University of Iceland

About: University of Iceland is a education organization based out in Reykjavik, Suðurnes, Iceland. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 5423 authors who have published 16199 publications receiving 694762 citations. The organization is also known as: Háskóli Íslands.

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future

Pharmaceutical applications of cyclodextrins: basic science and product development.

Abstract: Objectives Drug pipelines are becoming increasingly difficult to formulate. This is punctuated by both retrospective and prospective analyses that show that while 40% of currently marketed drugs are poorly soluble based on the definition of the biopharmaceutical classification system (BCS), about 90% of drugs in development can be characterized as poorly soluble. Although a number of techniques have been suggested for increasing oral bioavailability and for enabling parenteral formulations, cyclodextrins have emerged as a productive approach. This short review is intended to provide both some basic science information as well as data on the ability to develop drugs in cyclodextrin-containing formulations. Key findings There are currently a number of marketed products that make use of these functional solubilizing excipients and new product introduction continues to demonstrate their high added value. The ability to predict whether cyclodextrins will be of benefit in creating a dosage form for a particular drug candidate requires a good working knowledge of the properties of cyclodextrins, their mechanism of solubilization and factors that contribute to, or detract from, the biopharmaceutical characteristics of the formed complexes. Summary We provide basic science information as well as data on the development of drugs in cyclodextrin-containing formulations. Cyclodextrins have emerged as an important tool in the formulator's armamentarium to improve apparent solubility and dissolution rate for poorly water-soluble drug candidates. The continued interest and productivity of these materials bode well for future application and their currency as excipients in research, development and drug product marketing.

Morphological Attribute Profiles for the Analysis of Very High Resolution Images

Abstract: Morphological attribute profiles (APs) are defined as a generalization of the recently proposed morphological profiles (MPs). APs provide a multilevel characterization of an image created by the sequential application of morphological attribute filters that can be used to model different kinds of the structural information. According to the type of the attributes considered in the morphological attribute transformation, different parametric features can be modeled. The generation of APs, thanks to an efficient implementation, strongly reduces the computational load required for the computation of conventional MPs. Moreover, the characterization of the image with different attributes leads to a more complete description of the scene and to a more accurate modeling of the spatial information than with the use of conventional morphological filters based on a predefined structuring element. Here, the features extracted by the proposed operators were used for the classification of two very high resolution panchromatic images acquired by Quickbird on the city of Trento, Italy. The experimental analysis proved the usefulness of APs in modeling the spatial information present in the images. The classification maps obtained by considering different APs result in a better description of the scene (both in terms of thematic and geometric accuracy) than those obtained with an MP.

Abrupt onset of the Little Ice Age triggered by volcanism and sustained by sea‐ice/ocean feedbacks

Abstract: [1] Northern Hemisphere summer temperatures over the past 8000 years have been paced by the slow decrease in summer insolation resulting from the precession of the equinoxes. However, the causes of superposed century-scale cold summer anomalies, of which the Little Ice Age (LIA) is the most extreme, remain debated, largely because the natural forcings are either weak or, in the case of volcanism, short lived. Here we present precisely dated records of ice-cap growth from Arctic Canada and Iceland showing that LIA summer cold and ice growth began abruptly between 1275 and 1300 AD, followed by a substantial intensification 1430–1455 AD. Intervals of sudden ice growth coincide with two of the most volcanically perturbed half centuries of the past millennium. A transient climate model simulation shows that explosive volcanism produces abrupt summer cooling at these times, and that cold summers can be maintained by sea-ice/ocean feedbacks long after volcanic aerosols are removed. Our results suggest that the onset of the LIA can be linked to an unusual 50-year-long episode with four large sulfur-rich explosive eruptions, each with global sulfate loading >60 Tg. The persistence of cold summers is best explained by consequent sea-ice/ocean feedbacks during a hemispheric summer insolation minimum; large changes in solar irradiance are not required.