Two-nucleon knockout contributions to the 12^{12}C(e,e′p)(e,e'p) reaction in the dip and {Δ\Delta}(1232) regions

The contributions from $^{12}$C$(e,e'pn)$ and $^{12}$C$(e,e'pp)$ to the semi-exclusive $^{12}$C$(e,e'p)$ cross section have been calculated in an unfactorized model for two-nucleon emission. We assume direct two-nucleon knockout after virtual photon coupling with the two-body pion-exchange currents in the target nucleus. Results are presented at several kinematical conditions in the dip and $\Delta$(1232) regions. The calculated two-nucleon knockout strength is observed to account for a large fraction of the measured $(e,e'p)$ strength above the two-nucleon emission threshold.Comment: 12 Revtex pages, 4 postscript figures (available upon request), University of Gent preprint SSF94-02-0

Qualitative grading of aortic regurgitation: a pilot study comparing CMR 4D flow and echocardiography.

Over the past 10 years there has been intense research in the development of volumetric visualization of intracardiac flow by cardiac magnetic resonance (CMR).This volumetric time resolved technique called CMR 4D flow imaging has several advantages over standard CMR. It offers anatomical, functional and flow information in a single free-breathing, ten-minute acquisition. However, the data obtained is large and its processing requires dedicated software. We evaluated a cloud-based application package that combines volumetric data correction and visualization of CMR 4D flow data, and assessed its accuracy for the detection and grading of aortic valve regurgitation using transthoracic echocardiography as reference. Between June 2014 and January 2015, patients planned for clinical CMR were consecutively approached to undergo the supplementary CMR 4D flow acquisition. Fifty four patients(median age 39 years, 32 males) were included. Detection and grading of the aortic valve regurgitation using CMR4D flow imaging were evaluated against transthoracic echocardiography. The agreement between 4D flow CMR and transthoracic echocardiography for grading of aortic valve regurgitation was good (j = 0.73). To identify relevant,more than mild aortic valve regurgitation, CMR 4D flow imaging had a sensitivity of 100 % and specificity of 98 %. Aortic regurgitation can be well visualized, in a similar manner as transthoracic echocardiography, when using CMR 4D flow imaging

Adaptations in mitochondrial function parallel, but fail to rescue, the transition to severe hyperglycemia and hyperinsulinemia: a study in Zucker diabetic fatty rats.

Cross-sectional human studies have associated mitochondrial dysfunction to type 2 diabetes. We chose Zucker diabetic fatty (ZDF) rats as a model of progressive insulin resistance to examine whether intrinsic mitochondrial defects are required for development of type 2 diabetes. Muscle mitochondrial function was examined in 6-, 12-, and 19-week-old ZDF (fa/fa) and fa/+ control rats (n = 8-10 per group) using respirometry with pyruvate, glutamate, and palmitoyl-CoA as substrates. Six-week-old normoglycemic-hyperinsulinemic fa/fa rats had reduced mitochondrial fat oxidative capacity. Adenosine diphosphate (ADP)-driven state 3 and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)-stimulated state uncoupled (state u) respiration on palmitoyl-CoA were lower compared to controls (62.3 ± 9.5 vs. 119.1 ± 13.8 and 87.8 ± 13.3 vs. 141.9 ± 14.3 nmol O2/mg/min.). Pyruvate oxidation in 6-week-old fa/fa rats was similar to controls. Remarkably, reduced fat oxidative capacity in 6-week-old fa/fa rats was compensated for by an adaptive increase in intrinsic mitochondrial function at week 12, which could not be maintained toward week 19 (140.9 ± 11.2 and 57.7 ± 9.8 nmol O2/mg/min, weeks 12 and 19, respectively), whereas hyperglycemia had developed (13.5 ± 0.6 and 16.1 ± 0.3 mmol/l, weeks 12 and 19, respectively). This mitochondrial adaptation failed to rescue the progressive development of insulin resistance in fa/fa rats. The transition of prediabetes state toward advanced hyperglycemia and hyperinsulinemia was accompanied by a blunted increase in uncoupling protein-3 (UCP3). Thus, in ZDF rats insulin resistance develops progressively in the absence of mitochondrial dysfunction. In fact, improved mitochondrial capacity in hyperinsulinemic hyperglycemic rats does not rescue the progression toward advanced stages of insulin resistance

DGAT1 overexpression in muscle by in vivo DNA electroporation increases intramyocellular lipid content.

In adipose tissue, the microsomal enzyme 1,2-acyl CoA:diacylglyceroltransferase-1 (DGAT1) plays an important role in triglyceride storage. Because DGAT1 is expressed in skeletal muscle as well, we aimed to directly test the effect of DGAT1 on muscular triglyceride storage by overexpressing DGAT1 using in vivo DNA electroporation. A pcDNA3.1-DGAT1 construct in saline was injected in the left tibialis anterior muscle of rats, followed by the application of eight transcutaneous pulses, using the contralateral leg as sham-electroporated control. Electroporation of the DGAT1 construct led to significant overexpression of the DGAT1 protein. The functionality of DGAT1 overexpression is underscored by the pronounced diet-responsive increase in intramyocellular lipid (IMCL) storage. In chow-fed rats, DGAT1-positive myocytes showed significantly higher IMCL content compared with the control leg, which was almost devoid of IMCL (1.99 +/- 1.13% vs. 0.017 +/- 0.014% of total area fraction; P <0.05). High-fat feeding increased IMCL levels in both DGAT1-positive and control myocytes, resulting in very high IMCL levels in DGAT1-overexpressing myocytes (4.96 +/- 1.47% vs. 0.80 +/- 0.14%; P <0.05). Our findings indicate that DGAT1 contributes to the storage of IMCL and that in vivo DNA electroporation is a promising tool to examine the functional consequences of altered gene expression in mature skeletal muscle

Crystal Graphs and qq-Analogues of Weight Multiplicities for the Root System AnA_n

We give an expression of the $q$-analogues of the multiplicities of weights in irreducible \sl_{n+1}-modules in terms of the geometry of the crystal graph attached to the corresponding U_q(\sl_{n+1})-modules. As an application, we describe multivariate polynomial analogues of the multiplicities of the zero weight, refining Kostant's generalized exponents.Comment: LaTeX file with epic, eepic pictures, 17 pages, November 1994, to appear in Lett. Math. Phy

Non-polynomial Worst-Case Analysis of Recursive Programs

We study the problem of developing efficient approaches for proving worst-case bounds of non-deterministic recursive programs. Ranking functions are sound and complete for proving termination and worst-case bounds of nonrecursive programs. First, we apply ranking functions to recursion, resulting in measure functions. We show that measure functions provide a sound and complete approach to prove worst-case bounds of non-deterministic recursive programs. Our second contribution is the synthesis of measure functions in nonpolynomial forms. We show that non-polynomial measure functions with logarithm and exponentiation can be synthesized through abstraction of logarithmic or exponentiation terms, Farkas' Lemma, and Handelman's Theorem using linear programming. While previous methods obtain worst-case polynomial bounds, our approach can synthesize bounds of the form $\mathcal{O}(n\log n)$ as well as $\mathcal{O}(n^r)$ where $r$ is not an integer. We present experimental results to demonstrate that our approach can obtain efficiently worst-case bounds of classical recursive algorithms such as (i) Merge-Sort, the divide-and-conquer algorithm for the Closest-Pair problem, where we obtain $\mathcal{O}(n \log n)$ worst-case bound, and (ii) Karatsuba's algorithm for polynomial multiplication and Strassen's algorithm for matrix multiplication, where we obtain $\mathcal{O}(n^r)$ bound such that $r$ is not an integer and close to the best-known bounds for the respective algorithms.Comment: 54 Pages, Full Version to CAV 201

Reduced incorporation of Fatty acids into triacylglycerol in myotubes from obese individuals with type 2 diabetes.

Altered skeletal muscle lipid metabolism is a hallmark feature of type 2 (T2D). Here we investigated muscle lipid turnover in T2D versus BMI- controls and examined if putative in vivo differences would be preserved myotubes.Male obese T2D individuals (T2D) (n=6) and their BMI-matched (C) (n=6) underwent a hyperinsulinemic-euglycemic clamp, VO2max test, underwater weighing and muscle biopsy of v. lateralis. 14C-palmitate and 14C-oleate oxidation rates and incorporation into lipids were measured tissue, as well as in primary myotubes.Palmitate oxidation (C: 0.99 +/- T2D: 0.53 +/- 0.07nmol/mg protein; P=0.03) and incorporation of fatty into triacylglycerol (TAG) (C: 0.45 +/- 0.13, T2D: 0.11 +/- 0.02nmol/mg P=0.047) were significantly reduced in muscle homogenates of T2D. These reductions were not retained for palmitate oxidation in primary myotubes (P=0.38); however, incorporation of FAs into TAG was lower in T2D oleate and P=0.11 for palmitate), with a strong correlation of TAG between muscle tissue and primary myotubes (r=0.848, P=0.008).Our data that the ability to incorporate FAs into TAG is an intrinsic feature of muscle cells that is reduced in individuals with T2D

Augmenting muscle diacylglycerol and triacylglycerol content by blocking fatty acid oxidation does not impede insulin sensitivity

A low fat oxidative capacity has been linked to muscle diacylglycerol (DAG) accumulation and insulin resistance. Alternatively, a low fat oxidation rate may stimulate glucose oxidation, thereby enhancing glucose disposal. Here, we investigated whether an ethyl-2-[6-(4-chlorophenoxy)hexyl]-oxirane-2-carboxylate (etomoxir)-induced inhibition of fat oxidation leads to muscle fat storage and insulin resistance. An intervention in healthy male subjects was combined with studies in human primary myotubes. Furthermore, muscle DAG and triacylglycerol (TAG), mitochondrial function, and insulin signaling were examined in etomoxir-treated C57bl6 mice. In humans, etomoxir administration increased glucose oxidation at the expense of fat oxidation. This effect was accompanied by an increased abundance of GLUT4 at the sarcolemma and a lowering of plasma glucose levels, indicative of improved glucose homeostasis. In mice, etomoxir injections resulted in accumulation of muscle TAG and DAG, yet improved insulin-stimulated GLUT4 translocation. Also in human myotubes, insulin signaling was improved by etomoxir, in the presence of increased intramyocellular lipid accumulation. These insulin-sensitizing effects in mice and human myotubes were accompanied by increased phosphorylation of AMP-activated protein kinase (AMPK). Our results show that a reduction in fat oxidation leading to accumulation of muscle DAG does not necessarily lead to insulin resistance, as the reduction in fat oxidation may activate AMPK

Efficacy and Safety of High Potent P2Y12 Inhibitors Prasugrel and Ticagrelor in Patients With Coronary Heart Disease Treated With Dual Antiplatelet Therapy: A Sex-Specific Systematic Review and Meta-Analysis

Background Sex differences in efficacy and safety of dual antiplatelet therapy remain uncertain because of the underrepresentation of women in cardiovascular trials. The aim of this study was to perform a sex-specific analysis of the pooled efficacy and safety data of clinical trials comparing a high potent P2Y12 inhibitor+aspirin with clopidogrel+aspirin in patients with acute coronary syndrome. Methods and Results A systematic literature search was performed. Randomized clinical trials that compared patients following percutaneous coronary intervention/acute coronary syndrome who were taking high potent P2Y12 inhibitors+aspirin versus clopidogrel+aspirin were selected. Random effects estimates were calculated and relative risks with 95% CIs on efficacy and safety end points were determined per sex. We included 6 randomized clinical trials comparing prasugrel/ticagrelor versus clopidogrel in 43 990 patients (13 030 women), with a median follow-up time of 1.06 years. Women and men had similar relative risk (RR) reduction for major cardiovascular events (women: RR, 0.89 [95% CI, 0.80-1.00; men: RR, 0.84 [95% CI, 0.79-0.91) (P for interaction=0.39). Regarding safety, women and men had similar risk of major bleeding by high-potency dual antip

Exercise-induced modulation of cardiac lipid content in healthy lean young men

Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m2) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance spectroscopy (1H-MRS) at baseline, directly after exercise and again 4 h post-exercise, together with systolic function (by multi-slice cine-MRI) and cardiac energy status (by 31P-MRS). Plasma FA concentrations were increased threefold during exercise and ninefold during recovery in the fasted state compared with the glucose-fed state (p < 0.01). Cardiac lipid content was elevated at the end of the fasted test day (from 0.26 ± 0.04 to 0.44 ± 0.04%, p = 0.003), while it did not change with glucose supplementation (from 0.32 ± 0.03 to 0.26 ± 0.05%, p = 0.272). Furthermore, PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4 h post-exercise was higher compared with the low FA state (63 ± 2 vs. 59 ± 2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the fasted state, lead to increased cardiac lipid content, but do not acutely hamper systolic function. Although the lower cardiac energy status is in line with a lipotoxic action of cardiac lipid content, a causal relationship cannot be proven