341 research outputs found
Integrating Philosophy of Science Into Research on Ethical, Legal and Social Issues in the Life Sciences
This paper argues that research on normative issues in the life sciences will benefit from a tighter integration of philosophy of science. We examine research on ethical, legal and social issues in the life sciences (“ELSI”) and discuss three illustrative examples of normative issues that arise in different areas of the life sciences. These examples show that important normative questions are highly dependent on epistemic issues which so far have not been addressed sufficiently in ELSI, RRI and related areas of research. Accordingly, we argue for the integration of research on the epistemic aspects of the relevant areas of science into ELSI research to provide a better basis for addressing normative questions
Atomic-resolution three-dimensional structure of HET-s(218−289) amyloid fibrils by solid-state NMR spectroscopy.
Diamond wire-sawn silicon wafers - from the lab to the cell production
Wafers for the PV industry are mainly sawn with a multi-wire slurry saw. This process is slow (it takes almost half a day to complete a cut) and generates a lot of waste: around half the silicon is sawn away and contaminating the slurry, and the wire is worn and has lost strength. After each cut, the slurry has to be cleaned from the silicon debris and the wire has to be exchanged. In contrast, sawing the wafers with a diamond-plated wire is faster, requires only a cooling liquid that is easy to filter from silicon debris and uses a wire that can be kept for several cut. But this new sawing technique only has a chance to develop if the solar cell production lines developed for slurry sawn wafers is capable of processing these diamond-plated wire sawn wafers efficiently. This study focused on the differences of surface properties of wafers cut via a slurry wire-saw and via a diamond-plated wire-saw. From these surface differences, it is possible to explain the differences in cell processing behaviour and to update the cell production line. Finally, it is shown that wafers sawn with a diamond-plated wire can give cells that are as efficient as the slurry sawn wafers, which validates this new diamond-plated wire wafering method for the production of solar cells
Damping of post-impact vibrations
During the impact of a body on a plate, flexural waves are set which travel circularly outwards from the point of impact. These waves can be used to determine the properties of the impacting body. For accurate measurements, it is advantageous if both the flexural and compression waves pass the sensor just once without being backscattered or reflected from the boundaries.
In this paper, various plate shapes are analysed to evaluate the shape which offers the best damping properties against an impact.
Experimental analysis indicated that the reflection of the flexural waves can be halved using a plate with star-shaped 60° edges with a damping layer. The damping properties can be further doubled by using a star-shaped plate with power law edges in combination with a damping layer which is attached to the edges.
The work reported here offers a possible solution to get significant damping properties. This is achieved by combining a damping layer with edge shaping against a strong single excitation event. The results demonstrate that it is a promising approach for an impact detection systems which could be equally applicable to acoustic damping applications
Cleavage Fracture of Brittle Semiconductors from the Nanometer to the Centimeter Scale
The objective of this paper is to present the fundamental phenomena occurring during the scribing and subsequent fracturing process usually performed when preparing surfaces of brittle semiconductors. In the first part, an overview of nano-scratching experiments of different semiconductor surfaces (InP, Si and GaAs) is given. It is shown how phase transformation can occur in Si under a diamond tip, how single dislocations can be induced in InP wafers and how higher scratching load of GaAs wafer leads to the apparition of a crack network below the surface. A nano-scratching device, inside a scanning electron microscope (SEM), has been used to observe how spalling (crack and detachment of chips) and/or ductile formation of chips may happen at the semiconductor surface. In the second part cleavage experiments are described. The breaking load of thin GaAs (100) wafers is directly related to the presence of initial sharp cracks induced by scratching. By performing finite element modelling (FEM) of samples under specific loading conditions, it is found that the depth of the median crack below the scratch determines quantitatively the onset of crack propagation. By carefully controlling the position and measuring the force during the cleavage, it is demonstrated that crack propagation through a wafer can be controlled. Besides, the influence of the loading configuration on crack propagation and on the cleaved surface quality is explained. © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.
PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils
Self-assembled amyloid fibrils with controllable conformational heterogeneity
Amyloid fibrils are a hallmark of neurodegenerative diseases and exhibit a conformational diversity that governs their pathological functions. Despite recent findings concerning the pathological role of their conformational diversity, the way in which the heterogeneous conformations of amyloid fibrils can be formed has remained elusive. Here, we show that microwave-assisted chemistry affects the self-assembly process of amyloid fibril formation, which results in their conformational heterogeneity. In particular, microwave-assisted chemistry allows for delicate control of the thermodynamics of the self-assembly process, which enabled us to tune the molecular structure of ??-lactoglobulin amyloid fibrils. The heterogeneous conformations of amyloid fibrils, which can be tuned with microwave-assisted chemistry, are attributed to the microwave-driven thermal energy affecting the electrostatic interaction during the self-assembly process. Our study demonstrates how microwave-assisted chemistry can be used to gain insight into the origin of conformational heterogeneity of amyloid fibrils as well as the design principles showing how the molecular structures of amyloid fibrils can be controlledopen0
Screening for Toxic Amyloid in Yeast Exemplifies the Role of Alternative Pathway Responsible for Cytotoxicity
The relationship between amyloid and toxic species is a central problem since the discovery of amyloid structures in different diseases. Despite intensive efforts in the field, the deleterious species remains unknown at the molecular level. This may reflect the lack of any structure-toxicity study based on a genetic approach. Here we show that a structure-toxicity study without any biochemical prerequisite can be successfully achieved in yeast. A PCR mutagenesis of the amyloid domain of HET-s leads to the identification of a mutant that might impair cellular viability. Cellular and biochemical analyses demonstrate that this toxic mutant forms GFP-amyloid aggregates that differ from the wild-type aggregates in their shape, size and molecular organization. The chaperone Hsp104 that helps to disassemble protein aggregates is strictly required for the cellular toxicity. Our structure-toxicity study suggests that the smallest aggregates are the most toxic, and opens a new way to analyze the relationship between structure and toxicity of amyloid species
- …