3,559 research outputs found

    Improved impact performance of marine sandwich panels using through-thickness reinforcement: Experimental results

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    This paper presents results from a test developed to simulate the water impact (slamming) loading of sandwich boat structures. A weighted elastomer ball is dropped from increasing heights onto rigidly supported panels until damage is detected. Results from this test indicate that honeycomb core sandwich panels, the most widely used material for racing yacht hulls, start to damage due to core crushing at impact energies around 550 J. Sandwich panels of the same areal weight and with the same carbon/epoxy facings but using a novel foam core reinforced in the thickness direction with pultruded carbon fibre pins, do not show signs of damage until above 1200 J impact energy. This suggests that these will offer significantly improved resistance to wave impact. Quasi-static test results cannot be used to predict impact resistance here as the crush strength of the pinned foam is more sensitive to loading rate than that of the honeycomb core

    Weak and strong disjunction in possibilistic asp

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    Abstract. Possibilistic answer set programming (PASP) unites answer set programming (ASP) and possibilistic logic (PL) by associating certainty values with rules. The resulting framework allows to combine both non-monotonic reasoning and reasoning under uncertainty in a single framework. While PASP has been well-studied for possibilistic definite and possibilistic normal programs, we argue that the current semantics of possibilistic disjunctive programs are not entirely satisfactory. The problem is twofold. First, the treatment of negation-as-failure in existing approaches follows an all-or-nothing scheme that is hard to match with the graded notion of proof underlying PASP. Second, we advocate that the notion of disjunction can be interpreted in several ways. In particular, in addition to the view of ordinary ASP where disjunctions are used to induce a non-deterministic choice, the possibilistic setting naturally leads to a more epistemic view of disjunction. In this paper, we propose a semantics for possibilistic disjunctive programs, discussing both views on disjunction. Extending our earlier work, we interpret such programs as sets of constraints on possibility distributions, whose least specific solutions correspond to answer sets.

    Monovalent ions modulate the flux through multiple folding pathways of an RNA pseudoknot

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    The functions of RNA pseudoknots (PKs), which are minimal tertiary structural motifs and an integral part of several ribozymes and ribonucleoprotein complexes, are determined by their structure, stability and dynamics. Therefore, it is important to elucidate the general principles governing their thermodynamics/folding mechanisms. Here, we combine experiments and simulations to examine the folding/unfolding pathways of the VPK pseudoknot, a variant of the Mouse Mammary Tumor Virus (MMTV) PK involved in ribosomal frameshifting. Fluorescent nucleotide analogs (2-aminopurine and pyrrolocytidine) placed at different stem/loop positions in the PK, and laser temperature-jump approaches serve as local probes allowing us to monitor the order of assembly of VPK with two helices with different intrinsic stabilities. The experiments and molecular simulations show that at 50 mM KCl the dominant folding pathway populates only the more stable partially folded hairpin. As the salt concentration is increased a parallel folding pathway emerges, involving the less stable hairpin structure as an alternate intermediate. Notably, the flux between the pathways is modulated by the ionic strength. The findings support the principle that the order of PK structure formation is determined by the relative stabilities of the hairpins, which can be altered by sequence variations or salt concentrations. Our study not only unambiguously demonstrates that PK folds by parallel pathways, but also establishes that quantitative description of RNA self-assembly requires a synergistic combination of experiments and simulations.Comment: Supporting Information include

    Modeling Stable Matching Problems with Answer Set Programming

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    The Stable Marriage Problem (SMP) is a well-known matching problem first introduced and solved by Gale and Shapley (1962). Several variants and extensions to this problem have since been investigated to cover a wider set of applications. Each time a new variant is considered, however, a new algorithm needs to be developed and implemented. As an alternative, in this paper we propose an encoding of the SMP using Answer Set Programming (ASP). Our encoding can easily be extended and adapted to the needs of specific applications. As an illustration we show how stable matchings can be found when individuals may designate unacceptable partners and ties between preferences are allowed. Subsequently, we show how our ASP based encoding naturally allows us to select specific stable matchings which are optimal according to a given criterion. Each time, we can rely on generic and efficient off-the-shelf answer set solvers to find (optimal) stable matchings.Comment: 26 page

    Implementation of and Early Outcomes From Anal Cancer Screening at a Community-Engaged Health Care Facility Providing Care to Nigerian Men Who Have Sex With Men.

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    PurposeAnal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria.MethodsFrom August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort. HRA-directed biopsies were diagnosed by histology, and ablative treatment was offered for high-grade squamous intraepithelial lesions (HSIL). HRA proficiency was assessed by evaluating the detection of squamous intraepithelial lesions (SIL) over time and the proportion biopsied. Prevalence estimates of low-grade squamous intraepithelial lesions and HSIL with 95% CIs were calculated. Multinomial logistic regression was used to identify those at the highest risk of SIL.ResultsMedian age was 25 years (interquartile range [IQR], 22-29), median time since sexual debut was 8 years (IQR, 4-12), and 59% (95% CI, 54.2% to 63.6%) were HIV infected. Rate of detection of any SIL stabilized after 200 screenings, and less than 20% had two or more biopsies. Preliminary prevalence estimates of low-grade squamous intraepithelial lesions and HSIL were 50.0% (95% CI, 44.7% to 55.3%) and 6.3% (95% CI, 4.0% to 9.3%). HIV infection, at least 8 years since anal coital debut, concurrency, and external warts were independently statistically associated with SIL.ConclusionProficiency with HRA increased with experience over time. However, HSIL detection rates were low, potentially affected by obstructed views from internal warts and low biopsy rates, highlighting the need for ongoing evaluation and mentoring to validate this finding. HRA is a feasible first-line screening tool at an MSM-friendly health care facility. Years since anal coital debut and external warts could prioritize screening

    Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12.

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    Although chemokines are well established to function in immunity and endothelial cell activation and proliferation, a rapidly growing literature suggests that CXC Chemokine receptors CXCR3, CXCR4 and CXCR7 are critical in the development and progression of solid tumors. The effect of these chemokine receptors in tumorigenesis is mediated via interactions with shared ligands I-TAC (CXCL11) and SDF-1 (CXCL12). Over the last decade, CXCR4 has been extensively reported to be overexpressed in most human solid tumors and has earned considerable attention toward elucidating its role in cancer metastasis. To enrich the existing armamentarium of anti-cancerous agents, many inhibitors of CXCL12-CXCR4 axis have emerged as additional or alternative agents for neo-adjuvant treatments and even many of them are in preclinical and clinical stages of their development. However, the discovery of CXCR7 as another receptor for CXCL12 with rather high binding affinity and recent reports about its involvement in cancer progression, has questioned the potential of "selective blockade" of CXCR4 as cancer chemotherapeutics. Interestingly, CXCR7 can also bind another chemokine CXCL11, which is an established ligand for CXCR3. Recent reports have documented that CXCR3 and their ligands are overexpressed in different solid tumors and regulate tumor growth and metastasis. Therefore, it is important to consider the interactions and crosstalk between these three chemokine receptors and their ligand mediated signaling cascades for the development of effective anti-cancer therapies. Emerging evidence also indicates that these receptors are differentially expressed in tumor endothelial cells as well as in cancer stem cells, suggesting their direct role in regulating tumor angiogenesis and metastasis. In this review, we will focus on the signals mediated by this receptor trio via their shared ligands and their role in tumor growth and progression

    Opportunities for Enhanced Strategic Use of Surveys, Medical Records, and Program Data for HIV Surveillance of Key Populations: Scoping Review.

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    BACKGROUND: Normative guidelines from the World Health Organization recommend tracking strategic information indicators among key populations. Monitoring progress in the global response to the HIV epidemic uses indicators put forward by the Joint United Nations Programme on HIV/AIDS. These include the 90-90-90 targets that require a realignment of surveillance data, routinely collected program data, and medical record data, which historically have developed separately. OBJECTIVE: The aim of this study was to describe current challenges for monitoring HIV-related strategic information indicators among key populations ((men who have sex with men [MSM], people in prisons and other closed settings, people who inject drugs, sex workers, and transgender people) and identify future opportunities to enhance the use of surveillance data, programmatic data, and medical record data to describe the HIV epidemic among key populations and measure the coverage of HIV prevention, care, and treatment programs. METHODS: To provide a historical perspective, we completed a scoping review of the expansion of HIV surveillance among key populations over the past three decades. To describe current efforts, we conducted a review of the literature to identify published examples of SI indicator estimates among key populations. To describe anticipated challenges and future opportunities to improve measurement of strategic information indicators, particularly from routine program and health data, we consulted participants of the Third Global HIV Surveillance Meeting in Bangkok, where the 2015 World Health Organization strategic information guidelines were launched. RESULTS: There remains suboptimal alignment of surveillance and programmatic data, as well as routinely collected medical records to facilitate the reporting of the 90-90-90 indicators for HIV among key populations. Studies (n=3) with estimates of all three 90-90-90 indicators rely on cross-sectional survey data. Programmatic data and medical record data continue to be insufficiently robust to provide estimates of the 90-90-90 targets for key populations. CONCLUSIONS: Current reliance on more active data collection processes, including key population-specific surveys, remains warranted until the quality and validity of passively collected routine program and medical record data for key populations is optimized
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