A008 Presence of tissue factor and other components of atherosclerosis in human aortic valve stenosis

BackgroundIt is now generally accepted that calcific aortic valve disease is an atherosclerotic-like process. Recent studies in an experimental model of aortic valve sclerosis demonstrated the presence of tissue factor (TF), the main contributor to atherosclerotic plaque thrombogenicity, in diseased valve leaflets. We assessed the hypothesis that human aortic valve disease is an atherosclerotic-like process in which TF plays an important role and evaluated the valvular expression and localization of TF and other components of atherosclerosis.MethodsCalcified aortic valves (n=52) were obtained from patients undergoing aortic valve replacement. Leaflet structure, cellular and lipid infiltration and expression of TF, its inhibitors, VEGF and other components of atherosclerosis were evaluated by histological and immunohistochemical staining. TF, TFPI, osteopontin, MMP- 9, TIMP-1 and VEGF antigen were measured by ELISA and TF and alkaline phosphatase activity were determined using chromogenic assays. Finally, we performed semi-quantification of TF transcripts by RT- PCR and further analyzed protein expression by Western blot.ResultsHistological and immunohistochemical staining of the valve leaflets revealed neovascularisation at the centre of the lesions, overall macrophage and myofibroblast infiltration and the abundant presence of MMP-9. On the other hand, TF and TFPI were associated with calcification and extracellular lipid deposits in the fibrosa and the subendothelial layer of the aortic side of the leaflets. Correspondingly, TF antigen and activity were found to be higher in calcified regions of the valve leaflets (733.29±70.49pg/mgvs 429.40±73.17pg/mg and 144.75±14.65pg/mgvs 40.15±6.19pg/mg respectively (p<0.0001)). Similar results were found for osteopontin, MMP-9, TIMP-1 and VEGF. In contrast, TFPI antigen was found to be much lower in these calcified regions (722.54±153.92pg/mgvs 2459.28±285.36pg/mg (p<0.0001)).ConclusionThese results demonstrate that aortic valve lesions display several characteristics of atherosclerosis, including TF expression. In addition, we showed that TF is colocalized with calcification and lipid deposition. Further studies are now set up to evaluate the role of TF in aortic valve disease and its association with other components of the atherosclerotic process

Let’s Get Physical: Computer Science Meets Systems

In cyber-physical systems (CPS) computing, networking and control (typically regarded as the "cyber" part of the system) are tightly intertwined with mechanical, electrical, thermal, chemical or biological processes (the "physical" part). The increasing sophistication and heterogeneity of these systems requires radical changes in the way sense-and-control platforms are designed to regulate them. In this paper, we highlight some of the design challenges due to the complexity and heterogeneity of CPS. We argue that such challenges can be addressed by leveraging concepts that have been instrumental in fostering electronic design automation while dealing with complexity in VLSI system design. Based on these concepts, we introduce a design methodology whereby platform-based design is combined with assume-guarantee contracts to formalize the design process and enable realization of CPS architectures and control software in a hierarchical and compositional manner. We demonstrate our approach on a prototype design of an aircraft electric power system. © 2014 Springer-Verlag Berlin Heidelberg

High throughput quantitative expression screening and purification applied to recombinant disulfide-rich venom proteins produced in E. coli

Escherichia coli (E. coli) is the most widely used expression system for the production of recombinant proteins for structural and functional studies. However, purifying proteins is sometimes challenging since many proteins are expressed in an insoluble form. When working with difficult or multiple targets it is therefore recommended to use high throughput (HTP) protein expression screening on a small scale (1-4 ml cultures) to quickly identify conditions for soluble expression. To cope with the various structural genomics programs of the lab, a quantitative (within a range of 0.1-100 mg/L culture of recombinant protein) and HTP protein expression screening protocol was implemented and validated on thousands of proteins. The protocols were automated with the use of a liquid handling robot but can also be performed manually without specialized equipment

Linearly scaling direct method for accurately inverting sparse banded matrices

In many problems in Computational Physics and Chemistry, one finds a special kind of sparse matrices, termed "banded matrices". These matrices, which are defined as having non-zero entries only within a given distance from the main diagonal, need often to be inverted in order to solve the associated linear system of equations. In this work, we introduce a new O(n) algorithm for solving such a system, being n X n the size of the matrix. We produce the analytical recursive expressions that allow to directly obtain the solution, as well as the pseudocode for its computer implementation. Moreover, we review the different options for possibly parallelizing the method, we describe the extension to deal with matrices that are banded plus a small number of non-zero entries outside the band, and we use the same ideas to produce a method for obtaining the full inverse matrix. Finally, we show that the New Algorithm is competitive, both in accuracy and in numerical efficiency, when compared to a standard method based in Gaussian elimination. We do this using sets of large random banded matrices, as well as the ones that appear when one tries to solve the 1D Poisson equation by finite differences.Comment: 24 pages, 5 figures, submitted to J. Comp. Phy

An Efficient Wire Routing and Wire Sizing Algorithm for Weight Minimization of Automotive Systems

As the complexities of automotive systems increase, designing a system is a difficult task that cannot be done manually. In this paper, we propose an algorithm for weight minimization of wires used for connecting electronic devices in a system. The wire routing problem is formulated as a Steiner tree problem with capacity constraints, and the location of a Steiner vertex is selected for adding a splice connecting more than two wires. Besides wire routing, wire sizing is also done to satisfy resistance constraints and minimize the total wiring weight. Experimental results show the effectiveness and efficiency of our algorithm. Copyright 2014 ACM

3D Environment Modeling for Falsification and Beyond with Scenic 3.0

We present a major new version of Scenic, a probabilistic programming language for writing formal models of the environments of cyber-physical systems. Scenic has been successfully used for the design and analysis of CPS in a variety of domains, but earlier versions are limited to environments which are essentially two-dimensional. In this paper, we extend Scenic with native support for 3D geometry, introducing new syntax which provides expressive ways to describe 3D configurations while preserving the simplicity and readability of the language. We replace Scenic's simplistic representation of objects as boxes with precise modeling of complex shapes, including a ray tracing-based visibility system that accounts for object occlusion. We also extend the language to support arbitrary temporal requirements expressed in LTL, and build an extensible Scenic parser generated from a formal grammar of the language. Finally, we illustrate the new application domains these features enable with case studies that would have been impossible to accurately model in Scenic 2.Comment: 13 pages, 6 figures. Full version of a CAV 2023 tool paper, to appear in the Springer Lecture Notes in Computer Science serie

Physical Constraints from Near-infrared Fast Photometry of the Black Hole Transient GX 339–4

We present results from the first multi-epoch X-ray/IR fast-photometry campaign on the black hole transient GX 339–4, during its 2015 outburst decay. We studied the evolution of the power spectral densities finding strong differences between the two bands. The X-ray power spectral density follows standard patterns of evolution, plausibly reflecting changes in the accretion flow. The IR power spectral density instead evolves very slowly, with a high-frequency break consistent with remaining constant at 0.63 ± 0.03 Hz throughout the campaign. We discuss this result in the context of the currently available models for the IR emission in black hole transients. While all models will need to be tested quantitatively against this unexpected constraint, we show that an IR-emitting relativistic jet that filters out the short-timescale fluctuations injected from the accretion inflow appears as the most plausible scenario

Unveiling optical signatures of outflows in accreting white dwarfs

Accreting white dwarfs are known to show signatures of wind-type outflows in the ultraviolet. At optical wavelengths, however, wind detections have only been reported for a few sources. We present GTC-10.4m optical spectroscopy of four accreting white dwarfs (BZ Cam, V751 Cyg, MV Lyr, and V425 Cas) observed during luminous epochs, when their optical emission is expected to be dominated by the accretion disc. We focused the analysis on four emission lines: H$\alpha$ and He I $\lambda$5876, $\lambda$6678, $\lambda$7065. Line profiles are complex and variable on short (minutes) and long (days to weeks) time scales, with transient absorption and emission components. Among them, we detect strong blue-shifted absorptions at $\gtrsim 1000$ km s$^{-1}$. These high-velocity components, present only in the blue wing of the emission lines, are observed in all four sources and could be associated with accretion disc winds. For MV Lyr and V425 Cas, these would represent the first detection of optical outflows in these objects, while in the case of BZ Cam and V751 Cyg, the presence of outflows has been previously reported. This study suggests that, in addition to ultraviolet winds, optical outflows might be also common in accreting white dwarfs. We discuss the observational properties of these winds and their possible similarity to those detected in accreting black holes and neutrons stars.Comment: Accepted for publication in A&