ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM

The solid tumor microenvironment, pre-metastatic niche, and fibrotic environment are known to have significant biochemical and biomechanical similarities to the fibrotic environment. All have significantly increased levels of factors such as TGFβ, HIF1α, TNFα, PDGF, VEGF, FGF, interleukins and other growth factors that are known to be pro-tumorigenic. Clinical and basic science research has shown that fibrosis presents an environment that favors tumor growth, such as hepatocellular carcinoma being commonly preceded by liver cirrhosis, or bleomycin induced lung fibrosis enhancing pulmonary metastasis in mouse models of breast cancer. In addition to the evidence indicating that fibrosis enhances primary tumor growth and metastasis it is also well characterized that primary tumor metastasis has specific organotropism, for example breast cancer commonly spreads to the lungs, brain, bone, liver and lymph nodes. However, whether non-organtropic fibrosis can redirect metastasis to the damaged organ has not been investigated. To elucidate the fibrotic effect on tumor organotropism we induced fibrosis in the organotropic lungs and in the non-organotropic kidney of two mouse models of breast cancer, the 4T1 murine cancer cell line model and the genetic MMTV-Pymt model, both of which are known to metastasize. Using histopathology, microarrays, gene expression by polymerase chain reaction, ELISA, chemokine array, and in vitro experiments we demonstrate that despite the pro-tumorigenic environment, kidney fibrosis does not redirect metastasis to the non-organotropic damaged organ. However, mice with kidney fibrosis had increased metastasis to their lungs. Furthermore, we found that kidney fibrosis increases the circulating levels of the pro-angiogenic factor Angiopoietin 2 that increased vascular permeability of the lungs, but not the kidneys. In fact, while fibrotic lungs showed decreased expression of endothelial tight gap junction protein Claudin-5, the fibrotic kidneys had an elevated expression of Claudin-5. Our findings suggest that despite the similarities between fibrosis, the tumor microenvironment and the pre-metastatic niche, that while it can enhance tropic metastatic disease, it cannot redirect organotropism indicating that other factors must be involved in directing organotropism. Here we report that tumor organotropism may be a result of organ specific vascular responses to excess circulating factors and increased fibrotic factors. These findings indicate that organotropism is directly related to and as a result of organ specific vascular alterations

Knowledge assimilation processes of rapidly internationalising firms: longitudinal case studies of Scottish SMEs

<p>Purpose – The accumulation of knowledge and learning by firms has been identified as being critical to their internationalisation. This paper aims to explore the knowledge assimilation processes of rapidly internationalising small to medium-sized enterprises (SMEs).</p> <p>Design/methodology/approach – This is a qualitative enquiry in two stages. First, four case studies were selected from firms that were participating in an internationalisation programme run by Scottish Enterprise, the regional development agency. Data collection involved semi-structured interviews with chief executive officers (CEOs) and programme providers, and archival data. Second, two focus groups were held with six CEOs participating in the programme.</p> <p>Findings – The findings indicate that knowledge sharing is important for rapidly internationalising SMEs and that firms adopted high levels of formality in assimilating knowledge. Two key aspects of formality were identified as important; formal planned events to share explicit and tacit knowledge and the codification of tacit to explicit knowledge. Knowledge may be assimilated less formally by the retention of tacit knowledge as tacit, while utilising elements of formality. The paper finds that learning for internationalisation can be transferred to support domestic growth.</p> <p>Practical implications – It is important for firms to develop appropriate knowledge assimilation processes within their management systems to support internationalisation. The CEO and management team need to take the lead in marshalling commitment to learning processes and in cultivating an organisational culture that is supportive of learning.</p> <p>Originality/value – This research contributes to international entrepreneurship by providing insights into the knowledge assimilation processes employed by rapidly internationalising SMEs to manage the tensions between the need for greater formality to be efficient at learning, and informality to enable speedy decision making.</p&gt

Mathematical morphology and applications in automated sunspot detection

This presentation discusses the mathematical morphology and applications in automated sunspot detection

Onset of Electron Acceleration in a Flare Loop

We carried out detailed analysis of X-ray and radio observations of a simple flare loop that occurred on 12th August 2002, with the impulsive hard X-ray (HXR) light curves dominated by a single pulse. The emission spectra of the early impulsive phase are consistent with an isothermal model in the coronal loop with a temperature reaching several keVs. A power-law high-energy spectral tail is evident near the HXR peak time, in accordance with the appearance of footpoints at high energies, and is well correlated with the radio emission. The energy content of the thermal component keeps increasing gradually after the disappearance of this nonthermal component. These results suggest that electron acceleration only covers a central period of a longer and more gradual energy dissipation process and that the electron transport within the loop plays a crucial role in the formation of the inferred power-law electron distribution. The spectral index of power-law photons shows a very gradual evolution indicating a quasi-steady state of the electron accelerator, which is confirmed by radio observations. These results are consistent with the theory of stochastic electron acceleration from a thermal background. Advanced modeling with coupled electron acceleration and spatial transport processes is needed to explain these observations more quantitatively, which may reveal the dependence of the electron acceleration on the spatial structure of the acceleration region

Effect of blade geometry on the aerodynamic loads produced by vertical-axis wind turbines

Accurate aerodynamic modelling of vertical-axis wind turbines poses a significant challenge. The rotation of the turbine induces large variations in the angle of attack of its blades that can manifest as dynamic stall. In addition, interactions between the blades of the turbine and the wake that they produce can result in impulsive changes to the aerodynamic loading. The Vorticity Transport Model has been used to simulate the aerodynamic performance and wake dynamics of three different vertical-axis wind turbine configurations. It is known that vertical-axis turbines with either straight or curved blades deliver torque to their shaft that fluctuates at the blade passage frequency of the rotor. In contrast, a turbine with helically twisted blades delivers a relatively steady torque to the shaft. In this article, the interactions between helically twisted blades and the vortices within their wake are shown to result in localized perturbations to the aerodynamic loading on the rotor that can disrupt the otherwise relatively smooth power output that is predicted by simplistic aerodynamic tools that do not model the wake to sufficient fidelity. Furthermore, vertical-axis wind turbines with curved blades are shown to be somewhat more susceptible to local dynamic stall than turbines with straight blades

Heat transfer between surfaces in contact: An analytical and experimental study of thermal contact resistance of metallic interfaces

Dimensionless correlation for predicting thermal contact resistance between similar metal surfaces in vacuum environmen

On the Spatial Distribution of Hard X-Rays from Solar Flare Loops

The aim of this paper is to investigate the spatial structure of the impulsive phase hard X-ray emission from solar flares. This work is motivated by the YOHKOH and the forthcoming HESSI observations. Summarizing past results, it is shown that the transport effects can account for the observations by inhomogeneous loops where there is a strong field convergence and/or density enhancement at the top of the flaring loop. Scattering by plasma turbulence at the acceleration site or pancake type pitch angle distribution of the accelerated electrons can also give rise to enhanced emission at the loop tops. These could be a natural consequence of acceleration by plasma waves. This paper considers a general case of stochastic scattering and acceleration that leads to an isotropic pitch angle distribution and an enhanced emission from the loop tops or the acceleration site. Following the formalism developed in earlier papers the strength and the spectrum of the radiation expected from the acceleration site and the foot points are evaluated and their dependence on the parameters describing the acceleration process and the flare plasma are determined. The theoretical ratio of these two intensities and relative values of their spectral indices are compared with the YOHKOH observations, demonstrating that the above mentioned parameters can be constrained with such observations. It is shown that future high spatial and spectral resolution observations, for example those expected from HESSI, can begin to distinguish between different models and constrain their parameters.Comment: 37 pages with 20 figures. Accepted for publication in ApJ http://www.astronomy.stanford.ed

Analytical Investigation of the Reentry Behavior of the ''flying Wind Tunnel'' Test Vehicle, with Some Effects of Threshold and Torque Level of a Roll-rate Control System

Analytical investigation of reentry behavior of flying wind tunnel test vehicle with some effects of threshold and torque level of roll-rate control syste