Visualizing internetworked argumentation

In this chapter, we outline a project which traces its source of inspiration back to the grand visions of Vannevar Bush (scholarly trails of linked concepts), Doug Engelbart (highly interactive intellectual tools, particularly for argumentation), and Ted Nelson (large scale internet publishing with recognised intellectual property). In essence, we are tackling the age-old question of how to organise distributed, collective knowledge. Specifically, we pose the following question as a foil: In 2010, will scholarly knowledge still be published solely in prose, or can we imagine a complementary infrastructure that is ‘native’ to the emerging semantic, collaborative web, enabling more effective dissemination and analysis of ideas

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Runaway electron modelling in the self-consistent core European Transport Simulator

Relativistic runaway electrons are a major concern in tokamaks. Although significant theoretical development had been undertaken in recent decades, we still lack a self-consistent simulator that could simultaneously capture all aspects of this phenomenon. The European framework for Integrated Modelling (EU-IM) facilitates the integration of different plasma simulation tools by providing a standard data structure for communication that enables relatively easy integration of different physics codes. A three-level modelling approach was adopted for runaway electron simulations within the EU-IM. Recently, a number of runaway electron modelling modules have been integrated into this framework. The first level of modelling (Runaway Indicator) is limited to the indication if runaway electron generation is possible or likely. The second level (Runaway Fluid) adopts an approach similar to e.g. the GO code, using analytical formulas to estimate changes in the runaway electron current density. The third level is based on the solution of the electron kinetics. One such code is LUKE that can handle the toroidicity-induced effects by solving the bounce-averaged Fokker-Planck equation. Another approach is used in NORSE, which features a fully nonlinear collision operator that makes it capable of simulating major changes in the electron distribution, for example slide-away. Both codes handle the effect of radiation on the runaway distribution. These runaway-electron modelling codes are in different stages of integration into the EU-IM infrastructure, and into the European Transport Simulator (ETS), which is a fully capable modular 1.5D core transport simulator. The ETS with Runaway Fluid was benchmarked to the GO code implementing similar physics. Coherent integration of kinetic solvers requires more effort on the coupling, especially regarding the definition of the boundary between runaway and thermal populations, and on consistent calculation of resistivity. Some of these issues are discussed

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired \u3b2-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology.RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of 3c2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates.RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 7 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 7 10(-4)), improved \u3b2-cell function (P = 1.1 7 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 7 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets.CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis