Synthesis of bicyclo-DNA nucleosides with additional functionalization in the carbocyclic ring

Two novel bicyclo nucleoside isomers carrying the base thymine in the furanose ring and an ester substituent in the carbocyclic ring were synthesized from a common bicyclic sugar precursor via a cyclopropanation/fragmentation pathway in nine steps. The relative configuration of the ester substituent in both isomers as well as the anomeric configuration in one nucleoside was determined by 1H-NMR difference NOE spectroscopy

A CURE for noisy magnetic resonance images: Chi-square unbiased risk estimation

In this article we derive an unbiased expression for the expected mean-squared error associated with continuously differentiable estimators of the noncentrality parameter of a chi-square random variable. We then consider the task of denoising squared-magnitude magnetic resonance image data, which are well modeled as independent noncentral chi-square random variables on two degrees of freedom. We consider two broad classes of linearly parameterized shrinkage estimators that can be optimized using our risk estimate, one in the general context of undecimated filterbank transforms, and another in the specific case of the unnormalized Haar wavelet transform. The resultant algorithms are computationally tractable and improve upon state-of-the-art methods for both simulated and actual magnetic resonance image data.Comment: 30 double-spaced pages, 11 figures; submitted for publicatio

Image-based deep learning reveals the responses of human motor neurons to stress and VCP-related ALS

OBJECTIVES: Although morphological attributes of cells and their substructures are recognized readouts of physiological or pathophysiological states, these have been relatively understudied in amyotrophic lateral sclerosis (ALS) research. MATERIALS AND METHODS: In this study, we integrate multichannel fluorescence high-content microscopy data with deep-learning imaging methods to reveal - directly from unsegmented images - novel neurite-associated morphological perturbations associated with (ALS-causing) VCP-mutant human motor neurons (MNs). RESULTS: Surprisingly, we reveal that previously unrecognized disease-relevant information is withheld in broadly used and often considered 'generic' biological markers of nuclei (DAPI) and neurons (β III-tubulin). Additionally, we identify changes within the information content of ALS-related RNA binding protein (RBP) immunofluorescence imaging that is captured in VCP-mutant MN cultures. Furthermore, by analysing MN cultures exposed to different extrinsic stressors, we show that heat stress recapitulates key aspects of ALS. CONCLUSIONS: Our study therefore reveals disease-relevant information contained in a range of both generic and more specific fluorescent markers, and establishes the use of image-based deep learning methods for rapid, automated and unbiased identification of biological hypotheses

Trajectory Analysis for Sport and Video Surveillance

In video surveillance and sports analysis applications, object trajectories offer the possibility of extracting rich information on the underlying behavior of the moving targets. To this end we introduce an extension of Point Distribution Models (PDM) to analyze the object motion in their spatial, temporal and spatiotemporal dimensions. These trajectory models represent object paths as an average trajectory and a set of deformation modes, in the spatial, temporal and spatiotemporal domains. Thus any given motion can be expressed in terms of its modes, which in turn can be ascribed to a particular behavior. The proposed analysis tool has been tested on motion data extracted from a vision system that was tracking radio-guided cars running inside a circuit. This affords an easier interpretation of results, because the shortest lap provides a reference behavior. Besides showing an actual analysis we discuss how to normalize trajectories to have a meaningful analysis

Use of an experimental design model to determine the impact of different fermentation parameters on the development of flavour compounds in wine

An experimental design developed by YOUDEN and STEINER (1975) was successfully applied to micro-fermentation experiments with two different grape musts. This tool allowed the verification of the impact of several fermentation parameters on the fermentation course and on flavour development with a restricted number of experiments. The positive effects of a higher fermentation temperature on the development of 3-mercaptohexanol, an important contributor to the characteristic aroma of the Petite Arvine wine, could be demonstrated.

Shape and orientation effects on the ballistic phonon thermal properties of ultra-scaled Si nanowires

The effect of geometrical confinement, atomic position and orientation of Silicon nanowires (SiNWs) on their thermal properties are investigated using the phonon dispersion obtained using a Modified Valence Force Field (MVFF) model. The specific heat ($C_{v}$) and the ballistic thermal conductance ($\kappa^{bal}_{l}$) shows anisotropic variation with changing cross-section shape and size of the SiNWs. The $C_{v}$ increases with decreasing cross-section size for all the wires. The triangular wires show the largest $C_{v}$ due to their highest surface-to-volume ratio. The square wires with [110] orientation show the maximum $\kappa^{bal}_{l}$ since they have the highest number of conducting phonon modes. At the nano-scale a universal scaling law for both $C_{v}$ and $\kappa^{bal}_{l}$ are obtained with respect to the number of atoms in the unit cell. This scaling is independent of the shape, size and orientation of the SiNWs revealing a direct correlation of the lattice thermal properties to the atomistic properties of the nanowires. Thus, engineering the SiNW cross-section shape, size and orientation open up new ways of tuning the thermal properties at the nanometer regime.Comment: 11 figures, 4 tables, submitted to JA

Theory and simulation of quantum photovoltaic devices based on the non-equilibrium Green's function formalism

This article reviews the application of the non-equilibrium Green's function formalism to the simulation of novel photovoltaic devices utilizing quantum confinement effects in low dimensional absorber structures. It covers well-known aspects of the fundamental NEGF theory for a system of interacting electrons, photons and phonons with relevance for the simulation of optoelectronic devices and introduces at the same time new approaches to the theoretical description of the elementary processes of photovoltaic device operation, such as photogeneration via coherent excitonic absorption, phonon-mediated indirect optical transitions or non-radiative recombination via defect states. While the description of the theoretical framework is kept as general as possible, two specific prototypical quantum photovoltaic devices, a single quantum well photodiode and a silicon-oxide based superlattice absorber, are used to illustrated the kind of unique insight that numerical simulations based on the theory are able to provide.Comment: 20 pages, 10 figures; invited review pape

Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology

Amyotrophic Lateral Sclerosis (ALS) causes motor neuron degeneration, with 97% of cases exhibiting TDP-43 proteinopathy. Elucidating pathomechanisms has been hampered by disease heterogeneity and difficulties accessing motor neurons. Human induced pluripotent stem cell-derived motor neurons (iPSMNs) offer a solution; however, studies have typically been limited to underpowered cohorts. Here, we present a comprehensive compendium of 429 iPSMNs from 15 datasets, and 271 post-mortem spinal cord samples. Using reproducible bioinformatic workflows, we identify robust upregulation of p53 signalling in ALS in both iPSMNs and post-mortem spinal cord. p53 activation is greatest with C9orf72 repeat expansions but is weakest with SOD1 and FUS mutations. TDP-43 depletion potentiates p53 activation in both post-mortem neuronal nuclei and cell culture, thereby functionally linking p53 activation with TDP-43 depletion. ALS iPSMNs and post-mortem tissue display enrichment of splicing alterations, somatic mutations, and gene fusions, possibly contributing to the DNA damage response