Using Fiber Optic Bundles to Miniaturize Vision-Based Tactile Sensors

Vision-based tactile sensors have recently become popular due to their combination of low cost, very high spatial resolution, and ease of integration using widely available miniature cameras. The associated field of view and focal length, however, are difficult to package in a human-sized finger. In this paper we employ optical fiber bundles to achieve a form factor that, at 15 mm diameter, is smaller than an average human fingertip. The electronics and camera are also located remotely, further reducing package size. The sensor achieves a spatial resolution of 0.22 mm and a minimum force resolution 5 mN for normal and shear contact forces. With these attributes, the DIGIT Pinki sensor is suitable for applications such as robotic and teleoperated digital palpation. We demonstrate its utility for palpation of the prostate gland and show that it can achieve clinically relevant discrimination of prostate stiffness for phantom and ex vivo tissue.Comment: We open source the design of DIGIT Pinki at https://github.com/facebookresearch/digit-desig

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA

The bias of A-rich codons in HIV-1 pol is thought to be a record of hypermutations in viral genomes that lack biological functions. Bioinformatic analysis predicted that A-rich sequences are generally associated with minimal local RNA structures. Using codon modifications to reduce the amount of A-rich sequences within HIV-1 genomes, we have reduced the flexibility of RNA sequences in pol to analyze the functional significance of these A-rich ‘structurally poor’ RNA elements in HIV-1 pol. Our data showed that codon modification of HIV-1 sequences led to a suppression of virus infectivity by 5–100-fold, and this defect does not correlate with, viral entry, viral protein expression levels, viral protein profiles or virion packaging of genomic RNA. Codon modification of HIV-1 pol correlated with an enhanced dimer stability of the viral RNA genome, which was associated with a reduction of viral cDNA synthesis both during HIV-1 infection and in a cell free reverse transcription assay. Our data provided direct evidence that the HIV-1 A-rich pol sequence is not merely an evolutionary artifact of enzyme-induced hypermutations, and that HIV-1 has adapted to rely on A-rich RNA sequences to support the synthesis of viral cDNA during reverse transcription, highlighting the utility of using ‘structurally poor’ RNA domains in regulating biological process

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

The Rat Genome Database (RGD): developments towards a phenome database

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination.

BACKGROUND: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. METHODS: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. RESULTS: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls' questionnaire and 17% for the parents'. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). CONCLUSIONS: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed.British Journal of Cancer advance online publication: 22 August 2017; doi:10.1038/bjc.2017.284 www.bjcancer.com

Cell cyclins: triggering elements of cancer or not?

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy

Creating 'good' self-managers?: Facilitating and governing an online self care skills training course

<p>Abstract</p> <p>Background</p> <p>In chronic disease management, patients are increasingly called upon to undertake a new role as lay tutors within self-management training programmes. The internet constitutes an increasingly significant healthcare setting and a key arena for self-management support and communication. This study evaluates how a new quasi-professional health workforce – volunteer tutors – engage, guide and attempt to manage people with long-term conditions in the ways of 'good' self-management within the context of an online self-management course.</p> <p>Methods</p> <p>A qualitative analysis of postings to the discussion centre of 11 online classes (purposively selected from 27) run as part of the Expert Patients Programme. Facilitators (term for tutors online) and participants posted questions, comments and solutions related to self-management of long-term conditions; these were subjected to a textual and discursive analysis to explore:</p> <p>a) how facilitators, through the internet, engaged participants in issues related to self-management;</p> <p>b) how participants responded to and interacted with facilitators.</p> <p>Results</p> <p>Emergent themes included: techniques and mechanisms used to engage people with self-management; the process facilitators followed – 'sharing', 'modelling' and 'confirming'; and the emergence of a policing role regarding online disclosure. Whilst exchanging medical advice was discouraged, facilitators often professed to understand and give advice on psychological aspects of behaviour.</p> <p>Conclusion</p> <p>The study gave an insight into the roles tutors adopt – one being their ability to 'police' subjective management of long-term conditions and another being to attempt to enhance the psychological capabilities of participants.</p