1,679 research outputs found
Managing energy tariffs with agents: a field study of a future smart energy system at home
© 2015 ACM.Interactive autonomous systems are likely to be more involved in future energy systems to assist human users. Given this, we prototyped a future scenario in which householders are assisted in switching electricity tariffs by an agent-based interactive system. The system uses real-time electricity monitoring to instantiate a scenario where participants may have to make, or delegate to their agent (in a variety ways), tariff switching decisions given uncertainty about their own consumption. We carried out a field trial with 12 households for 6 weeks in order to study the notion of autonomy. The results show nuanced ways in which monitoring system performance and taking control is balanced in everyday practice. Our field study provides promising directions for future use of smart systems that help householders manage their energy
Hadronic production of bottom-squark pairs with electroweak contributions
We present the complete computation of the tree-level and the next-to-leading
order electroweak contributions to bottom-squark pair production at the LHC.
The computation is performed within the minimal supersymmetric extension of the
Standard Model. We discuss the numerical impact of these contributions in
several supersymmetric scenarios.Comment: 33 pages, v2: preprint numbers correcte
Phenotypic microarrays suggest Escherichia coli ST131 is not a metabolically distinct lineage of extra-intestinal pathogenic E. coli
Extraintestinal pathogenic E. coli (ExPEC) are the major aetiological agent of urinary tract infections (UTIs) in humans. The emergence of the CTX-M producing clone E. coli ST131 represents a major challenge to public health worldwide. A recent study on the metabolic potential of E. coli isolates demonstrated an association between the E. coli ST131 clone and enhanced utilisation of a panel of metabolic substrates. The studies presented here investigated the metabolic potential of ST131 and other major ExPEC ST isolates using 120 API test reagents and found that ST131 isolates demonstrated a lower metabolic activity for 5 of 120 biochemical tests in comparison to non-ST131 ExPEC isolates. Furthermore, comparative phenotypic microarray analysis showed a lack of specific metabolic profile for ST131 isolates countering the suggestion that these bacteria are metabolically fitter and therefore more successful human pathogens
Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families
The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins
The Effect of Race and Chronic Obstructive Pulmonary Disease on Long-Term Survival after Coronary Artery Bypass Grafting
Background: Chronic obstructive pulmonary disease (COPD) is a known predictor of decreased long-term survival after coronary artery bypass grafting (CABG). Differences in survival by race have not been examined.
Methods: A retrospective cohort study was conducted of CABG patients between 2002 and 2011. Long-term survival was compared in patients with and without COPD and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model.
Results: A total of 984 (20%) patients had COPD (black n = 182; white n = 802) at the time of CABG (N = 4,801). The median follow-up for study participants was 4.4 years. COPD was observed to be a statistically significant predictor of decreased survival independent of race following CABG (no COPD: HR = 1.0; white COPD: adjusted HR = 1.9, 95% CI = 1.7–2.3; black COPD: adjusted HR = 1.6, 95% CI = 1.1–2.2).
Conclusion: Contrary to the expected increased risk of mortality among black COPD patients in the general population, a similar survival disadvantage was not observed in our CABG population
Hadronic production of squark-squark pairs: The electroweak contributions
We compute the electroweak (EW) contributions to squark--squark pair
production processes at the LHC within the framework of the Minimal
Supersymmetric Standard Model (MSSM). Both tree-level EW contributions, of
O(alpha_s alpha + alpha^2), and next-to-leading order (NLO) EW corrections, of
O(alpha_s^2 alpha), are calculated. Depending on the flavor and chirality of
the produced quarks, many interferences between EW-mediated and QCD-mediated
diagrams give non-zero contributions at tree-level and NLO. We discuss the
computational techniques and present an extensive numerical analysis for
inclusive squark--squark production as well as for subsets and single
processes. While the tree-level EW contributions to the integrated cross
sections can reach the 20% level, the NLO EW corrections typically lower the LO
prediction by a few percent.Comment: 36 pages, 18 figure
SUSY parameter determination at the LHC using cross sections and kinematic edges
We study the determination of supersymmetric parameters at the LHC from a
global fit including cross sections and edges of kinematic distributions. For
illustration, we focus on a minimal supergravity scenario and discuss how well
it can be constrained at the LHC operating at 7 and 14 TeV collision energy,
respectively. We find that the inclusion of cross sections greatly improves the
accuracy of the SUSY parameter determination, and allows to reliably extract
model parameters even in the initial phase of LHC data taking with 7 TeV
collision energy and 1/fb integrated luminosity. Moreover, cross section
information may be essential to study more general scenarios, such as those
with non-universal gaugino masses, and distinguish them from minimal,
universal, models.Comment: 22 pages, 8 figure
Identification of cytosolic phosphodiesterases in the erythrocyte: A possible role for PDE5
Background
Within erythrocytes (RBCs), cAMP levels are regulated by phosphodiesterases (PDEs). Increases in cAMP and ATP release associated with activation of β-adrenergic receptors (βARs) and prostacyclin receptors (IPRs) are regulated by PDEs 2, 4 and PDE 3, respectively. Here we establish the presence of cytosolic PDEs in RBCs and determine a role for PDE5 in regulating levels of cGMP.
Material/Methods
Purified cytosolic proteins were obtained from isolated human RBCs and western analysis was performed using antibodies against PDEs 3A, 4 and 5. Rabbit RBCs were incubated with dbcGMP, a cGMP analog, to determine the effect of cGMP on cAMP levels. To determine if cGMP affects receptor-mediated increases in cAMP, rabbit RBCs were incubated with dbcGMP prior to addition of isoproterenol (ISO), a βAR receptor agonist. To demonstrate that endogenous cGMP produces the same effect, rabbit and human RBCs were incubated with SpNONOate (SpNO), a nitric oxide donor, and YC1, a direct activator of soluble guanylyl cyclase (sGC), in the absence and presence of a selective PDE5 inhibitor, zaprinast (ZAP).
Results
Western analysis identified PDEs 3A, 4D and 5A. dbcGMP produced a concentration dependent increase in cAMP and ISO-induced increases in cAMP were potentiated by dbcGMP. In addition, incubation with YC1 and SpNO in the presence of ZAP potentiated βAR-induced increases in cAMP.
Conclusions
PDEs 2, 3A and 5 are present in the cytosol of human RBCs. PDE5 activity in RBCs regulates cGMP levels. Increases in intracellular cGMP augment cAMP levels. These studies suggest a novel role for PDE5 in erythrocytes
Elevated Endogenous Erythropoietin Concentrations Are Associated with Increased Risk of Brain Damage in Extremely Preterm Neonates
Background
We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO) concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI).
Methods
Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO) was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age.
Results
Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55) Mental (OR 2.3; 95% CI 1.5-3.5) and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7) Development Indices (MDI, PDI), and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8). Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3), but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI.
Conclusion
hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly
Structure and mechanism of human DNA polymerase η
The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites
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