Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Shock wave physics and detonation physics – a stimulus for the emergence of numerous new branches in science and engineering

In the period of the Cold War (1945−1991), Shock Wave Physics and Detonation Physics (SWP&DP) – until the beginning of WWII mostly confined to gas dynamics, high-speed aerodynamics, and military technology (such as aero- and terminal ballistics, armor construction, chemical explosions, supersonic gun, and other firearms developments) – quickly developed into a large interdisciplinary field by its own. This rapid expansion was driven by an enormous financial support and two efficient feedbacks: the Terminal Ballistic Cycle and the Research & Development Cycle. Basic knowledge in SWP&DP, initially gained in the Classic Period (from 1808) and further extended in the Post-Classic Period (from the 1930s to present), is now increasingly used also in other branches of Science and Engineering (S&E). However, also independent S&E branches developed, based upon the fundamentals of SWP&DP, many of those developments will be addressed (see Tab. 2). Thus, shock wave and detonation phenomena are now studied within an enormous range of dimensions, covering microscopic, macroscopic, and cosmic dimensions as well as enormous time spans ranging from nano-/picosecond shock durations (such as produced by ultra-short laser pulses) to shock durations that continue for centuries (such as blast waves emitted from ancient supernova explosions). This paper reviews these developments from a historical perspective

Physics and technology of the Next Linear Collider: a report submitted to Snowmass '96

We present the current expectations for the design and physics program of an e+e- linear collider of center of mass energy 500 GeV -- 1 TeV. We review the experiments that would be carried out at this facility and demonstrate its key role in exploring physics beyond the Standard Model over the full range of theoretical possibilities. We then show the feasibility of constructing this machine, by reviewing the current status of linear collider technology and by presenting a precis of our `zeroth-order' design

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 b-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 3 10-4), improved b-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