164 research outputs found
Phase locking and flux-flow resonances in Josephson oscillators driven by homogeneous microwave fields
We investigate both analytically and numerically phase locking and flux-flow resonances of long Josephson junctions in the presence of homogeneous microwave fields. We use a power balance analysis and a perturbation expansion around the uniform rotating solution to derive analytical expressions for IV curves. The dependence of the flux-flow step on the amplitude of the rf field and the appearance of satellite steps are explained. As a result we show that satellite steps around the main flux-flow resonance are spaced by both odd and even harmonics of the rf frequency. An analytical expression for the locking range in current of the phase-lock steps is also derived. These results are found to be in good agreement with numerical results
Tyrosine Phosphorylation of Rac1: A Role in Regulation of Cell Spreading
Rac1 influences a multiplicity of vital cellular- and tissue-level control functions, making it an important candidate for targeted therapeutics. The activity of the Rho family member Cdc42 has been shown to be modulated by tyrosine phosphorylation at position 64. We therefore investigated consequences of the point mutations Y64F and Y64D in Rac1. Both mutations altered cell spreading from baseline in the settings of wild type, constitutively active, or dominant negative Rac1 expression, and were accompanied by differences in Rac1 targeting to focal adhesions. Rac1-Y64F displayed increased GTP-binding, increased association with ÎČPIX, and reduced binding with RhoGDI as compared with wild type Rac1. Rac1-Y64D had less binding to PAK than Rac1-WT or Rac1-64F. In vitro assays demonstrated that Y64 in Rac1 is a target for FAK and Src. Taken together, these data suggest a mechanism for the regulation of Rac1 activity by non-receptor tyrosine kinases, with consequences for membrane extension
Caenorhabditis elegans BAH-1 Is a DUF23 Protein Expressed in Seam Cells and Required for Microbial Biofilm Binding to the Cuticle
The cuticle of Caenorhabditis elegans, a complex, multi-layered extracellular matrix, is a major interface between the animal and its environment. Biofilms produced by the bacterial genus Yersinia attach to the cuticle of the worm, providing an assay for surface characteristics. A C. elegans gene required for biofilm attachment, bah-1, encodes a protein containing the domain of unknown function DUF23. The DUF23 domain is found in 61 predicted proteins in C. elegans, which can be divided into three distinct phylogenetic clades. bah-1 is expressed in seam cells, which are among the hypodermal cells that synthesize the cuticle, and is regulated by a TGF-ÎČ signaling pathway
Maternal High Fat Diet Is Associated with Decreased Plasma nâ3 Fatty Acids and Fetal Hepatic Apoptosis in Nonhuman Primates
To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6â¶n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6â¶n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate
Angular distributions in the decay B -> K*l(+)l(-)
We use a sample of 384 million BBbar events collected with the Babar detector at the PEP-II e+e- collider to study angular distributions in the rare decays B -> K* l+l-, where l+l- is either e+e- or mu+mu-. For low dilepton invariant masses, m(l+l-)3.2$ GeV/c^2, we measure AFB=0.76 (+0.52,-0.32) +/- 0.07 FL=0.71 (+0.20,-0.22) +/- 0.04.We are grateful for the excellent luminosity and machine
conditions provided by our PEP-II colleagues, and
for the substantial dedicated effort from the computing
organizations that support BABAR. The collaborating
institutions wish to thank SLAC for its support and
kind hospitality. This work is supported by DOE and
NSF (USA), NSERC (Canada), CEA and CNRS-IN2P3
(France), BMBF and DFG (Germany), INFN (Italy),
FOM (The Netherlands), NFR (Norway), MES (Russia),
MEC (Spain), and STFC (United Kingdom). Individuals
have received support from the Marie Curie EIF (European
Union) and the A. P. Sloan Foundation.Peer reviewe
Observation of B0âÏc0K*0 and evidence for B+âÏc0K*+
We present the observation of the decay B 0 â Ï c 0 K * 0 as well as evidence of B + â Ï c 0 K * + , with an 8.9 and a 3.6 standard deviation significance, respectively, using a data sample of 454 Ă 10 6 ΄ ( 4 S ) â B ÂŻÂŻÂŻ B decays collected with the BABAR detector at the PEP-II B meson factory located at the Stanford Linear Accelerator Center (SLAC). The measured branching fractions are B ( B 0 â Ï c 0 K * 0 ) = ( 1.7 ± 0.3 ± 0.2 ) Ă 10 â 4 and B ( B + â Ï c 0 K * + ) = ( 1.4 ± 0.5 ± 0.2 ) Ă 10 â 4 , where the first quoted errors are statistical and the second are systematic. We obtain a branching fraction upper limit of B ( B + â Ï c 0 K * + ) < 2.1 Ă 10 â 4 at the 90% confidence level
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
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