ArrayInitiative - a tool that simplifies creating custom Affymetrix CDFs

<p>Abstract</p> <p>Background</p> <p>Probes on a microarray represent a frozen view of a genome and are quickly outdated when new sequencing studies extend our knowledge, resulting in significant measurement error when analyzing any microarray experiment. There are several bioinformatics approaches to improve probe assignments, but without in-house programming expertise, standardizing these custom array specifications as a usable file (e.g. as Affymetrix CDFs) is difficult, owing mostly to the complexity of the specification file format. However, without correctly standardized files there is a significant barrier for testing competing analysis approaches since this file is one of the required inputs for many commonly used algorithms. The need to test combinations of probe assignments and analysis algorithms led us to develop ArrayInitiative, a tool for creating and managing custom array specifications.</p> <p>Results</p> <p>ArrayInitiative is a standalone, cross-platform, rich client desktop application for creating correctly formatted, custom versions of manufacturer-provided (default) array specifications, requiring only minimal knowledge of the array specification rules and file formats. Users can import default array specifications, import probe sequences for a default array specification, design and import a custom array specification, export any array specification to multiple output formats, export the probe sequences for any array specification and browse high-level information about the microarray, such as version and number of probes. The initial release of ArrayInitiative supports the Affymetrix 3' IVT expression arrays we currently analyze, but as an open source application, we hope that others will contribute modules for other platforms.</p> <p>Conclusions</p> <p>ArrayInitiative allows researchers to create new array specifications, in a standard format, based upon their own requirements. This makes it easier to test competing design and analysis strategies that depend on probe definitions. Since the custom array specifications are easily exported to the manufacturer's standard format, researchers can analyze these customized microarray experiments using established software tools, such as those available in Bioconductor.</p

Discovery of a New Soft Gamma Repeater, SGR 1627-41

We report the discovery of a new soft gamma repeater (SGR), SGR 1627-41, and present BATSE observations of the burst emission and BeppoSAX NFI observations of the probable persistent X-ray counterpart to this SGR. All but one burst spectrum are well fit by an optically thin thermal bremsstrahlung (OTTB) model with kT values between 25 and 35 keV. The spectrum of the X-ray counterpart, SAX J1635.8-4736, is similar to that of other persistent SGR X-ray counterparts. We find weak evidence for a periodic signal at 6.41 s in the light curve for this source. Like other SGRs, this source appears to be associated with a young supernova remnant G337.0-0.1. Based upon the peak luminosities of bursts observed from this SGR, we find a lower limit on the dipole magnetic field of the neutron star B_dipole > 5 * 10^14 Gauss.Comment: 5 pages, 4 figures, submitted to ApJ Letter

Unveiling Soft Gamma-Ray Repeaters with INTEGRAL

Thanks to INTEGRAL's long exposures of the Galactic Plane, the two brightest Soft Gamma-Ray Repeaters, SGR 1806-20 and SGR 1900+14, have been monitored and studied in detail for the first time at hard-X/soft gamma rays. This has produced a wealth of new scientific results, which we will review here. Since SGR 1806-20 was particularly active during the last two years, more than 300 short bursts have been observed with INTEGRAL. and their characteristics have been studied with unprecedented sensitivity in the 15-200 keV range. A hardness-intensity anticorrelation within the bursts has been discovered and the overall Number-Intensity distribution of the bursts has been determined. In addition, a particularly active state, during which ~100 bursts were emitted in ~10 minutes, has been observed on October 5 2004, indicating that the source activity was rapidly increasing. This eventually led to the Giant Flare of December 27th 2004, for which a possible soft gamma-ray (>80 keV) early afterglow has been detected. The deep observations allowed us to discover the persistent emission in hard X-rays (20-150 keV) from 1806-20 and 1900+14, the latter being in a quiescent state, and to directly compare the spectral characteristics of all Magnetars (two SGRs and three Anomalous X-ray Pulsars) detected with INTEGRAL.Comment: 8 pages, 7 figures, Presented at the conference "Isolated Neutron Stars: from the Surface to the Interior", London, UK, 24-28 April 200

Approaches to Understanding and Measuring Interdisciplinary Scientific Research (IDR): A Review of the Literature

Interdisciplinary scientific research (IDR) challenges the study of science from a number of fronts, including one of creating output science and engineering (S&E) indicators. This literature review began with a narrow focus on quantitative measures of the output of IDR, but expanded the scope as it became clear that differing definitions, assessment tools, evaluation processes, and measures all shed light on aspects of IDR. Key among the broader aspects are (a) characterizing the concept of knowledge integration, and (b) recognizing that it can occur within a single mind or as the result of team dynamics. Output measures alone cannot adequately capture this process. Among the quantitative measures considered, bibliometrics (co-authorships, collaborations, references, citations and co-citations) are the most developed, but leave considerable gaps in understanding. Emerging measures in diversity, entropy, and network dynamics are promising, but require sophisticated interpretations and thus would not serve well as S&E indicators. Combinations of quantitative and qualitative assessments coming from evaluation studies appear to reveal S&E processes but carry burdens of expense, intrusion, and lack of reproducibility. This review is a first step toward providing a more holistic view of measuring IDR; several avenues for future research highlight the need for metrics to reflect the actual practice of IDR

Optogenetic stimulation of the brainstem dorsal motor nucleus ameliorates acute pancreatitis

IntroductionInflammation is an inherently self-amplifying process, resulting in progressive tissue damage when unresolved. A brake on this positive feedback system is provided by the nervous system which has evolved to detect inflammatory signals and respond by activating anti-inflammatory processes, including the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Acute pancreatitis, a common and serious condition without effective therapy, develops when acinar cell injury activates intrapancreatic inflammation. Prior study has shown that electrical stimulation of the carotid sheath, which contains the vagus nerve, boosts the endogenous anti-inflammatory response and ameliorates acute pancreatitis, but it remains unknown whether these anti-inflammatory signals originate in the brain.MethodsHere, we used optogenetics to selectively activate efferent vagus nerve fibers originating in the brainstem dorsal motor nucleus of the vagus (DMN) and evaluated the effects on caerulein-induced pancreatitis.ResultsStimulation of the cholinergic neurons in the DMN significantly attenuates the severity of pancreatitis as indicated by reduced serum amylase, pancreatic cytokines, tissue damage, and edema. Either vagotomy or silencing cholinergic nicotinic receptor signaling by pre-administration of the antagonist mecamylamine abolishes the beneficial effects.DiscussionThese results provide the first evidence that efferent vagus cholinergic neurons residing in the brainstem DMN can inhibit pancreatic inflammation and implicate the cholinergic anti-inflammatory pathway as a potential therapeutic target for acute pancreatitis

Diel turbidity cycles in a headwater stream: evidence of nocturnal bioturbation?

Purpose: A small number of recent studies have linked daily cycles in stream turbidity to nocturnal bioturbation by aquatic fauna, principally crayfish, and demonstrated this process can significantly impact upon water quality under baseflow conditions. Adding to this limited body of research, we use high-resolution water quality monitoring data to investigate evidence of diel turbidity cycles in a lowland, headwater stream with a known signal crayfish (Pacifastacus leniusculus) population and explore a range of potential causal mechanisms. Materials and methods: Automatic bankside monitoring stations measured turbidity and other water quality parameters at 30-min resolution at three locations on the River Blackwater, Norfolk, UK during 2013. Specifically, we focused on two 20-day periods of baseflow conditions during January and April 2013 which displayed turbidity trends typical of winter and spring seasons, respectively. The turbidity time-series, which were smoothed with 6.5 hour Savitzky-Golay filters to highlight diel trends, were correlated against temperature, stage, dissolved oxygen and pH to assess the importance of abiotic influences on turbidity. Turbidity was also calibrated against suspended particulate matter (SPM) over a wide range of values via linear regression. Results and discussion: Pronounced diel turbidity cycles were found at two of the three sites under baseflow conditions during April. Spring night-time turbidity values consistently peaked between 21:00 and 04:00 with values increasing by ~10 nephelometric turbidity units (NTU) compared with the lowest recorded daytime values which occurred between 10:00 and 14:00. This translated into statistically significant increases in median midnight SPM concentration of up to 76% compared with midday, with night-time (18:00 – 05:30) SPM loads also up to 30% higher than that recorded during the daytime (06:00 – 17:30). Relating turbidity to other water quality parameters exhibiting diel cycles revealed there to be neither any correlation that might indicate a causal link, nor any obvious mechanistic connections to explain the temporal turbidity trends. Diel turbidity cycles were less prominent at all sites during the winter. Conclusions: Considering the seasonality and timing of elevated turbidity, visual observations of crayfish activity, and an absence of mechanistic connections with other water quality parameters, the results presented here are consistent with the hypothesis that nocturnal bioturbation is responsible for generating diel turbidity cycles under baseflow conditions in headwater streams. However, further research in a variety of fluvial environments is required to better assess the spatial extent, importance and causal mechanisms of this phenomenon

Interspecies competition in oral biofilms mediated by Streptococcus gordonii extracellular deoxyribonuclease SsnA

Abstract Extracellular DNA (eDNA) is a key component of many microbial biofilms including dental plaque. However, the roles of extracellular deoxyribonuclease (DNase) enzymes within biofilms are poorly understood. Streptococcus gordonii is a pioneer colonizer of dental plaque. Here, we identified and characterised SsnA, a cell wall-associated protein responsible for extracellular DNase activity of S. gordonii. The SsnA-mediated extracellular DNase activity of S. gordonii was suppressed following growth in sugars. SsnA was purified as a recombinant protein and shown to be inactive below pH 6.5. SsnA inhibited biofilm formation by Streptococcus mutans in a pH-dependent manner. Further, SsnA inhibited the growth of oral microcosm biofilms in human saliva. However, inhibition was ameliorated by the addition of sucrose. Together, these data indicate that S. gordonii SsnA plays a key role in interspecies competition within oral biofilms. Acidification of the medium through sugar catabolism could be a strategy for cariogenic species such as S. mutans to prevent SsnA-mediated exclusion from biofilms

Coronal X-Ray Emission from Nearby, Low-Mass, Exoplanet Host Stars Observed by the MUSCLES and Mega-MUSCLES HST Treasury Survey Projects

The high energy X-ray and ultraviolet (UV) radiation fields of exoplanet host stars play a crucial role in controlling the atmospheric conditions and the potential habitability of exoplanets. Major surveys of the X-ray/UV emissions from late-type (K and M spectral type) exoplanet hosts have been conducted by the MUSCLES and Mega-MUSCLES Hubble Space Telescope (HST) Treasury programs. These samples primarily consist of relatively old, ``inactive'', low mass stars. In this paper we present results from X-ray observations of the coronal emission from these stars obtained using the Chandra X-ray Observatory, the XMM-Newton Observatory, and the Neil Gehrels Swift Observatory. The stars effectively sample the coronal activity of low-mass stars at a wide range of masses and ages. The vast majority (21 of 23) of the stars are detected and their X-ray luminosities measured. Short-term flaring variability is detected for most of the fully-convective (M $\leq$ 0.35 M$_{\odot}$) stars but not for the more massive M dwarfs during these observations. Despite this difference, the mean X-ray luminosities for these two sets of M dwarfs are similar with more massive (0.35 M$_{\odot}$ $\leq$ M $\leq$ 0.6 M$_{\odot}$) M dwarfs at $\sim$5 $\times$ 10$^{26}$ erg s$^{-1}$ compared to $\sim$2 $\times$ 10$^{26}$ erg s$^{-1}$ for fully-convective stars older than 1 Gyr. Younger, fully-convective M dwarfs have X-ray luminosities between 3 and 6 $\times$ 10$^{27}$ erg s$^{-1}$.The coronal X-ray spectra have been characterized and provide important information that is vital for the modeling of the stellar EUV spectra.Comment: 39 pages, 15 figures. Accepted for publication in The Astronomical Journa

A Metabolomic Endotype of Bioenergetic Dysfunction Predicts Mortality in Critically Ill Patients with Acute Respiratory Failure

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors\u27 biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition