348 research outputs found
Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, abeta, and alzheimer's disease.
No full textBackground: The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD). Methodology/Principal findings: We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8), fold-increase = 2.12,); the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003). Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2)-C (p = 0.006) and HepG2 (p = 0.02) cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879), we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011) and total measured plasma Abeta levels (b = -0.130, p = 0.009). Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03), and the eleven IDE haplotypes (global p = 0.02) also showed significant association. Conclusions: Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Ass40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs) strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect
Determinants of cross-country income inequality : an augmented Kuznets hypothesis
No full textWhy does income inequality differ among countries? Using a sample of 80 countries from the 1980s, the author shows that two types of factors explain variations in income inequality. The first are factors that are, in the short term, independent of economic policies and are included in the standard formulation of the Kuznets'curve: the level of per capita income and the country's regional heterogeneity. From the viewpoint of economic policy, these are"given"factors, resulting in a"given inequality."The second group of factors are the social-choice factors reflected in the sizeof social transfers and of state sector employment, both of which reduce inequality. For this sample, the reduction amounts to about a quarter of"given"inequality. The importance of social-choice factors rises as the level of income rises. The divergence between actual inequality and the inequality predicted by the standard Kuznets'curve therefore systematically widens as a society develops. This discrepancy is systematic, the author contends. Inequality in richer societies decreases not only because of economic factors but also because societies choose less inequalities as they grow richer.Inequality,Poverty Impact Evaluation,Environmental Economics&Policies,Services&Transfers to Poor,Safety Nets and Transfers
SmartTutor: Creating IDE-based Interactive Tutorials via Editable Replay
No full textInteractive tutorials, like Eclipse's cheat sheets, are good for novice programmers to learn how to perform tasks (e.g., checking out a CVS project) in an Integrated Development Environment (IDE). Creating these tutorials often requires programming effort that is time-consuming and difficult. In this paper, we propose an approach using editable replay of user actions to help authors create interactive tutorials with little programming effort. User actions of performing a task can be recorded, edited, and presented as a tutorial. The tutorial can be replayed interactively for mentoring. We present our SmartTutor implementation in the Eclipse IDE and conduct a preliminary evaluation on it, which demonstrates efficiency gains for the tutorial authors.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000271438200053&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Computer Science, Software EngineeringEICPCI-S(ISTP)
HBV Drug Resistance Substitutions Existed before the Clinical Approval of Nucleos(t)ide Analogues: A Bioinformatic Analysis by GenBank Data Mining
No full textNaturally occurring nucleos(t)ide analogue resistance (NUCr) substitution frequencies in the reverse transcriptase (RT) of the hepatitis B virus (HBV) were studied extensively after the clinical approval of nucleos(t) ide analogues (NUCs; year of approval 1998). We aimed to study NUCr substitutions in HBV RT sequences obtained before 1998 and better understand the evolution of RT sequences without NUC pressures. Our strategy was to retrieve HBV sequences from GenBank deposited before 1998. The initial search used the keywords "hepatitis B virus" or "HBV" and 1139 sequences were found. Data analyses included information extraction: sequence quality control and amino acid substitution analysis on 8 primary NUCr and 3 secondary substitution codons. Three hundred and ninety-four RT-containing sequences of 8 genotypes from 25 countries in 4 continents were selected. Twenty-seven (6.9%) sequences were found to harbor substitutions at NUCr-related codons. Secondary substitutions (rtL80V and rtV173G/A/L) occurred more frequently than primary NUCr substitutions (rtI169L; rtA181G; T184A/S; rtS202T/R; rtM204L and rtM250K). Typical amino acid substitutions associated with NUCr were of rtL80V, rtV173L and rtT184A/S. We confirm the presence of naturally occurring typical HBV NUCr substitutions with very low frequencies, and secondary substitutions are more likely to occur than primary NUCr substitutions without the selective pressure of NUCs.Major Science and Technology Special Project of China Twelfth Five-year Plan [2012ZX10002003-003-013]; Major Science and Technology Special Project of China Thirteenth Five-Year Plan [2017ZX10202202-004-004]SCI(E)ARTICLE8
Kinetics and prediction of HBsAg loss during long-term therapy with nucleos(t)ide analogues of different potency in patients with chronic hepatitis B.
No full textBACKGROUND & AIMS: About 350-400 million people are infected with hepatitis B virus (HBV) chronically and 1 million people die of hepatitis B virus (HBV)-related liver diseases. Nucleos(t)ide analogues (NAs) have been used for the treatment against HBV. However, few studies have investigated the long-term effects of different nucleos(t)ide analogues on levels of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB). The aims of this study were to measure the magnitude of HBsAg reduction by long-term monotherapy with adefovir dipivoxil (ADV) and entecavir (ETV), to compare HBsAg reduction between the two drugs of different potency and to predict the expected time needed to achieve HBsAg loss. METHODS: We retrospectively evaluated the kinetics of HBsAg in 67 patients with CHB who all exhibited persistent viral suppression. These patients were treated with ADV or ETV for at least 6 years. HBV genotype was determined at baseline. Liver biochemistry, HBV serological markers, serum HBV DNA and HBsAg titers were determined at baseline, half year and yearly from year 1 to 6. RESULTS: Serum HBsAg titers after treatment with ADV or ETV were significantly lower than the baseline titers (P0.05). CONCLUSION: Serum HBsAg titers gradually decreased during long-term treatment with either ADV or ETV. It appears that the potency of ADV on HBsAg reduction is close to that of ETV, as long as patients have achieved persistent viral suppression
Reasoning techniques used for data processing
No full textMaster's thesis in Computer scienceIn the oil industry, it is very important to know the current status of drilling processes which can be obtained by analyzing the data from sensors on the drilling engines. The data which oil companies get is complicated, so, in order to analyse the data, it has to be processed first.
There are several methods of intelligent data analysis such as JESS, Petri Nets, R functions, Bayesian Networks and so on. Which of the reasoning techniques can be used to process the data and how to use it in a system are left for users to research and develop. To resolve the problem, upon the study of many other data-processing methods, this paper proposes several novel models for data processing step by step.To validate the effectiveness and the feasibility of the models, the author designs and implements several related systems to interface the reasoning techniques into the systems. The functions of every module in the system and the interrelations between them are achieved in the form of class and the core data structure is described in detail as well.
In chapter 2, the author first analyses the characteristics of reasoning technologies for identifying use. In chapter 3, the author chooses JESS as the reasoning technique to process and monitor the data. Based on the monitoring results from chapter 3 and Petri Net technique, chapter 4 developes another data processing system called ‟SUP system‟ and also analyses the performance of the system. The first 2 models are only used for single server, but when there is a lot of data need to be processed, multi servers are required. In order to solve this problem, the author also does some research on Rserve in a distributed environment in chapter 5.
The results prove that some models and systems are well developed and the reasoning techniques are well used in the systems, but some other reasoning techniques have limitations in the related models due to the reason of researching time and the author‟s knowledge
A Low-Power MEMS IDE Capacitor with Integrated Microhotplate: Application as Methanol Sensor using a Metal-Organic Framework Coating as Affinity Layer
No full textCapacitors made of interdigitated electrodes (IDEs) as a transducer platform for the sensing of volatile organic compounds (VOCs) have advantages due to their lower power operation and fabrication using standard micro-fabrication techniques. Integrating a micro-electromechanical system (MEMS), such as a microhotplate with IDE capacitor, further allows study of the temperature- dependent sensing response of VOCs. In this paper, the design, fabrication, and characterization of a low-power MEMS microhotplate with IDE capacitor to study the temperature-dependent sensing response to methanol using Zeolitic imidazolate framework (ZIF-8), a class of metal-organic framework (MOF), is presented. A Titanium nitride (TiN) microhotplate with aluminum IDEs suspended on a silicon nitride membrane is fabricated and characterized. The power consumption of the ZIF-8 MOF-coated device at an operating temperature of 50 ∘ C is 4.5 mW and at 200 ∘ C it is 26 mW. A calibration methodology for the effects of temperature of the isolation layer between the microhotplate electrodes and the capacitor IDEs is developed. The device coated with ZIF-8 MOF shows a response to methanol in the concentration range of 500 ppm to 7000 ppm. The detection limit of the sensor for methanol vapor at 20 ∘ C is 100 ppm. In situ study of sensing properties of ZIF-8 MOF to methanol in the temperature range from 20 ∘ C to 50 ∘ C using the integrated microhotplate and IDE capacitor is presented. The kinetics of temperature-dependent adsorption and desorption of methanol by ZIF-8 MOF are fitted with double-exponential models. With the increase in temperature from 20 ∘ C to 50 ∘ C, the response time for sensing of methanol vapor concentration of 5000 ppm decreases by 28%, whereas the recovery time decreases by 70%.Electronic Components, Technology and MaterialsOLD ChemE/Organic Materials and InterfacesElectrical Engineering, Mathematics and Computer ScienceEKL ProcessingElectronic InstrumentationChemE/O&O groe
Future Conflicts Are Inevitable: Causes of Interpersonal Conflicts According to Immanuel Kant and Thomas R. Malthus
No full textThe paper entitled “Future Conflicts Are Inevitable: Causes of Interpersonal Conflicts According to Immanuel Kant and Thomas R. Malthus” is composed of four parts. The first part outlines the validity and importance of the issue of interpersonal conflicts, as well as the need to unveil their deepest causes. The second fragment is devoted to the vision of discord between people, developed by Immanuel Kant. The author emphasizes that, in the opinion of the German philosopher, due to the “unsociable sociability” of people, one has to take into account the impossibility of eliminating conflicts from interpersonal relations. The next part presents the concept proposed by Thomas R. Malthus concerning the causes of conflicts. The author observes that the Anglican cleric, supplementing Kant’s reflections, identifies non-human conflict-generating factors, among which the key factor is an indelible shortage in the environment of goods and values desired by people. To summarize the reflections made, in the last part of the paper, the author emphasizes that in the light of Kant’s and Malthus’ observations, it seems easier to understand why the dream of building a world entirely free of interpersonal conflicts is a utopian ide
Type 2 Diabetes Risk Alleles Are Associated With Reduced Size at Birth
No full textOBJECTIVE: Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight. RESEARCH DESIGN AND METHODS: We genotyped single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring. RESULTS: We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11-31], P = 2 x 10(-5), and 14 g [4-23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39-120) lighter at birth than the 8% carrying none (P(trend) = 5 x 10(-7)). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus. CONCLUSIONS: Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype
A study of diabetes mellitus within a large sample of Australian twins.
No full textUdgivelsesdato: 2008-FebTwin studies of diabetes mellitus can help elucidate genetic and environmental factors in etiology and can provide valuable biological samples for testing functional hypotheses, for example using expression and methylation studies of discordant pairs. We searched the volunteer Australian Twin Registry (19,387 pairs) for twins with diabetes using disease checklists from nine different surveys conducted from 1980-2000. After follow-up questionnaires to the twins and their doctors to confirm diagnoses, we eventually identified 46 pairs where one or both had type 1 diabetes (T1D), 113 pairs with type 2 diabetes (T2D), 41 female pairs with gestational diabetes (GD), 5 pairs with impaired glucose tolerance (IGT) and one pair with MODY. Heritabilities of T1D, T2D and GD were all high, but our samples did not have the power to detect effects of shared environment unless they were very large. Weight differences between affected and unaffected cotwins from monozygotic (MZ) discordant pairs were large for T2D and GD, but much larger again for discordant dizygotic (DZ) pairs. The bivariate genetic analysis (under the multifactorial threshold model) estimated the genetic correlation between body mass index (BMI) and T2D to be 0.46, and the environmental correlation at only 0.06
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