The early X-ray afterglows of optically bright and dark Gamma-Ray Bursts

A systematical study on the early X-ray afterglows of both optically bright and dark gamma-ray bursts (B-GRBs and D-GRBs) observed by Swift has been presented. Our sample includes 25 GRBs. Among them 13 are B-GRBs and 12 are D-GRBs. Our results show that the distributions of the X-ray afterglow fluxes ($F_{X}$), the gamma-ray fluxes ($S_{\gamma}$), and the ratio ($R_{\gamma, X}$) for both the D-GRBs and B-GRBs are similar. The differences of these distributions for the two kinds of GRBs should be statistical fluctuation. These results indicate that the progenitors of the two kinds of GRBs are the same population. Their total energy explosions are comparable. The suppression of the optical emissions from D-GRBs should results from circumburst but not their central engine.Comment: 10 pages, 3 figures, 1 table; accepted by ChJA

Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103

Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimerâ €™ s disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK 1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways

Type D Personality, Temperament, and Mental Health in Military Personnel Awaiting Deployment

Type D personality, temperament, and mental health in military personnel awaitin

The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome

Articles in International JournalsFeline Chronic Gingivostomatitis Syndrome (FCGS) is a common disease in clinical practice. Among the therapeutic options available, long-acting corticosteroids are frequently used due to their anti-inflammatory and immunosuppressive properties. Although they may improve the clinical symptoms, they can lead to a progressive form of the disease that becomes refractory to treatment. Furthermore, their direct relationship with type II diabetes mellitus (DM) is well known. Consequently, these drugs are controversial and not recommended for routine management of FCGS. Recombinant feline interferon-omega (rFeIFN-ω) is an immunomodulatory compound. Recently, its daily oral administration has been shown to be successful in treating refractory cases of FCGS. This case study describes two clinical cases of type II DM complicated by FCGS. Both animals were calicivirus positive and they had been previously treated with long-acting corticosteroids, which may have been the major cause of DM. The two cats were treated with glargine insulin (Lantus, starting dose 1 IU/cat twice daily (BID)), achieving remission 10 and 18 weeks later respectively. Considering the difficulty with control of FCGS in these animals, an oral daily dose of rFeIFN-ω was started as an alternative to long-acting corticosteroids. In both cats oral clinical signs gradually improved and 60 days after the start of therapy the owners reported a significant relief of pain during mastication. According to the authors’ knowledge, this is the first case report that describes the successful use of rFeIFN-ω in the management of FCGS in type II diabetic cats, in which long-acting corticosteroids are contraindicated

Identification of a Transcription Factor Controlling pH-Dependent Organic Acid Response in Aspergillus niger.

Acid formation in Aspergillus niger is known to be subjected to tight regulation, and the acid production profiles are fine-tuned to respond to the ambient pH. Based on transcriptome data, putative trans-acting pH responding transcription factors were listed and through knock out studies, mutants exhibiting an oxalate overproducing phenotype were identified. The yield of oxalate was increased up to 158% compared to the wild type and the corresponding transcription factor was therefore entitled Oxalic Acid repression Factor, OafA. Detailed physiological characterization of one of the ΔoafA mutants, compared to the wild type, showed that both strains produced substantial amounts of gluconic acid, but the mutant strain was more efficient in re-uptake of gluconic acid and converting it to oxalic acid, particularly at high pH (pH 5.0). Transcriptional profiles showed that 241 genes were differentially expressed due to the deletion of oafA and this supported the argument of OafA being a trans-acting transcription factor. Furthermore, expression of two phosphoketolases was down-regulated in the ΔoafA mutant, one of which has not previously been described in fungi. It was argued that the observed oxalate overproducing phenotype was a consequence of the efficient re-uptake of gluconic acid and thereby a higher flux through glycolysis. This results in a lower flux through the pentose phosphate pathway, demonstrated by the down-regulation of the phosphoketolases. Finally, the physiological data, in terms of the specific oxygen consumption, indicated a connection between the oxidative phosphorylation and oxalate production and this was further substantiated through transcription analysis

Exploiting MeSH indexing in MEDLINE to generate a data set for word sense disambiguation

<p>Abstract</p> <p>Background</p> <p>Evaluation of Word Sense Disambiguation (WSD) methods in the biomedical domain is difficult because the available resources are either too small or too focused on specific types of entities (e.g. diseases or genes). We present a method that can be used to automatically develop a WSD test collection using the Unified Medical Language System (UMLS) Metathesaurus and the manual MeSH indexing of MEDLINE. We demonstrate the use of this method by developing such a data set, called MSH WSD.</p> <p>Methods</p> <p>In our method, the Metathesaurus is first screened to identify ambiguous terms whose possible senses consist of two or more MeSH headings. We then use each ambiguous term and its corresponding MeSH heading to extract MEDLINE citations where the term and only one of the MeSH headings co-occur. The term found in the MEDLINE citation is automatically assigned the UMLS CUI linked to the MeSH heading. Each instance has been assigned a UMLS Concept Unique Identifier (CUI). We compare the characteristics of the MSH WSD data set to the previously existing NLM WSD data set.</p> <p>Results</p> <p>The resulting MSH WSD data set consists of 106 ambiguous abbreviations, 88 ambiguous terms and 9 which are a combination of both, for a total of 203 ambiguous entities. For each ambiguous term/abbreviation, the data set contains a maximum of 100 instances per sense obtained from MEDLINE.</p> <p>We evaluated the reliability of the MSH WSD data set using existing knowledge-based methods and compared their performance to that of the results previously obtained by these algorithms on the pre-existing data set, NLM WSD. We show that the knowledge-based methods achieve different results but keep their relative performance except for the Journal Descriptor Indexing (JDI) method, whose performance is below the other methods.</p> <p>Conclusions</p> <p>The MSH WSD data set allows the evaluation of WSD algorithms in the biomedical domain. Compared to previously existing data sets, MSH WSD contains a larger number of biomedical terms/abbreviations and covers the largest set of UMLS Semantic Types. Furthermore, the MSH WSD data set has been generated automatically reusing already existing annotations and, therefore, can be regenerated from subsequent UMLS versions.</p

Chondroprotection by urocortin involves blockade of the mechanosensitive ion channel Piezo1

Osteoarthritis (OA) is characterised by progressive destruction of articular cartilage and chondrocyte cell death. Here, we show the expression of the endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF-R2, in primary human articular chondrocytes (AC) and demonstrate its role as an autocrine/paracrine pro-survival factor. This effect could only be removed using the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1 when promoting chondrocyte survival. This cell death was characterised by an increase in p53 expression, and cleavage of caspase 9 and 3. Antagonism of CRF-R1 with CP-154526 caused an accumulation of intracellular calcium (Ca2+) over time and cell death. These effects could be prevented with the non-selective cation channel blocker Gadolinium (Gd3+). Therefore, opening of a non-selective cation channel causes cell death and Ucn1 maintains this channel in a closed conformation. This channel was identified to be the mechanosensitive channel Piezo1. We go on to determine that this channel inhibition by Ucn1 is mediated initially by an increase in cyclic adenosine monophosphate (cAMP) and a subsequent inactivation of phospholipase A2 (PLA2), whose metabolites are known to modulate ion channels. Knowledge of these novel pathways may present opportunities for interventions that could abrogate the progression of OA

Development of lower limb range of motion from early childhood to adolescence in cerebral palsy: a population-based study

<p>Abstract</p> <p>Background</p> <p>The decreasing range of joint motion caused by insufficient muscle length is a common problem in children with cerebral palsy (CP), often worsening with age. In 1994 a CP register and health care programme for children with CP was initiated in southern Sweden. The aim of this study was to analyse the development of the passive range of motion (ROM) in the lower limbs during all the growth periods in relation to gross motor function and CP subtype in the total population of children with CP.</p> <p>Methods</p> <p>In total, 359 children with CP born during 1990-1999, living in the southernmost part of Sweden in the year during which they reached their third birthday and still living in the area in the year of their seventh birthday were analysed. The programme includes a continuous standardized follow-up with goniometric measurements of ROM in the lower limbs. The assessments are made by each child's local physiotherapist twice a year until 6 years of age, then once a year. In total, 5075 assessments from the CPUP database from 1994 to 1 January 2007 were analysed.</p> <p>Results</p> <p>The study showed a decreasing mean range of motion over the period 2-14 years of age in all joints or muscles measured. The development of ROM varied according to GMFCS level and CP subtype.</p> <p>Conclusion</p> <p>We found a decreasing ROM in children with CP from 2-14 years of age. This information is important for both the treatment and follow-up planning of the individual child as well as for the planning of health care programmes for all children with CP.</p

Glioblastoma Surgery Imaging-Reporting and Data System: Validation and Performance of the Automated Segmentation Task

For patients with presumed glioblastoma, essential tumor characteristics are determined from preoperative MR images to optimize the treatment strategy. This procedure is time-consuming and subjective, if performed by crude eyeballing or manually. The standardized GSI-RADS aims to provide neurosurgeons with automatic tumor segmentations to extract tumor features rapidly and objectively. In this study, we improved automatic tumor segmentation and compared the agreement with manual raters, describe the technical details of the different components of GSI-RADS, and determined their speed. Two recent neural network architectures were considered for the segmentation task: nnU-Net and AGU-Net. Two preprocessing schemes were introduced to investigate the tradeoff between performance and processing speed. A summarized description of the tumor feature extraction and standardized reporting process is included. The trained architectures for automatic segmentation and the code for computing the standardized report are distributed as open-source and as open-access software. Validation studies were performed on a dataset of 1594 gadolinium-enhanced T1-weighted MRI volumes from 13 hospitals and 293 T1-weighted MRI volumes from the BraTS challenge. The glioblastoma tumor core segmentation reached a Dice score slightly below 90%, a patientwise F1-score close to 99%, and a 95th percentile Hausdorff distance slightly below 4.0 mm on average with either architecture and the heavy preprocessing scheme. A patient MRI volume can be segmented in less than one minute, and a standardized report can be generated in up to five minutes. The proposed GSI-RADS software showed robust performance on a large collection of MRI volumes from various hospitals and generated results within a reasonable runtime

Quantum phase slip phenomenon in ultra-narrow superconducting nanorings

The smaller the system, typically - the higher is the impact of fluctuations. In narrow superconducting wires sufficiently close to the critical temperature Tc thermal fluctuations are responsible for the experimentally observable finite resistance. Quite recently it became possible to fabricate sub-10 nm superconducting structures, where the finite resistivity was reported within the whole range of experimentally obtainable temperatures. The observation has been associated with quantum fluctuations capable to quench zero resistivity in superconducting nanowires even at temperatures T-->0. Here we demonstrate that in tiny superconducting nanorings the same phenomenon is responsible for suppression of another basic attribute of superconductivity - persistent currents - dramatically affecting their magnitude, the period and the shape of the current-phase relation. The effect is of fundamental importance demonstrating the impact of quantum fluctuations on the ground state of a macroscopically coherent system, and should be taken into consideration in various nanoelectronic applications.Comment: 20 pages, 4 figure