Freshness and Reactivity Analysis in Globally Asynchronous Locally Time-Triggered Systems

International audienceCritical embedded systems are often designed as a set of real-time tasks, running on shared computing modules, and communicating through networks. Because of their critical nature, such systems have to meet timing properties. To help the designers to prove the correctness of their system, the real-time systems community has developed numerous approaches for analyzing the worst case times either on the processors (e.g. worst case execution time of a task) or on the networks (e.g. worst case traversal time of a message). However, there is a growing need to consider the complete system and to be able to determine end-to-end properties. Such properties apply to a functional chain which describes the behavior of a sequence of functions, not necessarily hosted on a shared module, from an input until the production of an output. This paper explores two end-to-end properties: freshness and reactivity, and presents an analysis method based on Mixed Integer Linear Programming (MILP). This work is supported by the French National Research Agency within the Satrimmap project

The development and characterisation of porphyrin isothiocyanate–monoclonal antibody conjugates for photoimmunotherapy

A promising approach to increase the specificity of photosensitisers used in photodynamic therapy has been through conjugation to monoclonal antibodies (MAb) directed against tumour-associated antigens. Many of the conjugations performed to date have relied on the activated ester method, which can lead to impure conjugate preparations and antibody crosslinking. Here, we report the development of photosensitiser–MAb conjugates utilising two porphyrin isothiocyanates. The presence of a single reactive isothiocyanate allowed facile conjugation to MAb FSP 77 and 17.1A directed against internalising antigens, and MAb 35A7 that binds to a non-internalising antigen. The photosensitiser–MAb conjugates substituted with 1–3 mol of photosensitiser were characterised in vitro. No appreciable loss of immunoreactivity was observed and binding specificity was comparable to that of the unconjugated MAb. Substitution with photosensitiser had a minimal effect on antibody biodistribution in vivo for the majority of the conjugates, although a decreased serum half-life was observed using a cationic photosensitiser at the higher loading ratios. Tumour-to-normal tissue ratios as high as 33.5 were observed using MAb 35A7 conjugates. The internalising conjugate showed a higher level of phototoxicity as compared with the non-internalising reagent, using a cell line engineered to express both target antigens. These data demonstrate the applicability of the isothiocyanate group for the development of high-quality conjugates, and the use of internalising MAb to significantly increase the photodynamic efficiency of conjugates during photoimmunotherapy

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

Using polydimethylsiloxane as a thermocurable resist for a soft imprint lithography process

International audienceNanoimprint lithography has been investigated using polydimethylsiloxane as a thermocurable resist. This novel process allowed us to reduce both pressure (<10 bars) and temperature (80 °C) when compared to a conventional imprinting process with a thermoplastic polymer resist such as polymethylmethacrylate. Using a new formulation of the elastomeric material, we have demonstrated high quality imprinting of both micronic and nanometric structures with no evidence of any viscous flow problems. The excellent etching resistance of the polydimethylsiloxane structures to a reactive ion etching silicon process and the compatibility with a lift-off procedure for pattern transfer are also presented

Easy installation of 1,2,3-triazoles or iodo-1,2,3-triazoles onto indole-fused oxazinones via CuAAC-based MCR in the presence of 18-crown-6

International audienceAn efficient protocol was developed to prepare indole-fused oxazinones using silver nitrate. The latter substrates were subjected to multicomponent reactions in the presence of 18-crown-6, which afforded diverse new heterocycles based on an indole-fused oxazinone-1,2,3-triazole scaffold

4 Inch lift-off process by trilayer nanoimprint lithography

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