Neuropeptide Y polymorphism significantly magnifies diabetes and cardiovascular disease risk in obesity: the Hoorn Study

0.001) in the obese but not in the nonobese subjects. The results indicate that obesity may be a pivotal factor in multiplying the disease risk associated with the Leu7Pro polymorphism in preproNP

Deficiency of the TLR4 analogue RP105 aggravates vein graft disease by inducing a pro-inflammatory response.

Venous grafts are often used to bypass occlusive atherosclerotic lesions; however, poor patency leads to vein graft disease. Deficiency of TLR4, an inflammatory regulator, reduces vein graft disease. Here, we investigate the effects of the accessory molecule and TLR4 analogue RadioProtective 105 (RP105) on vein graft disease. RP105 deficiency resulted in a 90% increase in vein graft lesion area compared to controls. In a hypercholesterolemic setting (LDLr(-/-)/RP105(-/-) versus LDLr(-/-) mice), which is of importance as vein graft disease is usually characterized by excessive atherosclerosis, total lesion area was not affected. However we did observe an increased number of unstable lesions and intraplaque hemorrhage upon RP105 deficiency. In both setups, lesional macrophage content, and lesional CCL2 was increased. In vitro, RP105(-/-) smooth muscle cells and mast cells secreted higher levels of CCL2. In conclusion, aggravated vein graft disease caused by RP105 deficiency results from an increased local inflammatory response

Extended quantum conditional entropy and quantum uncertainty inequalities

Quantum states can be subjected to classical measurements, whose incompatibility, or uncertainty, can be quantified by a comparison of certain entropies. There is a long history of such entropy inequalities between position and momentum. Recently these inequalities have been generalized to the tensor product of several Hilbert spaces and we show here how their derivations can be shortened to a few lines and how they can be generalized. All the recently derived uncertainty relations utilize the strong subadditivity (SSA) theorem; our contribution relies on directly utilizing the proof technique of the original derivation of SSA.Comment: 4 page

Josephson-phase qubit without tunneling

We show that a complete set of one-bit gates can be realized by coupling the two logical states of a phase qubit to a third level (at higher energy) using microwave pulses. Thus, one can achieve coherent control without invoking any tunneling between the qubit levels. We propose two implementations, using rf-SQUIDs and d-wave Josephson junctions.Comment: REVTeX4, 4pp., 6 EPS figure files; N.B.: "Alec" is my first, and "Maassen van den Brink" my family name. v2: gate universality fleshed out, small fix in d-wave decoherence para, discussion expanded, two Refs. added. v3: some more Refs., a molecular example, and a few minor fixes; final, to appear in PRB Rapid

Low-frequency measurement of the tunneling amplitude in a flux qubit

We have observed signatures of resonant tunneling in an Al three-junction qubit, inductively coupled to a Nb LC tank circuit. The resonant properties of the tank oscillator are sensitive to the effective susceptibility (or inductance) of the qubit, which changes drastically as its flux states pass through degeneracy. The tunneling amplitude is estimated from the data. We find good agreement with the theoretical predictions in the regime of their validity.Comment: REVTeX4, 3pp., 3 EPS figures. v2: new sample, textual clarifications. v3: minor polishing; final, to appear in PRB Rapid

Genetic factors and insulin secretion: gene variants in the IGF genes

IGFs are important regulators of pancreatic beta-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes-related parameters were not significantly different for both the IGF-I and IGF-II gene variant. We conclude that gene variants in the IGF-I and IGF-II genes are not associated with detectable variations in glucose-stimulated insulin secretion in these three independent populations. Further studies are needed to examine the exact contributions of the IGF-I CA repeat alleles to variations in ISI and DI

European Headache Federation recommendations for placebo and nocebo terminology

Background and aim Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. Methods The working group identified relevant questions and agreed upon recommendations. Because no data were required to ans

Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene

Previously, we have shown that a mutation in the mitochondrial DNA-encoded tRNA(Leu(UUR)) gene is associated with type 2 diabetes. One of the consequences of this mutation is a reduced aminoacylation of tRNA(Leu(UUR)). In this study, we have examined whether variants in the leucyl tRNA synthetase gene (LARS2), involved in aminoacylation of tRNA(Leu(UUR)), associate with type 2 diabetes. Direct sequencing of LARS2 cDNA from 25 type 2 diabetic subjects revealed eight single nucleotide polymorphisms. Two of the variants were examined in 7,836 subjects from four independent populations in the Netherlands and Denmark. A -109 g/a variant was not associated with type 2 diabetes. Allele frequencies for the other variant, H324Q, were 3.5% in type 2 diabetic and 2.7% in control subjects, respectively. The common odds ratio across all four studies was 1.40 (95% CI 1.12-1.76), P = 0.004. There were no significant differences in clinical variables between carriers and noncarriers. In this study, we provide evidence that the LARS2 gene may represent a novel type 2 diabetes susceptibility gene. The mechanism by which the H324Q variant enhances type 2 diabetes risk needs to be further established. This is the first report of association between an aminoacyl tRNA synthetase gene and disease. Our results further highlight the important role of mitochondria in glucose homeostasis

Quasinormal modes of Schwarzschild black holes in four and higher dimensions

We make a thorough investigation of the asymptotic quasinormal modes of the four and five-dimensional Schwarzschild black hole for scalar, electromagnetic and gravitational perturbations. Our numerical results give full support to all the analytical predictions by Motl and Neitzke, for the leading term. We also compute the first order corrections analytically, by extending to higher dimensions, previous work of Musiri and Siopsis, and find excellent agreement with the numerical results. For generic spacetime dimension number D the first-order corrections go as $\frac{1}{n^{(D-3)/(D-2)}}$. This means that there is a more rapid convergence to the asymptotic value for the five dimensional case than for the four dimensional case, as we also show numerically.Comment: 12 pages, 5 figures, RevTeX4. v2. Typos corrected, references adde