170 research outputs found
Global Properties of Topological String Amplitudes and Orbifold Invariants
We derive topological string amplitudes on local Calabi-Yau manifolds in
terms of polynomials in finitely many generators of special functions. These
objects are defined globally in the moduli space and lead to a description of
mirror symmetry at any point in the moduli space. Holomorphic ambiguities of
the anomaly equations are fixed by global information obtained from boundary
conditions at few special divisors in the moduli space. As an illustration we
compute higher genus orbifold Gromov-Witten invariants for C^3/Z_3 and C^3/Z_4.Comment: 34 pages, 3 figure
Genetic and environmental influences on the stability of withdrawn behavior in children: A longitudinal, multi-informant twin study.
We examined the contribution of genetic and environmental influences on the stability of withdrawn behavior (WB) in childhood using a longitudinal multiple rater twin design. Maternal and paternal ratings on the withdrawn subscale of the Child Behavior Checklist (CBCL) were obtained from 14,889 families when the twins were 3, 7, 10 and 12 years old. A longitudinal psychometric model was fitted to the data and the fit of transmission and common factor models were evaluated for each variance component. WB showed considerable stability throughout childhood, with correlation coefficients ranging from about .30 for the 9-year time interval to .65 for shorter time intervals. Individual differences in WB as observed by the mother and the father were found to be largely influenced by genetic effects at all four time points, in both boys (50–66%) and girls (38–64%). Shared environmental influences explained a small to modest proportion (0–24%) of the variance at all ages and were slightly more pronounced in girls. Non-shared environmental influences were of moderate importance to the variance and slightly increased with age, from 22–28% at age 3 to 35–41% at age 12 years. The stability of WB was largely explained by genetic effects, accounting for 74% of stability in boys and 65% in girls. Shared environmental effects explained 7% (boys) and 17% (girls) of the behavioral stability. Most shared environmental effects were common to both raters, suggesting little influence of rater bias in the assessment of WB. The shared environmental effects common to both raters were best described by a common factor model, indicating that these effects are stable and persistent throughout childhood. Non-shared environmental effects accounted for the remaining covariance over time
Tetrahydrobiopterin modulates ubiquitin conjugation to UBC13/UBE2N and proteasome activity by S-nitrosation
Nitric Oxide (NO) is an intracellular signalling mediator, which affects many biological processes via the posttranslational modification of proteins through S-nitrosation. The availability of NO and NOS-derived reactive oxygen species (ROS) from enzymatic uncoupling are determined by the NO synthase cofactor Tetrahydrobiopterin (BH4). Here, using a global proteomics “biotin-switch” approach, we identified components of the ubiquitin-proteasome system to be altered via BH4-dependent NO signalling by protein S-nitrosation. We show S-nitrosation of ubiquitin conjugating E2 enzymes, in particular the catalytic residue C87 of UBC13/UBE2N, leading to impaired polyubiquitylation by interfering with the formation of UBC13~Ub thioester intermediates. In addition, proteasome cleavage activity in cells also seems to be altered by S-nitrosation, correlating with the modification of cysteine residues within the 19S regulatory particle and catalytic subunits of the 20S complex. Our results highlight the widespread impact of BH4 on downstream cellular signalling as evidenced by the effect of a perturbed BH4-dependent NO-Redox balance on critical processes within the ubiquitin-proteasome system (UPS). These studies thereby uncover a novel aspect of NO associated modulation of cellular homeostasis
Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach
Background: An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the\ud
optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access\ud
referral strategy for stage 4 (glomerular filtration rate ,30 ml/min/1.73 m2) chronic kidney disease patients using a decision\ud
analytic framework.\ud
Methods: A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an\ud
AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the\ud
probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy\ud
and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were\ud
performed using Monte Carlo simulation.\ud
Results: The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy\ud
(38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except\ud
at higher rates of progression and lower rates of ischemic steal syndrome.\ud
Conclusions: Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all predialysis\ud
patients. Further research on cost implications and patient preferences for treatment options needs to be done\ud
before recommending early AVF creation
Mechanisms of Vasorelaxation
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72633/1/j.1527-3466.1992.tb00249.x.pd
Mineralogical attenuation for metallic remediation in a passive system for mine water treatment
Passive systems with constructed wetlands have been consistently used to treat mine water from abandoned mines. Long-term and cost-effective remediation is a crucial expectation for these water treatment facilities. To achieve that, a complex chain of physical, chemical, biological, and mineralogical mechanisms for pollutants removal must be designed to simulate natural attenuation processes.
This paper aims to present geochemical and mineralogical data obtained in a recently constructed passive system (from an abandoned mine, Jales, Northern Portugal). It shows the role of different solid materials in the retention of metals and arsenic, observed during the start-up period of the treatment plant. The mineralogical study focused on two types of materials: (1) the ochre-precipitates, formed as waste products from the neutralization process, and (2) the fine-grained minerals contained in the soil of the wetlands.
The ochre-precipitates demonstrated to be poorly ordered iron-rich material, which gave rise to hematite upon artificial heating. The heating experiments also provided mineralogical evidence for the presence of an associated amorphous arsenic-rich compound. Chemical analysis on the freshly ochre-precipitates revealed high concentrations of arsenic (51,867 ppm) and metals, such as zinc (1,213 ppm) and manganese (821 ppm), indicating strong enrichment factors relative to the water from which they precipitate.
Mineralogical data obtained in the soil of the wetlands indicate that chlorite, illite, chlorite–vermiculite and mica–vermiculite mixedlayers, vermiculite, kaolinite and goethite are concentrated in the fine-grained fractions (<20 and <2 μm). The chemical analyses show that high levels of arsenic (up to 3%) and metals are also retained in these fractions, which may be enhanced by the low degree of order of the clay minerals as suggested by an XRD study.
The obtained results suggest that, although the treatment plant has been receiving water only since 2006, future performance will be strongly dependent on these identified mineralogical pollutant hosts.Fundação para a Ciência e a Tecnologia (FCT
Associations between an Obesity Related Genetic Variant (FTO rs9939609) and Prostate Cancer Risk
Observational studies suggest that obese men have a lower risk of incident prostate cancer, but an increased risk of advanced and fatal cancers. These observations could be due to confounding, detection bias, or a biological effect of obesity. Genetic studies are less susceptible to confounding than observational epidemiology and can suggest how associations between phenotypes (such as obesity) and diseases arise. To determine whether the associations between obesity and prostate cancer are causal, we conducted a genetic association study of the relationship between a single nucleotide polymorphism known to be associated with obesity (FTO rs9939609) and prostate cancer. Data are from a population-based sample of 1550 screen-detected prostate cancers, 1815 age- and general practice matched controls with unrestricted prostate specific antigen (PSA) values and 1175 low-PSA controls (PSA <0.5 ng/ml). The rs9939609 A allele, which was associated with higher BMI in the sample, was inversely associated with overall (odds ratio (OR) versus all controls  = 0.93; 95% confidence interval (CI): 0.85–1.02 p = 0.12 per allele) and low-grade (OR = 0.90; 0.81–0.99 p = 0.03 per allele) prostate cancer risk, but positively associated with high-grade cancer among cases (OR high- versus low-grade cancer  = 1.16; 0.99–1.37 p = 0.07 per allele). Although evidence for these effects was weak, they are consistent with observational data based on BMI phenotypes and suggest that the observed association between obesity and prostate cancer is not due to confounding. Further research should confirm these findings, extend them to other BMI-related genetic variants and determine whether they are due to detection bias or obesity-related hormonal changes
Psychosocial adaptation of adolescent migrants in a Swiss community survey
OBJECTIVE: The aim of this study was to compare psychosocial adaptation in adolescent (first generation) migrants, double-citizens (mainly second generation with one migrant parent), and native Swiss, and to compare migrants from various European regions. METHOD: Data from a community survey were based on 1,239 participants (mean age 13.8, SD = 1.6 years) with 996 natives, 55 double-citizens, and 188 migrants. The adolescents completed the youth self-report measuring emotional and behavioural problems, and various questionnaires addressing life events, personality variables, perceived parental behaviour (PPB), family functioning, school environment, and social network. RESULTS: Adolescent migrants had significantly higher scores for internalizing and externalizing problems. There was a pattern of various unfavourable psychosocial features including life events, coping, self-related cognitions, and PPB that was more common among adolescent migrants than natives. Double-citizens were similar to natives in all domains. Young adolescents from South and South-East Europe differed from natives in terms of more unfavourable psychosocial features. Migrant status was best predicted by adverse psychosocial features rather than emotional and behavioural problems. CONCLUSION: There is some indication that certain migrant adolescents are at risk of psychosocial mal-adaptation. Obviously, ethnic origin is an important moderator
Therapeutic potential of transdermal glyceryl trinitrate in the management of acute stroke
The nitric oxide donor, glyceryl trinitrate (GTN), is a candidate treatment for the management of acute stroke with haemodynamic and potential reperfusion and neuroprotective effects. When administered as a transdermal patch during the acute and subacute phases after stroke, GTN was safe, lowered blood pressure, maintained cerebral blood flow, and did not induce cerebral steal or alter functional outcome. However, when given within 6 h of stroke onset, GTN reduced death and dependency (odds ratio 0.52; 95% confidence interval 0.34–0.78), death, disability, cognitive impairment and mood disturbance, and improved quality of life (data from two trials, n = 312). In a pooled analysis of four studies (n = 186), GTN reduced between-visit systolic blood pressure variability over days 1–7 compared with no GTN (mean difference -2.09; 95% confidence interval -3.83 to -0.35; p = 0.019). The efficacy of GTN given in the ultra-acute/pre-hospital setting is currently being assessed and, if found to be beneficial, the implications for hyperacute stroke practice are significant. Here, we discuss the evidence to date, potential mechanisms of action and future possibilities, including unanswered questions, for the therapeutic potential of GTN in acute stroke
Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis
<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.</p> <p>Methods</p> <p>The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.</p> <p>Results</p> <p>Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.</p> <p>Conclusions</p> <p>The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.</p
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