12,161 research outputs found

    Derivation of SPH equations in a moving referential coordinate system

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    The conventional SPH method uses kernel interpolation to derive the spatial semi-discretisation of the governing equations. These equations, derived using a straight application of the kernel interpolation method, are not used in practice. Instead the equations, commonly used in SPH codes, are heuristically modified to enforce symmetry and local conservation properties. This paper revisits the process of deriving these semi-discrete SPH equations. It is shown that by using the assumption of a moving referential coordinate system and moving control volume, instead of the fixed referential coordinate system and fixed control volume used in the conventional SPH method, a set of new semi- discrete equations can be rigorously derived. The new forms of semi-discrete equations are similar to the SPH equations used in practice. It is shown through numerical examples that the new rigorously derived equations give similar results to those obtained using the conventional SPH equations

    Maintenance of ONC Terminology for i2b2 Metadata

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    ONC terminologies are constantly adding new content and deactivating existing codes. The University of Nebraska Medical Center (UNMC) deploys three primary code sets that require regular updating to support research: SNOMED CT, RXNORM / NDC, and LOINC. A problem across the i2b2 community is keeping these terminologies up-to-date and loading them into i2b2 for timely analysis of EHR data. We have developed tool kits for rapid deployment of SNOMED CT metadata and will be extending the work to RXNORM/NDC and LOINC.https://digitalcommons.unmc.edu/com_emerg_pres/1001/thumbnail.jp

    Solar sail formation flying for deep-space remote sensing

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    In this paper we consider how 'near' term solar sails can be used in formation above the ecliptic plane to provide platforms for accurate and continuous remote sensing of the polar regions of the Earth. The dynamics of the solar sail elliptical restricted three-body problem (ERTBP) are exploited for formation flying by identifying a family of periodic orbits above the ecliptic plane. Moreover, we find a family of 1 year periodic orbits where each orbit corresponds to a unique solar sail orientation using a numerical continuation method. It is found through a number of example numerical simulations that this family of orbits can be used for solar sail formation flying. Furthermore, it is illustrated numerically that Solar Sails can provide stable formation keeping platforms that are robust to injection errors. In addition practical trajectories that pass close to the Earth and wind onto these periodic orbits above the ecliptic are identified

    Signal transduction and activator of transcription-3 (STAT3) in patients with colorectal cancer: associations with the phenotypic features of the tumour and host

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    Purpose: In patients with colorectal cancer (CRC), a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL-6/JAK/STAT3 pathway. The present study examines the relationship between tumour total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses and survival in patients undergoing resection of stage I-III CRC. Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumour cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density and Klintrup-Mäkinen grade) and systemic inflammatory responses and cancer-specific survival were examined. Results: 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r=0.363, P<0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r=0.130, P=0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P=0.012), CD8+ (P=0.003) and FOXP3+ T-lymphocytes (P=0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P=0.004). The combination of nuclear STAT3/pSTAT3 stratified five-year survival from 81% to 62% (P=0.012), however was not associated with survival independent of venous invasion, tumour perforation or tumour budding. Conclusion In patients undergoing CRC resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Up-regulation of tumour STAT3 may be an important mechanism whereby the tumour deregulates local and systemic inflammatory responses

    Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling

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    Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their translocation to the nucleus, where they regulate gene expression. BMPs can also signal independently of SMAD4, but this pathway is poorly understood. Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. We also demonstrate that PAWS1 regulates the expression of several non-BMP target genes, suggesting roles for PAWS1 beyond the BMP pathway

    Evaluation of a tumor microenvironment-based prognostic score in primary operable colorectal cancer

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    Purpose: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment–based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer. Experimental Design: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup–Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I–III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined. Results: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36–2.73; P < 0.001), independent of TNM stage and venous invasion (both P < 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P < 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively). Conclusions: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer

    The effect of surgical approach on the histology of the femoral head following resurfacing of the hip : analysis of retrieval specimens

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    Objectives: We aimed to determine the effect of surgical approach on the histology of the femoral head following resurfacing of the hip. Methods: We performed a histological assessment of the bone under the femoral component taken from retrieval specimens of patients having revision surgery following resurfacing of the hip. We compared the number of empty lacunae in specimens from patients who had originally had a posterior surgical approach with the number in patients having alternative surgical approaches. Results: We found a statistically significant increase in the percentage of empty lacunae in retrieval specimens from patients who had the posterior approach compared with other surgical approaches (p < 0.001). Conclusions: This indicates that the vascular compromise that occurs during the posterior surgical approach does have long-term effects on the bone of the femoral head, even if it does not cause overt avascular necrosis
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