2,757 research outputs found
The geometry of the light-cone cell decomposition of moduli space
S.R. is supported by STFC consolidated Grant No. ST/L000415/1 “String Theory, Gauge Theory and Dualit
A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.
The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease
On the Relationship between Convex Bodies Related to Correlation Experiments with Dichotomic Observables
In this paper we explore further the connections between convex bodies
related to quantum correlation experiments with dichotomic variables and
related bodies studied in combinatorial optimization, especially cut polyhedra.
Such a relationship was established in Avis, Imai, Ito and Sasaki (2005 J.
Phys. A: Math. Gen. 38 10971-87) with respect to Bell inequalities. We show
that several well known bodies related to cut polyhedra are equivalent to
bodies such as those defined by Tsirelson (1993 Hadronic J. S. 8 329-45) to
represent hidden deterministic behaviors, quantum behaviors, and no-signalling
behaviors. Among other things, our results allow a unique representation of
these bodies, give a necessary condition for vertices of the no-signalling
polytope, and give a method for bounding the quantum violation of Bell
inequalities by means of a body that contains the set of quantum behaviors.
Optimization over this latter body may be performed efficiently by semidefinite
programming. In the second part of the paper we apply these results to the
study of classical correlation functions. We provide a complete list of tight
inequalities for the two party case with (m,n) dichotomic observables when
m=4,n=4 and when min{m,n}<=3, and give a new general family of correlation
inequalities.Comment: 17 pages, 2 figure
Automated bolus advisor control and usability study (ABACUS): does use of an insulin bolus advisor improve glycaemic control in patients failing multiple daily insulin injection (MDI) therapy? [NCT01460446]
BACKGROUND: People with T1DM and insulin-treated T2DM often do not follow and/or adjust their insulin regimens as needed. Key contributors to treatment non-adherence are fear of hypoglycaemia, difficulty and lack of self-efficacy associated with insulin dose determination. Because manual calculation of insulin boluses is both complex and time consuming, people may rely on empirical estimates, which can result in persistent hypoglycaemia and/or hyperglycaemia. Use of automated bolus advisors (BA) has been shown to help insulin pump users to more accurately meet prandial insulin dosage requirements, improve postprandial glycaemic excursions, and achieve optimal glycaemic control with an increased time within optimal range. Use of a BA containing an early algorithm based on sliding scales for insulin dosing has also been shown to improve HbA1c levels in people treated with multiple daily insulin injections (MDI). We designed a study to determine if use of an automated BA can improve clinical and psychosocial outcomes in people treated with MDI. METHODS/DESIGN: The Automated Bolus Advisor Control and Usability Study (ABACUS) is a 6-month, prospective, randomised, multi-centre, multi-national trial to determine if automated BA use improves glycaemic control as measured by a change in HbA1c in people using MDI with elevated HbA1c levels (#62;7.5%). A total of 226 T1DM and T2DM participants will be recruited. Anticipated attrition of 20% will yield a sample size of 90 participants, which will provide #62;80% power to detect a mean difference of 0.5%, with SD of 0.9%, using a one-sided 5% t-test, with 5% significance level. Other measures of glycaemic control, self-care behaviours and psychosocial issues will also be assessed. DISCUSSION: It is critical that healthcare providers utilise available technologies that both facilitate effective glucose management and address concerns about safety and lifestyle. Automated BAs may help people using MDI to manage their diabetes more effectively and minimise the risk of long-term diabetes related complications. Findings from a recent study suggest that BA use positively addresses both safety and lifestyle concerns; however, randomised trials are needed to confirm these perceptions and determine whether bolus advisor use improves clinical outcomes. Our study is designed to make these assessments. TRIAL REGISTRATION: NCT0146044
Usage of NASA's Near Real-Time Solar and Meteorological Data for Monitoring Building Energy Systems Using RETScreen International's Performance Analysis Module
This paper describes building energy system production and usage monitoring using examples from the new RETScreen Performance Analysis Module, called RETScreen Plus. The module uses daily meteorological (i.e., temperature, humidity, wind and solar, etc.) over a period of time to derive a building system function that is used to monitor building performance. The new module can also be used to target building systems with enhanced technologies. If daily ambient meteorological and solar information are not available, these are obtained over the internet from NASA's near-term data products that provide global meteorological and solar information within 3-6 days of real-time. The accuracy of the NASA data are shown to be excellent for this purpose enabling RETScreen Plus to easily detect changes in the system function and efficiency. This is shown by several examples, one of which is a new building at the NASA Langley Research Center that uses solar panels to provide electrical energy for building energy and excess energy for other uses. The system shows steady performance within the uncertainties of the input data. The other example involves assessing the reduction in energy usage by an apartment building in Sweden before and after an energy efficiency upgrade. In this case, savings up to 16% are shown
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TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling
Thymic stromal lymphopoietin (TSLP) is a four-helix bundle cytokine that plays a critical role in the regulation of immune responses and in the differentiation of hematopoietic cells. TSLP signals through a heterodimeric receptor complex consisting of an interleukin-7 receptor α chain and a unique TSLP receptor (TSLPR) [also known as cytokine receptor-like factor 2 (CRLF2)]. Cellular targets of TSLP include dendritic cells, B cells, mast cells, regulatory T (Treg) cells and CD4+ and CD8+ T cells. The TSLP/TSLPR axis can activate multiple signaling transduction pathways including the JAK/STAT pathway and the PI-3 kinase pathway. Aberrant TSLP/TSLPR signaling has been associated with a variety of human diseases including asthma, atopic dermatitis, nasal polyposis, inflammatory bowel disease, eosinophilic eosophagitis and, most recently, acute lymphoblastic leukemia. A centralized resource of the TSLP signaling pathway cataloging signaling events is not yet available. In this study, we present a literature-annotated resource of reactions in the TSLP signaling pathway. This pathway map is publicly available through NetPath (http://www.netpath.org/), an open access signal transduction pathway resource developed previously by our group. This map includes 236 molecules and 252 reactions that are involved in TSLP/TSLPR signaling pathway. We expect that the TSLP signaling pathway map will provide a rich resource to study the biology of this important cytokine as well as to identify novel therapeutic targets for diseases associated with dysregulated TSLP/TSLPR signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_2
The Identification of the X-ray Counterpart to PSR J2021+4026
We report the probable identification of the X-ray counterpart to the
gamma-ray pulsar PSR J2021+4026 using imaging with the Chandra X-ray
Observatory ACIS and timing analysis with the Fermi satellite. Given the
statistical and systematic errors, the positions determined by both satellites
are coincident. The X-ray source position is R.A. 20h21m30.733s, Decl. +40 deg
26 min 46.04sec (J2000) with an estimated uncertainty of 1.3 arsec combined
statistical and systematic error. Moreover, both the X-ray to gamma-ray and the
X-ray to optical flux ratios are sensible assuming a neutron star origin for
the X-ray flux. The X-ray source has no cataloged infrared-to-visible
counterpart and, through new observations, we set upper limits to its optical
emission of i' >23.0 mag and r' > 25.2mag. The source exhibits an X-ray
spectrum with most likely both a powerlaw and a thermal component. We also
report on the X-ray and visible light properties of the 43 other sources
detected in our Chandra observation.Comment: Accepted for publication in the Astrophysical Journa
Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries
Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials
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