Listening to Music in the First, but not the Last 1.5 km of a 5-km Running Trial Alters Pacing Strategy and Improves Performance

We examined the effects of listening to music on attentional focus, rating of perceived exertion (RPE), pacing strategy and performance during a simulated 5-km running race. 15 participants performed 2 controlled trials to establish their best baseline time, followed by 2 counterbalanced experimental trials during which they listened to music during the first (M-start) or the last (M-finish) 1.5 km. The mean running velocity during the first 1.5 km was significantly higher in M-start than in the fastest control condition (p < 0.05), but there was no difference in velocity between conditions during the last 1.5 km (p > 0.05). The faster first 1.5 m in M-start was accompanied by a reduction in associative thoughts compared with the fastest control condition. There were no significant differences in RPE between conditions (p > 0.05). These results suggest that listening to music at the beginning of a trial may draw the attentional focus away from internal sensations of fatigue to thoughts about the external environment. However, along with the reduction in associative thoughts and the increase in running velocity while listening to music, the RPE increased linearly and similarly under all conditions, suggesting that the change in velocity throughout the race may be to maintain the same rate of RPE increase.Australian Department of Education, Employment and Workplace RelationsAustralian Department of Education, Employment and Workplace Relation

Thermostability of cardosin A from Cynara cardunculus L.

The structural stability of cardosin A, a plant aspartic proteinase (AP) from Cynara cardunculus L., has been investigated by high-sensitivity differential scanning calorimetry, intrinsic fluorescence and circular dichroism spectroscopy, and enzymatic activity assays. Even though the thermal denaturation of cardosin A is partially irreversible, valid thermodynamic data can be obtained within a wide pH region. Also, although cardosin A is a heterodimeric enzyme its thermal denaturation occurs without simultaneous dissociation to unfolded monomers. Moreover, in the 3-7 pH region the excess heat capacity can be deconvoluted into two components corresponding to two elementary two-state transitions, suggesting that the two polypeptide chains of cardosin A unfold independently. Detailed thermodynamic and structural investigations of cardosin A at pH=5.0, at which value the enzyme demonstrates maximum stability and enzymatic activity, revealed that after thermal denaturation the polypeptide chains of this protein retain most of their secondary structure motifs and are not completely hydrated.http://www.sciencedirect.com/science/article/B6THV-47P1SF6-4/1/edc14f851e47459fcd87b748d068439

Toward a better system for short range precision force measurements

Many precision experiments have been done in the Casimir regime and in short range gravity when the separation between the interacting bodies is in the sub-micron range. Experimental complexity is minimized when one of the bodies is a sphere and the other one is a plate, making the alignment between the two bodies ubiquitous. Our group has produced the most precise Casimir measurements, and the best limits on predicted Yukawa-like potentials by measuring a force between a R∼150μm sphere attached to a (500μm)2 micro-mechanical oscillator and a planar source mass. By replacing the spherical surface with a fraction of a 500μm long cylinder with R∼150μm, the force sensitivity can be greatly enhanced. Here, it is paramount to know the angular deviation between the long axis of the cylinder and both the axis of rotation of the oscillator and the plate. Tests between a cylinder and a structure etched into a silicon wafer show that deviations of 20μrad are readily accessible. Additionally, a scaled up experiment is used to investigate if capacitance measurements can determine the orientation of the cylinder with respect to a plane with the required precision

High-precision αs\alpha_s measurements from LHC to FCC-ee

This document provides a writeup of all contributions to the workshop on "High precision measurements of $\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\pm$p DIS and $\gamma$-p photoproduction, (ix) photon structure function in $\gamma$-$\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\alpha_s(m_Z)$ = 0.1177 $\pm$ 0.0013, is about 1\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.Comment: 135 pages, 56 figures. CERN-PH-TH-2015-299, CoEPP-MN-15-13. This document is dedicated to the memory of Guido Altarell

EPP in T: More Controversial Subjects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72351/1/j.1467-9612.2005.00075.x.pd

Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment

Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-β, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-β, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.publishersversionpublishe

Proximity-Induced Nucleic Acid Degrader (PINAD) approach to targeted RNA degradation using small molecules

Nature has evolved intricate machinery to target and degrade RNA, and some of these molecular mechanisms can be adapted for therapeutic use. Small interfering RNAs and RNase H-inducing oligonucleotides have yielded therapeutic agents against diseases that cannot be tackled using protein-centered approaches. Because these therapeutic agents are nucleic acid-based, they have several inherent drawbacks which include poor cellular uptake and stability. Here we report a new approach to target and degrade RNA using small molecules, proximity-induced nucleic acid degrader (PINAD). We have utilized this strategy to design two families of RNA degraders which target two different RNA structures within the genome of SARS-CoV-2: G-quadruplexes and the betacoronaviral pseudoknot. We demonstrate that these novel molecules degrade their targets using in vitro, in cellulo, and in vivo SARS-CoV-2 infection models. Our strategy allows any RNA binding small molecule to be converted into a degrader, empowering RNA binders that are not potent enough to exert a phenotypic effect on their own. PINAD raises the possibility of targeting and destroying any disease-related RNA species, which can greatly expand the space of druggable targets and diseases.info:eu-repo/semantics/publishedVersio