Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

First results from the CERN Axion Solar Telescope (CAST)

Hypothetical axion-like particles with a two-photon interaction would be produced in the Sun by the Primakoff process. In a laboratory magnetic field (``axion helioscope'') they would be transformed into X-rays with energies of a few keV. Using a decommissioned LHC test magnet, CAST has been running for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling < 1.16 10^{-10} GeV^-1 at 95% CL for m_a <~0.02 eV. This limit is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment in this axion mass range.Comment: 4 pages, accepted by PRL. Final version after the referees comment

Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11

Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the prometastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking. Ectopic expression of the EMT-activating transcription factor ZEB1 stimulated Golgi compaction and relieved microRNA-mediated repression of the Golgi scaffolding protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired anterograde vesicle transport to the plasma membrane as well as retrograde vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was associated with key regulators of Golgi compaction and vesicle transport in pull-down assays and was required to reconstitute Golgi compaction in PAQR11-deficient tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude that EMT initiates a PAQR11-mediated Golgi compaction process that drives metastasis

Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms

Background:Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart.Methods:Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.Results:Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells.Conclusions:Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actionsThis work was supported by national funding from Ministerio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/ BIO-5289), and a unrestricted grant from by Merck/MS

The search for solar axions in the CAST experiment

The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV.The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV

Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

The molecular mechanisms that drive mucosal T helper type 2 (T[subscript H]2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell–derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T[subscript H]2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T[subscript H]2 responses

Viral evasion of innate immune defense: The case of resistance of pandemic H1N1 influenza A virus to human mannose-binding proteins

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IA

Fast ReRoute on Programmable Switches

Highly dependable communication networks usually rely on some kind of Fast Re-Route (FRR) mechanism which allows to quickly re-route traffic upon failures, entirely in the data plane. This paper studies the design of FRR mechanisms for emerging reconfigurable switches. Our main contribution is an FRR primitive for programmable data planes, PURR, which provides low failover latency and high switch throughput, by avoiding packet recirculation. PURR tolerates multiple concurrent failures and comes with minimal memory requirements, ensuring compact forwarding tables, by unveiling an intriguing connection to classic ``string theory'' (i.e., stringology), and in particular, the shortest common supersequence problem. PURR is well-suited for high-speed match-action forwarding architectures (e.g., PISA) and supports the implementation of a broad variety of FRR mechanisms. Our simulations and prototype implementation (on an FPGA and a Tofino switch) show that PURR improves TCAM memory occupancy by a factor of 1.5x-10.8x compared to a naïve encoding when implementing state-of-the-art FRR mechanisms. PURR also improves the latency and throughput of datacenter traffic up to a factor of 2.8x-5.5x and 1.2x-2x, respectively, compared to approaches based on recirculating packets

Methyl-donor depletion of head and neck cancer cells in vitro establishes a less aggressive tumour cell phenotype

PURPOSE: DNA methylation plays a fundamental role in the epigenetic control of carcinogenesis and is, in part, influenced by the availability of methyl donors obtained from the diet. In this study, we developed an in-vitro model to investigate whether methyl donor depletion affects the phenotype and gene expression in head and neck squamous cell carcinoma (HNSCC) cells. METHODS: HNSCC cell lines (UD-SCC2 and UPCI-SCC72) were cultured in medium deficient in methionine, folate, and choline or methyl donor complete medium. Cell doubling-time, proliferation, migration, and apoptosis were analysed. The effects of methyl donor depletion on enzymes controlling DNA methylation and the pro-apoptotic factors death-associated protein kinase-1 (DAPK1) and p53 upregulated modulator of apoptosis (PUMA) were examined by quantitative-PCR or immunoblotting. RESULTS: HNSCC cells cultured in methyl donor deplete conditions showed significantly increased cell doubling times, reduced cell proliferation, impaired cell migration, and a dose-dependent increase in apoptosis when compared to cells cultured in complete medium. Methyl donor depletion significantly increased the gene expression of DNMT3a and TET-1, an effect that was reversed upon methyl donor repletion in UD-SCC2 cells. In addition, expression of DAPK1 and PUMA was increased in UD-SCC2 cells cultured in methyl donor deplete compared to complete medium, possibly explaining the observed increase in apoptosis in these cells. CONCLUSION: Taken together, these data show that depleting HNSCC cells of methyl donors reduces the growth and mobility of HNSCC cells, while increasing rates of apoptosis, suggesting that a methyl donor depleted diet may significantly affect the growth of established HNSCC

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA