Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: Development of an imaging biomarker

Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS. © 2014 Abhinav, Yeh, El-Dokla, Ferrando, Chang, Lacomis, Friedlander and Fernandez-Miranda

Markers for the identification of late breast cancer recurrence

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Rectification of electronic heat current by a hybrid thermal diode

We report the realization of an ultra-efficient low-temperature hybrid heat current rectifier, thermal counterpart of the well-known electric diode. Our design is based on a tunnel junction between two different elements: a normal metal and a superconducting island. Electronic heat current asymmetry in the structure arises from large mismatch between the thermal properties of these two. We demonstrate experimentally temperature differences exceeding $60$ mK between the forward and reverse thermal bias configurations. Our device offers a remarkably large heat rectification ratio up to $\sim 140$ and allows its prompt implementation in true solid-state thermal nanocircuits and general-purpose electronic applications requiring energy harvesting or thermal management and isolation at the nanoscale.Comment: 8 pages, 6 color figure

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Ambient fabrication of flexible and large-area organic light-emitting devices using slot-die coating

The grand vision of manufacturing large-area emissive devices with low-cost roll-to-roll coating methods, akin to how newspapers are produced, appeared with the emergence of the organic light-emitting diode about 20 years ago. Today, small organic light-emitting diode displays are commercially available in smartphones, but the promise of a continuous ambient fabrication has unfortunately not materialized yet, as organic light-emitting diodes invariably depend on the use of one or more time- and energy-consuming process steps under vacuum. Here we report an all-solution-based fabrication of an alternative emissive device, a light-emitting electrochemical cell, using a slot-die roll-coating apparatus. The fabricated flexible sheets exhibit bidirectional and uniform light emission, and feature a fault-tolerant >1-μm-thick active material that is doped in situ during operation. It is notable that the initial preparation of inks, the subsequent coating of the constituent layers and the final device operation all could be executed under ambient air

Comparative study: the effect of annealing conditions on the properties of P3HT:PCBM blends

This paper presents a detailed study on the role of various annealing treatments on organic poly(3-hexylthiophene) and [6]-phenyl-C61-butyric acid methyl ester blends under different experimental conditions. A combination of analytical tools is used to study the alteration of the phase separation, structure and photovoltaic properties of the P3HT:PCBM blend during the annealing process. Results showed that the thermal annealing yields PCBM ‘‘needle-like’’ crystals and that prolonged heat treatment leads to extensive phase separation, as demonstrated by the growth in the size and quantity of PCBM crystals. The substrate annealing method demonstrated an optimal morphology by eradicating and suppressing the formation of fullerene clusters across the film, resulting in longer P3HT fibrils with smaller diameter. Improved optical constants, PL quenching and a decrease in the P3HT optical bad-gap were demonstrated for the substrate annealed films due to the limited diffusion of the PCBM molecules. An effective strategy for determining an optimized morphology through substrate annealing treatment is therefore revealed for improved device efficiency.Web of Scienc

Seismically induced landslide hazard and exposure modelling in Southern California based on the 1994 Northridge, California earthquake event

Quantitative modelling of landslide hazard, as opposed to landslide susceptibility, as a function of the earthquake trigger is vital in understanding and assessing future potential exposure to landsliding. Logistic regression analysis is a method commonly used to assess susceptibility to landsliding; however, estimating probability of landslide hazard as a result of an earthquake trigger is rarely undertaken. This paper utilises a very detailed landslide inventory map and a comprehensive dataset on peak ground acceleration for the 1994 Mw6.7 Northridge earthquake event to fit a landslide hazard logistic regression model. The model demonstrates a high success rate for estimating probability of landslides as a result of earthquake shaking. Seven earthquake magnitude scenarios were simulated using the Open Source Seismic Hazard Analysis (OpenSHA) application to simulate peak ground acceleration, a covariate of landsliding, for each event. The exposure of assets such as population, housing and roads to high levels of shaking and high probabilities of landsliding was estimated for each scenario. There has been urban development in the Northridge region since 1994, leading to an increase in prospective exposure of assets to the earthquake and landslide hazards in the event of a potential future earthquake. As the earthquake scenario magnitude increases, the impact from earthquake shaking initially increases then quickly levels out, but potential losses from landslides increase at a rapid rate. The modelling approach, as well as the specific model, developed in this paper can be used to estimate landslide probabilities as a result of an earthquake event for any scenario where the peak ground acceleration variable is available

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)