Line creep in paper peeling

The dynamics of a "peeling front" or an elastic line is studied under creep (constant load) conditions. Our experiments show an exponential dependence of the creep velocity on the inverse force (mass) applied. In particular, the dynamical correlations of the avalanche activity are discussed here. We compare various avalanche statistics to those of a line depinning model with non-local elasticity, and study various measures of the experimental avalanche-avalanche and temporal correlations such as the autocorrelation function of the released energy and aftershock activity. From all these we conclude, that internal avalanche dynamics seems to follow "line depinning" -like behavior, in rough agreement with the depinning model. Meanwhile, the correlations reveal subtle complications not implied by depinning theory. Moreover, we also show how these results can be understood from a geophysical point of view.Comment: 22 pages, 14 fig

Developments in low-cost laser detection: wide field of view implementation and direction determination

The availability of low cost but relatively high power laser pointers (hundreds of mW) has led to misuse with potentially dangerous consequences, such as dazzling aircraft which has raised concerns about aircraft safety. A low cost laser detection system based on coherence detection has been developed and is able to detect weak, continuous laser sources even against bright background light. In this paper, we introduce the use of a cone mirror to extend the horizontal field of view of the detector (originally at 3°) to 360° to detect incoming beams from different directions. With the additional use of a camera in the system, we also determine the direction of the incoming laser beam. Finally, the sensitivity between the original system and the cone mirror system are compared: the new system showed promising results with a sensitivity below 100nW

Microarray analysis identifies candidate genes for key roles in coral development

Background: Anthozoan cnidarians are amongst the simplest animals at the tissue level of organization, but are surprisingly complex and vertebrate-like in terms of gene repertoire. As major components of tropical reef ecosystems, the stony corals are anthozoans of particular ecological significance. To better understand the molecular bases of both cnidarian development in general and coral-specific processes such as skeletogenesis and symbiont acquisition, microarray analysis was carried out through the period of early development – when skeletogenesis is initiated, and symbionts are first acquired. Results: Of 5081 unique peptide coding genes, 1084 were differentially expressed (P ≤ 0.05) in comparisons between four different stages of coral development, spanning key developmental transitions. Genes of likely relevance to the processes of settlement, metamorphosis, calcification and interaction with symbionts were characterised further and their spatial expression patterns investigated using whole-mount in situ hybridization. Conclusion: This study is the first large-scale investigation of developmental gene expression for any cnidarian, and has provided candidate genes for key roles in many aspects of coral biology, including calcification, metamorphosis and symbiont uptake. One surprising finding is that some of these genes have clear counterparts in higher animals but are not present in the closely-related sea anemone Nematostella. Secondly, coral-specific processes (i.e. traits which distinguish corals from their close relatives) may be analogous to similar processes in distantly related organisms. This first large-scale application of microarray analysis demonstrates the potential of this approach for investigating many aspects of coral biology, including the effects of stress and disease.Lauretta C Grasso, John Maindonald, Stephen Rudd, David C Hayward, Robert Saint, David J Miller and Eldon E Bal

Intermittent dislocation flow in viscoplastic deformation

The viscoplastic deformation (creep) of crystalline materials under constant stress involves the motion of a large number of interacting dislocations. Analytical methods and sophisticated `dislocation-dynamics' simulations have proved very effective in the study of dislocation patterning, and have led to macroscopic constitutive laws of plastic deformation. Yet, a statistical analysis of the dynamics of an assembly of interacting dislocations has not hitherto been performed. Here we report acoustic emission measurements on stressed ice single crystals, the results of which indicate that dislocations move in a scale-free intermittent fashion. This result is confirmed by numerical simulations of a model of interacting dislocations that successfully reproduces the main features of the experiment. We find that dislocations generate a slowly evolving configuration landscape which coexists with rapid collective rearrangements. These rearrangements involve a comparatively small fraction of the dislocations and lead to an intermittent behavior of the net plastic response. This basic dynamical picture appears to be a generic feature in the deformation of many other materials. Moreover, it should provide a framework for discussing fundamental aspects of plasticity, that goes beyond standard mean-field approaches that see plastic deformation as a smooth laminar flow

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p < 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Current perspectives on bone metastases in castrate-resistant prostate cancer

Prostate cancer is the most frequent noncutaneous cancer occurring in men. On average, men with localized prostate cancer have a high 10-year survival rate, and many can be cured. However, men with metastatic castrate-resistant prostate cancer have incurable disease with poor survival despite intensive therapy. This unmet need has led to recent advances in therapy aimed at treating bone metastases resulting from prostate cancer. The bone microenvironment lends itself to metastases in castrate-resistant prostate cancer, as a result of complex interactions between the microenvironment and tumor cells. The development of 223radium dichloride (Ra-223) to treat symptomatic bone metastases has improved survival in men with metastatic castrate-resistant prostate cancer. Moreover, Ra-223 may have effects on the tumor microenvironment that enhance its activity. Ra-223 treatment has been shown to prolong survival, and its effects on the immune system are under investigation. Because prostate cancer affects a sizable portion of the adult male population, understanding how it metastasizes to bone is an important step in advancing therapy. Clinical trials that are underway should yield new information on whether Ra-223 synergizes effectively with immunotherapy agents and whether Ra-223 has enhancing effects on the immune system in patients with prostate cancer

Geographic Variations in Retention in Care among HIV-Infected Adults in the United States

ObjectiveTo understand geographic variations in clinical retention, a central component of the HIV care continuum and key to improving individual- and population-level HIV outcomes.DesignWe evaluated retention by US region in a retrospective observational study.MethodsAdults receiving care from 2000–2010 in 12 clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) contributed data. Individuals were assigned to Centers for Disease Control and Prevention (CDC)-defined regions by residential data (10 cohorts) and clinic location as proxy (2 cohorts). Retention was ≥2 primary HIV outpatient visits within a calendar year, >90 days apart. Trends and regional differences were analyzed using modified Poisson regression with clustering, adjusting for time in care, age, sex, race/ethnicity, and HIV risk, and stratified by baseline CD4+ count.ResultsAmong 78,993 adults with 444,212 person-years of follow-up, median time in care was 7 years (Interquartile Range: 4–9). Retention increased from 2000 to 2010: from 73% (5,000/6,875) to 85% (7,189/8,462) in the Northeast, 75% (1,778/2,356) to 87% (1,630/1,880) in the Midwest, 68% (8,451/12,417) to 80% (9,892/12,304) in the South, and 68% (5,147/7,520) to 72% (6,401/8,895) in the West. In adjusted analyses, retention improved over time in all regions (p<0.01, trend), although the average percent retained lagged in the West and South vs. the Northeast (p<0.01).ConclusionsIn our population, retention improved, though regional differences persisted even after adjusting for demographic and HIV risk factors. These data demonstrate regional differences in the US which may affect patient care, despite national care recommendations

Peak grain forecasts for the US High Plains amid withering waters

Irrigated agriculture contributes 40% of total global food production. In the US High Plains, which produces more than 50 million tons per year of grain, as much as 90% of irrigation originates from groundwater resources, including the Ogallala aquifer. In parts of the High Plains, groundwater resources are being depleted so rapidly that they are considered nonrenewable, compromising food security. When groundwater becomes scarce, groundwater withdrawals peak, causing a subsequent peak in crop production. Previous descriptions of finite natural resource depletion have utilized the Hubbert curve. By coupling the dynamics of groundwater pumping, recharge, and crop production, Hubbert-like curves emerge, responding to the linked variations in groundwater pumping and grain production. On a state level, this approach predicted when groundwater withdrawal and grain production peaked and the lag between them. The lags increased with the adoption of efficient irrigation practices and higher recharge rates. Results indicate that, in Texas, withdrawals peaked in 1966, followed by a peak in grain production 9 y later. After better irrigation technologies were adopted, the lag increased to 15 y from 1997 to 2012. In Kansas, where these technologies were employed concurrently with the rise of irrigated grain production, this lag was predicted to be 24 y starting in 1994. In Nebraska, grain production is projected to continue rising through 2050 because of high recharge rates. While Texas and Nebraska had equal irrigated output in 1975, by 2050, it is projected that Nebraska will have almost 10 times the groundwater-based production of Texas