Hydrostatic pressure does not cause detectable changes to survival of human retinal ganglion

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (<24h post mortem) were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD). Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1) and RGC number by immunohistochemistry (NeuN). Activated p38 and JNK were detected by Western blot. Results: Exposure of HORCs to constant (60mmHg) or fluctuating (10-100mmHg; 1 cycle/min) pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina

The effects of daily cold-water recovery and postexercise hot-water immersion on training-load tolerance during 5 days of heat-based training

PURPOSE: To examine the effects of daily cold- and hot-water recovery on training load (TL) during 5 days of heat-based training. METHODS: Eight men completed 5 days of cycle training for 60 minutes (50% peak power output) in 4 different conditions in a block counter-balanced-order design. Three conditions were completed in the heat (35°C) and 1 in a thermoneutral environment (24°C; CON). Each day after cycling, participants completed 20 minutes of seated rest (CON and heat training [HT]) or cold- (14°C; HTCWI) or hot-water (39°C; HTHWI) immersion. Heart rate, rectal temperature, and rating of perceived exertion (RPE) were collected during cycling. Session-RPE was collected 10 minutes after recovery for the determination of session-RPE TL. Data were analyzed using hierarchical regression in a Bayesian framework; Cohen d was calculated, and for session-RPE TL, the probability that d > 0.5 was also computed. RESULTS: There was evidence that session-RPE TL was increased in HTCWI (d = 2.90) and HTHWI (d = 2.38) compared with HT. The probabilities that d > 0.5 were .99 and .96, respectively. The higher session-RPE TL observed in HTCWI coincided with a greater cardiovascular (d = 2.29) and thermoregulatory (d = 2.68) response during cycling than in HT. This result was not observed for HTHWI. CONCLUSION: These findings suggest that cold-water recovery may negatively affect TL during 5 days of heat-based training, hot-water recovery could increase session-RPE TL, and the session-RPE method can detect environmental temperature-mediated increases in TL in the context of this study.</p

The Swift X-Ray Telescope: Status and Performance

We present science highlights and performance from the Swift X-ray Telescope (XRT), which was launched on November 20, 2004. The XRT covers the 0.2-10 keV band, and spends most of its time observing gamma-ray burst (GRB)afterglows, though it has also performed observations of many other objects. By mid-August 2007, the XRT had observed over 220 GRB afterglows, detecting about 96% of them. The XRT positions enable followup ground-based optical observations, with roughly 60% of the afterglows detected at optical or near IR wavelengths. Redshifts are measured for 33% of X-ray afterglows. Science highlights include the discovery of flaring behavior at quite late times, with implications for GRB central engines; localization of short GRBs, leading to observational support for compact merger progenitors for this class of bursts; a mysterious plateau phase to GRB afterglows; as well as many other interesting observations such as X-ray emission from comets, novae, galactic transients, and other objects.Comment: 9 pages, 14 figure

Transcriptomic and metabolite analyses of Cabernet Sauvignon grape berry development

BACKGROUND: Grape berry development is a dynamic process that involves a complex series of molecular genetic and biochemical changes divided into three major phases. During initial berry growth (Phase I), berry size increases along a sigmoidal growth curve due to cell division and subsequent cell expansion, and organic acids (mainly malate and tartrate), tannins, and hydroxycinnamates accumulate to peak levels. The second major phase (Phase II) is defined as a lag phase in which cell expansion ceases and sugars begin to accumulate. Véraison (the onset of ripening) marks the beginning of the third major phase (Phase III) in which berries undergo a second period of sigmoidal growth due to additional mesocarp cell expansion, accumulation of anthocyanin pigments for berry color, accumulation of volatile compounds for aroma, softening, peak accumulation of sugars (mainly glucose and fructose), and a decline in organic acid accumulation. In order to understand the transcriptional network responsible for controlling berry development, mRNA expression profiling was conducted on berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0 spanning seven stages of berry development from small pea size berries (E-L stages 31 to 33 as defined by the modified E-L system), through véraison (E-L stages 34 and 35), to mature berries (E-L stages 36 and 38). Selected metabolites were profiled in parallel with mRNA expression profiling to understand the effect of transcriptional regulatory processes on specific metabolite production that ultimately influence the organoleptic properties of wine. RESULTS: Over the course of berry development whole fruit tissues were found to express an average of 74.5% of probes represented on the Vitis microarray, which has 14,470 Unigenes. Approximately 60% of the expressed transcripts were differentially expressed between at least two out of the seven stages of berry development (28% of transcripts, 4,151 Unigenes, had pronounced (≥2 fold) differences in mRNA expression) illustrating the dynamic nature of the developmental process. The subset of 4,151 Unigenes was split into twenty well-correlated expression profiles. Expression profile patterns included those with declining or increasing mRNA expression over the course of berry development as well as transient peak or trough patterns across various developmental stages as defined by the modified E-L system. These detailed surveys revealed the expression patterns for genes that play key functional roles in phytohormone biosynthesis and response, calcium sequestration, transport and signaling, cell wall metabolism mediating expansion, ripening, and softening, flavonoid metabolism and transport, organic and amino acid metabolism, hexose sugar and triose phosphate metabolism and transport, starch metabolism, photosynthesis, circadian cycles and pathogen resistance. In particular, mRNA expression patterns of transcription factors, abscisic acid (ABA) biosynthesis, and calcium signaling genes identified candidate factors likely to participate in the progression of key developmental events such as véraison and potential candidate genes associated with such processes as auxin partitioning within berry cells, aroma compound production, and pathway regulation and sequestration of flavonoid compounds. Finally, analysis of sugar metabolism gene expression patterns indicated the existence of an alternative pathway for glucose and triose phosphate production that is invoked from véraison to mature berries. CONCLUSION: These results reveal the first high-resolution picture of the transcriptome dynamics that occur during seven stages of grape berry development. This work also establishes an extensive catalog of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern berry development in a widely grown cultivar of wine grape. More importantly, this analysis identified a set of previously unknown genes potentially involved in critical steps associated with fruit development that can now be subjected to functional testing.National Science Foundation Plant Genome Project (DBI-0217653); Bioinformatics program (DBI-0136561); National Institute of Health Biomedical Research Infrastructure Network (NIH-NCRR P20 RR16464; National Institute of Health IDeA Network of Biomedical Research Excellence (INBRE, RR-03-008); Nevada Agricultural Experimental Statio

lp-Recovery of the Most Significant Subspace among Multiple Subspaces with Outliers

We assume data sampled from a mixture of d-dimensional linear subspaces with spherically symmetric distributions within each subspace and an additional outlier component with spherically symmetric distribution within the ambient space (for simplicity we may assume that all distributions are uniform on their corresponding unit spheres). We also assume mixture weights for the different components. We say that one of the underlying subspaces of the model is most significant if its mixture weight is higher than the sum of the mixture weights of all other subspaces. We study the recovery of the most significant subspace by minimizing the lp-averaged distances of data points from d-dimensional subspaces, where p>0. Unlike other lp minimization problems, this minimization is non-convex for all p>0 and thus requires different methods for its analysis. We show that if 0<p<=1, then for any fraction of outliers the most significant subspace can be recovered by lp minimization with overwhelming probability (which depends on the generating distribution and its parameters). We show that when adding small noise around the underlying subspaces the most significant subspace can be nearly recovered by lp minimization for any 0<p<=1 with an error proportional to the noise level. On the other hand, if p>1 and there is more than one underlying subspace, then with overwhelming probability the most significant subspace cannot be recovered or nearly recovered. This last result does not require spherically symmetric outliers.Comment: This is a revised version of the part of 1002.1994 that deals with single subspace recovery. V3: Improved estimates (in particular for Lemma 3.1 and for estimates relying on it), asymptotic dependence of probabilities and constants on D and d and further clarifications; for simplicity it assumes uniform distributions on spheres. V4: minor revision for the published versio

A study of the prompt and afterglow emission of the Short GRB 061201

Our knowledge of the intrinsic properties of short duration Gamma-Ray Bursts has relied, so far, only upon a few cases for which the estimate of the distance and an extended, multiwavelength monitoring of the afterglow have been obtained. We carried out multiwavelength observations of the short GRB 061201 aimed at estimating its distance and studying its properties. We performed a spectral and timing analysis of the prompt and afterglow emission and discuss the results in the context of the standard fireball model. A clear temporal break was observed in the X-ray light curve about 40 minutes after the burst trigger. We find that the spectral and timing behaviour of the X-ray afterglow is consistent with a jet origin of the observed break, although the optical data can not definitively confirm this and other scenarios are possible. No underlying host galaxy down to R~26 mag was found after fading of the optical afterglow. Thus, no secure redshift could be measured for this burst. The nearest galaxy is at z=0.111 and shows evidence of star formation activity. We discuss the association of GRB 061201 with this galaxy and with the ACO S 995 galaxy cluster, from which the source is at an angular distance of 17'' and 8.5', respectively. We also test the association with a possible undetected, positionally consistent galaxy at z~1. In all these cases, in the jet interpretation, we find a jet opening angle of 1-2 degrees.Comment: 10 pages, 7 figures, accepted for publication in A&

Velocity, oxygen uptake and metabolic cost of pull, kick and whole body swimming

Purpose: The contributions of the limbs to velocity and metabolic parameters in front-crawl swimming at different intensities have not been identified considering both stroke and kick rate. Consequently, velocity, oxygen uptake (VO2), and metabolic cost of swimming with the whole body (swim), the upper limbs only (pull), and lower limbs only (kick) were compared with stroke and kick rate controlled. Methods: Twenty elite swimmers completed six 200-m trials: 2 swim, 2 pull, and 2 kick. Swim trials were guided by underwater lights at paces equivalent to 65% +/- 3% and 78% +/- 3% of participants' 200-m-freestyle personal-best pace; paces were described as low and moderate, respectively. In the pull and kick trials, swimmers aimed to match the stroke and kick rates, respectively, recorded during the swim trials. (V)over dot O-2 was measured continuously, with velocity and metabolic cost calculated for each 200-m effort. Results: The velocity contribution of the upper limbs (mean +/- SD; low 63.9% +/- 6.2%, moderate 59.6% +/- 4.2%) was greater than that of the lower limbs to a large extent at both intensities (low ES = 4.40, moderate ES = 4.60). The (V) over dot O-2 used by the upper limbs differed between the intensities (low 55.5% +/- 6.9%, moderate 51.4% +/- 4.0%; ES = 0.74). The lower limbs were responsible for a greater percentage of the metabolic cost than the upper limbs at both intensities (low 56.1% +/- 9.5%, ES = 1.30; moderate 55.1% +/- 6.6%, ES = 1.55). Conclusions: Implementation of this testing protocol before and after a pull-or kick-training block will enable sport scientists to determine how the velocity contributions and/or metabolic cost of the upper-and lower-limb actions have responded to the training program

Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Elevated c-Src protein expression has been shown in breast cancer and &lt;i&gt;in vitro&lt;/i&gt; evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (&lt;i&gt;P&lt;/i&gt;=0.047) and lower recurrence rates on tamoxifen (&lt;i&gt;P&lt;/i&gt;=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (&lt;i&gt;P&lt;/i&gt;&#60;0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (&lt;i&gt;P&lt;/i&gt;=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in &lt;i&gt;de novo&lt;/i&gt; endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials