Essential Role of Lyn in Fibrosis.

Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation, and collagen production, is a key target for preventing fibrosis

Reaction, Levy Flights, and Quenched Disorder

We consider the A + A --> emptyset reaction, where the transport of the particles is given by Levy flights in a quenched random potential. With a common literature model of the disorder, the random potential can only increase the rate of reaction. With a model of the disorder that obeys detailed balance, however, the rate of reaction initially increases and then decreases as a function of the disorder strength. The physical behavior obtained with this second model is in accord with that for reactive turbulent flow, indicating that Levy flight statistics can model aspects of turbulent fluid transport.Comment: 6 pages, 5 pages. Phys. Rev. E. 65 (2002) 011109--1-

Salt-assisted vapor-liquid-solid growth of one-dimensional van der Waals materials

We have combined the benefits of two catalytic growth phenomena to form nanostructures of transition metal trichalcogenides (TMTs), materials that are challenging to grow in a nanostructured form by conventional techniques, as required to exploit their exotic physics. Our growth strategy combines the benefits of vapor-liquid-solid (VLS) growth in controlling dimension and growth location, and salt-assisted growth for fast growth at moderate temperatures. This salt-assisted VLS growth is enabled through use of a catalyst that includes Au and an alkali metal halide. We demonstrate high yields of NbS3 1D nanostructures with sub-ten nanometer diameter, tens of micrometers length, and distinct 1D morphologies consisting of nanowires and nanoribbons with [010] and [100] growth orientations, respectively. We present strategies to control the growth location, size, and morphology. We extend the growth method to synthesize other TMTs, NbSe3 and TiS3, as nanowires. Finally, we discuss the growth mechanism based on the relationships we measure between the materials characteristics (growth orientation, morphology and dimensions) and the growth conditions (catalyst volume and growth time). Our study introduces opportunities to expand the library of emerging 1D vdW materials and their heterostructures with controllable nanoscale dimensions.Comment: 16 pages, 5 figure

Tourism destination modelling: building a sustainable planning tool for Australian tourism destinations

The Ningaloo Destination Model is a tourism planning tool for the Ningaloo Coast region of Western Australia that assesses the economic, social and environmental impacts of different planning decisions and events. This report describes the features of the tourism destination model, and analyses its application in the region and to other parts of Australia. Destination modelling integrates a number of research methodologies developed through past STCRC projects (on visitor spending and characteristics, social impacts and economic impacts), secondary data and ecological research. The key to this process is a model development technique that uses scenario planning methodologies to facilitate stakeholder engagement and conceptual modelling techniques to facilitate research integration. The report describes the methodologies used for model development and for data collection, provides two case studies demonstrating outputs, and explores applications of the Ningaloo Destination Model to the region, to other locations and to other sectors. The Ningaloo Destination Model provides estimates of the impacts of plans and events related to tourism in four dimensions: tourism specific; economy; social; and environmental (both resource use and ecological). These outputs are explored through two case studies: a nodal coastal development; and a large resort development. The model can be used for four broad (oftentimes overlapping) categories of assessment: operational planning and decision making for specific organisations and groups (such as local government or agencies that manage land or sea use), regional planning, participatory planning and collaborations and to assist monitoring and evaluation.The Ningaloo Destination Model will be available to the general public (in a limited format) through websites; to agencies through a desktop version; and through integration into a larger model of the region being developed by the CSIRO. Destination modelling is relevant for other tourism destinations and a process for the rapid and cost-effective application of destination modelling is feasible. While much of the data is available, a broader roll-out would require benchmarking of water, electricity and waste data, and developing a wireframe for all tourism destinations. Making destination modelling tools broadly available would significantly broaden the impacts considered in tourism planning and lead to enhancement of desirable effects of tourism development, and early mitigation of negative impacts across Australia. The techniques developed for destination modelling were also found to be applicable to other sectors

Well Water Screening in Suffolk, VA, for Contaminants Affecting Human Health

Purpose: Despite regulations, one area that remains outside the scope of the clean water policies is well water. With the lack of oversight, the millions of home that rely on well water remain susceptible to numerous pollutants and contaminants. To ensure the safety of well water, development of screening and testing protocols is imperative. Many households in Suffolk, VA still use well water making it an apt location to conduct a preliminary study screening for potential water contaminants. Methods: Water samples from kitchen and garden sources were collected from households in Suffolk, VA. These samples assessed for TDS via Milwaukee EC59 pen, pH via Sper Scientific test tube pen, arsenic via Quick Rapid Arsenic Test Kit, E. coli and coliform, and lead via Simpletek Micro Tester Pro self-filling test ampoules. Findings: Four of the thirty kitchen-sourced samples tested positive for coliform contamination. The positive findings may represent hazards for health thus warranting further investigation. Conclusion: Many Suffolk homes rely on well water but lack of regulations can bring risk for contamination. This study indicated a potential coliform problem in Suffolk and more work must be done to evaluate for coliform contamination and its resultant health consequences

Toward Sensor Modular Autonomy for Persistent Land Intelligence Surveillance and Reconnaissance (ISR)

Currently, most land Intelligence, Surveillance and Reconnaissance (ISR) assets (e.g. EO/IR cameras) are simply data collectors. Understanding, decision making and sensor control are performed by the human operators, involving high cognitive load. Any automation in the system has traditionally involved bespoke design of centralised systems that are highly specific for the assets/targets/environment under consideration, resulting in complex, non-flexible systems that exhibit poor interoperability. We address a concept of Autonomous Sensor Modules (ASMs) for land ISR, where these modules have the ability to make low-level decisions on their own in order to fulfil a higher-level objective, and plug in, with the minimum of preconfiguration, to a High Level Decision Making Module (HLDMM) through a middleware integration layer. The dual requisites of autonomy and interoperability create challenges around information fusion and asset management in an autonomous hierarchical system, which are addressed in this work. This paper presents the results of a demonstration system, known as Sensing for Asset Protection with Integrated Electronic Networked Technology (SAPIENT), which was shown in realistic base protection scenarios with live sensors and targets. The SAPIENT system performed sensor cueing, intelligent fusion, sensor tasking, target hand-off and compensation for compromised sensors, without human control, and enabled rapid integration of ISR assets at the time of system deployment, rather than at design-time. Potential benefits include rapid interoperability for coalition operations, situation understanding with low operator cognitive burden and autonomous sensor management in heterogenous sensor systems

Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets

Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues. Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression. Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species

Effect of DMF on liver I/R

AIM To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODS Rats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTS Histological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSION DMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI