179,669 research outputs found

    How to use Rosen's normalised equilibrium to enforce a socially desirable Pareto efficient solution

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    We consider a situation, in which a regulator believes that constraining a complex good created jointly by competitive agents, is socially desirable. Individual levels of outputs that generate the constrained amount of the externality can be computed as a Pareto efficient solution of the agents' joint utility maximisation problem. However, generically, a Pareto efficient solution is not an equilibrium. We suggest the regulator calculates a Nash-Rosen coupled-constraint equilibrium (or a “generalised” Nash equilibrium) and uses the coupled-constraint Lagrange multiplier to formulate a threat, under which the agents will play a decoupled Nash game. An equilibrium of this game will possibly coincide with the Pareto efficient solution. We focus on situations when the constraints are saturated and examine, under which conditions a match between an equilibrium and a Pareto solution is possible. We illustrate our findings using a model for a coordination problem, in which firms' outputs depend on each other and where the output levels are important for the regulator.

    Intervalloperatoren einer Funktion, deren Lipschitzmatrix eine M-Intervallmatrix ist. Eine Bemerkung zur Konvergenz von Intervallfolgen

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    Krawczyk, R.: Intervalloperatoren einer ...; Eine Bemerkung zur Konvergenz ...; Neumaier, A.: A distributive ...SIGLEDEGerman

    InfSOCSol2 An updated MATLAB Package for Approximating the Solution to a Continuous-Time Infinite Horizon Stochastic Optimal Control Problem with Control and State Constraints

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    This paper is a successor of [AK08]. Both papers describe the same suite of MATLAB R° routines devised to provide an approximately optimal solution to an infinite horizon stochastic optimal control problem. The difference is that this paper explains how to allow for state and control constraints. The suite routines implement a policy improvement algorithm to optimise a Markov decision chain approximating the original control problem, as described in [Kra01c] and [Kra01b].Computational economics, Financial engineering, Approximating Markov decision chains

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Crystal structure of 7-cyano-6,7-dimethyl-1-phenyl-1,3,6,7-tetrahydro-2,1-benzoxaphospole 1-oxide

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    The crystals (C16H18NO2P, Mr=287.30) are orthorhombic, space group Pbca with a=8.200(2), b=14.857(2), and c=24.396(5)Å, V=2972.1 Å3, Z=8, Dx=1.284 mg m-3, λ(Mo Kα)=0.71069 Å, μ=1.90 cm-1, F(000)=216, T=295K. Final R=0.044 for 1673 observed reflections collected on a diffractometer. Structure solved by direct methods. Cis-junction and double bond in the six-membered ring cause its almost ideal sofa conformation. The two neighboring methyl groups are cis, and cyano substituent is in an equatorial position. There is a short intramolecular H(o-phenyl)⋯O(endocyclic) contact of 2.53(3)Å and the phenyl ring is in a less favorable rotational orientation due to molecular packing. © 1989 Plenum Publishing Corporation

    The Lifecycle of a Digital Historical Document: Structure and Content

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    This paper describes the lifecycle of a digital historical document, from template-based structure definition through to content extraction from the scanned pages and its final reconstitution as an electronic document (combining content and semantic information) along with the tools that have been created to realise each stage in the lifecycle. The whole approach is described in the context of different types of typewritten documents relating to prisoners in World-War II concentration camps and is the result of a multinational collaboration under the MEMORIAL project funded (€1.5M) by the European Union (www.memorial-project.info). Extensive tests with historians/archivists and evaluation of the content extraction results indicate the superior performance of the whole semantics-driven approach both over manual transcription and over the semi-automated application of off-the-shelf OCR and the use of a conventional (text and layout) document format

    "Closing the R&D Gap, Evaluating the Sources of R&D Spending"

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    Both spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Goldreich-Krawczyk Revisited: A Note on the Zero Knowledge of Proofs of Knowledge

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    The seminal work of Goldreich and Krawczyk (SIAM Journal on Computing) shows that any constant-round public-coin interactive proof for languages not in BPP{\sf BPP} cannot be black-box zero knowledge. Their result says nothing, however, about proofs (or arguments) of knowledge for languages in BPP{\sf BPP}. As a special case, their work leaves open the question of whether Schnorr\u27s protocol for proving knowledge of discrete logarithms in cyclic groups is black-box zero knowledge.In this work we focus on the zero knowledge of proofs of knowledge, centering on Schnorr\u27s protocol as a prominent example. We prove two lower bounds, ruling out two different classes of simulators through which Schnorr\u27s protocol can be proven zero knowledge: We prove that if a relation R\mathcal{R} has a public-coin interactive proof of knowledge that is black-box zero knowledge and this protocol is compatible with the Fiat-Shamir transform in the random oracle model, then R\mathcal{R} must be efficiently searchable. As an immediate corollary, we deduce that Schnorr\u27s protocol cannot be black-box zero knowledge in groups in which discrete log is hard. We define a new class of simulators for Schnorr\u27s protocol, which we call generic simulators. A generic simulator is one that works in any cyclic group, and does not use the representation of the specific group in which Schnorr\u27s protocol is instantiated. We prove that Schnorr\u27s protocol cannot have generic simulators. As an additional contribution, we generalize the original lower bound of Goldreich and Krawczyk, to prove that a language not in BPP{\sf BPP} cannot have an interactive proof (not necessarily of knowledge) that is both black-box zero knowledge and compatible with the Fiat-Shamir transform in the random oracle model. In conjunction with recent works, this extends the Goldreich-Krawczyk lower bound to public-coin protocols that are not constant-round but have round-by-round soundness, including the parallel repetition of any public-coin interactive proof. </p

    krawczyk

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    Recently the common adiponutrin (PNPLA3) polymorphism p.I148M has been identified as a genetic determinant of severe forms of non-alcoholic fatty liver disease and alcoholic liver disease. Additionally, insulin resistance -linked to the development of non-alcoholic steatohepatitis -increases the risk of developing gallstones. Here we assessed whether the PNPLA3 p.I148M (c.444 C&gt;G) polymorphism affects glucose and lipid levels and increases gallstone risk. We analysed 229 individuals with gallstones from 108 families (age 24-80 years, BMI 17-55 kg/m 2 ) and 258 gallstone-free controls (age 20-70 years, BMI 14-43 kg/m 2 ). Fasting glucose, triglyceride and cholesterol serum levels were determined. The p.I148M polymorphism was genotyped using a PCR-based assay with 5&apos;-nuclease and fluorescence detection. Case-control association tests and nonparametric linkage (NPL) analysis in sib-pairs were performed. Individuals carrying the [GG] genotype had significantly (P&lt;0.0001) higher median fasting glucose levels as compared to [GC] and [CC] carriers. After adjustment for multiple testing, we detected a trend for an association between triglyceride levels and variant adiponutrin in gallstone patients (P=0.032), and gallstone cases carrying the genotype [CC] presented with significantly higher triglyceride levels than the corresponding controls (P&lt;0.003). No significant effects on cholesterol metabolism were detected. Neither genotype distributions nor NPL scores provided evidence for association or linkage between the PNPLA3 variant and gallstones. In conclusion, homozygous carriers of the PNPLA3 risk allele display higher fasting glucose. Although this adiponutrin variant may affect triglyceride homeostasis, it does not increase the risk of cholelithiasis. K e y w o r d s : adiponutrin, insulin resistance, metabolic syndrome, PNPLA3, single nucleotide polymorphism, triglyceride 25) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus infection Taking into account the previously reported association between the adiponutrin variant and non-genetic risk factors for gallstones (e.g. hepatic fat accumulation, liver injury, distorted glucose metabolism), we now aimed to dissect the possible role of the PNPLA3 SNP in gallstone formation. In this respect we genotyped a cohort of sibs with gallstones and unrelated gallstone-free controls. To investigate the role of variant adiponutrin in other metabolic traits, we related PNPLA3 genotypes to serum lipid and glucose levels. MATERIAL AND METHODS Patients Only individuals with documented Caucasian ethnicity were included in the study. As shown in In all study participants glucose, TG and cholesterol levels in serum (mg/dL) were determined by standard assays after an overnight fasting period. The study was conducted according to a study design approved by the local ethical committee, and all participants signed an informed consent form. Genotyping Genomic DNA was isolated from EDTA anticoagulated blood according to the membrane-based QIAamp DNA extraction protocol (Qiagen, Hilden, Germany). The PNPLA3 coding SNP p.I148M (rs738409) was genotyped using solutionphase hybridization reactions with 5&apos;-nuclease and fluorescence detection (TaqMan assays) in a 7300 real-time PCR system (Applera, Norwalk, CT). Primer and probe sequences were: forward primer 5&apos;-AACTTCTCTCTCCTTTGCTTTCACA-3&apos;; reverse primer 5&apos;-TCTACAGTGGCCTTATCCCTCC-3&apos;; VIC 5&apos;-TTCCTGCTTCATGCC-3&apos;; FAM 5&apos;-CCTGCTTCATCCC-3&apos;. To ensure genotyping quality, we included negative controls and DNA samples with known PNPLA3 genotypes as internal controls. PCR reactions contained 20 ng DNA, 900 nM of each primer, 1× TaqMan Universal Master Mix, and 200 nM of VIClabelled and FAM-labelled probes in 25 µL-reactions. Amplification conditions were 95°C for 10 min, 40 cycles of 92°C for 15 s, and 60°C for 1 min. Statistics Unless stated otherwise, statistical analysis was performed with SPSS 18.0 (SPSS, Munich, Germany). All phenotypic quantitative data were expressed as medians and ranges, unless stated specifically. Because we performed multiple tests (n=17), the significance threshold was corrected for multiple testing and two-sided P values &lt;0.003 were considered as significant. The effects of the adiponutrin SNP and of other potential lithogenic factors (age, BMI, gender, serum glucose and lipid levels) Exact tests were performed to check the consistency of genotyping results with Hardy-Weinberg equilibrium (HWE) (http://ihg2.helmholtz-muenchen.de/cgi-bin/hw/hwa1.pl). We performed power calculations using PS: Power and Sample Size Calculation v.3.0 (http://biostat. mc.vanderbilt.edu/wiki/ Main/PowerSampleSize) (35). Association case-control analysis and non-parametric linkage (NPL) tests were performed to investigate the role of the PNPLA3 p.I148M variant in the development of gallstones. For the association analysis, all gallstone-free controls and a single randomly selected member (these individuals are denoted cases throughout this report) of each sib-pair family were included. The association between the adiponutrin variant and cholelithiasis was tested in contingency tables (genotypes: Armitrage&apos;s trend test; alleles: chi 2 test). NPL scores were calculated using GENEHUNTER-MODSCORE v2.0.1 (www.staff.uni-marburg.de/_strauch/software.html) (36) both for the risk (minor) allele frequencies (MAF) in our ASP cohort and for alleles frequencies provided in the Entrez SNP database (http://www.ncbi.nlm.nih.gov/snp). In short, the NPL score allows estimation of the significance of a given allele shared among the family members in the development of the disease; for this the allele frequencies at the analysed genetic locus are compared with the null hypothesis of no linkage (4). Thus, if gallstone disease is linked to the PNPLA3 polymorphism, affected sibs are more likely to share the same allele. RESULTS Obesity enhances gallstone risk PNPLA3 p.I148M variant and gallstone risk: case-control association and sib-pairs analyses The adiponutrin p.I148M variant was successfully genotyped in all individuals with gallstones (n=229, Association between variant adiponutrin and metabolic traits For this analysis we included only unrelated cases (n=108) and all controls (n=258). DISCUSSION This study demonstrates that the adiponutrin p.I148M variant influences glucose and triglyceride levels in our study population. On the other hand, although it has been previously shown that fatty liver disease and enhanced liver fibrosis are both risk factors for cholelithiasis, the variant does not increase gallstone risk per se. Since our case-control study investigating the effect of the adiponutrin variant on gallstone formation is underpowered, we also performed a non-parametric linkage analysis. Indeed, the study cohort let us previously identify the ABCG8 p.D19H variant as the first genetic risk factor for gallstone formation in humans (4). In this study the analysis of sib-pairs showed that this variant was strongly associated with cholelithiasis (NPL score =7.1, P=4.6 x 10 -13 ), which was in line with results of a large GWAS in gallstone patients (3). Hence, the cohort of sib-pairs can be regarded as robust framework for identifying genes associated with gallstone formation. Additionally, sib-pair analysis omits the bias that is encountered in case-control analysis as controls could develop gallbladder stones later in life. Hence, the present analysis of sib-pairs, which did not reveal an association between gallstones and the PNPLA3 variant p.I148M, excludes this SNP as a major risk factor for cholelithiasis. BMI and serum glucose levels are known risk factors for gallstone formation (11). Our results show that each of these factors increases the disease risk, which is in line with the notion that cholelithiasis is a complex multifactorial disorder. Interestingly, we observed that increased serum cholesterol levels lowered the chance of developing gallstones. In contrast, previous studies have demonstrated that patients carrying the ABCG8 (35) and SLC10A2 (7) cholelithiasis risk variants present with lower total serum cholesterol concentrations. It can be hypothesised that the lower risk of developing gallstones in patients with increased serum cholesterol levels might be primarily due to decreased transport of cholesterol into bile. This might lead to increased serum cholesterol but lower biliary cholesterol concentrations. On the other hand, the use of cholesterol lowering drugs (e.g. statins) may significantly lower the risk of developing gallstones (37-39). Hence a functional link between cholesterol levels, hepatobiliary transporters and gallstone formation has not yet been thoroughly investigated and future studies are warranted. It has been previously shown that the PNPLA3 risk allele is associated with severe forms of hepatic fat accumulation In summary, our current study underscores the possible metabolic role of the adiponutrin p.I148M polymorphism. Nevertheless, given the negative results from the previous large studies this effect might be apparent only in selected individuals, for example in those who have gallstones as an additional phenotype. Although the variant does not increase the risk of developing gallstones per se, additional functional studies are warranted to define the molecular link between adiponutrin and metabolic traits
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