Optimal Experimental Design for Biophysical Modelling in Multidimensional Diffusion MRI

Computational models of biophysical tissue properties have been widely used in diffusion MRI (dMRI) research to elucidate the link between microstructural properties and MR signal formation. For brain tissue, the research community has developed the so-called Standard Model (SM) that has been widely used. However, in clinically applicable acquisition protocols, the inverse problem that recovers the SM parameters from a set of MR diffusion measurements using pairs of short pulsed field gradients was shown to be ill-posed. Multidimensional dMRI was shown to solve this problem by combining linear and planar tensor encoding data. Given sufficient measurements, multiple choices of b-tensor sets provide enough information to estimate all SM parameters. However, in the presence of noise, some sets will provide better results. In this work, we develop a framework for optimal experimental design of multidimensional dMRI sequences applicable to the SM. This framework is based on maximising the determinant of the Fisher information matrix, which is averaged over the full SM parameter space. This averaging provides a fairly objective information metric tailored for the expected signal but that only depends on the acquisition configuration. The optimisation of this metric can be further restricted to any subclass of desirable design constraints like, for instance, hardware-specific constraints. In this work, we compute the optimal acquisitions over the set of all b-tensors with fixed eigenvectors

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

TEM and HREM of diamond crystals grown on Si tips: structure and results of ion-beam-treatment.

Diamond single crystals were grown on the silicon whiskers by a hot filament chemical vapor deposition technique at the filament temperature about 2100 degrees C and the temperature of support 800 degrees C. Specimens were examined by SEM, TEM, HRTEM and SAED. When the filament temperature was about 1900 degrees C globular polycrystalline diamond particles were grown. At a support temperature more then 800 degrees C SiC nanoparticles were formed. To investigate the ion etching process of the silicon tip/diamond system, tips were treated with an Ar(+) beam with energy up to 30 kV. The results depend on fluence: at 4 x 10(18)ion/cm(2) diamonds and partially Si tips were destroyed, amorphous layer was formed (sometimes with nanometric size fragments of diamond); at 1 x 10(18)ion/cm(2) sharpened diamonds (radius of curvature about 20 nm) covered with amorphous layer (radius about 80 nm) probably with nanoclusters of diamond were observed; at 4.4 x 10(17) ion/cm(2) there was no visible tip sharpening but formation of amorphous thick layer occurred. The emission characteristics of Si tips covered with diamond were improved due to ion treatment. Since such tips in our case were covered with amorphous layer containing nanometric size fragments of diamond, we suppose this layer is responsible for electron emission improvement