A High-level EDA Environment for the Automatic Insertion of HD-BIST Structures

This paper presents a High-Level EDA environment based on the Hierarchical Distributed BIST (HD-BIST), a flexible and reusable approach to solve BIST scheduling issues in System-on-Chip applications. HD-BIST allows activating and controlling different BISTed blocks at different levels of hierarchy, with a minimum overhead in terms of area and test time. Besides the hardware layer, the authors present the HD-BIST application layer, where a simple modeling language, and a prototypical EDA tool demonstrate the effectiveness of the automation of the HD-BIST insertion in the test strategy definition of a complex System-on-Chip

Theoretical Investigation on Monomer and Dimers of Inhibitor of Cytochrome P450 Enzymes: 1-Aminobenzotriazole

In this research, structures and properties of monomer and two dimers (1 and 2) of inhibitor of cytochrome P450 enzymes, 1-Aminobenzotriazole (ABT) have been studied by using functional hybrid B3LYP/6-311++G** calculations. The very good correlations observed between theoretical and experimental 1H-, 13C-NMR, FT-IR and FT-Raman spectra suggest that C-H···N interactions of dimeric species should be expected in the solid phase, as was observed in the experimental crystalline structure of a quinolin benzotriazole derivative. NBO and AIM calculations suggest that dimer 2 with inverted positions of its monomers could be present in the solid phase because it evidence higher stabilities in both media. On the other hand, frontier orbitals studies support a higher reactivity of dimer 2 of ABT higher than the monomer and dimer 1, for which, the presence of dimer 2 containing N-NH2 groups in ABT could justify the biological activities observed for this species with gap values between 4.5933 and 4.8164 eV different from antiviral agents containing the C-NH2 moiety, as amantadine and chloroquine whose gap values are around 4.3012-4.1116 eV. Finally, the presence of bands of monomer and of both dimers are predicted in the vibrational spectra and, hence, its completes assignments have been performed. The scaled force constants for the three studied species are also reported

performance assessment of a new optimization system for robotic sbrt mlc based plans

Abstract Purpose To assess the performance of a new optimization system, VOLO, for CyberKnife MLC-based SBRT plans in comparison with the existing Sequential optimizer. Methods MLC-plans were created for 25 SBRT cases (liver, prostate, pancreas and spine) using both VOLO and Sequential. Monitor units (MU), delivery time (DT), PTV coverage, conformity (nCI), dose gradient (R50%) and OAR doses were used for comparison and combined to obtain a mathematical score (MS) of plan quality for each solution. MS strength was validated by changing parameter weights and by a blinded clinical plan evaluation. The optimization times (OT) and the average segment areas (SA) were also compared. Results VOLO solutions offered significantly lower mean DT (−19%) and MU (−13%). OT were below 15 min for VOLO, whereas for Sequential, values spanned from 8 to 160 min. SAs were significantly larger for VOLO: on average 10 cm2 versus 7 cm2. VOLO optimized plans achieved a higher MS than Sequential for all tested parameter combinations. PTV coverage and OAR sparing were comparable for both groups of solutions. Although slight differences in R50% and nCI were found, the parameters most affecting MS were MU and DT. VOLO solutions were selected in 80% of cases by both physicians with 88% inter-observer agreement. Conclusions The good performance of the VOLO optimization system, together with the large reduction in OT, make it a useful tool to improve the efficiency of CK SBRT planning and delivery. The proposed methodology for comparing different planning solutions can be applied in other contexts

Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis.

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2

Microglia Polarization, Gene-Environment Interactions and Wnt/β-Catenin Signaling: Emerging Roles of Glia-Neuron and Glia-Stem/Neuroprogenitor Crosstalk for Dopaminergic Neurorestoration in Aged Parkinsonian Brain.

Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD) physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA) neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors. Notably, with age, microglia may adopt a potent neurotoxic, pro-inflammatory "primed" (M1) phenotype when challenged with inflammatory or neurotoxic stimuli that hamper brain's own restorative potential and inhibit endogenous neurorepair mechanisms. In the last decade we have provided evidence for a major role of microglial crosstalk with astrocytes, mDA neurons and neural stem progenitor cells (NSCs) in the MPTP- (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-) mouse model of PD, and identified Wnt/β-catenin signaling, a pivotal morphogen for mDA neurodevelopment, neuroprotection, and neuroinflammatory modulation, as a critical actor in glia-neuron and glia-NSCs crosstalk. With age however, Wnt signaling and glia-NSC-neuron crosstalk become dysfunctional with harmful consequences for mDA neuron plasticity and repair. These findings are of importance given the deregulation of Wnt signaling in PD and the emerging link between most PD related genes, Wnt signaling and inflammation. Especially, in light of the expanding field of microRNAs and inflammatory PD-related genes as modulators of microglial-proinflammatory status, uncovering the complex molecular circuitry linking PD and neuroinflammation will permit the identification of new druggable targets for the cure of the disease. Here we summarize recent findings unveiling major microglial inflammatory and oxidative stress pathways converging in the regulation of Wnt/β-catenin signaling, and reciprocally, the ability of Wnt signaling pathways to modulate microglial activation in PD. Unraveling the key factors and conditons promoting the switch of the proinflammatory M1 microglia status into a neuroprotective and regenerative M2 phenotype will have important consequences for neuroimmune interactions and neuronal outcome under inflammatory and/or neurodegenerative conditions