested the hypothesis that this functional impairment recovers spontaneously with advancing age in perinatal treated rats. 2 Hypoxia‐induced chemoreflexes were examined by measuring integrated phrenic responses to strictly controlled isocapnic hypoxia in urethane‐anaesthetized, vagotomized, paralysed and ventilated rats at different ages. 3 At 50 mmHg Pa,O2 (arterial O2 partial pressure), the hypoxia‐induced increase in minute phrenic activity was significantly attenuated in both 3‐ to 5‐month‐old (166 ± 15 % of baseline) and 6‐month‐old (130 ± 17 %) perinatal treated rats, relative to 3‐ to 6‐month‐old, untreated control rats (279 ± 28 %; both P < 0.05). However, at 40 mmHg Pa,O2, the hypoxic minute phrenic activity response was attenuated only in 3‐ to 5‐month‐old (154 ± 33 %), but not 6‐month‐old (232 ± 33 %) perinatal treated rats versus control rats (293 ± 30 %). 4 The minute phrenic activity response to hypoxia was not significantly different between geriatric perinatal treated rats (14–15 months) and untreated geriatric control rats at either 50 mmHg (treated: 250 ± 20 %versus control: 274 ± 23 %) or 40 mmHg Pa,O2 (treated: 292 ± 19 %versus control: 315 ± 36 %). 5 These data suggest that partial spontaneous recovery may occur in 6‐month‐old perinatal treated rats and that full recovery occurs by 15 months of age.
Measuring Multidimensional Poverty in Latin America: Previous Experience and the Way Forward

This paper states the need to design a multidimensional poverty index for the Latin America region (LA-MPI) that can monitor poverty trends in a cross-country comparable way, yet is also relevant to the particular regional context. We review the region’s rich experience with multidimensional poverty measurement, as well as Europe’s experiences with multidimensional measurement. We set a number of requirements for the LA-MPI to satisfy and specify the methodological criterions necessary to fulfil such requirements. Drawing from the review, we outline an LA-MPI composed of five dimensions: basic consumptions, education, health, housing and basic services, and work. We list the indicators within those dimensions that are desirable, as well as what indicators are feasible given existing data constraints.
Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug–botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John’s wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug–botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug–botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism.
M(DM): an open framework for interoperation of multimodel multidatabase systems

The authors present M(DM), an extensible metalevel system in which the syntax and the semantics of data models, schemas, and databases can be uniformly represented. M(DM) consists primarily of a set of metatypes that capture and express data-model constructs in second-order logic: a data model is represented as a collection of M(DM) metatypes. To achieve extensibility, M(DM)'s metatypes are organized into an inheritance lattice. The robustness and openness of the approach are demonstrated by expressing a variety of data models in M(DM), and the authors show how to exploit M(DM)'s metalevel capabilities for hiding representational heterogeneities in multimodel multidatabase systems. <<ETX>>