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Due to the black and glossy appearance of the carbon fiber prepreg bundle surface, the accurate identification of surface defects in automated fiber placement (AFP) presents a high level of difficulty. Currently, the enhanced YOLOv7 algorithm demonstrates certain performance advantages in this detection task, yet issues with missed detections, false alarms, and low confidence levels persist. Therefore, this study proposes an improved YOLOv7 algorithm to further enhance the performance and generalization of surface defect detection in AFP. Firstly, to enhance the model’s feature extraction capability, the BiFormer attention mechanism is introduced to make the model pay more attention to small target defects, thereby improving feature discriminability. Next, the AFPN structure is used to replace the PAFPN at the neck layer to strengthen feature fusion, preserve semantic information to a greater extent, and finely integrate multi-scale features. Finally, WIoU is adopted to replace CIoU as the bounding box regression loss function, making it more sensitive to small targets, enabling more accurate prediction of object bounding boxes, and enhancing the model’s detection accuracy and generalization capability. Through a series of ablation experiments, the improved YOLOv7 shows a 10.5% increase in mAP and a 14 FPS increase in frame rate, with a maximum detection speed of 35 m/min during the AFP process, meeting the requirements of online detection and thus being able to be applied to surface defect detection in AFP operations.

Carbon-fiber-reinforced polymer (CFRP) composites are widely used in industries such as aerospace due to their lightweight nature and high strength. However, weak interfacial bonding strength is one of the main problems of resin-based composites. In this study, a prepreg was prepared by melt mixing. By dispersing nanoreinforcement particles in the resin, the interlaminar shear strength of the CFRP was increased by approximately 23.6%. When only 0.5 wt% multiwalled carbon nanotube (MWCNT) was used for reinforcement, scanning electron microscopy (SEM) micrographs showed that cracks were hindered by the MWCNTs during propagation, causing crack deflection. At the same time, the mechanism of MWCNTs pulling out increased the energy required for crack propagation. When only 0.5 wt% graphene oxide (GO) was added, the reinforcement effect was inferior to that of using the same amount of MWCNTs. The laminar structure formed by GO and the resin matrix adhered to the carbon fiber surface, reducing the degree of destruction of the resin matrix, but its hindering effect on crack propagation was weak. When 0.5 wt% of MWCNT and GO mixture was added, the interlayer shear strength increased from 55.6 MPa in the blank group to 68.7 MPa. The laminar structure of GO provided a platform for the MWCNTs to form a mesh structure inside its matrix. At the same time, the tubular structure of the MWCNTs inhibited the stacking of GO, providing better dispersion and forming a synergistic enhancement effect.

Recently, the ship energy consumption issue has been in the spotlight. Meanwhile, new conventions and standards of ship energy conservation as well as ship emission reduction have been continuously introduced by the International Maritime Organization and governments around the world. Energy conservation is a crucial factor in ship route planning. This paper proposes an improved ant colony algorithm that can handle a complicated ocean current environment and find an optimal energy-saving path. Firstly, this paper focuses on both the path length and energy consumption. To reduce energy consumption, a comprehensive energy cost function is introduced by a conventional ant colony algorithm. In addition, this paper analyzes the influence of the ocean current speed and setting on a marine vehicle and establishes an improved ant colony algorithm model based on the influence of the ocean current. Finally, simulation tests are carried out in Lianyungang and its surrounding areas to test the energy consumption performance of the improved ant colony algorithm. The simulation result shows that the improved ant colony algorithm can significantly reduce the energy consumption by 3.326% compared with the traditional algorithm.

Background: Amino acid (AA) metabolic patterns have emerged as an analytical technique to characterize biomarkers compromising normal growth and elucidate underlying nutritional exposure. This study aimed to identify AA metabolites most likely associated with poor growth and examine the association between AA metabolites and nutrition regimens in preterm infants during transition from parenteral nutrition (PN) to enteral nutrition (EN), using gas chromatography-mass spectrometry (GC-MS).Methods: This observational cohort study was conducted in infants born at

In this work, we successfully developed a fluorinated cross-linked polymer Bragg waveguide grating-based optical biosensor to detect effective drug concentrations of ginkgolide A for the inhibition of pulmonary microvascular endothelial cell (PMVEC) apoptosis. Fluorinated photosensitive polymer SU-8 (FSU-8) as the sensing core layer and polymethyl methacrylate (PMMA) as the sensing window cladding were synthesized. The effective drug concentration range (5–10 µg/mL) of ginkgolide A for inhibition of PMVEC apoptosis was analyzed and obtained by pharmacological studies. The structure of the device was optimized to be designed and fabricated by direct UV writing technology. The properties of the biosensor were simulated with various refractive indices of different drug concentrations. The actual sensitivity of the biosensor was measured as 1606.2 nm/RIU. The resolution and detection limit were characterized as 0.05 nm and 3 × 10−5 RIU, respectively. The technique is suitable for safe and accurate detection of effective organic drug dosages of Chinese herbal ingredients.

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information.

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]

Escherichia coli O157:H7 (E. coli O157) is known for causing severe foodborne illnesses such as hemorrhagic colitis and hemolytic uremic syndrome. Although E. coli O157 is typically regarded as an extracellular pathogen and a weak biofilm producer, some E. coli O157 strains, including a clinical strain ATCC 43895, exhibit a notable ability to invade bovine crypt cells and other epithelial cells, as well as to form robust biofilm. This invasive strain persists in the bovine host significantly longer than non-invasive strains. Various surface-associated factors, including lipopolysaccharides (LPS), flagella, and other adhesins, likely contribute to this enhanced invasiveness and biofilm formation. In this study, we constructed a series of LPS-core deletion mutations (waaI, waaG, waaF, and waaC) in E. coli O157 ATCC 43895, resulting in stepwise truncations of the LPS. This approach enabled us to investigate the effects on the biosynthesis of key surface factors, such as flagella and curli, and the ability of this invasive strain to invade host cells. We confirmed the LPS structure and found that all LPS-core mutants failed to form biofilms, highlighting the crucial role of core oligosaccharides in biofilm formation. Additionally, the LPS inner-core mutants ΔwaaF and ΔwaaC lost the ability to produce flagella and curli. Furthermore, these inner-core mutants exhibited a dramatic reduction in adherence to and invasion of epithelial cells (MAC-T), showing an approximately 100-fold decrease in cell invasion compared with the outer-core mutants (waaI and waaG) and the wild type. These findings underscore the critical role of LPS-core truncation in impairing flagella and curli biosynthesis, thereby reducing the invasion capability of E. coli O157 ATCC 43895.

Pathogenic Escherichia coli and Salmonella enterica pose serious public health threats due to their ability to cause severe gastroenteritis and life-threatening sequela, particularly in young children. Moreover, the emergence and dissemination of antibiotic resistance in these bacteria have complicated control of infections. Alternative strategies that effectively target these enteric pathogens and negate or reduce the need of antibiotics are urgently needed. Such an alternative is the CRISPR-Cas9 system because it can generate sequence-specific lethal double stranded DNA breaks. In this study, two self-transmissible broad host range conjugative plasmids, pRK24 and pBP136, were engineered to deliver multiplexed CRSIPR-Cas9 systems that specifically target Enterohemorrhagic and Enteropathogenic strains of E. coli (EHEC and EPEC), S. enterica, and blaCMY-2 antibiotic resistance plasmids. Using in vitro mating assays, we show that the conjugative delivery of pRK24-CRISPR-Cas9 carrying guide RNAs to the EPEC/EHEC eae (intimin) gene can selectively kill enterohemorrhagic E. coli O157 eae+ cells (3 log kill at 6 h) but does not kill the isogenic Δeae mutant (P

The article presents a genome-wide association study of low-density lipoprotein cholesterol (LDL-C) levels and coronary artery calcification (CAC) in Amish individuals. A sample of 841 Amish individuals aged 20 to 80 years were studied, with replication in a second sample of 663. Scanning was performed for CAC in 1,018 of the individuals. The results reveal the presence of the mutation responsible for familial defective apolipoprotein B-100, a major determinant of LDL-C levels and CAC in the Amish.

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]

The article examines the association of matrix metalloproteinease (MMP) with serum MMP-1 levels in 776 healthy Amish adults to determine the role of MMP1 in cardiovascular disease susceptibility. The method involved a genome wide association analysis of circulating MMP1 levels using 500 K single nucleotide polymorphisms (SNP) to identify genes influencing variation in serum MMP 1 levels. The study suggests strong evidence that the serum MMP1 level is highly heritable and that SNP near MMP on chromosome 11q explains variation in MMP1 levels.

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]

The article focuses on the study regarding the impact of lifestyle factors, such as physical activity, on the management of weight gain and obesity among individuals with underlying fat mass and obesity (FTO) genetic predisposition. Around 700 Old Order Amish (OOA) adults from the Heredity and Phenotype Intervention (HAPI) Heart Study were selected for the study. The phenotypic assessment, genotyping and statistical analyses are taken into account. Information on the association of FTO single-nucleotide polymorphisms (SNP) with obesity is presented.

Identifying genetic variants that influence human height will advance our understanding of skeletal growth and development. Several rare genetic variants have been convincingly and reproducibly associated with height in mendelian syndromes, and common variants in the transcription factor gene HMGA2 are associated with variation in height in the general population. Here we report genome-wide association analyses, using genotyped and imputed markers, of 6,669 individuals from Finland and Sardinia, and follow-up analyses in an additional 28,801 individuals. We show that common variants in the osteoarthritis-associated locus GDF5-UQCC contribute to variation in height with an estimated additive effect of 0.44 cm (overall P < 10−15). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development. [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]

Examines the elucidation of the genetic factors predisposing to Type 1 diabetes mellitus. Therapeutic approaches on decreasing the human suffering and the societal costs resulting from diabetes; Chromosomal regions that contain potential diabetes susceptibility genes.

Escherichia coli O157:H7 (O157) is noninvasive and a weak biofilm producer; however, a subset of O157 are exceptions. O157 ATCC 43895 forms biofilms and invades epithelial cells. Tn5 mutagenesis identified a mutation responsible for both phenotypes. The insertion mapped within the curli csgB fimbriae locus. Screening of O157 strains for biofilm formation and cell invasion identified a bovine and a clinical isolate with those characteristics. A single base pair A to T transversion, intergenic to the curli divergent operons csgDEFG and csgBAC, was present only in biofilm-producing and invasive strains. Using site-directed mutagenesis, this single base change was introduced into two curli-negative/noninvasive O157 strains and modified strains to form biofilms, produce curli, and gain invasive capability. Transmission electron microscopy (EM) and immuno-EM confirmed curli fibers. EM of bovine epithelial cells (MAC-T) co-cultured with curli-expressing O157 showed intracellular bacteria. The role of curli in O157 persistence in cattle was examined by challenging cattle with curli-positive and -negative O157 and comparing carriage. The duration of bovine colonization with the O157 curli-negative mutant was shorter than its curli-positive isogenic parent. These findings definitively demonstrate that a single base pair stably confers biofilm formation, epithelial cell invasion, and persistence in cattle.

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]

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]

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]

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]