Eta and Etaprime Photoproduction on the Nucleon with the Isobar Model EtaMAID2018

The isobar model EtaMAID has been updated with new and high precision data for eta and etaprime photoproduction on protons and neutrons from MAMI, ELSA, GRAAL and CLAS. The background is described in a recently developed Regge-cut model, and for the resonance part the whole list of nucleon resonances has been investigated with 21 N* states contributing to eta photoproduction and 12 N* states contributing to etaprime photoproduction. A new approach is discussed to avoid double counting in the overlap region of Regge and resonances. A comparison is done among four newly updated partial waves analyses for observables and partial waves. Finally, the possibility of a narrow resonance near W=1900 MeV is discussed, that would be able to explain unexpected energy and angular dependence of observables in p(gamma,etaprime)p near etaprime threshold.Comment: 31 pages, 29 figures, replaced with revised versio

Life Expectancy After Surgical Aortic Valve Replacement.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Surgical risk, age, perceived life expectancy, and valve durability influence the choice between surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation. The contemporaneous life expectancy after SAVR, in relation to surgical risk and age, is unknown. Objectives: The purpose of this study was to determine median survival time in relation to surgical risk and chronological age in SAVR patients. Methods: Patients ≥60 years with aortic stenosis who underwent isolated SAVR with a bioprosthesis (n = 8,353) were risk-stratified before surgery into low, intermediate, or high surgical risk using the logistic EuroSCORE (2001-2011) or EuroSCORE II (2012-2017) and divided into age groups. Median survival time and cumulative 5-year mortality were estimated with Kaplan-Meier curves. Cox regression analysis was used to further determine the importance of age. Results: There were 7,123 (85.1%) low-risk patients, 942 (11.3%) intermediate-risk patients, and 288 (3.5%) high-risk patients. Median survival time was 10.9 years (95% confidence interval: 10.6-11.2 years) in low-risk, 7.3 years (7.0-7.9 years) in intermediate-risk, and 5.8 years (5.4-6.5 years) in high-risk patients. The 5-year cumulative mortality was 16.5% (15.5%-17.4%), 30.7% (27.5%-33.7%), and 43.0% (36.8%-48.7%), respectively. In low-risk patients, median survival time ranged from 16.2 years in patients aged 60 to 64 years to 6.1 years in patients aged ≥85 years. Age was associated with 5-year mortality only in low-risk patients (interaction P < 0.001). Conclusions: Eighty-five percent of SAVR patients receiving bioprostheses have low surgical risk. Estimated survival is substantial following SAVR, especially in younger, low-risk patients, which should be considered in Heart Team discussions. Keywords: aortic stenosis; aortic valve replacement; epidemiology; valvular heart disease.Swedish Heart-Lung Foundation Swedish government Swedish county councils concerning economic support of research and education of doctors (ALF agreement) ALFGBG-725131 Vastra Gotaland Region Family Nils Winberg's Foundatio

The Distinct Conformational Dynamics of K-Ras and H-Ras A59G

Ras proteins regulate signaling cascades crucial for cell proliferation and differentiation by switching between GTP- and GDP-bound conformations. Distinct Ras isoforms have unique physiological functions with individual isoforms associated with different cancers and developmental diseases. Given the small structural differences among isoforms and mutants, it is currently unclear how these functional differences and aberrant properties arise. Here we investigate whether the subtle differences among isoforms and mutants are associated with detectable dynamical differences. Extensive molecular dynamics simulations reveal that wild-type K-Ras and mutant H-Ras A59G are intrinsically more dynamic than wild-type H-Ras. The crucial switch 1 and switch 2 regions along with loop 3, helix 3, and loop 7 contribute to this enhanced flexibility. Removing the gamma-phosphate of the bound GTP from the structure of A59G led to a spontaneous GTP-to-GDP conformational transition in a 20-ns unbiased simulation. The switch 1 and 2 regions exhibit enhanced flexibility and correlated motion when compared to non-transitioning wild-type H-Ras over a similar timeframe. Correlated motions between loop 3 and helix 5 of wild-type H-Ras are absent in the mutant A59G reflecting the enhanced dynamics of the loop 3 region. Taken together with earlier findings, these results suggest the existence of a lower energetic barrier between GTP and GDP states of the mutant. Molecular dynamics simulations combined with principal component analysis of available Ras crystallographic structures can be used to discriminate ligand- and sequence-based dynamic perturbations with potential functional implications. Furthermore, the identification of specific conformations associated with distinct Ras isoforms and mutants provides useful information for efforts that attempt to selectively interfere with the aberrant functions of these species

Both the C-Terminal Polylysine Region and the Farnesylation of K-RasB Are Important for Its Specific Interaction with Calmodulin

Background: Ras protein, as one of intracellular signal switches, plays various roles in several cell activities such as differentiation and proliferation. There is considerable evidence showing that calmodulin (CaM) binds to K-RasB and dissociates K-RasB from membrane and that the inactivation of CaM is able to induce K-RasB activation. However, the mechanism for the interaction of CaM with K-RasB is not well understood. Methodology/Principal Findings: Here, by applying fluorescence spectroscopy and isothermal titration calorimetry, we have obtained thermodynamic parameters for the interaction between these two proteins and identified the important elements of K-RasB for its interaction with Ca 2+ /CaM. One K-RasB molecule interacts with one CaM molecule in a GTP dependent manner with moderate, micromolar affinity at physiological pH and physiologic ionic strength. Mutation in the polybasic domain of K-Ras decreases the binding affinity. By using a chimera in which the C-terminal polylysine region of K-RasB has been replaced with that of H-Ras and vice versa, we find that at physiological pH, H-Ras-(KKKKKK) and Ca 2+ /CaM formed a 1:1 complex with an equilibrium association constant around 10 5 M 21, whereas no binding reaction of K-RasB-(DESGPC) with Ca 2+ /CaM is detected. Furthermore, the interaction of K-RasB with Ca 2+ /CaM is found to be enhanced by the farnesylation of K-RasB. Conclusions/Significance: We demonstrate that the polylysine region of K-RasB not only contributes importantly to th

Cell Death or Survival Promoted by Alternative Isoforms of ErbB4

The report demonstrates that two distinct isoforms of the ErbB4 receptor tyrosine kinase stimulate either proliferation or apoptosis by mechanisms involving differential transcriptional regulation of the PDGFRA gene. These data have implications for developing approaches to target ErbB4 signaling in cancer

An exploration of the determinants for decision to migrate existing resources to cloud computing using an integrated TOE-DOI model

Migrating existing resources to cloud computing is a strategic organisational decision that can be difficult. It requires the consideration and evaluation of a wide range of technical and organisational aspects. Although a significant amount of attention has been paid by many industrialists and academics to aid migration decisions, the procedure remains difficult. This is mainly due to underestimation of the range of factors and characteristics affecting the decision for cloud migration. Further research is needed to investigate the level of effect these factors have on migration decisions and the overall complexity. This paper aims to explore the level of complexity of the decision to migrate the cloud. A research model based on the diffusion of innovation (DOI) theory and the technology-organization-environment (TOE) framework was developed. The model was tested using exploratory and confirmatory factor analysis. The quantitative analysis shows the level of impact of the identified variables on the decision to migrate. Seven determinants that contribute to the complexity of the decisions are identified. They need to be taken into account to ensure successful migration. This result has expanded the collective knowledge about the complexity of the issues that have to be considered when making decisions to migrate to the cloud. It contributes to the literature that addresses the complex and multidimensional nature of migrating to the cloud

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p <0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe