Toeplitz Operators on Dirichlet-Type Space of Unit Ball

We construct a function u in L2Bn, dV which is unbounded on any neighborhood of each boundary point of Bn such that Toeplitz operator Tu is a Schatten p-class 0<p<∞ operator on Dirichlet-type space DBn, dV. Then, we discuss some algebraic properties of Toeplitz operators with radial symbols on the Dirichlet-type space DBn, dV. We determine when the product of two Toeplitz operators with radial symbols is a Toeplitz operator. We investigate the zero-product problem for several Toeplitz operators with radial symbols. Furthermore, the corresponding commuting problem of Toeplitz operators whose symbols are of the form ξku is studied, where k ∈ Zn, ξ ∈ ∂Bn, and u is a radial function

Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk: A Fine-Mapping Study in Chinese Population

Background: Genome-wide association studies (GWAS) in populations of European ancestry have mapped a type 2 diabetes susceptibility region to chromosome 10q23.33 containing IDE, KIF11 and HHEX genes (IDE-KIF11-HHEX), which has also been replicated in Chinese populations. However, the functional relevance for genetic variants at this locus is still unclear. It is critical to systematically assess the relationship of genetic variants in this region with the risk of type 2 diabetes. Methodology/Principal Findings: A fine-mapping study was conducted by genotyping fourteen tagging single-nucleotide polymorphisms (SNPs) in a 290-kb linkage disequilibrium (LD) region using a two-stage case-control study of type 2 diabetes in a Chinese Han population. Suggestive associations (P,0.05) observed from 1,200 cases and 1,200 controls in the first stage were further replicated in 1,725 cases and 2,081 controls in the second stage. Seven tagging SNPs were consistently associated with type 2 diabetes in both stages (P,0.05), with combined odds ratios (ORs) ranging from 1.14 to 1.33 in the combined analysis. The most significant locus was rs7923837 [OR = 1.33, 95 % confidence interval (CI): 1.21–1.47] at the 39-flanking region of HHEX gene. SNP rs1111875 was found to be another partially independent locus (OR = 1.23, 95% CI: 1.13–1.35) in this region that was associated with type 2 diabetes risk. A cumulative effect of rs7923837 and rs1111875 was observed with individuals carrying 1, 2, and 3 or 4 risk alleles having a 1.27, 1.44, and 1.73-fold increased risk, respectively, for type 2 diabetes (P for trend = 4.1E-10)

Lentiviral gene transfer into the dorsal root ganglion of adult rats

<p>Abstract</p> <p>Background</p> <p>Lentivector-mediated gene delivery into the dorsal root ganglion (DRG) is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. In this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the requirements for efficient transduction into neuronal cells <it>in vitro </it>and adult rat DRG <it>in vivo</it>.</p> <p>Results</p> <p><it>In vitro</it>, lentivectors expressing enhanced green fluorescent protein (EGFP) under control of the human elongation factor 1α (EF1α) promoter and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV-G) envelope exhibited the best performance in the transfer of EGFP into an immortalized DRG sensory neuron cell line at low multiplicities of infection (MOIs), and into primary cultured DRG neurons at higher MOIs. <it>In vivo</it>, injection of either first or second-generation EF1α-EGFP lentivectors directly into adult rat DRGs led to transduction rates of 19 ± 9% and 20 ± 8% EGFP-positive DRG neurons, respectively, detected at 4 weeks post injection. Transduced cells included a full range of neuronal phenotypes, including myelinated neurons as well as both non-peptidergic and peptidergic nociceptive unmyelinated neurons.</p> <p>Conclusion</p> <p>VSV-G pseudotyped lentivectors containing the human elongation factor 1α (EF1α)-EGFP expression cassette demonstrated relatively efficient transduction to sensory neurons following direct injection into the DRG. These results clearly show the potential of lentivectors as a viable system for delivering target genes into DRGs to explore basic mechanisms of neuropathic pain, with the potential for future clinical use in treating chronic pain.</p

Normal-weight central obesity: implications for diabetes mellitus

BackgroundCurrent guidelines for obesity prevention and control focus on body mass index (BMI) and rarely address central obesity. Few studies have been conducted on the association between normal-weight central obesity and the risk of diabetes mellitus (DM).Methods26,825 participants from the National Health and Nutrition Examination Survey (NHANES) were included in our study. A weighted multivariate logistic regression model was used to analyze the relationship between different obesity patterns and the risk of DM.ResultsOur results suggest that normal-weight central obesity is associated with an increased risk of DM (OR: 2.37, 95% CI: 1.75–3.23) compared with normal-weight participants without central obesity. When stratified by sex, men with normal-weight central obesity, obesity and central obesity were found to have a similar risk of DM (OR: 3.83, 95% CI: 2.10–5.97; OR: 4.20, 95% CI: 3.48–5.08, respectively) and a higher risk than all other types of obesity, including men who were overweight with no central obesity (OR: 1.21, 95% CI: 0.96–1.51) and obese with no central obesity (OR: 0.53, 95% CI: 0.30–0.91).ConclusionOur results highlight the need for more attention in people with central obesity, even if they have a normal BMI

Genetic Variants at 1p11.2 and Breast Cancer Risk: A Two-Stage Study in Chinese Women

BACKGROUND: Genome-wide association studies (GWAS) have identified several breast cancer susceptibility loci, and one genetic variant, rs11249433, at 1p11.2 was reported to be associated with breast cancer in European populations. To explore the genetic variants in this region associated with breast cancer in Chinese women, we conducted a two-stage fine-mapping study with a total of 1792 breast cancer cases and 1867 controls. METHODOLOGY/PRINCIPAL FINDINGS: Seven single nucleotide polymorphisms (SNPs) including rs11249433 in a 277 kb region at 1p11.2 were selected and genotyping was performed by using TaqMan® OpenArray™ Genotyping System for stage 1 samples (878 cases and 900 controls). In stage 2 (914 cases and 967 controls), three SNPs (rs2580520, rs4844616 and rs11249433) were further selected and genotyped for validation. The results showed that one SNP (rs2580520) located at a predicted enhancer region of SRGAP2 was consistently associated with a significantly increased risk of breast cancer in a recessive genetic model [Odds Ratio (OR)  =  1.66, 95% confidence interval (CI)  =  1.16-2.36 for stage 2 samples; OR  =  1.51, 95% CI  =  1.16-1.97 for combined samples, respectively]. However, no significant association was observed between rs11249433 and breast cancer risk in this Chinese population (dominant genetic model in combined samples: OR  =  1.20, 95% CI  =  0.92-1.57). CONCLUSIONS/SIGNIFICANCE: Genotypes of rs2580520 at 1p11.2 suggest that Chinese women may have different breast cancer susceptibility loci, which may contribute to the development of breast cancer in this population

Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis

BACKGROUND: Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and a 6-bp deletion/insertion in the TYMS 3'-untranslated region (TS 3'-UTR)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk. METHODS: To test the hypothesis that polymorphisms of the TYMS gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population. RESULTS: We found that the distribution of TS3'-UTR (1494del6) genotype frequencies were significantly different between the cases and controls (P = 0.026). Compared with the TS3'-UTR del6/del6 wild-type genotype, a significantly reduced risk was associated with the ins6/ins6 homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35–0.97) but not the del6/ins6 genotype (OR = 1.09, 95% CI = 0.82–1.46). Furthermore, breast cancer risks associated with the TS3'-UTR del6/del6 genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the TSER polymorphism and breast cancer risks. CONCLUSION: These findings suggest that the TS3'-UTR del6 polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings

Smoking and Genetic Risk Variation Across Populations of E uropean, A sian, and A frican A merican Ancestry—A Meta‐Analysis of Chromosome 15q25

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91126/1/gepi21627.pd

Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population: a case-control study

<p>Abstract</p> <p>Background</p> <p>The nucleotide excision repair (NER) protein, xeroderma pigmentosum C (XPC), participates in recognizing DNA lesions and initiating DNA repair in response to DNA damage. Because mutations in <it>XPC </it>cause a high risk of cancer in XP patients, we hypothesized that inherited sequence variations in <it>XPC </it>may alter DNA repair and thus susceptibility to cancer.</p> <p>Methods</p> <p>In this hospital-based case-control study, we investigated five <it>XPC </it>tagging, common single nucleotide polymorphisms (tagging SNPs) in 1,010 patients with newly diagnosed lung cancer and 1,011 matched cancer free controls in a Chinese population.</p> <p>Results</p> <p>In individual tagging SNP analysis, we found that rs3731055<it>AG+AA </it>variant genotypes were associated with a significantly decreased risk of lung adenocarcinoma [adjusted odds ratio (OR), 0.71; 95% confidence interval (CI), 0.56–0.90] but an increased risk of small cell carcinomas [adjusted OR, 1.79; 95% CI, 1.05–3.07]. Furthermore, we found that haplotype <it>ACCCA </it>was associated with a decreased risk of lung adenocarcinoma [OR, 0.78; 95% CI, 0.62–0.97] but an increased risk of small cell carcinomas [OR, 1.68; 95% CI, 1.04–2.71], which reflected the presence of rs3731055<it>A </it>allele in this haplotype. Further stratified analysis revealed that the protective effect of rs3731055<it>AG+AA </it>on risk of lung adenocarcinoma was more evident among young subjects (age ≤ 60) and never smokers.</p> <p>Conclusion</p> <p>These results suggest that inherited sequence variations in <it>XPC </it>may modulate risk of lung cancer, especially lung adenocarcinoma, in Chinese populations. However, these findings need to be verified in larger confirmatory studies with more comprehensively selected tagging SNPs.</p