Assessment of existing Sierra/Fuego capabilities related to grid-to-rod-fretting (GTRF).

The following report presents an assessment of existing capabilities in Sierra/Fuego applied to modeling several aspects of grid-to-rod-fretting (GTRF) including: fluid dynamics, heat transfer, and fluid-structure interaction. We compare the results of a number of Fuego simulations with relevant sources in the literature to evaluate the accuracy, efficiency, and robustness of using Fuego to model the aforementioned aspects. Comparisons between flow domains that include the full fuel rod length vs. a subsection of the domain near the spacer show that tremendous efficiency gains can be obtained by truncating the domain without loss of accuracy. Thermal analysis reveals the extent to which heat transfer from the fuel rods to the coolant is improved by the swirling flow created by the mixing vanes. Lastly, coupled fluid-structure interaction analysis shows that the vibrational modes of the fuel rods filter out high frequency turbulent pressure fluctuations. In general, these results allude to interesting phenomena for which further investigation could be quite fruitful

Adiponectin-leptin Ratio is a Functional Biomarker of Adipose Tissue Inflammation

Obesity favors the development of cardiometabolic alterations such as type 2 diabetes (T2D) and the metabolic syndrome (MS). Obesity and the MS are distinguished by an increase in circulating leptin concentrations, in parallel to a drop in the levels of adiponectin. Consequently, the Adpn/Lep ratio has been suggested as a maker of dysfunctional adipose tissue. We aimed to investigate in humans (n = 292) the reliability of the Adpn/Lep ratio as a biomarker of adipose tissue dysfunction. We considered that an Adpn/Lep ratio of ≥1.0 can be considered normal, a ratio of ≥0.5 <1.0 suggests moderate-medium increased risk, and a ratio of <0.5 indicates a severe increase in cardiometabolic risk. Using these cut-offs, 5%, 54% and 48% of the lean, normoglycemic and without-MS subjects, respectively, fall within the group with an Adpn/Lep ratio below 0.5; while 89%, 86% and 90% of the obese, with T2D and with MS patients fall within the same group (p < 0.001). A significant negative correlation (r = -0.21, p = 0.005) between the Adpn/Lep ratio and serum amyloid A (SAA) concentrations, a marker of adipose tissue dysfunction, was found. We concluded that the Adpn/Lep ratio is a good indicator of a dysfunctional adipose tissue that may be a useful estimator of obesity- and MS-associated cardiometabolic risk, allowing the identification of a higher number of subjects at risk

Resting energy expenditure is not altered in children and adolescents with obesity. Effect of age and gender and association with serum Leptin levels

In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age-and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8–10 (n = 38), 11–13 (n = 50), and 14–17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p &lt; 0.001), but REE/FFM decreases (p &lt; 0.001) and there is an interaction between gender and age (p &lt; 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8–10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8–10 year-olds

Association of increased Visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity

BACKGROUND AND AIMS: Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine with physiological effects on the control of glucose homeostasis as well as potentially involved in inflammation. The association of circulating NAMPT concentrations with obesity has not been clearly established. The aim of the present work was to evaluate the effect of obesity on circulating concentrations and gene expression levels of NAMPT in human peripheral blood cells (PBCs) as well as its involvement in inflammation, glucose and lipid metabolism. METHODS AND RESULTS: Forty-four serum samples obtained from 14 lean and 30 obese volunteers were used to analyse the circulating concentrations of NAMPT. In addition, PBC, omental adipose tissue (OM) and liver biopsy samples obtained from a subgroup of subjects were used to determine transcript levels of NAMPT by Real-time PCR. Glucose and lipid profile as well as several inflammatory factors and hepatic enzymes were analysed. NAMPT circulating concentrations (P<0.01) and gene expression levels in PBC (P<0.05) were significantly increased in obese patients as compared to lean subjects. Total-cholesterol (P=0.016), HDL-cholesterol (P=0.036) and triglycerides (P=0.050) were significant and independent determinants of circulating concentrations of NAMPT (P<0.01). Moreover, a positive correlation (P<0.01) was found with the hepatic enzymes alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase after BMI adjustment. CONCLUSION: Our work shows that NAMPT circulating concentrations and mRNA expression levels in PBC are increased in obese patients and that plasma NAMPT levels are related to inflammation, lipid metabolism and hepatic enzymes suggesting a potential involvement in fatty liver disease and in the obesity-associated inflammatory stat

Circulating GDF11 levels are decreased with age but are unchanged with obesity and type 2 diabetes

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β (TGFβ) superfamily which declines with age and exerts anti‐aging regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting casting doubts about its true functional actions. The aim of the present study was to compare the circulating concentrations of GDF11 in individuals of different ages as well as body weight and glycemic status. Serum concentrations of GDF11 were measured by ELISA in 319 subjects. There was a significant increase in GDF11 concentrations in people in the 41‐50 y group and a decline in the elder groups (61‐70 and 71‐80 y groups, P=0.008 for the comparison between all age groups). However, no significant correlation between fat‐free mass index (FFMI), a formula used to estimate the amount of muscle mass in relation to height, and logGDF11 was observed (r=0.08, P=0.197). Moreover, no significant differences in circulating concentrations of GDF11 regarding obesity or glycemic status were found. Serum GDF11 concentrations in humans decrease in older ages being unaltered in obesity and T2D. Further studies should determine the exact pathophysiological role of GDF11 in aging

Increased circulating and visceral adipose tissue expression levels of YKL-40 in obesity-associated type 2 diabetes are related to inflammation: impact of conventional weight loss and gastric bypass

Context: Plasma YKL-40 is elevated in patients with type 2 diabetes. The potential role of visceral adipose tissue (VAT) as a significant source of YKL-40 is unknown. Objective: In the study circulating and expression levels of YKL-40 were examined in VAT analyzing the contribution of adipocytes and stromovascular fraction cells (SVFCs).Wealso explored YKL-40’s implication in insulin resistance and inflammation and the effect of weight loss on plasma YKL-40 concentrations. PatientsandMethods: Samples obtained from 53 subjects were used in the study.Geneandprotein expression levels of YKL-40 were analyzed in VAT as well as in both adipocytes and SVFCs. In addition, circulating YKL-40 concentrations were measured before and after weight loss achieved either by Roux-en-Y gastric bypass (n 26) or after a conventional dietetic program (n 20). Results: Circulating concentrations and VAT expression of YKL-40 were increased in obese patients with type 2 diabetes (P 0.01) as well as associated with variables of insulin resistance and inflammation. No differences in YKL-40 expression levels between adipocytes and SVFCs were detected. Monocyte chemoattractant protein-1 and homeostasis model assessment emerged (P 0.01) as independent factors predicting circulating YKL-40. Elevated levels of YKL-40 in obese patients decreased after weight loss following a conventional hypocaloric diet (P 0.05) but not via a surgery-induced negative energy balance mediated by the Roux-en-Y gastric bypass. Conclusions: The association of increased YKL-40 mRNA and protein levels in VAT with its circulating concentrations indicates an important contribution of VAT in YKL-40 regulation. Furthermore, our data suggest a relevant role of glucose metabolism and inflammation on YKL-40 regulation

Plasma osteopontin levels and expression in adipose tissue are increased in obesity

Obesity acts as a cardiovascular risk factor by mechanisms that are not fully understood. Osteopontin (OPN) is a proinflammatory mediator involved in tissue remodeling that plays a role in atherosclerosis and diabetes. OBJECTIVE: The aim of the present study was to compare the circulating concentrations of OPN and its mRNA expression in omental adipose tissue of lean, overweight, and obese individuals and to analyze the effect of weight loss. SUBJECTS AND METHODS: Plasma concentrations of OPN were measured in 77 volunteers. OPN mRNA expression in omental adipose tissue obtained from 12 women was quantified by real-time PCR. In addition, the concentrations of OPN in 12 obese men were measured before and after weight loss following a dietetic program. SETTING: The study was conducted at a University Hospital. RESULTS: Obese and overweight patients exhibited significantly increased circulating OPN concentrations as compared with lean subjects (obese 72.6 +/- 28.5, overweight 68.2 +/- 20.8, lean 42.7 +/- 27.9 ng/ml; P < 0.001). A significant positive correlation was found between OPN levels and body fat (r = 0.45; P < 0.0001). Obese individuals showed significantly increased (P < 0.05) mRNA expression of OPN in omental adipose tissue as compared with lean volunteers, which was further increased in obese diabetic patients. Diet-induced weight loss significantly decreased OPN concentrations from 64.7 +/- 22.1 to 36.6 +/- 20.1 ng/ml (P = 0.006). CONCLUSIONS: These findings represent the first observation that plasma OPN and mRNA expression of OPN in omental adipose tissue are increased in overweight/obese patients with the latter being further elevated in obesity-associated diabetes. Moreover, weight loss reduces OPN concentrations, which may contribute to the beneficial effects accompanying weight reduction. Measurement of OPN might be useful for evaluating the outcomes of various clinical interventions for obesity-related cardiovascular disease

Circulating concentrations of GDF11 are positively associated with TSH levels in humans

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-beta superfamily which declines with age and has been proposed as an anti-aging factor with regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting, casting doubts about its true functional actions. The aim of the present study was to analyze the potential involvement of GFD11 in energy homeostasis in particular in relation with thyroid hormones. Serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay (ELISA) in 287 subjects. A highly significant positive correlation was found between GDF11 and thyroid-stimulating hormone (TSH) concentrations (r = 0.40, p 0.05 for both) with GDF11 levels. In a multiple linear regression analysis, the model that best predicted logGDF11 included logTSH, leptin, body mass index (BMI), age, and C-reactive protein (logCRP). This model explained 37% of the total variability of logGDF11 concentrations (p < 0.001), with only logTSH being a significant predictor of logGDF11. After segregating subjects by TSH levels, those within the low TSH group exhibited significantly decreased (p < 0.05) GDF11 concentrations as compared to the normal TSH group or the high TSH group. A significant correlation of GDF11 levels with logCRP (r = 0.19, p = 0.025) was found. GDF11 levels were not related to the presence of hypertension or cardiopathy. In conclusion, our results show that circulating concentrations of GDF11 are closely associated with TSH concentrations and reduced in subjects with low TSH levels. However, GDF11 is not related to the regulation of energy expenditure. Our data also suggest that GDF11 may be involved in the regulation of inflammation, without relation to cardiac function. Further research is needed to elucidate the role of GDF11 in metabolism and its potential involvement in thyroid pathophysiology

Increase of the Adiponectin/Leptin Ratio in Patients with Obesity and Type 2 Diabetes after Roux-en-Y Gastric Bypass

Bariatric surgery remains the most effective option for achieving important and sustained weight loss. We explored the effects of Roux-en-Y gastric bypass (RYGB) on the circulating levels of adiponectin, leptin, and the adiponectin/leptin (Adpn/Lep) ratio in patients with obesity and type 2 diabetes (T2D). Twenty-five T2D volunteers undergoing RYGB were included in the study, and further subclassified as patients that responded or not to RYBG, regarding remission of T2D. Anthropometric and biochemical variables were evaluated before and after RYGB. Obese patients with T2D exhibited an increase (p < 0.0001) in the Adpn/Lep ratio after RYGB. Changes in the Adpn/Lep ratio correlated better with changes in anthropometric data (p < 0.001) than with the variations of adiponectin or leptin alone. Multiple regression analysis revealed that the change in the Adpn/Lep ratio in patients with T2D was an independent predictor of the changes in body mass index (p < 0.001) and body fat percentage (p = 0.022). However, the Adpn/Lep ratio did not differ between individuals with or without T2D remission after RYGB. In summary, the current study demonstrated that after weight and body fat loss following RYGB, the Adpn/Lep ratio increased in patients with obesity and T2D

Microfluidic‐assisted blade coating of compositional libraries for combinatorial applications: the case of organic photovoltaics

Microfluidic technologies are highly adept at generating controllable compositional gradients in fluids, a feature that has accelerated the understanding of the importance of chemical gradients in biological processes. That said, the development of versatile methods to generate controllable compositional gradients in the solid‐state has been far more elusive. The ability to produce such gradients would provide access to extensive compositional libraries, thus enabling the high‐throughput exploration of the parametric landscape of functional solids and devices in a resource‐, time‐, and cost‐efficient manner. Herein, the synergic integration of microfluidic technologies is reported with blade coating to enable the controlled formation of compositional lateral gradients in solution. Subsequently, the transformation of liquid‐based compositional gradients into solid‐state thin films using this method is demonstrated. To demonstrate efficacy of the approach, microfluidic‐assisted blade coating is used to optimize blending ratios in organic solar cells. Importantly, this novel technology can be easily extended to other solution processable systems that require the formation of solid‐state compositional lateral gradients