Infrared thermochromic antenna composite for self-adaptive thermoregulation

Self-adaptive thermoregulation, the mechanism living organisms use to balance their temperature, holds great promise for decarbonizing cooling and heating processes. The functionality can be effectively emulated by engineering the thermal emissivity of materials to adapt to background temperature variations. Yet, solutions that marry large emissivity switching (${\Delta}\epsilon$) with scalability, cost-effectiveness and design freedom are still lacking. Here, we fill this gap by introducing infrared dipole antennas made of tunable thermochromic materials. We demonstrate that non-spherical antennas (rods, stars and flakes) made of vanadium-dioxide can exhibit a massive (~200-fold) increase in their absorption cross-section as temperature rises. Embedding these antennas in polymer films, or simply spraying them directly, creates free-form thermoregulation composites, featuring an outstanding ${\Delta}\epsilon\sim0.6$ in spectral ranges that can be tuned at will. Our research paves the way for versatile self-adaptive heat management solutions (coatings, fibers, membranes and films) that could find application in radiative-cooling, heat-sensing, thermal-camouflage, and other

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

Resonant Ta Doping for Enhanced Mobility in Transparent Conducting SnO2

Transparent conducting oxides (TCOs) are ubiquitous in modern consumer electronics. SnO2 is an earth abundant, cheaper alternative to In2O3 as a TCO. However, its performance in terms of mobilities and conductivities lags behind that of In2O3. On the basis of the recent discovery of mobility and conductivity enhancements in In2O3 from resonant dopants, we use a combination of state-of-the-art hybrid density functional theory calculations, high resolution photoelectron spectroscopy, and semiconductor statistics modeling to understand what is the optimal dopant to maximize performance of SnO2-based TCOs. We demonstrate that Ta is the optimal dopant for high performance SnO2, as it is a resonant dopant which is readily incorporated into SnO2 with the Ta 5d states sitting ∼1.4 eV above the conduction band minimum. Experimentally, the band edge electron effective mass of Ta doped SnO2 was shown to be 0.23m0, compared to 0.29m0 seen with conventional Sb doping, explaining its ability to yield higher mobilities and conductivities

Aerosol-assisted chemical vapour deposition of transparent superhydrophobic film by using mixed functional alkoxysilanes

A method for the preparation of transparent superhydrophobic silica coatings on glass substrates via aerosol-assisted chemical vapour deposition (AACVD) is described. A multi-layer process to produce dual scale silica nanoparticles films, by using different functional alkoxysilanes was investigated. A first layer of 3-methacryloxypropyltrimethoxysilane (MPS) and a second layer of tetraethylorthosilicate (TEOS) were deposited at different temperatures to generate micro and nano particles of silica. Finally, a layer of perfluorooctyltriethoxysilane was deposited on top of the two layers to achieve superhydrophobicity. The transparent superhydrophobic film showed transparency of 90% in the visible light region with a static water contact angle of 165° and a sliding angle lower than 1°. Various durability tests were performed on the transparent superhydrophobic film, showing a constant water repellency after corrosion and organic solvents tests, strong resistance under UV light, and thermal stability up to 400 °C. Sandpaper mechanical robustness durability test showed superhydrophobicity for up to 5 rubbing cycles. In this study, a novel strategy to achieve highly transparent superhydrophobic glass surfaces using AACVD of alkoxysilanes, to produce surfaces with excellent durability is described. This shows great potential to obtain silica superhydrophobic films for large-scale applications

Robust Protection of III-V Nanowires in Water Splitting by a Thin Compact TiO2 Layer.

Narrow-band-gap III-V semiconductor nanowires (NWs) with a suitable band structure and strong light-trapping ability are ideal for high-efficiency low-cost solar water-splitting systems. However, due to their nanoscale dimension, they suffer more severe corrosion by the electrolyte solution than the thin-film counterparts. Thus, short-term durability is the major obstacle for using these NWs for practical water-splitting applications. Here, we demonstrated for the first time that a thin layer (∼7 nm thick) of compact TiO2 deposited by atomic layer deposition can provide robust protection to III-V NWs. The protected GaAs NWs maintain 91.4% of its photoluminescence intensity after 14 months of storage in ambient atmosphere, which suggests the TiO2 layer is pinhole-free. Working as a photocathode for water splitting, they exhibited a 45% larger photocurrent density compared with unprotected counterparts and a high Faraday efficiency of 91% and can also maintain a record-long highly stable performance among narrow-band-gap III-V NW photoelectrodes; after 67 h photoelectrochemical stability test reaction in a strong acid electrolyte solution (pH = 1), they show no apparent indication of corrosion, which is in stark contrast to the unprotected NWs that fully failed after 35 h. These findings provide an effective way to enhance both stability and performance of III-V NW-based photoelectrodes, which are highly important for practical applications in solar-energy-based water-splitting systems

Alternative processing of human HTT mRNA with implications for Huntington's disease therapeutics

Huntington disease is caused by a CAG repeat expansion in exon 1 of the huntingtin gene (HTT) that is translated into a polyglutamine stretch in the huntingtin protein (HTT). We previously showed that HTT mRNA carrying an expanded CAG repeat was incompletely spliced to generate HTT1a, an exon 1 only transcript, which was translated to produce the highly aggregation-prone and pathogenic exon 1 HTT protein. This occurred in all knock-in mouse models of Huntington's disease and could be detected in patient cell lines and post-mortem brains. To extend these findings to a model system expressing human HTT, we took advantage of YAC128 mice that are transgenic for a yeast artificial chromosome carrying human HTT with an expanded CAG repeat. We discovered that the HTT1a transcript could be detected throughout the brains of YAC128 mice. We implemented RNAscope to visualise HTT transcripts at the single molecule level and found that full-length HTT and HTT1a were retained together in large nuclear RNA clusters, as well as being present as single transcripts in the cytoplasm. Homogeneous time-resolved fluorescence analysis demonstrated that the HTT1a transcript had been translated to produce the exon 1 HTT protein. The levels of exon 1 HTT in YAC128 mice, correlated with HTT aggregation, supportive of the hypothesis that exon 1 HTT initiates the aggregation process. Huntingtin-lowering strategies are a major focus of therapeutic development for Huntington's disease. These approaches often target full-length HTT alone and would not be expected to reduce pathogenic exon 1 HTT levels. We have established YAC128 mouse embryonic fibroblast lines and shown that, together with our QuantiGene multiplex assay, these provide an effective screening tool for agents that target HTT transcripts. The effects of current targeting strategies on nuclear RNA clusters are unknown, structures that may have a pathogenic role, or alternatively could be protective by retaining HTT1a in the nucleus and preventing it from being translated. In light of recently halted antisense oligonucleotide trials, it is vital that agents targeting HTT1a are developed, and that the effects of HTT-lowering strategies on the subcellular levels of all HTT transcripts and their various HTT protein isoforms are understood

NetDiff – Bayesian model selection for differential gene regulatory network inference

Differential networks allow us to better understand the changes in cellular processes that are exhibited in conditions of interest, identifying variations in gene regulation or protein interaction between, for example, cases and controls, or in response to external stimuli. Here we present a novel methodology for the inference of differential gene regulatory networks from gene expression microarray data. Specifically we apply a Bayesian model selection approach to compare models of conserved and varying network structure, and use Gaussian graphical models to represent the network structures. We apply a variational inference approach to the learning of Gaussian graphical models of gene regulatory networks, that enables us to perform Bayesian model selection that is significantly more computationally efficient than Markov Chain Monte Carlo approaches. Our method is demonstrated to be more robust than independent analysis of data from multiple conditions when applied to synthetic network data, generating fewer false positive predictions of differential edges. We demonstrate the utility of our approach on real world gene expression microarray data by applying it to existing data from amyotrophic lateral sclerosis cases with and without mutations in C9orf72, and controls, where we are able to identify differential network interactions for further investigation

Correlative light and electron microscopy suggests that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington’s disease

Huntington’s disease (HD) is a late onset, inherited neurodegenerative disorder for which early pathogenic events remain poorly understood. Here we show that mutant exon 1 HTT proteins are recruited to a subset of cytoplasmic aggregates in the cell bodies of neurons in brain sections from presymptomatic HD, but not wild-type, mice. This occurred in a disease stage and polyglutamine-length dependent manner. We successfully adapted a high-resolution correlative light and electron microscopy methodology, originally developed for mammalian and yeast cells, to allow us to correlate light microscopy and electron microscopy images on the same brain section within an accuracy of 100 nm. Using this approach, we identified these recruitment sites as single membrane bound, vesicle-rich endolysosomal organelles, specifically as (1) multivesicular bodies (MVBs), or amphisomes and (2) autolysosomes or residual bodies. The organelles were often found in close-proximity to phagophore-like structures. Immunogold labeling localized mutant HTT to non-fibrillar, electron lucent structures within the lumen of these organelles. In presymptomatic HD, the recruitment organelles were predominantly MVBs/amphisomes, whereas in late-stage HD, there were more autolysosomes or residual bodies. Electron tomograms indicated the fusion of small vesicles with the vacuole within the lumen, suggesting that MVBs develop into residual bodies. We found that markers of MVB-related exocytosis were depleted in presymptomatic mice and throughout the disease course. This suggests that endolysosomal homeostasis has moved away from exocytosis toward lysosome fusion and degradation, in response to the need to clear the chronically aggregating mutant HTT protein, and that this occurs at an early stage in HD pathogenesis

Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of huntington's disease

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI), as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear. © 2013 Rattray et al

Genetic Knock-Down of Hdac3 Does Not Modify Disease-Related Phenotypes in a Mouse Model of Huntington's Disease

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by an expansion of a CAG/polyglutamine repeat for which there are no disease modifying treatments. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression and has been recapitulated across multiple HD models. Altered histone acetylation has been proposed to underlie this transcriptional dysregulation and histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA), have been shown to improve polyglutamine-dependent phenotypes in numerous HD models. However potent pan-HDAC inhibitors such as SAHA display toxic side-effects. To better understand the mechanism underlying this potential therapeutic benefit and to dissociate the beneficial and toxic effects of SAHA, we set out to identify the specific HDAC(s) involved in this process. For this purpose, we are exploring the effect of the genetic reduction of specific HDACs on HD-related phenotypes in the R6/2 mouse model of HD. The study presented here focuses on HDAC3, which, as a class I HDAC, is one of the preferred targets of SAHA and is directly involved in histone deacetylation. To evaluate a potential benefit of Hdac3 genetic reduction in R6/2, we generated a mouse carrying a critical deletion in the Hdac3 gene. We confirmed that the complete knock-out of Hdac3 is embryonic lethal. To test the effects of HDAC3 inhibition, we used Hdac3+/− heterozygotes to reduce nuclear HDAC3 levels in R6/2 mice. We found that Hdac3 knock-down does not ameliorate physiological or behavioural phenotypes and has no effect on molecular changes including dysregulated transcripts. We conclude that HDAC3 should not be considered as the major mediator of the beneficial effect induced by SAHA and other HDAC inhibitors in HD