X-ray Temperature and Mass Measurements to the Virial Radius of Abell 1413 with Suzaku

We present X-ray observations of the northern outskirts of the relaxed galaxy cluster A1413 with Suzaku, whose XIS instrument has the low intrinsic background needed to make measurements of these low surface brightness regions. We excise 15 point sources superimposed on the image above a flux of $1\times 10^{-14}$ \fluxunit (2--10keV) using XMM-Newton and Suzaku images of the cluster. We quantify all known systematic errors as part of our analysis, and show our statistical errors encompasses them for the most part. Our results extend previous measurements with Chandra and XMM-Newton, and show a significant temperature drop to about 3keV at the virial radius, $r_{200}$. Our entropy profile in the outer region ($> 0.5 r_{200}$) joins smoothly onto that of XMM-Newton, and shows a flatter slope compared with simple models, similar to a few other clusters observed at the virial radius. The integrated mass of the cluster at the virial radius is approximately $7.5\times10^{14}M_{\odot}$ and varies by about 30% depending on the particular method used to measure it.Comment: 32pages, 9 figures, accepted for publication in PAS

X-ray Spectroscopy of the Core of the Perseus Cluster with Suzaku: Elemental Abundances in the Intracluster Medium

The results from Suzaku observations of the central region of the Perseus cluster are presented. Deep exposures with the X-ray Imaging Spectrometer provide high quality X-ray spectra from the intracluster medium. X-ray lines from helium-like Cr and Mn have been detected significantly for the first time in clusters. In addition, elemental abundances of Ne, Mg, Si, S, Ar, Ca, Fe, and Ni are accurately measured within 10' (or 220 kpc) from the cluster center. The relative abundance ratios are found to be within a range of 0.8-1.5 times the solar value. These abundance ratios are compared with previous measurements, those in extremely metal-poor stars in the Galaxy, and theoretical models.Comment: 10 pages, 3 figures, accepted for ApJ

Accuracy of magnetic resonance imaging in detecting lumbo-sacral nerve root compromise: A systematic literature review

Background: MRI is considered to be the diagnostic tool of choice in diagnosing nerve root compromise among patients presenting with clinical suspicion of lumbo-sacral radiculopathy. There exists controversy among researchers and clinicians regarding the diagnostic utility and accuracy of MRI in detecting nerve root compromise and radiculopathy. This review evaluated 4 primary diagnostic accuracy studies that specifically assessed the accuracy of MRI in detecting nerve root compromise, as established in the current literature. Methods: Eight electronic data bases were searched for relevant articles from inception until January 2014. All primary diagnostic studies which investigated the accuracy of MRI in diagnosing nerve root compromise among patients with low back and referred leg symptoms were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the 'Quality Assessment of Diagnostic tests Accuracy Studies' criteria. Results: Four studies qualified for inclusion in this review. The sensitivity of MRI in detecting lumbar nerve root compromise was very low at 0.25 (95 % CI) while the specificity was relatively high at 0.92 (95 % CI). Conclusions: There is lack of sufficient high quality scientific evidence in support or against the use of MRI in diagnosing nerve root compression and radiculopathy. Therefore, clinicians should always correlate the findings of MRI with the patients' medical history and clinical presentation in clinical decision making.IS

Eco-aesthetic dimensions: Herbert Marcuse, ecollogy and art

In his last book, The Aesthetic Dimension (1978), Marcuse argued that a concern for aesthetics is justified when political change is unlikely. But the relation between aesthetics and politics is oblique: “Art cannot change the world, but it can contribute to changing the consciousness … of the men and women who could change the world.” (p. 33). Marcuse also linked his critique of capitalism to environmentalism in the early 1970s: “the violation of the Earth is a vital aspect of the counterrevolution.” (Ecology and Revolution, in The New Left and the 1960s, Collected Papers 3, 2005, p. 173). This article revisits Marcuse’s ideas on aesthetics and ecology, and reviews two recent art projects which engage their audiences in ecological issues: The Jetty Project (2014) by Wolfgang Weileder—which used recycled material and community participation to construct a temporary monument within a wider conservation project on the Tyne, N-E England—and Fracking Futures by HeHe (Helen Evans and Heiko Hansen)—which turned the interior of the gallery at FACT, Liverpool, into what appeared to be a fracking site. The aim is not to evaluate the projects, nor to test the efficacy of Marcuse’s ideas, more to ask again whether art has a role in a shift of attitude which might contribute to dealing with the political and economic causes of climate change

Kinetic and thermodynamic characterization of single-mismatch discrimination using single-molecule imaging

A single-molecule detection setup based on total internal reflection fluorescence (TIRF) microscopy has been used to investigate association and dissociation kinetics of unlabeled 30mer DNA strands. Single-molecule sensitivity was accomplished by letting unlabeled DNA target strands mediate the binding of DNA-modified and fluorescently labeled liposomes to a DNA-modified surface. The liposomes, acting as signal enhancer elements, enabled the number of binding events as well as the residence time for high affinity binders (Kd < 1 nM, koff < 0.01 s−1) to be collected under equilibrium conditions at low pM concentrations. The mismatch discrimination obtained from the residence time data was shown to be concentration and temperature independent in intervals of 1–100 pM and 23–46°C, respectively. This suggests the method as a robust means for detection of point mutations at low target concentrations in, for example, single nucleotide polymorphism (SNP) analysis

Search for Oxygen Emission from Warm-Hot Intergalactic Medium around A2218 with Suzaku

We searched for redshifted O emission lines from the possible warm-hot intergalactic medium (WHIM) surrounding the cluster of galaxies A2218 at z=0.1756 using the XIS instrument on Suzaku. This cluster is thought to have an elongated structure along the line of sight based on previous studies. We studied systematic uncertainties in the spectrum of the Galactic emission and in the soft X-ray response of the detectors due to the contamination building up on the XIS filters. We detected no significant redshifted O lines, and set a tight constraint on the intensity with upper limits for the surface brightness of OVII and OVIII lines of 1.1 x 10^-7 and 3.0 x 10^-7 photons cm^-2 s^-1 arcmin^-2, respectively. These upper limits are significantly lower than the previously reported fluxes from the WHIM around other clusters of galaxies. We also discuss the prospect for the detection of the WHIM lines with Suzaku XIS in the future.Comment: 12 pages, 13 figures. Accepted for publication in PASJ Suzaku special issue (Vol.59, No.SP1

Towards a target label-free suboptimum oligonucleotide displacement-based detection system

A novel method for the future development of label-free DNA sensors is proposed here. The approach is based on the displacement of a labelled suboptimum mutated oligonucleotide hybridised with the immobilised biotin-capture probe. The target fully complementary to the biotin-capture probe can displace the labelled oligonucleotide causing a subsequent decrease of the signal that verifies the presence of the target. The decrease of signal was demonstrated to be proportional to the target concentration. A study of the hybridisation of mutated and complementary labelled oligonucleotides with an immobilised biotin-capture probe was carried out. Different kinetic and thermodynamic behaviour was observed for heterogeneous hybridisation of biotin-capture probe with complementary or suboptimum oligonucleotides. The displacement method evaluated colourimetrically achieved the objective of decreasing the response time from 1 h for direct hybridisation of 19-mer oligonucleotides in the direct enzyme-linked oligonucleotide assay (ELONA) to 5 min in the case of displacement detection in the micromolar concentration range

A physicochemical descriptor-based scoring scheme for effective and rapid filtering of kinase-like chemical space

<p>Abstract</p> <p>Background</p> <p>The current chemical space of known small molecules is estimated to exceed 10⁶⁰structures. Though the largest physical compound repositories contain only a few tens of millions of unique compounds, virtual screening of databases of this size is still difficult. In recent years, the application of physicochemical descriptor-based profiling, such as Lipinski's rule-of-five for drug-likeness and Oprea's criteria of lead-likeness, as early stage filters in drug discovery has gained widespread acceptance. In the current study, we outline a kinase-likeness scoring function based on known kinase inhibitors.</p> <p>Results</p> <p>The method employs a collection of 22,615 known kinase inhibitors from the ChEMBL database. A kinase-likeness score is computed using statistical analysis of nine key physicochemical descriptors for these inhibitors. Based on this score, the kinase-likeness of four publicly and commercially available databases, i.e., National Cancer Institute database (NCI), the Natural Products database (NPD), the National Institute of Health's Molecular Libraries Small Molecule Repository (MLSMR), and the World Drug Index (WDI) database, is analyzed. Three of these databases, i.e., NCI, NPD, and MLSMR are frequently used in the virtual screening of kinase inhibitors, while the fourth WDI database is for comparison since it covers a wide range of known chemical space. Based on the kinase-likeness score, a kinase-focused library is also developed and tested against three different kinase targets selected from three different branches of the human kinome tree.</p> <p>Conclusions</p> <p>Our proposed methodology is one of the first that explores how the narrow chemical space of kinase inhibitors and its relevant physicochemical information can be utilized to build kinase-focused libraries and prioritize pre-existing compound databases for screening. We have shown that focused libraries generated by filtering compounds using the kinase-likeness score have, on average, better docking scores than an equivalent number of randomly selected compounds. Beyond library design, our findings also impact the broader efforts to identify kinase inhibitors by screening pre-existing compound libraries. Currently, the NCI library is the most commonly used database for screening kinase inhibitors. Our research suggests that other libraries, such as MLSMR, are more kinase-like and should be given priority in kinase screenings.</p

Muscle wasting in chronic kidney disease: the role of the ubiquitin proteasome system and its clinical impact

Muscle wasting in chronic kidney disease (CKD) and other catabolic diseases (e.g. sepsis, diabetes, cancer) can occur despite adequate nutritional intake. It is now known that complications of these various disorders, including acidosis, insulin resistance, inflammation, and increased glucocorticoid and angiotensin II production, all activate the ubiquitin–proteasome system (UPS) to degrade muscle proteins. The initial step in this process is activation of caspase-3 to cleave the myofibril into its components (actin, myosin, troponin, and tropomyosin). Caspase-3 is required because the UPS minimally degrades the myofibril but rapidly degrades its component proteins. Caspase-3 activity is easily detected because it leaves a characteristic 14kD actin fragment in muscle samples. Preliminary evidence from several experimental models of catabolic diseases, as well as from studies in patients, indicates that this fragment could be a useful biomarker because it correlates well with the degree of muscle degradation in dialysis patients and in other catabolic conditions