Solution-processable, niobium-doped titanium oxide nanorods for application in low-voltage, large-area electronic devices

We report for the first time the one-step synthesis of solution-processable, highly crystalline, niobium-doped titanium dioxide (Nb-TiO2) nanorods in the anatase phase by the hydrolytic condensation of Ti(OiPr)4 and niobium(V) ethoxide using oleic acid as a structure-directing and stabilising agent. These novel surface-stabilised nanorods can be easily dispersed in common solvents at relatively high concentration (∼10%) and deposited as uniform, thin and transparent films on planar substrates for the fabrication of electronic devices. The small size of the nanoparticles synthesized represents an important advance in achieving high-k dielectric thin films smooth enough to be suitable for OFET applications and the plastic electronics filed in general. Preliminary investigations show that the dielectric constant, k, of niobium-doped (7.1 wt%) titanium dioxide (Nb-TiO2) nanorods at frequencies in the region of 100 kHz–1 MHz, are more a third greater (k > 8) than that (k = 6) determined for the corresponding undoped titanium dioxide (TiO2) nanorods. The current–voltage (J–V) behaviour of these devices reveal that niobium-doping improves, by reducing, the leakage current of these devices, thereby preventing hard dielectric breakdown of devices incorporating these new nanorods

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies

Insulin and IGF1 signalling pathways in human astrocytes <i>in vitro</i> and <i>in vivo</i>; characterisation, subcellular localisation and modulation of the receptors.

Background The insulin/IGF1 signalling (IIS) pathways are involved in longevity regulation and are dysregulated in neurons in Alzheimer’s disease (AD). We previously showed downregulation in IIS gene expression in astrocytes with AD-neuropathology progression, but IIS in astrocytes remains poorly understood. We therefore examined the IIS pathway in human astrocytes and developed models to reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R). Results We determined IIS was present and functional in human astrocytes by immunoblotting and showed astrocytes express the insulin receptor (IR)-B isoform of Ir. Immunocytochemistry and cell fractionation followed by western blotting revealed the phosphorylation status of insulin receptor substrate (IRS1) affects its subcellular localisation. To validate IRS1 expression patterns observed in culture, expression of key pathway components was assessed on post-mortem AD and control tissue using immunohistochemistry. Insulin signalling was impaired in cultured astrocytes by treatment with insulin + fructose and resulted in decreased IR and Akt phosphorylation (pAkt S473). A monoclonal antibody against IGF1R (MAB391) induced degradation of IGF1R receptor with an associated decrease in downstream pAkt S473. Neither treatment affected cell growth or viability as measured by MTT and Cyquant® assays or GFAP immunoreactivity. Discussion IIS is functional in astrocytes. IR-B is expressed in astrocytes which differs from the pattern in neurons, and may be important in differential susceptibility of astrocytes and neurons to insulin resistance. The variable presence of IRS1 in the nucleus, dependent on phosphorylation pattern, suggests the function of signalling molecules is not confined to cytoplasmic cascades. Down-regulation of IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments, results in decreased downstream signalling, though the lack of effect on viability suggests that astrocytes can compensate for changes in single pathways. Changes in signalling in astrocytes, as well as in neurons, may be important in ageing and neurodegeneration

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A comparative examination of healthcare use related to hearing impairment in europe

Introduction: The economic burden of hearing impairment is an area of increased interest. In this paper we examine the relationship between hearing impairment and service use in 14 European countries. Methods: Based on the Survey of Health Ageing and Retirement in Europe (SHARE) undertaken in 2013, Poisson regression models are used to analyse the relationship between the number of visits/number of nights in hospital, and hearing impairment controlling for a number of covariates. Results: We find that hearing impairment is generally associated with increased use of primary and secondary healthcare services when other aspects of health have been controlled. Comparative analysis revealed that where access to hearing assistive technology was greatest the additional use of services was least. Conclusions: The comparative analysis suggests that variations exist across countries in respect of the additional healthcare use occasioned by hearing impairment. They may also provide valuable insights into how the burden of illness might be reduced

Understanding how breast cancer patients use risk information from genomic tests

BACKGROUND: We sought to examine how patients’ treatment decisions incorporate potentially conflicting information from standard clinical indicators (e.g., tumor size) and genomic tests for breast cancer recurrence risk. METHODS: Participants were 77 early stage breast cancer survivors who previously received genomic testing. They read six hypothetical vignettes that varied recurrence risk indicated by standard tests (low or high risk) coupled with the genomic test (low, intermediate or high risk). For each vignette, women reported their perceived recurrence risk and treatment preferences. RESULTS: Test results indicating high recurrence risk increased perception of risk and preference for chemotherapy (p<.001 for all). Perceived risk explained (i.e., mediated) the effect of test results on chemotherapy preferences. When test results conflicted, women gave more weight to genomic over standard test results. DISCUSSION: Hypothetical genomic test results had the intended effect of influencing women’s perceptions of recurrence risk and interest in chemotherapy

Remote sensing of Arctic atmospheric aerosols

In this chapter remote sensing techniques as applied to studies of Arctic aerosol are surveyed. They include the analysis of ground and shipborne observations of atmospheric aerosol using sunphotometers and also airborne/satellite observations using optical instrumentation (lidars, imagers, radiometers)