Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

This study was supported by a grant from the National Institute for Health Research (NIHR) under its Health Technology Assessment programme (reference No 13/03/25, to ARM

A new investigation of electron neutrino appearance oscillations with improved sensitivity in the MiniBooNE+ experiment

Submitted as whitepaper for Snowmass'13 proceedings - 8 pages, 3 figures; version 2: Minor change to title and author listSubmitted as whitepaper for Snowmass'13 proceedings - 8 pages, 3 figures; version 2: Minor change to title and author listWe propose the addition of scintillator to the existing MiniBooNE detector to allow a test of the neutral-current/charged-current (NC/CC) nature of the MiniBooNE low-energy excess. Scintillator will enable the reconstruction of 2.2 MeV $\gamma$s from neutron-capture on protons following neutrino interactions. Low-energy CC interactions where the oscillation excess is observed should have associated neutrons with less than a 10% probability. This is in contrast to the NC backgrounds that should have associated neutrons in approximately 50% of events. We will measure these neutron fractions with $\nu_\mu$ CC and NC events to eliminate that systematic uncertainty. This neutron-fraction measurement requires $6.5\times10^{20}$ protons on target delivered to MiniBooNE with scintillator added in order to increase the significance of an oscillation excess to over $5\sigma$. This new phase of MiniBooNE will also enable additional important studies such as the spin structure of nucleon ($\Delta s$) via NC elastic scattering, a low-energy measurement of the neutrino flux via \numu ^{12}C \rightarrow \mu^{-} ^{12}N_\textrm{g.s.} scattering, and a test of the quasielastic assumption in neutrino energy reconstruction. These topics will yield important, highly-cited results over the next 5 years for a modest cost, and will help to train Ph.D. students and postdocs. This enterprise offers complementary information to that from the upcoming liquid Argon based MicroBooNE experiment. In addition, MicroBooNE is scheduled to receive neutrinos in early 2014, and there is minimal additional cost to also deliver beam to MiniBooNE

Splicing Reporter Mice Revealed the Evolutionally Conserved Switching Mechanism of Tissue-Specific Alternative Exon Selection

Since alternative splicing of pre-mRNAs is essential for generating tissue-specific diversity in proteome, elucidating its regulatory mechanism is indispensable to understand developmental process or tissue-specific functions. We have been focusing on tissue-specific regulation of mutually exclusive selection of alternative exons because this implies the typical molecular mechanism of alternative splicing regulation and also can be good examples to elicit general rule of “splice code”. So far, mutually exclusive splicing regulation has been explained by the outcome from the balance of multiple regulators that enhance or repress either of alternative exons discretely. However, this “balance” model is open to questions of how to ensure the selection of only one appropriate exon out of several candidates and how to switch them. To answer these questions, we generated an original bichromatic fluorescent splicing reporter system for mammals using fibroblast growth factor-receptor 2 (FGFR2) gene as model. By using this splicing reporter, we demonstrated that FGFR2 gene is regulated by the “switch-like” mechanism, in which key regulators modify the ordered splice-site recognition of two mutually exclusive exons, eventually ensure single exon selection and their distinct switching. Also this finding elucidated the evolutionally conserved “splice code,” in which combination of tissue-specific and broadly expressed RNA binding proteins regulate alternative splicing of specific gene in a tissue-specific manner. These findings provide the significant cue to understand how a number of spliced genes are regulated in various tissue-specific manners by a limited number of regulators, eventually to understand developmental process or tissue-specific functions

Fox-1 family of RNA-binding proteins

The Fox-1 family of RNA-binding proteins are evolutionarily conserved regulators of tissue-specific alternative splicing in metazoans. The Fox-1 family specifically recognizes the (U)GCAUG stretch in regulated exons or in flanking introns, and either promotes or represses target exons. Recent unbiased bioinformatics analyses of alternatively spliced exons and comparison of various vertebrate genomes identified the (U)GCAUG stretch as a highly conserved and widely distributed element enriched in intronic regions surrounding exons with altered inclusion in muscle, heart, and brain, consistent with specific expression of Fox-1 and Fox-2 in these tissues. Global identification of Fox-2 target RNAs in living cells revealed that many of the Fox-2 target genes themselves encode splicing regulators. Further systematic elucidation of target genes of the Fox-1 family and other splicing regulators in various tissues will lead to a comprehensive understanding of splicing regulatory networks

Muscle pain induced by hypertonic saline in the knee extensors decreases single-limb isometric time to task failure

Purpose: Increased nociceptive activity and the experience of exercise-induced pain (EIP) may contribute to fatigue during endurance exercise. To investigate this, a pain model that produces pain similar to EIP and decouples its’ relationship to exercise intensity is required. This study 1) compared the quality of pain caused by a hypertonic saline injection into the vastus lateralis in resting and exercise conditions, and 2) investigated whether this pain contributes to changes in time to task failure. Methods: On separate days, eighteen participants completed a time to task failure at 20% maximal voluntary torque (MVT), a resting hypertonic saline intramuscular injection, and in a further three visits a time to task failure at 10% MVT following injection of isotonic saline, hypertonic saline or a control (no injection). Results: In a subset of eligible participants (n = 12), the hypertonic saline combined with 10% MVT produced a qualitative experience of pain (assessed by the McGill Pain Questionnaire) that felt similar to EIP. 10% MVT with hypertonic saline significantly elevated pain intensity in the first 20% of the time to task failure and caused a significantly (P < 0.05) shorter time to task failure (448 ± 240 s) compared with the isotonic saline (605 ± 285 s) and control (514 ± 197 s) conditions. Conclusion: These findings demonstrate that hypertonic saline increases the intensity of pain during exercise, which results in a faster occurrence of exercise-induced fatigue. These results provide important evidence supporting pain as a limiting factor in endurance performance

Endurance performance is influenced by perceptions of pain and temperature: Theory, applications and safety considerations.

Models of endurance performance now recognise input from the brain, including an athlete’s ability to cope with various non-pleasurable perceptions during exercise, such as pain and temperature. Exercise training can reduce perceptions of both pain and temperature over time, partly explaining why athletes generally have a higher pain tolerance, despite a similar pain threshold, compared with active controls. Several strategies with varying efficacy may ameliorate the perceptions of pain (e.g. acetaminophen, transcranial direct current stimulation and transcutaneous electrical stimulation) and temperature (e.g. menthol beverages, topical menthol products and other cooling strategies, especially those targeting the head) during exercise to improve athletic performance. This review describes both the theory and practical applications of these interventions in the endurance sport setting, as well as the potentially harmful health consequences of their use

Neutrinos

229 pages229 pages229 pagesThe Proceedings of the 2011 workshop on Fundamental Physics at the Intensity Frontier. Science opportunities at the intensity frontier are identified and described in the areas of heavy quarks, charged leptons, neutrinos, proton decay, new light weakly-coupled particles, and nucleons, nuclei, and atoms

Shear-induced variability in the United States pharmacopeia apparatus 2: Modifications to the existing system

The hydrodynamics within the United States Pharmacopeia Apparatus 2 have been shown to be highly non-uniform with a potential to yield substantial variability in dissolution rate measurements. Through the use of readily available engineering tools, several geometric modifications to the device were evaluated in this study. Specifically, we examined the influence of impeller clearance, agitator type (radial and axial), and vessel geometry (PEAK vessel) on the fluid flow properties and their relation to measured dissolution rates. Increasing the impeller clearance was observed to exacerbate the heterogeneity in shear and would likely result in greater variability in dissolution measurements. Altering the impeller type was shown to yield changes in the hydrodynamic behavior; however, the overall properties and problems with the test remain the same. Use of the PEAK vessel was observed to reduce shear heterogeneity in the regions where tablets are most likely to visit during testing; however, higher shear rates may result in the inability to discriminate between true differences in dissolution rates