Extracting HI cosmological signal with Generalized Needlet Internal Linear Combination

HI intensity mapping is a new observational technique to map fluctuations in the large-scale structure of matter using the 21 cm emission line of atomic hydrogen (HI). Sensitive radio surveys have the potential to detect Baryon Acoustic Oscillations (BAO) at low redshifts (z < 1) in order to constrain the properties of dark energy. Observations of the HI signal will be contaminated by instrumental noise and, more significantly, by astrophysical foregrounds, such as Galactic synchrotron emission, which is at least four orders of magnitude brighter than the HI signal. Foreground cleaning is recognised as one of the key challenges for future radio astronomy surveys. We study the ability of the Generalized Needlet Internal Linear Combination (GNILC) method to subtract radio foregrounds and to recover the cosmological HI signal for a general HI intensity mapping experiment. The GNILC method is a new technique that uses both frequency and spatial information to separate the components of the observed data. Our results show that the method is robust to the complexity of the foregrounds. For simulated radio observations including HI emission, Galactic synchrotron, Galactic free-free, radio sources and 0.05 mK thermal noise, we find that we can reconstruct the HI power spectrum for multipoles 30 < l < 150 with 6% accuracy on 50% of the sky for a redshift z ~ 0.25.Comment: 20 pages, 13 figures. Updated to match version accepted by MNRA

New Approach for Boat Motion Analysis in Rowing

In rowing, the study of the movement of the boat and of the rower in the boat is difficult. Indeed, the shell is quite narrow and fragile and it is impossible to use the classical apparatus for physiological and biomechanical analysis. For this reason, the physiological studies of rowers (cardiac and pulmonary parameters) have been more easily realised on specific and non specific ergometers (see Hagerman for an extensive review 1984): it is well known now, that rowers have exceptional aerobic possibilities and also use anaerobiosis for the start and the final part of the race (Hagerman 1984). In contrast, only a few publications deal with the movement of the boat and the rower. The velocity of the boat at different stroke rates (Martin and Bernfield 1980), the angular velocities of various articulations of the rowers (Nelson and Widule 1983) were studied by kinematic analysis. Though this technique is very useful, it does not catch the movements behind the subjects and is of no use to record physiological and mechanical parameters (Ishiko 1967). Some authors used DC recorder placed in a motor boat following the racing shell to record different parameters (Baird and Soroka 1952; Di Prampero 1971; Celentano 1974). But, this technique is not practical because of the need of a second operator to keep the cables out of the water. With the miniaturization, Ishiko proposed and used multichanneltelemetry to record the force of the rower and the acceleration of the boat (Ishiko 1967; Ishiko 1971). Schneider also used the same technique to record the force of the rower in the boat (Schneider 1978). Though this technique is excellent and powerful, it is also very expensive and quite sophisticated. Our goal was thus to take advantage of the miniaturization of the elements and to build and use a recorder and transducers that can be placed into the boat to record the acceleration of the boat and the propulsive force of the rower

The Function of Hypoxia-Inducible Factor (HIF) Is Independent of the Endoplasmic Reticulum Protein OS-9

The protein “amplified in osteosarcoma-9” (OS-9) has been shown previously to interact with the prolyl hydroxylases PHD2 and PHD3. These enzymes initiate oxygen-dependent degradation of the α-subunit of hypoxia-inducible factor (HIF), a transcription factor that adapts cells to insufficient oxygen supply (hypoxia). A new model has been proposed where OS-9 triggers PHD dependent degradation of HIF-α. It was the aim of our study to define the molecular mode of action of OS-9 in the regulation of PHD and HIF activity. Although initial co-immunoprecipitation experiments confirmed physical interaction between OS-9 and PHD2, neither overexpression nor lentiviral inhibition of OS-9 expression affected HIF regulation. Subcellular localization experiments revealed a distinct reticular staining pattern for OS-9 while PHD2 was mainly localized in the cytoplasm. Further cell fractionation experiments and glycosylation tests indicated that OS-9 is a luminal ER protein. In vivo protein interaction analysis by fluorescence resonance energy transfer (FRET) showed no significant physical interaction of overexpressed PHD2-CFP and OS-9-YFP. We conclude that OS-9 plays no direct functional role in HIF degradation since physical interaction of OS-9 with oxygen sensing HIF prolyl hydroxylases cannot occur in vivo due to their different subcellular localization

Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model

<p>Abstract</p> <p>Background</p> <p>Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. To elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness associated with AQM, a gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.</p> <p>Results</p> <p>During the observation period, 1583 genes were significantly up- or down-regulated by factors of two or greater. A significant temporal gene expression pattern was constructed at short (6 h-4 days), intermediate (5-8 days) and long (9-14 days) durations. A striking early and maintained up-regulation (6 h-14d) of muscle atrogenes (muscle ring-finger 1/tripartite motif-containing 63 and F-box protein 32/atrogin-1) was observed, followed by an up-regulation of the proteolytic systems at intermediate and long durations (5-14d). Oxidative stress response genes and genes that take part in amino acid catabolism, cell cycle arrest, apoptosis, muscle development, and protein synthesis together with myogenic factors were significantly up-regulated from 5 to 14 days. At 9-14 d, genes involved in immune response and the caspase cascade were up-regulated. At 5-14d, genes related to contractile (myosin heavy chain and myosin binding protein C), regulatory (troponin, tropomyosin), developmental, caveolin-3, extracellular matrix, glycolysis/gluconeogenesis, cytoskeleton/sarcomere regulation and mitochondrial proteins were down-regulated. An activation of genes related to muscle growth and new muscle fiber formation (increase of myogenic factors and JunB and down-regulation of myostatin) and up-regulation of genes that code protein synthesis and translation factors were found from 5 to 14 days.</p> <p>Conclusions</p> <p>Novel temporal patterns of gene expression have been uncovered, suggesting a unique, coordinated and highly complex mechanism underlying the muscle wasting associated with AQM in ICU patients and providing new target genes and avenues for intervention studies.</p

Protein quality control: the who’s who, the where’s and therapeutic escapes

In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins

Age and Diet Affect Gene Expression Profile in Canine Skeletal Muscle

We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridize extracted RNA. Age had the greatest effect on gene transcription (262 differentially expressed genes), whereas the effect of diet was relatively small (22 differentially expressed genes). Effects of age (regardless of diet) were most notable on genes related to metabolism, cell cycle and cell development, and transcription function. All these genes were predominantly down-regulated in geriatric dogs. Age-affected genes that were differentially expressed on only one of two diets were primarily noted in the PPB diet group (144/165 genes). Again, genes related to cell cycle (22/35) and metabolism (15/19) had predominantly decreased transcription in geriatric dogs, but 6/8 genes related to muscle development had increased expression. Effects of diet on muscle gene expression were mostly noted in geriatric dogs, but no consistent patterns in transcription were observed. The insight these data provide into gene expression profiles of canine skeletal muscle as affected by age, could serve as a foundation for future research pertaining to age-related muscle diseases

Extending cosmological tests of General Relativity with the Square Kilometre Array

Tests of general relativity (GR) are still in their infancy on cosmological scales, but forthcoming experiments promise to greatly improve their precision over a wide range of distance scales and redshifts. One such experiment, the Square Kilometre Array (SKA), will carry out several wide and deep surveys of resolved and unresolved neutral hydrogen (H i) 21 cm line-emitting galaxies, mapping a significant fraction of the sky from $0\leqslant z\lesssim 6$. I present forecasts for the ability of a suite of possible SKA H i surveys to detect deviations from GR by reconstructing the cosmic expansion and growth history. SKA Phase 1 intensity mapping surveys can achieve sub-1% measurements of $f{\sigma }_{8}$ out to $z\approx 1$, with an SKA1-MID Band 2 survey out to z lesssim 0.6 able to surpass contemporary spectroscopic galaxy surveys such as DESI and Euclid in terms of constraints on modified gravity parameters if challenges such as foreground contamination can be tackled effectively. A more futuristic Phase 2 H i survey of $\sim {10}^{9}$ spectroscopic galaxy redshifts would be capable of detecting a $\sim 2\%$ modification of the Poisson equation out to z ≈ 2

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701