Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Objective: To study the association of vaspin with glucose metabolism. Design: Cross-sectional and intervention study. Subjects and methods: The association of serum vaspin with metabolic and anthropometric characteristics was investigated in 108 volunteers. Euglycemic–hyperinsulinemic clamps (EHC) were performed in 83 of the participants. Changes of circulating vaspin levels were additionally studied in a crossover study using 300 min EHC with lipid versus saline infusion (n=10). Results: Neither glucose tolerance status nor insulin sensitivity, both as measured using EHCs and using homeostasis model assessment for insulin resistance (HOMA-IR), was significantly associated with serum vaspin in the cross-sectional study. Furthermore, there was no effect of short-term lipid-induced insulin resistance due to a 300 min intravenous lipid challenge on circulating vaspin. However, circulating vaspin levels were significantly elevated in women using oral contraceptives (OC), both compared to women without OC intake (1.17±0.26 vs 0.52±0.09 ng/ml, P=0.02) and males (1.17±0.26 vs 0.29±0.04 ng/ml, P=0.01). After exclusion of OC using females and stratification according to body mass index (BMI), a significant sexual dimorphism in subjects with a BMI <25 kg/m2 was observed (males 0.21±0.04 ng/ml versus females 0.70±0.16 ng/ml, P=0.009). Conclusion: Our results support the existence of a sexual dimorphism regarding circulating vaspin. The lack of an association of serum vaspin with HOMA-IR and M value indicates, however, no major role for vaspin concerning insulin sensitivity in nondiabetic humans

The Impact of Universal Extra Dimensions on the Unitarity Triangle and Rare K and B Decays

We calculate the contributions of the Kaluza-Klein (KK) modes to the K_L-K_S mass difference \Delta M_K, the parameter \epsilon_K, the B^0_{d,s}-\bar B^0_{d,s} mixing mass differences \Delta M_{d,s} and rare decays K^+\to \pi^+\nu\bar\nu, K_L\to \pi^0\nu\bar\nu, K_L\to\mu\bar\mu, B\to X_{s,d}\nu\bar\nu and B_{s,d}\to\mu\bar\mu in the Appelquist, Cheng and Dobrescu (ACD) model with one universal extra dimension. For the compactification scale 1/R= 200 GeV the KK effects in these processes are governed by a 17% enhancement of the \Delta F=2 box diagram function S(x_t,1/R) and by a 37% enhancement of the Z^0 penguin diagram function C(x_t/1/R) relative to their Standard Model (SM) values. This implies the suppressions of \vtd by 8%, of \bar\eta by 11% and of the angle \gamma in the unitarity triangle by 10^\circ. \Delta M_s is increased by 17%. \Delta M_K is essentially uneffected. All branching ratios considered in this paper are increased with a hierarchical structure of enhancements: K^+\to \pi^+\nu\bar\nu (16%), K_L\to \pi^0\nu\bar\nu (17%), B\to X_{d}\nu\bar\nu (22%), (K_L\to\mu\bar\mu)_{\rm SD} (38%), B\to X_{s}\nu\bar\nu (44%), B_{d}\to\mu\bar\mu (46%) and B_{s}\to\mu\bar\mu (72%). For 1/R= 250 (300) GeV all these effects are decreased roughly by a factor of 1.5 (2.0). We emphasize that the GIM mechanism assures the convergence of the sum over the KK modes in the case of Z^0 penguin diagrams and we give the relevant Feynman rules for the five dimensional ACD model. We also emphasize that a consistent calculation of branching ratios has to take into account the modifications in the values of the CKM parameters

Neural-symbolic computing: An effective methodology for principled integration of machine learning and reasoning

Current advances in Artificial Intelligence and machine learning in general, and deep learning in particular have reached unprecedented impact not only across research communities, but also over popular media channels. However, concerns about interpretability and accountability of AI have been raised by influential thinkers. In spite of the recent impact of AI, several works have identified the need for principled knowledge representation and reasoning mechanisms integrated with deep learning-based systems to provide sound and explainable models for such systems. Neural-symbolic computing aims at integrating, as foreseen by Valiant, two most fundamental cognitive abilities: the ability to learn from the environment, and the ability to reason from what has been learned. Neural-symbolic computing has been an active topic of research for many years, reconciling the advantages of robust learning in neural networks and reasoning and interpretability of symbolic representation. In this paper, we survey recent accomplishments of neural-symbolic computing as a principled methodology for integrated machine learning and reasoning. We illustrate the effectiveness of the approach by outlining the main characteristics of the methodology: principled integration of neural learning with symbolic knowledge representation and reasoning allowing for the construction of explainable AI systems. The insights provided by neural-symbolic computing shed new light on the increasingly prominent need for interpretable and accountable AI systems

Global assessment of nitrogen deposition effects on terrestrial plant diversity : a synthesis

Atmospheric nitrogen (N) deposition is it recognized threat to plant diversity ill temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems. from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such its direct toxicity of nitrogen gases and aerosols long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem, and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase. in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition. and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America. especially for the more sensitive ecosystem types. including several ecosystems of high conservation importance. The results of this assessment Show that the Vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and Southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe). and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted Studies are required in low background areas, especially in the G200 ecoregions

Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21

OBJECTIVE—Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator–activator receptor (PPAR) –dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPAR, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS—The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPAR activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS—Oleate and linoleate increased FGF-21 expression and secretion in a PPAR-dependent fashion, as demonstrated by small-interfering RNA–induced PPAR knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS—The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity

The Discovery Potential of a Super B Factory

The Proceedings of the 2003 SLAC Workshops on flavor physics with a high luminosity asymmetric e+e- collider. The sensitivity of flavor physics to physics beyond the Standard Model is addressed in detail, in the context of the improvement of experimental measurements and theoretical calculations.Comment: 476 pages. Printed copies may be obtained by request to [email protected] . arXiv admin note: v2 appears to be identical to v

An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study

Background: Epigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub- Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of adiposity among Ghanaians aiming to identify DNA methylation loci that are significantly associated. Methods: The Illumina 450k DNA methylation array was used to profile DNA methylation in whole blood samples of 547 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. Differentially methylated positions (DMPs) and differentially methylation regions (DMRs) were identified for BMI and obesity (BMI ≥ 30 kg/m2), as well as for waist circumference (WC) and abdominal obesity (WC ≥ 102 cm in men, ≥88 cm in women). All analyses were adjusted for age, sex, blood cell distribution estimates, technical covariates, recruitment site and population stratification. We also did a replication study of previously reported EWAS loci for anthropometric indices in other populations. Results: We identified 18 DMPs for BMI and 23 for WC. For obesity and abdominal obesity, we identified three and one DMP, respectively. Fourteen DMPs overlapped between BMI and WC. DMP cg00574958 annotated to gene CPT1A was the only DMP associated with all outcomes analysed, attributing to 6.1 and 5.6% of variance in obesity and abdominal obesity, respectively. DMP cg07839457 (NLRC5) and cg20399616 (BCAT1) were significantly associated with BMI, obesity and with WC and had not been reported by previous EWAS on adiposity. Conclusions: This first EWAS for adiposity in Africans identified three epigenome-wide significant loci (CPT1A, NLRC5 and BCAT1) for both general adiposity and abdominal adiposity. The findings are a first step in understanding the role of DNA methylation in adiposity among sub-Saharan Africans. Studies on other sub-Saharan African populations as well as translational studies are needed to determine the role of these DNA methylation variants in the high burden of adiposity among sub- Saharan Africans