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Fluorescent Filter-Trap Assay for Amyloid Fibril Formation Kinetics in Complex Solutions.

Amyloid fibrils are the most distinct components of the plaques associated with various neurodegenerative diseases. Kinetic studies of amyloid fibril formation shed light on the microscopic mechanisms that underlie this process as well as the contributions of internal and external factors to the interplay between different mechanistic steps. Thioflavin T is a widely used noncovalent fluorescent pr

Between-Monitor Differences in Step Counts Are Related to Body Size: Implications for Objective Physical Activity Measurement

Background: The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation. Methods: Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day du

Targeting Expression of the Leukemogenic PML-RAR alpha Fusion Protein by Lentiviral Vector-Mediated Small Interfering RNA Results in Leukemic Cell Differentiation and Apoptosis

Acute promyelocytic leukemia (APL) results from a chromosomal translocation that gives rise to the leukemogenic fusion protein PML-RAR alpha (promyelocytic leukemia-retinoic acid alpha receptor). Differentiation of leukemic cells and complete remission of APL are achieved by treatment of patients with pharmacological doses of all-trans retinoic acid (ATRA), making APL a model disease for different

Analytic Input to Societal Emergency Management - On the Design of Methods

Information from performed risk and vulnerability analyses, evaluation of responses in relation to actual emergencies etcetera can be very useful in efforts directed at preventing, mitigating and/or preparing for future emergencies. This thesis focuses on the development of methods for such analysis and evaluation. A general process for systematic design of methods is introduced and discussed and

Challenges in Designing Resilient Socio-technical Systems: A Case Study of Railway Tunnel Projects

This paper presents a case study of decision-making at the design stage of a socio-technical system where resilience at the global level of the system was constrained by the local perspectives adopted by the different stakeholders. The study is based on interviews with key decision-makers involved in the design stage of six railway tunnel projects in Sweden. The results show that differences in ro

A Model for Vulnerability Analysis of Interdependent Infrastructure Networks

The technical infrastructures of the society are becoming more and more interconnected and in-terdependent, i.e. the function of an infrastructure influences the function of other infrastructures. Distur-bances in one infrastructure therefore often traverse to other dependent infrastructures and possibly even back to the infrastructure where the failure originated. It is becoming increasingly impo

Treatment of Uncertainty in Risk Based Regulations and Standards for Risk Analysis

The role of quantitative risk analysis as a foundation for decision making, regarding hazardous activities and establishments, has gained increased importance during the last decades. When performing a quantitative risk analysis, a wide range of uncertainties will inevitably be introduced during the process. The impact of these uncertainties must somehow be addressed if the analysis is to serve as

Proliferation of amyloid-beta 42 aggregates occurs through a secondary nucleation mechanism

The generation of toxic oligomers during the aggregation of the amyloid-beta (A beta) peptide A beta 42 into amyloid fibrils and plaques has emerged as a central feature of the onset and progression of Alzheimer's disease, but the molecular pathways that control pathological aggregation have proved challenging to identify. Here, we use a combination of kinetic studies, selective radiolabeling expe

Surface nanostructures for fluorescence probing of supported lipid bilayers on reflective substrates.

The fluorescence interference contrast (FLIC) effect prevents the use of fluorescence techniques to probe the continuity and fluidity of supported lipid bilayers on reflective materials due to a lack of detectable fluorescence. Here we show that adding nanostructures onto reflective surfaces to locally confer a certain distance between the deposited fluorophores and the reflecting surface enables

Invited commentary: Gene x lifestyle interactions and complex disease traits--inferring cause and effect from observational data, sine qua non.

Observational epidemiology has made outstanding contributions to the discovery and elucidation of relations between lifestyle factors and common complex diseases such as type 2 diabetes. Recent major advances in the understanding of the human genetics of this disease have inspired studies that seek to determine whether the risk conveyed by bona fide risk loci might be modified by lifestyle factors