Virtual Thrower Versus Real Goalkeeper: The Influence of Different Visual Conditions on Performance

In order to use virtual reality as a sport analysis tool, we need to be sure that an immersed athlete reacts realistically in a virtual environment. This has been validated for a real handball goalkeeper facing a virtual thrower. However, we currently ignore which visual variables induce a realistic motor behavior of the immersed handball goalkeeper. In this study, we used virtual reality to dissociate the visual information related to the movements of the player from the visual information related to the trajectory of the ball. Thus, the aim is to evaluate the relative influence of these different visual information sources on the goalkeeper's motor behavior. We tested 10 handball goalkeepers who had to predict the final position of the virtual ball in the goal when facing the following: only the throwing action of the attacking player (TA condition), only the resulting ball trajectory (BA condition), and both the throwing action of the attacking player and the resulting ball trajectory (TB condition). Here we show that performance was better in the BA and TB conditions, but contrary to expectations, performance was substantially worse in the TA condition. A significant effect of ball landing zone does, however, suggest that the relative importance between visual information from the player and the ball depends on the targeted zone in the goal. In some cases, body-based cues embedded in the throwing actions may have a minor influence on the ball trajectory and vice versa. Kinematics analysis was then combined with these results to determine why such differences occur depending on the ball landing zone and consequently how it can clarify the role of different sources of visual information on the motor behavior of an athlete immersed in a virtual environment.

Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells

BACKGROUND AND PURPOSE: NF-κB-driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA3 ) is a plant-derived diterpenoid with documented anti-inflammatory activity, which is reported to induce A20-like zinc finger proteins in plants. Here, we sought to investigate the anti-inflammatory effect of GA3 in airway epithelial cells and determine if the anti-inflammatory action relates to A20 induction.</p>

EXPERIMENTAL APPROACH: Primary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o-) were used. Cells were pre-incubated with GA3 , stimulated with Pseudomonas aeruginosa LPS; IL-6 and IL-8 release, A20, NF-κB and IκBα expression were then evaluated. To determine if any observed anti-inflammatory effect occurred via an A20-dependent mechanism, A20 was silenced using siRNA.>>KEY RESULTS: Cells pre-incubated with GA3 had significantly increased levels of A20 mRNA (4 h) and protein (24 h), resulting in a significant reduction in IL-6 and IL-8 release. This effect was mediated via reduced IκBα degradation and reduced NF-κB (p65) expression. Furthermore, the anti-inflammatory action of GA3 was abolished in A20-silenced cells.</p>

CONCLUSIONS AND IMPLICATIONS: We showed that A20 induction by GA3 attenuates inflammation in airway epithelial cells, at least in part through its effect on NF-κB and IκBα. GA3 or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction.</p>

Nong Thale Pron - a key site from southern Thailand for studying monsoon variability during the past 15000 years

Studies of marine sediments, cave speleothemes, annually laminated corals, and tree rings from Asian monsoon regions have added knowledge to our understanding of the factors that control inter-annual to millennial monsoon variability in the past and have provided important constraints for climate modeling scenarios. In contrast, the spatial and temporal pattern of sub-millennial scale monsoon variability and its impact on land cover in SE Asia are still unresolved. This shortcoming stems from the fact that temporally well-resolved paleo-environmental studies are missing from large parts of SE Asia, especially from Thailand. Given that global and regional climate models are increasingly using terrestrial paleo- data to test their performance, past changes in land cover are therefore important variables to better understand feedbacks between different Earth systems. We obtained sediments from Lake Nong Thale Pron, in southern Thailand (8º 10`N, 99 º23`E; 380 m.asl). The aim of our study is to reconstruct lake status changes and to evaluate whether the extent of these changes are linked to known shifts in monsoon intensity and variability. Preliminary results show that lake infilling started more than 15,000 years ago and that the sediments cover the last deglaciation and the Holocene. Current analyses include Itrax XRF core scanning, loss-on-ignition (LOI at 950 and 550ºC), CN elemental and isotopic composition. We expect that our results will be able to give a picture of how the lake's status has changed over time and whether the extent of these changes is linked to known shifts in monsoon intensity and variability.

Application-Level Energy Awareness for OpenMP

Power, and consequently energy, has recently attained first-class system resource status, on par with conventional metrics such as CPU time. To reduce energy consumption, many hardware- and OS-level solutions have been investigated. However, application-level information - which can provide the system with valuable insights unattainable otherwise - was only considered in a handful of cases. We introduce OpenMPE, an extension to OpenMP designed for power management. OpenMP is the de-facto standard for programming parallel shared memory systems, but does not yet provide any support for power control. Our extension exposes (i) per-region multi-objective optimization hints and (ii) application-level adaptation parameters, in order to create energy-saving opportunities for the whole system stack. We have implemented OpenMPE support in a compiler and runtime system, and empirically evaluated its performance on two architectures, mobile and desktop. Our results demonstrate the effectiveness of OpenMPE with geometric mean energy savings across 9 use cases of 15 % while maintaining full quality of service.

Pharmacokinetics of melatonin in preterm infants

Aims: Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials. Methods: Melatonin was administered to 18 preterm infants in doses ranging from 0.04-0.6μgkgp>-1sup> over 0.5-6h. Pharmacokinetic profiles were analyzed individually and by population methods. Results: Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1μgkgp>-1sup>h^{-1up> for 2h showed a median half-life of 15.82h and median maximum plasma concentration of 203.3pgmlp>-1sup>. On population pharmacokinetics, clearance was 0.045lhup>-1}, volume of distribution 1.098l and elimination half-life 16.91h with gender (P = 0.047) and race (P &lt; 0.0001) as significant covariates. Conclusions: A 2h infusion of 0.1μgkgp>-1sup>h<sup>-1up> increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants. © 2013 The British Pharmacological Society.</p>

Early ultraviolet emission in the Type Ia supernova LSQ12gdj: No evidence for ongoing shock interaction

We present photospheric-phase observations of LSQ12gdj, a slowly declining, UV-bright Type Ia supernova. Classified well before maximum light, LSQ12gdj has extinction-corrected absolute magnitude MB = -19.8, and pre-maximum spectroscopic evolution similar to SN 1991T and the super-Chandrasekhar-mass SN 2007if. We use ultraviolet photometry from Swift, ground-based optical photometry, and corrections from a near-infrared photometric template to construct the bolometric (1600-23 800 Å) light curve out to 45 d past B-band maximum light. We estimate that LSQ12gdj produced 0.96 ± 0.07 M· of 56Ni, with an ejected mass near or slightly above the Chandrasekhar mass. As much as 27 per cent of the flux at the earliest observed phases, and 17 per cent at maximum light, is emitted bluewards of 3300 Å. The absence of excess luminosity at late times, the cutoff of the spectral energy distribution bluewards of 3000 Å and the absence of narrow line emission and strong Na I D absorption all argue against a significant contribution from ongoing shock interaction. However, ~10 per cent of LSQ12gdj's luminosity near maximum light could be produced by the release of trapped radiation, including kinetic energy thermalized during a brief interaction with a compact, hydrogen-poor envelope (radius <;1013 cm) shortly after explosion; such an envelope arises generically in double-degenerate merger scenarios.p>

PS1-10afx at z = 1.388: Pan-STARRS1 Discovery of a New Type of Superluminous Supernova

We present the Pan-STARRS1 discovery of PS1-10afx, a unique hydrogen-deficient superluminous supernova (SLSN) at redshift z = 1.388. The light curve peaked at z P1 = 21.7 mag, making PS1-10afx comparable to the most luminous known SNe, with Mu = -22.3 mag. Our extensive optical and near-infrared observations indicate that the bolometric light curve of PS1-10afx rose on the unusually fast timescale of ~12 days to the extraordinary peak luminosity of 4.1 × 1044 erg s-1 (M bol = -22.8 mag) and subsequently faded rapidly. Equally important, the spectral energy distribution is unusually red for an SLSN, with a color temperature of ~6800 K near maximum light, in contrast to previous hydrogen-poor SLSNe, which are bright in the ultraviolet (UV). The spectra more closely resemble those of a normal SN Ic than any known SLSN, with a photospheric velocity of ~11, 000 km s-1 and evidence for line blanketing in the rest-frame UV. Despite the fast rise, these parameters imply a very large emitting radius (gsim 5 × 1015 cm). We demonstrate that no existing theoretical model can satisfactorily explain this combination of properties: (1) a nickel-powered light curve cannot match the combination of high peak luminosity with the fast timescale; (2) models powered by the spindown energy of a rapidly rotating magnetar predict significantly hotter and faster ejecta; and (3) models invoking shock breakout through a dense circumstellar medium cannot explain the observed spectra or color evolution. The host galaxy is well detected in pre-explosion imaging with a luminosity near L*, a star formation rate of ~15 M ⊙ yr-1, and is fairly massive (~2 × 1010 M ⊙), with a stellar population age of ~108 yr, also in contrast to the young dwarf hosts of known hydrogen-poor SLSNe. PS1-10afx is distinct from known examples of SLSNe in its spectra, colors, light-curve shape, and host galaxy properties, suggesting that it resulted from a different channel than other hydrogen-poor SLSNe.

Laser-driven three-stage heavy-ion acceleration from relativistic laser-plasma interaction

A three-stage heavy ion acceleration scheme for generation of high-energy quasimonoenergetic heavy ion beams is investigated using two-dimensional particle-in-cell simulation and analytical modeling. The scheme is based on the interaction of an intense linearly polarized laser pulse with a compound two-layer target (a front heavy ion layer + a second light ion layer). We identify that, under appropriate conditions, the heavy ions preaccelerated by a two-stage acceleration process in the front layer can be injected into the light ion shock wave in the second layer for a further third-stage acceleration. These injected heavy ions are not influenced by the screening effect from the light ions, and an isolated high-energy heavy ion beam with relatively low-energy spread is thus formed. Two-dimensional particle-in-cell simulations show that ∼100MeV/u quasimonoenergetic Fe24+ beams can be obtained by linearly polarized laser pulses at intensities of 1.1×1021W/cmp>2up>. >

Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer

Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p &lt; 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p &lt; 0.0001) and BPH (11.43% (4/35), p &lt; 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.>

IGFBP7 promoter methylation and gene expression analysis in prostate cancer

PURPOSE: IGFBP7 belongs to a family of insulin-like growth factor-1 regulatory binding proteins. IGFBP7 hypermethylation is associated with its down-regulation in various carcinomas. In prostate cancer IGFBP7 down-regulation has been widely reported but to our knowledge the mechanisms behind this event are unknown. We performed a denaturing high performance liquid chromatography screening and validation strategy to profile the methylation status of IGFBP7 in prostate cancer.</p>

MATERIALS AND METHODS: We combined denaturing high performance liquid chromatography and bisulfite sequencing to examine IGFBP7 methylation in a panel of prostate cancer cell lines. Quantitative methylation specific polymerase chain reaction was used to determine methylation levels in prostate tissue specimens of primary prostate cancer, histologically benign prostate adjacent to tumor, high grade prostatic intraepithelial neoplasia and benign prostatic hyperplasia. IGFBP7 gene expression was measured by quantitative methylation specific polymerase chain reaction in cell lines and tissue specimens.>>RESULTS: IGFBP7 was methylated in the 4 prostate cancer cell lines DU145, LNCaP, PC-3 and 22RV1. Quantitative methylation specific polymerase chain reaction analysis revealed that promoter methylation was associated with decreased IGFBP7 expression. Quantitative methylation specific polymerase chain reaction showed that IGFBP7 methylation was more frequently detected in prostate cancer (60% (31/52)) and high grade prostatic intraepithelial neoplasia (40% (6/15)) samples compared to histologically benign prostate adjacent to tumor (10%) and benign prostatic hyperplasia (0%) samples.p><p>CONCLUSIONS: To our knowledge this is the first report of aberrant IGFBP7 promoter hypermethylation and concurrent IGFBP7 gene silencing in prostate cancer cell lines. Results demonstrate that CpG methylation of IGFBP7 may represent a novel biomarker of prostate cancer and pre-invasive neoplasms. Thus, future examination of IGFBP7 methylation and expression in a larger patient cohort, including bodily fluids, is justified to further evaluate its role in a diagnostic and prognostic setting.>

The pyrrolo-1,5-benzoxazepine, PBOX-6, inhibits the growth of breast cancer cells in vitro independent of estrogen receptor status and inhibits breast tumour growth in vivo

Members of a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds have been shown to induce apoptosis in a number of human leukemia cell lines of different haematological lineage, suggesting their potential as anti-cancer agents. In this study, we sought to determine if PBOX-6, a well characterised member of the PBOX series of compounds, is also an effective inhibitor of breast cancer growth. Two estrogen receptor (ER)-positive (MCF-7 and T-47-D) and two ER-negative (MDA-MB-231 and SK-BR-3) cell lines were examined. The 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine reduction in cell viability. PBOX-6 reduced the cell viability of all four cell lines tested, regardless of ER status, with IC(50) values ranging from 1.0 to 2.3 microM. PBOX-6 was most effective in the SK-BR-3 cells, which express high endogenous levels of the HER-2 oncogene. Overexpression of the HER-2 oncogene has been associated with aggressive disease and resistance to chemotherapy. The mechanism of PBOX-6-induced cell death was due to apoptosis, as indicated by the increased proportion of cells in the pre-G1 peak and poly(ADP-ribose) polymerase (PARP) cleavage. Moreover, intratumoural administration of PBOX-6 (7.5 mg/kg) significantly inhibited tumour growth in vivo in a mouse mammary carcinoma model (p=0.04, n=5, Student's t-test). Thus, PBOX-6 could be a promising anti-cancer agent for both hormone-dependent and -independent breast cancers.p>

Towards a Cyber-physical Resilience Framework for Smart Grids

As modern power grids move towards becoming a smart grid, there is an increasing reliance on the data that is transmitted and processed by ICT systems. This reliance introduces new digital attack vectors. Many of the proposed approaches that aim to address this problem largely focus on applying well-known ICT security solutions. However, what is needed are approaches that meet the complex concerns of the smart grid as a cyber-physical system. Furthermore, to support the automatic control loops that exist in a power grid, similarly automatic security and resilience mechanisms are needed that rely on minimal operator intervention. The research proposed in this paper aims to develop a framework that ensures resilient smart grid operation in light of successful cyber-attacks.

Smoking and All-cause Mortality in Older Adults: Results From the CHANCES Consortium

INTRODUCTION: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years.>>METHODS: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014.p><p>RESULTS: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit &lt;10, 10 to 19, and ≥20 years ago, respectively.p><p>CONCLUSIONS: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority.p>