An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct

A major obstacle to 3-dimensional tissue engineering is incorporation of a functional vascular supply to support the expanding new tissue. This is overcome in an in vivo intrinsic vascularization model where an arteriovenous loop (AVL) is placed in a noncollapsible space protected by a polycarbonate chamber. Vascular development and hypoxia were examined from 3 days to 112 days by vascular casting, morphometric, and morphological techniques to understand the model's vascular growth and remodeling parameters for tissue engineering purposes. At 3 days a fibrin exudate surrounded the AVL, providing a scaffold to migrating inflammatory, endothelial, and mesenchymal cells. Capillaries formed between 3 and 7 days. Hypoxia and cell proliferation were maximal at 7 days, followed by a peak in percent vascular volume at 10 days (23.20±3.14% compared with 3.59±2.68% at 3 days, P<0.001). Maximal apoptosis was observed at 112 days. The protected space and spontaneous microcirculatory development in this model suggest it would be applicable for in vivo tissue engineering. A temporal window in a period of intense angiogenesis at 7 to 10 days is optimal for exogenous cell seeding and survival in the chamber, potentially enabling specific tissue outcomes to be achieved.

MTI-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression

Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. We investigated the effects of MT1-MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1-MMP or MMP-2. MT1-MMP and MMP-2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1-MMP 1) were able to activate endogenous or exogenous pro-MMP-2, 2) displayed an enhanced in vitro invasiveness through matrigel-coated filters independent of MMP-2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutanously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1-MMP regardless of MMP-2 expression levels, suggesting that the production of MMP-2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1-MMP-producing cells was associated with an up-regulation of VEGF expression. These results emphasize the importance of MT1-MMP during tumor angiogenesis and open new opportunities for the development of antiangiogenic strategies combining inhibitors of MT1-MMP and VEGF antagonists. - Sounni, N. E., Devy, L., Hajitou, A., Frankenne, F., Munaut, C., Gilles, C., Deroanne, C., Thompson, E. W., Foidart, J. M., Noel, A. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression.

Contact with existing adipose tissue is inductive for adipogenesis in matrigel

The effect of adipose tissue on inductive adipogenesis within Matrigel (BD Biosciences) was assessed by using a murine chamber model containing a vascular pedicle. Three-chamber configurations that varied in the access to an adipose tissue source were used, including sealed- and open-chamber groups that had no access and limited access, respectively, to the surrounding adipose tissue, and a sealed-chamber group in which adipose tissue was placed as an autograft. All groups showed neovascularization, but varied in the amount of adipogenesis seen in direct relation to their access to preexisting adipose tissue: open chambers showed strong adipogenesis, whereas the sealed chambers had little or no adipose tissue; adipogenesis was restored in the autograft chamber group that contained 2- to 5-mg fat autografts. These showed significantly more adipogenesis than the sealed chambers with no autograft (p < 0.01). Autografts with 1 mg of fat were capable of producing adipogenesis but did so less consistently than the larger autografts. These findings have important implications for adipose tissue engineering strategies and for understanding de novo production of adipose tissue.

Reversible transdifferentiation of blood vascular endothelial cells to a lymphatic-like phenotype in vitro

Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs of fetal or adult origin show altered gene expression that is indicative of transition to a lymphatic-like phenotype. This change occurs in BECs undergoing tubulogenesis in fibrin, collagen or Matrigel assays, but is independent of tube formation per se, because it is not inhibited by a metalloproteinase inhibitor that blocks tubulogenesis. It is also reversible, since cells removed from 3D tubules revert to a BEC expression profile upon monolayer culture. Induction of the lymphatic-like phenotype is partially inhibited by co-culture of HUVECs with perivascular cells. These data reveal an unexpected plasticity in endothelial phenotype, which is regulated by contact with the ECM environment and/or cues from supporting cells.

Integrated access control for smart buildings using building information models

This thesis investigates the use of building information models for access control and security applications in critical infrastructures and complex building environments. It examines current problems in security management for physical and logical access control and proposes novel solutions that exploit the detailed information available in building information models. The project was carried out as part of the Airports of the Future Project and the research was modelled based on real-world problems identified in collaboration with our industry partners in the project.

Reproductive Health as a Human Right: A Matter of Access or Provision?

This article seeks to understand why, despite over three decades of claiming women's reproductive health as a human right, we have seen little progress in reducing their health inequalities and poor health outcomes. I argue that one reason for this lack of progress may be due to a failure to clearly articulate the responsibilities of key actors, crucially states, in ensuring that women have access to, and provision of, services required to realize their reproductive rights. What is needed, this article suggests, is a framework that can translate decades of rights language into action and specifically identify the provisions required to address women's health.

SCRAMSPACE : Radical-Farming Scramjet for access to space

Scramjet-based launch systems offer considerable promise for safe, reliable and economical access to space. A general Scramjets introduction is first provided, followed by the specifics of Australian Scramjet Research and the recent progress in inlet-injection radical-farming scramjets as part of the SCRAMSPACE program. Through both flight and ground tests, leveraging Australias world leadership in scramjet R&D, the SCRAMSPACE project is designed to answer key scientific and technological questions and build an industry-ready talent pool for a future Australian space industry. An extensive descriptions of all phases of the development of the SCRAMSPACE I scramjet-powered free-flight experiment are described in these lecture notes.

Efficiency of lexical access in children with autism spectrum disorders : does modality matter?

The provision of visual support to individuals with an autism spectrum disorder (ASD) is widely recommended. We explored one mechanism underlying the use of visual supports: efficiency of language processing. Two groups of children, one with and one without an ASD, participated. The groups had comparable oral and written language skills and nonverbal cognitive abilities. In two semantic priming experiments, prime modality and prime–target relatedness were manipulated. Response time and accuracy of lexical decisions on the spoken word targets were measured. In the first uni-modal experiment, both groups demonstrated significant priming effects. In the second experiment which was cross-modal, no effect for relatedness or group was found. This result is considered in the light of the attentional capacity required for access to the lexicon via written stimuli within the developing semantic system. These preliminary findings are also considered with respect to the use of visual support for children with ASD.

Co-regulatory potential of vascular endothelial growth factor–A and vascular endothelial growth factor–C in thyroid carcinoma

Vascular endothelial growth factor (VEGF) promotes growth of blood or lymphatic vessels. The aim of the current study is to identify relationships between VEGF-A and VEGF-C, and their impact in angiogenesis and metastases in thyroid cancers. VEGF-A and VEGF-C mRNA and protein expression was investigated in 136 thyroid cancers (123 papillary thyroid carcinomas and 13 undifferentiated thyroid carcinomas) and 40 matched lymph node metastases with papillary thyroid carcinoma using reverse transcription polymerase chain reaction and immunohistochemistry. VEGF-A and VEGF-C mRNA expression was significantly different between conventional papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma, and undifferentiated thyroid carcinomas (P = 1 x 10(-6) and 1 x 10(-5), respectively). In undifferentiated carcinoma, VEGF-A and VEGF-C protein overexpression was noted in all cases. VEGF-A and VEGF-C mRNA overexpression was noted in 51% (n = 62) and 27% (n = 33) of the papillary thyroid carcinomas, whereas VEGF-A and VEGF-C protein overexpression was also identified in 70% (n = 86) and 62% (n = 76) of the carcinomas. VEGF-A mRNA was significantly higher in cancers with lymph node metastases compared with nonmetastatic cancers (P = .001), whereas most metastatic cancers underexpressed VEGF-C (P = .0002), with a similar trend for protein. The expression of VEGF-A and VEGF-C correlated with each other at both mRNA and protein levels (P = .00004 and .003, respectively). In summary, VEGF-A and -C expressions correlate with the pathological parameters and metastatic status of thyroid carcinomas. The significant correlations between the expressions of these genes add weight to hypotheses concerning VEGF-A and -C interaction in cancer progression.

Angiogenesis in old-aged subjects after ischemic stroke : a cautionary note for investigators

Angiogenesis represents a form of neovascularisation of exceptional importance in numerous pathological conditions including stroke. In this context it is directly related to neuroregeneration which is seen in close proximity. However, numerous experimental data have been drawn from studies that have ignored the age criterion. This is extremely important as angiogenesis is different in young versus old subjects. Extrapolating data obtained from studies performed in young subjects or "in vitro" to old-age patients could lead to inexact conclusions since the dynamics of angiogenesis is age-dependent.The current review covers the key features of brain senescence including morphological and functional changes related to the brain parenchyma, its vascular network and blood flow which could possibly influence the process of angiogenesis. This is followed by a description of post-stroke angiogenesis and its relationship to neuroregeneration and its modulation by vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF 1), the most important factors active in old brain after ischemic injury.

The effect of cryotherapy on the vascular regeneration following closed soft tissue trauma

INTRODUCTION Icing (cryotherapy) is being widely used for the treatment of closed soft tissue trauma (CSTT), such as those resulting from sport injuries. It is believed that cryotherapy induces vasoconstriction and through this mechanism reduces inflammation [1]. However, the impact of this technique on the healing of impaired vasculature and muscle injuries following trauma remains controversial. Recent evidence suggests that the muscle regeneration is delayed after cryotherapy [2]. Consequently, we aimed to investigate the effect of cryotherapy on the vascular morphology following CSTT using an experimental model in rats by contrast-enhanced micro-CT imaging. METHODS Fifty four rats were divided into three main groups: control (no injury, n=6), sham (CSTT but no icing treatment, n=24) and icing (CSTT, treated with one session of ice block massaged directly on the injured muscle for 20 minutes, n=24). The CSTT was induced to the left thigh (Biceps Femoris) of anaesthetised rats (Male, Wistar) to create a standardized and reproducible vascular and muscle injury using an impact device [3]. Following trauma, animals were euthanized after 1, 3, 7, and 28 days healing time (n=6 for each time point). For a three-dimensional vascular morphological assessment, the blood vessels of euthanised rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil, MV 122, Flowtech, USA) using an infusion pump. Both hind-limbs were dissected, and then the injured and non-injured limbs were imaged using a micro-CT scanner (µCT 40, Scanco Medical, Switzerland) and total volume of the perfused blood vessels (TVV) was calculated. More detailed morphological parameters such as vessel volume (VV), diameter (VD), spacing (VSp), number (VN) and connectivity (VConn) were quantified through high resolution (6 µm), micro-CT-scanned biopsy samples (diameter: 8mm) taken directly from the region of the injured muscles. The biopsies were then analysed histologically to confirm the results derived from contrast-enhanced micro-CT imaging. RESULTS AND DISCUSSION The TVV was significantly higher in the injured legs compared to the non-injured legs at day 1 and 7 in the sham group and at day 28 in both sham and icing groups. The biopsies from the injured legs of the icing group showed a significant reduction in VV, VN, VD, VConn and an increase in VSp compared to those in the sham and control groups at days 1, 3 and 7, post injury. While the injured legs of the sham group exhibited a decrease in VN and VConn 28 days post trauma, indicating a return to the original values prior to trauma, these parameters had increased in the icing group (Figure 1). Also, at day 1 post injury, VV and VD of the injured legs were significantly higher in the sham group compared to the icing group, which may be attributed to the effect of vasoconstriction induced by icing. Further histomorphological evaluation of day 1 post injury, indicated that although cryotherapy significantly reduced the injury size and influx of inflammatory cells, including macrophages and neutrophils, a delay in vascular and muscle fiber regeneration was found at later time points confirming other reports from the literature [2]. CONCLUSIONS We have demonstrated using micro-CT imaging that the vascular morphology changes after CSTT, and that its recovery is affected by therapeutic modalities such as icing. This may be useful for the development of future clinical monitoring, diagnosis and treatment of CSTT. While icing reduces the swelling after trauma, our results suggest that it may delay the recovery of the vasculature in the injured tissue.

A policy model for access control using building information models

Building information models have created a paradigm shift in how buildings are built and managed by providing a dynamic repository for building data that is useful in many new operational scenarios. This change has also created an opportunity to use building information models as an integral part of security operations and especially as a tool to facilitate fine-grained access control to building spaces in smart buildings and critical infrastructure environments. In this paper, we identify the requirements for a security policy model for such an access control system and discuss why the existing policy models are not suitable for this application. We propose a new policy language extension to XACML, with BIM specific data types and functions based on the IFC specification, which we call BIM-XACML.

Graph theory based representation of building information models for access control applications

Building information models are increasingly being utilised for facility management of large facilities such as critical infrastructures. In such environments, it is valuable to utilise the vast amount of data contained within the building information models to improve access control administration. The use of building information models in access control scenarios can provide 3D visualisation of buildings as well as many other advantages such as automation of essential tasks including path finding, consistency detection, and accessibility verification. However, there is no mathematical model for building information models that can be used to describe and compute these functions. In this paper, we show how graph theory can be utilised as a representation language of building information models and the proposed security related functions. This graph-theoretic representation allows for mathematically representing building information models and performing computations using these functions.