Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a genetic disorder associated to mutations in the ABCC6 gene; however, the pathogenetic mechanisms leading to elastic fibre calcifications and to clinical manifestations are still unknown. Dermal fibroblasts, directly involved in the production of the extracellular milieu, have been isolated from healthy subjects and from patients affected by PXE, cultured in vitro and characterized for their ability to produce reactive oxygen species, for structural and functional properties of their cell membranes, for changes in their protein profile. Data demonstrate that oxidative stress has profound and endurable consequences on PXE fibroblast phenotype being responsible for: reduced levels of global DNA methylation, increased amount of carbonylated proteins and of lipid peroxidation products, altered structural properties of cell membranes, modified protein expression. Data shed new light on the pathogenetic pathways in PXE, by identifying a network of proteins affecting elastic fibre calcification through inefficient vitamin K recycling, and highlight the role of differentially expressed proteins as targets for validating the efficacy of future therapeutic strategies aiming to delay and/or revert the pathologic phenotype of PXE fibroblasts. Moreover, data open new perspectives for investigating PXE-like phenotypes in the absence of ABCC6 mutations.     

Reusable abstractions for modeling languages

Model-driven engineering proposes the use of models to describe the relevant aspects of the system to be built and synthesize the final application from them. Models are normally described using Domain-Specific Modeling Languages (DSMLs), which provide primitives and constructs of the domain. Still, the increasing complexity of systems has raised the need for abstraction techniques able to produce simpler versions of the models while retaining some properties of interest. The problem is that developing such abstractions for each DSML from scratch is time and resource consuming.     

Option pricing under a jump-telegraph diffusion model with jumps of random size

ABSTRACT

We present a finite difference method to solve a system of two Partial-Integro Differential Equations which arise from pricing an option under a Jump-Telegraph Diffusion Model for the underlying asset, considering the risk-neutral valuation formula under an equivalent martingale measure. This system is fully discretized using an Implicit–Explicit two-time level scheme and quadrature formulas. The resulting two tridiagonal algebraic linear systems are solved recursively using the Thomas Algorithm. Some numerical results are presented and the numerical order of convergence for the method is estimated. Finally, the robustness of the method is validated against an exact solution obtained for a perturbed problem.     

Plasminogen activator system modulates invasive capacity and proliferation in prostatic tumor cells

The malignant phenotype of prostatic tumor cells correlates with the expression of both uPA and its cell-membrane receptor (uPAR); however, there is little information concerning the role of cell-bound uPA in matrix degradation and invasion. Our results suggest that cell-associated uPA plays a key role in regulating the amount of plasmin present at the surface of prostatic carcinoma (PRCA) cells and show that differential production of uPA corresponds with the capacity to bind and activate plasminogen. In addition, we provide direct evidence that both uPA secretion and the presence of uPA-uPAR complexes characterize the invasive phenotype of PRCA cells and suggest the existence of several pathways by which tumor cells acquire plasmin activity. LNCaP cells (which do not produce uPA but express uPAR) may activate plasmin through exogenous uPA. In vivo, the source of uPA may be infiltrating macrophages and/or fibroblasts as observed in several other systems. PAI-1 accumulation in the conditioned medium (CM) limits plasmin action to the pericellular microenvironment. Our results indicate that MMP-9 and MMP-2 are also activated by plasmin generated by cell-bound but not by soluble, extracellular uPA. Plasmin activation and triggering of the proteolytic cascade involved in Matrigel invasion is blocked by antibodies against uPA (especially by anti- A-chain of uPA which interacts with uPAR) and by PA inhibitors such as p-aminobenzamidine which may regulate levels of cell-bound uPA. uPA may also regulate growth in PRCA cells. Indeed, antibodies against uPA A-chain (and also p-aminobenzamidine treatment) interfere with the ATF domain and inhibit cell growth in uPA-producing PC3 and DU145 prostate cancer cell lines, whereas exogenous uPA (HMW-uPA with ATF) induces growth of LNCaP prostate tumor cell line. These data support the hypothesis that in prostatic cancer patients at risk of progression, uPA/plasmin blockade may be of therapeutic value by blocking both growth of the primary tumor and dissemination of metastatic cells.     

Low-power architectural synthesis and the impact of exploiting locality

Recently there has been increased interest in the development of high-level architectural synthesis tools targeting power optimization. In this paper, we first present an overview of the various architecture synthesis tasks and analyze their influence on power consumption. A survey of previously proposed techniques is given, and areas of opportunity are identified. We next propose a new architecture synthesis technique for low-power implementation of real-time applications. The technique uses algorithm partitioning to preserve locality in the assignment of operations to hardware units. Preserving locality results in more compact layouts, reduced usage of long high-capacitance buses, and reduced power consumption in multiplexors and buffers. Experimental results show reductions in bus and multiplexor power of up to 80% and 60%, respectively, resulting in 10–25% reduction in total power.     

Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese

The mitochondrial uncoupling protein (UCP) in the mitochondrial inner membrane of mammalian brown adipose tissue generates heat by uncoupling oxidative phosphorylation. This process protects against cold and regulates energy balance. Manipulation of thermogenesis could be an effective strategy against obesity. Here we determine the role of UCP in the regulation of body mass by targeted inactivation of the gene encoding it. We find that UCP-deficient mice consume less oxygen after treatment with a beta3-adrenergic-receptor agonist and that they are sensitive to cold, indicating that their thermoregulation is defective. However, this deficiency caused neither hyperphagia nor obesity in mice fed on either a standard or a high-fat diet. We propose that the loss of UCP may be compensated by UCP2, a newly discovered homologue of UCP; this gene is ubiquitously expressed and is induced in the brown fat of UCP-deficient mice.     

External Noise Measurements in the Medium Wave Band

This paper presents an up to date study on external noise levels in the medium wave band based on field trials carried out in Spain and Mexico during years 2004 and 2005 respectively. External noise levels predicted by the ITU-R P.372 recommendation are based on measurements carried out more than 30 years ago and no updated results for the medium wave band have been published in this time. An increment on these noise levels have been measured, which leads to a significant impact on the minimum usable field strength requirements for the broadcasting systems used in this frequency band, such as the new Digital Radio Mondiale (DRM) and In-Band/On-Channel (IBOC) systems     

Investigation of Dead Times and Dead Zones in Wire Chambers Operated in the Self-Quenching Streamer Mode

The large saturated pulses of the type referred to as "self-quenching streamer" promise to provide an inexpensive method of radiation detection. We have continued our investigations of the performance of wire chambers operating in this mode, with particular emphasis on measurements of dead times and dead zones. The results of these measurements and their effect on the application of such chambers in high rate environments and for digital gas sampling calorimetry are discussed.