Association of eNOS polymorphisms with primary angle-closure glaucoma

Author version made available in accordance with the publisher's policy.Purpose: Recently, several studies have investigated genetic associations between Cytochrome P450 (CYP1B1), Endothelial nitric oxide synthase (eNOS) and Neurotrophin-4 (NTF4) with primary angle-closure glaucoma (PACG) in various ethnic groups. Here we investigate the association of these candidate genes with PACG in samples from Australia and Nepal. Method: A total of 235 patients with PACG (106 Nepalese and 129 Australian) and 492 controls (204 Nepalese and 288 Australian) were included. Tag single nucleotide polymorphisms (SNPs) were selected to cover the majority of common variation within the candidate genes and genotyped in DNA extracted from peripheral whole blood. Allele and haplotype analyses were conducted in PLINK. Bonferroni correction was applied for the total number of SNPs in this study (p=0.05/15=0.003) Results: In the Australian cohort, one eNOS SNP rs3793342 shows significance association with PACG in the Australian cohort after Bonferroni correction (p-value 0.003, OR 0.5 95% CI 0.3-0.8). After adjusting the results for sex and age both SNPs rs3793342 and rs7830 showed significance after Bonferroni correction (p-value of 0.001 and 0.003, respectively). The eNOS haplotype of all 7 typed SNPs showed significant association with a global p-value of 0.019, with the CGCAATC haplotype giving a specific p-value of 0.008 and odds ratio of 1.5 (95% CI 0.9-2.4). In the Nepalese cohort, SNPs in CYP1B1 and NTF4 genes showed borderline association with PACG but did not survive Bonferroni correction. Conclusions: The present data support the involvement of common variations in eNOS with PACG pathogenesis. Differences were observed in the two populations studied, and additional replication studies in other populations are necessary to confirm these association

A cross-ethnicity investigation of genes previously implicated in primary angle closure glaucoma

Purpose: To investigate the underlying genetic variation between candidate genes and primary angle closure glaucoma (PACG) in both Nepalese and Australian populations. Methods: A total of 213 patients with PACG (106 Nepalese and 107 Australian) and 492 age and sex matched controls (204 Nepalese and 288 Australian) were included in the current study. Three candidate genes were selected; methyltetrahydrofolate reductase (MTHFR), calcitonin receptor-like receptor gene (CALCRL), and membrane frizzled-related protein (MFRP). Tag single nucleotide polymorphisms (SNPs) were selected and genotyped to capture the majority of common variation across each locus. Allele and haplotype analyses were conducted using PLINK. Results: SNPs in the nanophthalmos gene MFRP were found to be nominally associated with PACG under the allelic model. Two SNPs were associated in the Australian cohort (rs948414; p=0.02 and rs36015759; p=0.02), and a single SNP in the Nepalese cohort (rs10790289; p=0.03), however these SNPs failed to remain significant after adjustment for sex and age. A haplotype at the CALCRL gene (AATACAGAT) was associated in the Australian cohort (corrected p-value= 0.024). No association was observed in either cohort for MTHFR. Conclusions: This study implicates genetic variation at the CALCRL gene in the pathogenesis of PACG in an Australian Caucasian cohort. Additionally, the MFRP gene shows tendency to be associated with PACG in both the Australian and Nepalese cohorts. Further investigation in a larger cohort is warranted to confirm these findings. No statistically significant associations were identified between MTHFR and PACG in either population

Association of genetic variants with primary angle closure glaucoma in two different populations

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: A recent large genome-wide association study (GWAS) identified multiple variants associated with primary angle-closure glaucoma (PACG). The present study investigated the role of these variants in two cohorts with PACG recruited from Australia and Nepal. METHOD: Patients with PACG and appropriate controls were recruited from eye clinics in Australia (n = 232 cases and n = 288 controls) and Nepal (n = 106 cases and 204 controls). Single nucleotide polymorphisms (SNPs) rs3753841 (COL11A1), rs1015213 (located between PCMTD1 and ST18), rs11024102 (PLEKHA7), and rs3788317 (TXNRD2) were selected and genotyped on the Sequenom. Analyses were conducted using PLINK and METAL. RESULTS: After adjustment for age and sex, SNP rs3753841 was found to be significantly associated with PACG in the Australian cohort (p = 0.017; OR = 1.34). SNPs rs1015213 (p = 0.014; OR 2.35) and rs11024102 (p = 0.039; OR 1.43) were significantly associated with the disease development in the Nepalese cohort. None of these SNPs survived Bonferroni correction (p = 0.05/4 = 0.013). However, in the combined analysis, of both cohorts, rs3753841 and rs1015213 showed significant association with p-values of 0.009 and 0.004, respectively both surviving Bonferroni correction. SNP rs11024102 showed suggestive association with PACG (p-value 0.035) and no association was found with rs3788317. CONCLUSION: The present results support the initial GWAS findings, and confirm the SNP's contribution to PACG. This is the first study to investigate these loci in both Australian Caucasian and Nepalese populations

Quantifying the Likelihood of Regional Cimate Change: A hybridized Approach

The growing need for risk-based assessments of impacts and adaptation to climate change calls for increased capability in climate projections: the quantification of the likelihood of regional outcomes and the representation of their uncertainty. Herein, we present a technique that extends the latitudinal projections of the 2-D atmospheric model of the MIT Integrated Global System Model (IGSM) by applying longitudinally resolved patterns from observations, and from climate-model projections archived from exercises carried out for the 4th Assessment Report (AR4) of the Intergovernmental Panel on Climate Change (IPCC). The method maps the IGSM zonal means across longitude using a set of transformation coefficients, and we demonstrate this approach in application to near-surface air temperature and precipitation, for which high-quality observational datasets and model simulations of climate change are available. The current climatology of the transformation coefficients is observationally based. To estimate how these coefficients may alter with climate, we characterize the climate models’ spatial responses, relative to their zonal mean, from transient increases in trace-gas concentrations and then normalize these responses against their corresponding transient global temperature responses. This procedure allows for the construction of meta-ensembles of regional climate outcomes, combining the ensembles of the MIT IGSM—which produce global and latitudinal climate projections, with uncertainty, under different global climate policy scenarios—with regionally resolved patterns from the archived IPCC climate-model projections. This approach also provides a hybridization of the climate-model longitudinal projections with the global and latitudinal patterns projected by the IGSM, and can be applied to any given state or flux variable that has the sufficient observational and model-based information.U.S. Department of Energy’s Abrupt Climate Change program, grant # DE-FG02-08ER64597

CliCrop: a Crop Water-Stress and Irrigation Demand Model for an Integrated Global Assessment Model Approach

http://globalchange.mit.edu/research/publications/2264This paper describes the use of the CliCrop model in the context of climate change general assessment modeling. The MIT Integrated Global System Model (IGSM) framework is a global integrated assessment modeling framework that uses emission predictions and economic outputs from the MIT Emission Prediction and Policy Analysis (EPPA) model and earth system modeling predictions from the IGSM to drive a land system component, a crop model (CliCrop) and a Water Resource System (WRS) model. The global Agriculture and Water System are dependant upon and interlinked with the global climate system. As irrigated agriculture provides 60% of grains and 40% of all crop production on 20% of global crop lands and accounts for 80% of global water consumption, it is crucial that the agricultural-water linkage be properly modeled. Crop models are used to predict future yields, irrigation demand and to understand the effect of crop and soil type on food productivity and soil fertility. In the context of an integrated global assessment, a crop water-stress and irrigation demand model must meet certain specifications that are different for other crop models; it needs to be global, fast and generic with a minimal set of inputs. This paper describes how CliCrop models the physical and biological processes of crop growth and yield production and its use within the MIT Integrated Global System Model (IGSM) framework, including the data inputs. This paper discusses the global data bases used as input to CliCrop and provides a comparison of the accuracy of CliCrop with the detailed biological-based crop model DSSAT as well as with measured crop yields over the U.S. at the country level using reanalyzed weather data. In both cases CliCrop performed well and the analysis validated its use for climate change impact assessment. We then show why correctly modeling the soil is important for irrigation demand calculation, especially in temperate areas. Finally, we discuss a method to estimate actual water withdrawal from modeled physical crop requirements using U.S. historical data.The initial funding for CliCrop was provided by USAID under a program on climate change adaptation in Niger. Further funding was provided by UN University World Institute for Development Economics Research for the Application and Development of CliCrop in Africa, the authors would like to particularly thank Prof. Finn Tarp, Prof. Channing Arndt and Dr. James Thurlow for their support. The authors also would like to thank Dr. Jawoo Koo of IFPRI for his review and contributions to the software development. The authors also gratefully acknowledge additional financial support for this work provided by the MIT Joint Program on the Science and Policy of Global Change through a consortium of industrial sponsors and Federal grants. Development of the IGSM applied in this research was supported by the U.S. Department of Energy, Office of Science (DE-FG02-94ER61937); the U.S. Environmental Protection Agency, EPRI, and other U.S. government agencies and a consortium of 40 industrial and foundation sponsors

The control of the drugstore beetle, Stegobium paniceum (Coleoptera: Anobiidae) with high and low temperatures

Botanicals; dried plants, roots, stems, leaves, seeds and flowers, have been used from the dawn of history as drugs or spices (Craker, 2007). Botanicals have been used in the health care system to improve blood circulation, reduce chronic fever and cure chronic constipation (Golob et al., 1999; Samy et al., 2008). The drugstore beetle, Stegobium paniceum (L.) (Coleoptera: Anobiidae), is a pest of stored medicinal and aromatic plants and one of the most common insects found in botanical warehouses (Abdelghany et al., 2010). Generally, mortality of each stage increased with an increase of temperature and exposure time. Heat tolerance for different stages from highest to lowest was; young larvae, old larvae, eggs, adult and pupae. The mortality after 7 h, at 42ºC for young larvae, old larvae, eggs, adult and pupae respectively was; 16 ± 5, 31 ± 6, 48 ± 3, 63 ± 8 and 86 ± 2% (mean + SEM). Similarly, the lethal time for 90% mortality (LT>sub>90) at 42ºC was; too low to estimate, 773, 144, 12 and 11 h. The LT90 value for young larvae at 42, 45, 50, 55 and 60ºC was 25, 20, 3.9, 0.18 and 0.08 h respectively. The cold tolerance of different stages at 0ºC from highest to lowest was adult, old larva, young larva, pupa, and egg. The LT90 at 0ºC was 298, 153, 151, 89 and 53 h, respectively. The LT90 value for adults at 5, -5, -10 and -15ºC was 792, 58, 2 and 0.8 h, respectively. The supercooling point of adults, young larvae, old larvae and pupae was -15.2 ± 2ºC, -9.0 ± 0.8ºC, -6.5 ± 0.5ºC, and -4.0 ± 1.4ºC respectively. Heat treatments that control young larvae should control all other stages of S. paniceum. Cold treatments that control adults should control all other stages of S. paniceum. Dried plants stored at 5ºC for 45 days or 42ºC for 30 h and then kept below 18ºC throughout the rest of the year, should remain pest-free without any chemical control. The full paper was submitted to Entomologia Experimentalis et Applicata. Keywords: Anobiidae, Heat, Cold, Supercooling point, Tolerance, Storage, Warehous

Acceptance criteria for corroded carbon steel piping containing weld defects

Acceptance criteria for corroded low temperature, low pressure carbon steel piping containing weld defects is presented along with a typical application of these criteria. They are intended to preclude gross rupture or rapidly propagating failure due to uniform wall thinning, local wall thinning, pitting corrosion and weld defects. The minimum allowable uniform wail thickness is based on the code-of-record allowable stress and fracture criteria. Weld defects are postulated as potential sites for fracture initiation. CEGB/R6 failure assessment diagram is used as the fracture criteria to determine the minimum allowable wall thickness. Design of a large portion of the low temperature, low pressure piping is dominated by axial stresses. Existing local wall thinning acceptance criteria address high pressure piping where hoop stress dominates the design. The existing criteria is over conservative, in some cases, when used on low pressure piping. Local wall thinning criteria is developed to limit the axial stress on the locally thinned section, based on a reduced average thickness. Limits on pit density are also developed to provide acceptance criteria for pitted piping