Electrospinning of tissue engineered blood vessel scaffolds utilising multimodal fibre distributions and dynamic liquid collected yarns

The successful replacement of small-diameter blood vessels, affected by cardiovascular disease, with natural and synthetic bypass grafts remains limited due to long-term patency issues. The development of a tissue engineered blood vessel (TEBV), with properties mimicking that of the native vessel to be replaced, may provide a potential solution. Electrospinning, a polymer processing technique capable of producing nano to micron-scale in diameter fibres has been studied extensively in the last decade as a potential technique for the fabrication of tissue scaffolds. Insufficient cell infiltration into electrospun constructs, and thus incomplete remodelling of the scaffolds, has however hindered their use in clinical applications todate. Electrospinning variations, including the production of multi-modal fibre diameter scaffolds and nanofibre bundles that offer increased porosities compared to traditional electrospun materials may allow these limitations to be overcome. This study looks at the development of a bi-layer scaffold consisting of a small diameter multi-modal core layer paired with highly porous nanofibre bundles. Electrospun tubular core layers possessing multi-modal fibre diameter populations were created using poly

A sequential dynamic Bayesian network for pore pressure estimation with uncertainty quantification

Pore-pressure estimation is an important part of oil-well drilling, since drilling into unexpected highly pressured fluids can be costly and dangerous. However, standard estimation methods rarely account for the many sources of uncertainty, or for the multivariate nature of the system. We propose the pore pressure sequential dynamic Bayesian network (PP SDBN) as an appropriate solution to both these issues. The PP SDBN models the relationships between quantities in the pore pressure system, such as pressures, porosity, lithology and wireline log data, using conditional probability distributions based on geophysical relationships to capture our uncertainty about these variables and the relationships between them. When wireline log data is given to the PP SDBN, the probability distributions are updated, providing an estimate of pore pressure along with a probabilistic measure of uncertainty that reflects the data acquired and our understanding of the system. This is the advantage of a Bayesian approach. Our model provides a coherent statistical framework for modelling the pore pressure system. The specific geophysical relationships used can be changed to better suit a particular setting, or reflect geoscientists’ knowledge. We demonstrate the PP SDBN on an offshore well from West Africa. We also perform a sensitivity analysis, demonstrating how this can be used to better understand the working of the model and which parameters are the most influential. The dynamic nature of the model makes it suitable for real time estimation during logging while drilling. The PP SDBN models shale pore pressure in shale rich formations with mechanical compaction as the overriding source of overpressure. The PP SDBN improves on existing methods since it produces a probabilistic estimate that reflects the many sources of uncertainty present

Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome

BACKGROUND: Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC). Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe the subtypes of CAFs in NSCLC.METHODS: Primary human NSCLC resections were assessed by flow cytometry and multiplex immunofluorescence for markers of fibroblast activation which allowed identification of CAF subsets. Survival data were analysed for our NSCLC cohort consisting of 163 patients to understand prognostic significance of CAF subsets.RESULTS: We identified five CAF populations, termed CAF S1-S5. CAF-S5 represents a previously undescribed population, and express FAP and PDPN but lack the myofibroblast marker αSMA, whereas CAF-S1 populations express all three. CAF-S5 are spatially further from tumour regions then CAF-S1 and scRNA data demonstrate an inflammatory phenotype. The presence of CAF-S1 or CAF-S5 is correlated to worse survival outcome in NSCLC, despite curative resection, highlighting the prognostic importance of CAF subtypes in NSCLC. TCGA data suggest the predominance of CAF-S5 has a poor prognosis across several cancer types.CONCLUSION: This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 subset where its presence correlates to worse survival outcome.</p

Fuel Efficiencies Through Airframe Improvements

The factors of continuing strong growth in air traffic volume, the vital role of the air transport system on the economy, and concerns about the environmental impact of aviation have added focus to the National Aeronautics Research Policy. To address these concerns in the context of the National Policy, NASA has set aggressive goals in noise reduction, emissions, and energy consumption. With respect to the goal of reducing energy consumption in the fleet, the development of promising airframe technologies is required to realize the significant improvements that are desired. Furthermore, the combination of advances in materials and structures with aerodynamic technologies may lead to a paradigm shift in terms of potential configurations for the future. Some of these promising airframe technologies targeted at improved efficiency are highlighted

Field Theory Entropy, the HH-theorem and the Renormalization Group

We consider entropy and relative entropy in Field theory and establish relevant monotonicity properties with respect to the couplings. The relative entropy in a field theory with a hierarchy of renormalization group fixed points ranks the fixed points, the lowest relative entropy being assigned to the highest multicritical point. We argue that as a consequence of a generalized $H$ theorem Wilsonian RG flows induce an increase in entropy and propose the relative entropy as the natural quantity which increases from one fixed point to another in more than two dimensions.Comment: 25 pages, plain TeX (macros included), 6 ps figures. Addition in title. Entropy of cutoff Gaussian model modified in section 4 to avoid a divergence. Therefore, last figure modified. Other minor changes to improve readability. Version to appear in Phys. Rev.

Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids

SIMPLE SUMMARY: Immunogenic cancer cell death and photodynamic therapy play an important emerging role in cancer treatment. Understanding mechanisms involved in tumor killing via immune cells in response to photodynamic therapy is important for developing new anticancer approaches. In this study, we report that methylene blue photodynamic therapy decreases the proliferation of lung cancer cells and patient derived non-small cell lung cancer organoids via immunogenic cells death and granzyme B mediated cytolysis. ABSTRACT: Augmenting T cell mediated tumor killing via immunogenic cancer cell death (ICD) is the cornerstone of emerging immunotherapeutic approaches. We investigated the potential of methylene blue photodynamic therapy (MB-PDT) to induce ICD in human lung cancer. Non-Small Cell Lung Cancer (NSCLC) cell lines and primary human lung cancer organoids were evaluated in co-culture killing assays with MB-PDT and light emitting diodes (LEDs). ICD was characterised using immunoblotting, immunofluorescence, flow cytometry and confocal microscopy. Phototherapy with MB treatment and low energy LEDs decreased the proliferation of NSCLC cell lines inducing early necrosis associated with reduced expression of the anti-apoptotic protein, Bcl2 and increased expression of ICD markers, calreticulin (CRT), intercellular cell-adhesion molecule-1 (ICAM-1) and major histocompatibility complex I (MHC-I) in NSCLC cells. MB-PDT also potentiated CD8(+) T cell-mediated cytolysis of lung cancer via granzyme B in lung cancer cells and primary human lung cancer organoids

Theory of Planned Behaviour and Parasuicide: An Exploratory Study

Recent evidence suggests that parasuicide (deliberate self-harm) should be considered in terms of ‘normal’ rather than ‘abnormal’ behaviour. This study aimed to address this assertion by applying a social cognition model, for the first time, to parasuicidal behaviour. An extended theory of planned behaviour (TPB) model was tested on 55 individuals drawn from hospital and non-hospital populations. Thirty-eight percent of the sample (n=21) reported a history of deliberate self-harm. Findings supported the utility of the TPB: attitudes, subjective norm, self-efficacy, moral norm and anticipated affect discriminated significantly between those with and without a history of parasuicide. The extended TPB explained more than 50% of the variance associated with intentions to deliberately self-harm. These findings have considerable theoretical and practical implications for intervention. Future research should investigate the utility of the TPB employed within a prospective framework

Fibroblast Activation Protein specific optical imaging in Non-Small Cell Lung Cancer

Fibroblast activation protein (FAP) is a cell surface propyl-specific serine protease involved in the regulation of extracellular matrix. Whilst expressed at low levels in healthy tissue, upregulation of FAP on fibroblasts can be found in several solid organ malignancies, including non-small cell lung cancer, and chronic inflammatory conditions such as pulmonary fibrosis and rheumatoid arthritis. Their full role remains unclear, but FAP expressing cancer associated fibroblasts (CAFs) have been found to relate to a poor prognosis with worse survival rates in breast, colorectal, pancreatic, and non-small cell lung cancer (NSCLC). Optical imaging using a FAP specific chemical probe, when combined with clinically compatible imaging systems, can provide a readout of FAP activity which could allow disease monitoring, prognostication and potentially stratify therapy. However, to derive a specific signal for FAP any sequence must retain specificity over closely related endopeptidases, such as prolyl endopeptidase (PREP), and be resistant to degradation in areas of active inflammation. We describe the iterative development of a FAP optical reporter sequence which retains FAP specificity, confers resistance to degradation in the presence of activated neutrophil proteases and demonstrates clinical tractability ex vivo in NSCLC samples with an imaging platform

T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease

T cells that produce both IL-17 and IFN-γ, and co-express ROR-γt and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-γt is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not impaired in T-bet(−/−) mice and was associated with low IFN-γ production and elevated IL-17 production among central nervous system (CNS) infiltrating CD4(+) T cells. T-bet(−/−) Th17 cells generated in the presence of IL-6/TGF-β/IL-1 and IL-23 produced GM-CSF and high levels of IL-17 and induced disease upon transfer to naïve mice. Unlike their WT counterparts, these T-bet(−/–) Th17 cells did not exhibit an IL-17→IFN-γ switch upon reencounter with antigen in the CNS, indicating that this functional change is not critical to disease development. In contrast, T-bet was absolutely required for the pathogenicity of myelin-responsive Th1 cells. T-bet-deficient Th1 cells failed to accumulate in the CNS upon transfer, despite being able to produce GM-CSF. Therefore, T-bet is essential for establishing Th1-mediated inflammation but is not required to drive IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation