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Adding methane to methanol can solve the problem of difficult cold starts of methanol engines. Therefore, it is important to understand the combustion of methane and methanol fuel blends. Because of this, this study explores the effect of methane addition on the laminar burning velocity and Markstein length of methanol/methane premixed flames under stoichiometric conditions at the initial temperatures of 353 K, 373 K, and 393 K, initial pressures of 1 bar, 2 bar, and 4 bar, using methane addition ratios of 0%, 25%, 50%, 75%, and 100% in a constant volume combustion chamber. The results show that the laminar burning velocity decreases linearly with the increase of methane addition ratio due to the linear decrease of the Arrhenius factor. The sensitivity analysis revealed that the kinetic effect is the main reason for the inhibition of laminar burning velocity, which is insensitive to initial temperature but enhanced at a high initial pressure. The Markstein length decreases with the addition of methane and the increase of initial pressure, which is mainly caused by the high mass diffusivity of methane and the decrease of flame thickness due to the increase of initial pressure. [ABSTRACT FROM AUTHOR]

Postprandial triglyceridemia is an emerging risk factor for cardiovascular disease. However, most of the genes that influence postprandial triglyceridemia are not known. We evaluated whether a common nonsynonymous SNP rs1260326/P446L in the glucokinase regulatory protein ( GCKR) gene influenced variation in the postprandial lipid response after a high-fat challenge in seven hundred and seventy participants in the Amish HAPI Heart Study who underwent an oral high-fat challenge and had blood samples taken in the fasting state and during the postprandial phase at 1, 2, 3, 4, and 6 h. We found that the minor T allele at rs1260326 was associated with significantly higher fasting TG levels after adjusting for age, sex, and family structure ( Pa = 0.06 for additive model, and Pr = 0.0003 for recessive model). During the fat challenge, the T allele was associated with significantly higher maximum TG level ( Pa = 0.006), incremental maximum TG level ( Pa = 0.006), TG area under the curve ( Pa = 0.02) and incremental TG area under the curve ( Pa = 0.03). Our data indicate that the rs1260326 T allele of GCKR is associated with both higher fasting levels of TG as well as the postprandial TG response, which may result in higher atherogenic risk. [ABSTRACT FROM AUTHOR]

Background and Objectives: Neonatal nutrition is critical for the growth and development of preterm infants. Dynamic changes in the amino acid profiles in preterm infants of different gestational ages and in different nutritional periods were investigated.Methods and Study Design: Premature infants who received parenteral nutrition support after birth were enrolled and divided into four groups based on their gestational ages. Blood samples were collected as a dried blood spot before nutritional support, and in the total parenteral nutrition, partial parenteral nutrition, and total enteral nutrition periods. Amino acid concentrations were detected in the samples by liquid chromatography tandem mass spectrometry and compared between the different nutritional periods and gestational ages.Results: Samples from 124 premature infants were statistically analyzed. Concentrations of all amino acids, except glutamine, were statistically different at distinct nutritional periods. Threonine and aspartic acid concentrations gradually increased, while valine, methionine, phenylalanine, and glycine concentrations gradually decreased with the transition from TPN to TEN. At different gestational ages, significant differences were observed in the concentrations of seven amino acids only in the PPN period but not in the others.Conclusions: The concentrations of amino acids in preterm infants vary with nutritional period. [ABSTRACT FROM AUTHOR]

Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-choleslerol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect. [ABSTRACT FROM AUTHOR]

Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted a genome-wide association study of systolic and diastolic blood pressure (SBP and DBP) in Amish subjects and found strong association signals with common variants in a serine/threonine kinase gene, STK39. We confirmed this association in an independent Amish and 4 non-Amish Caucasian samples including the Diabetes Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta-analysis combining all studies: n = 7,125, P < 10[sup-6]). The higher BP-associated alleles have frequencies > 0.09 and were associated with increases of 3.3/1.3 mm Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but consistent effects across the non-Amish studies. Cell- based functional studies showed that STK39 interacts with WNK kinases and cation-chloride cotransporters, mutations in which cause monogenic forms of BP dysregulation. We demonstrate that in vivo, STK39 is expressed in the distal nephron, where it may interact with these proteins. Although none of the associated SNPs alter protein structure, we identified and experimentally confirmed a highly conserved intronic element with allele-specific in vitro transcription activity as a functional candidate for this association. Thus, variants in STK39 may influence BP by increasing STK39 expression and consequently altering renal Na[sup+] excretion, thus unifying rare and common BP-regulating alleles in the same physiological pathway. [ABSTRACT FROM AUTHOR]

Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation. [ABSTRACT FROM AUTHOR]

Transcription factor 7-like 2 (TCF7L2) regulates genes involved in cell proliferation and differentiation. The TCF7L2 gene is located on chromosome 10q25 in a region of replicated linkage to type 2 diabetes. Recently, a microsatellite marker in intron 3 (DG10S478) and five correlated single nucleotide polymorphisms (SNPs) were identified in Icelandic individuals that showed strong association with type 2 diabetes, which was replicated in Danish and European-American cohorts. We genotyped four of the SNPs (rs7901695, rs7903146, rs11196205, and rs12255372) in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT; n = 139), and normal glucose tolerance (NGT; n = 342). We compared genotype frequencies in subjects with type 2 diabetes with those with NGT and found marginal association for rs7901695 (P = 0.05; odds ratio [OR] 1.51); comparison between NGT control subjects and the combined type 2 diabetes/IGT case group showed strong association with rs7901695 and rs7903146 (P = 0.008-0.01; OR 1.53-1.57) and marginal association with rs11196205 and rs12255372 (P = 0.07 and P = 0.04, respectively). In an expanded set of 698 Amish subjects without diabetes, we found no association with insulin and glucose levels during a 3-h oral glucose tolerance test. We also genotyped these SNPs in nondiabetic, non-Amish subjects (n = 48), in whom intravenous glucose tolerance tests were performed, and found an association between rs7901695 and rs7903146 and insulin sensitivity (P = 0.003 and P = 0.005, respectively) and disposition index (P = 0.04 and P = 0.007, respectively). These data provide replicating evidence that variants in TCF7L2 increase the risk for type 2 diabetes and novel evidence that the variants likely influence both insulin secretion and insulin sensitivity. Diabetes 55:2654-2659, 2006 [ABSTRACT FROM AUTHOR]

Perilipin is a lipid droplet surface protein present in adipocytes and steroidogenic cells. We examined five common single nucleotide polymorphisms (SNPs) at the perilipin ( PLIN) locus ( PLIN 6209C>T, 10171A>T, 11482G>A, 13041A>G, and 14995A>T) to investigate their association with obesity risk. The study population included 4,131 subjects of three ethnic groups (Chinese, Malay, and Indian) from Singapore. The prevalence of obesity in Malays and Indians was much higher than in Chinese. Moreover, in these groups the prevalence of obesity was three times higher in women than in men. Crude analysis indicated that haplotype 11212 (CAAAT) is shared by Malays and Indians and is significantly associated with increased obesity risk as compared to the most common haplotype 21111 (TAGAA): OR 1.65 (95% CI 1.11–2.46) in Malays and 1.94 (95% CI 1.06–3.53) in Indians. No associations between PLIN haplotypes and obesity risk were found in Chinese. To simplify the haplotype analyses we used a subgroup of three SNPs (11482G>A, 13041A>G, and 14995A>T) in positive linkage disequilibrium. These analyses revealed similar associations, showing that haplotypes XX212 (XXAAT) and XX222 (XXAGT) are associated with increased obesity risk in Malays OR 2.04 (95% CI 1.28–3.25) and 2.05 (95% CI 1.35–3.12) respectively, and that haplotype XXX212 (XXAAT) is significantly associated with increased obesity risk in Indians OR 2.16 (95% CI 1.10–4.26) after adjusting for covariates including age, sex, smoking, alcohol consumption, exercise, and diabetes status. Moreover, individual SNP analyses demonstrated that the PLIN 14995A>T SNP is the most informative single genetic marker for the observed haplotype association, being significantly associated with increased obesity risk in both Malays OR 2.28 (95% CI 1.45–3.57) and Indians OR 2.04 (95% CI 1.08–3.64). These results support the role of the PLIN locus as an ethnically dependent modulator of obesity risk in humans. [ABSTRACT FROM AUTHOR]

Obesity is strongly associated with insulin resistance, type 2 diabetes, cardiovascular diseases and dyslipidemia. How these seemingly distinctive diseases cluster together as the metabolic syndrome is a scientifically intriguing and clinically important question, but not well understood. Recent studies indicate that chronic systemic inflammation may be a cause behind the syndrome and that the adipose tissue may contribute to the inflammation since it is not only a storage depot for excess fat, but also is an endocrine organ secreting many polypeptides, known as adipokines. Dysregulation of adipokines may be responsible for the elevation of the inflammatory state in obesity and obesity-associated comorbidities. Numerous studies have investigated the change of adipokines in obesity and diabetes conditions, but the data from Chinese patients are very limited. In this study, we measured the serum levels of several representative adipokines in obese and diabetic Chinese patients treated with rosiglitazone. In non-diabetic subjects, the serum levels of serum amyloid A (SAA), C-reactive protein (CRP) and TNFa in obese people (BMI ≥ 24, n = 24) was significantly higher than the lean subjects (BMI < 24, n = 26, p < 0.01). In contrast, adiponectin levels were significantly lower in the obese group (p < 0.01). On the other hand, no difference in IL-6 and resistin levels was found between the lean and obese groups. Moreover, these adipokines were measured in 34 impaired glucose regulation (IGR) patients and 44 new-onset type 2 diabetes patients (T2D) patients before and after the treatment with rosiglitazone at 4 mg/day for 12 weeks. The rosiglitazone did not change BMI in both groups but decreased fasting glucose and HbA1c levels in the T2D group. The treatment reduced CRP, TNFa and SAA by 11-39% and increased adiponectin by 82% with statistical significance. In conclusion, we found that inflammatory adipokines were elevated in obesity and decreased in diabetics after rosiglitazone treatment, supporting that adipokines may be a mediator in the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Coronary artery calcification (CAC) and common carotid artery intima-media thickness (CIMT) are measures of subclinical vascular disease. This 2000–2006 study aimed to characterize the associations among coronary artery disease risk factors, CAC quantity, and CIMT and to estimate shared genetic and environmental contributions to both CAC and CIMT among 478 asymptomatic Amish adults in Lancaster County, Pennsylvania. Heritability for CAC quantity and CIMT, adjusted for age and sex, was 0.42 (P = 0.0001) and 0.29 (P = 0.003), respectively. CAC quantity and CIMT were modestly correlated (adjusted r = 0.14, P = 0.003) but showed little evidence of shared genetic or environmental factors. However, significant genetic correlations were found for CAC quantity and total cholesterol (0.44 (standard error, 0.19); P = 0.03), for CAC quantity and low density lipoprotein cholesterol (0.55 (standard error, 0.17); P = 0.005), and for CIMT and waist circumference (0.58 (standard error, 0.25); P = 0.046), suggesting shared genes for these risk factors and measures of subclinical disease. Results suggest that some of the same genes influence variation in CAC and low density lipoprotein cholesterol, whereas a different set of genes influences variation in CIMT and waist circumference. [ABSTRACT FROM AUTHOR]