Using the WinQSB Software in Critical Path Analysis

In the present paper will be appealed sub modules from the PERT/CPM module of WinQSB software, adequate to solve the scheduling problems.CPM, PERT, critical path, normal duration, crash duration

Contribution a la conception des systemes de controle reparti

SIGLEINIST T 77008 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

The Way of Establishing a Relative Position for Some Production Units

The CRAFT Method was at the basis of the development of the heuris-tic commuting models, in which one starts from an initial emplacement of units that is successively improved, through the successive commuting of units among them on the basis of some criteria. In the present paper we have resolved to the Facility Location and Layout module of the WinQSB program that uses the CRAFT Method in solving problems of the Functional Layout type

A systemically administered detoxified TLR4 agonist displays potent antitumor activity and an acceptable tolerance profile in preclinical models

Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity per se upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model. Liposomal encapsulation also allowed a 2-fold reduction in the induction of pro-inflammatory cytokines by LPS. Mice receiving an intravenous administration demonstrated a significant increase of neutrophils, monocytes and macrophages at the tumor site as well as an increase of macrophages in spleen. Further, we chemically detoxified LPS to obtain MP-LPS that was associated with a 200-fold decrease in the induction of proinflammatory cytokines. When encapsulated in a clinically approved liposomal formulation, toxicity, notably pyrogenicity (10-fold), was limited while the antitumor activity and immunoadjuvant effect were maintained. This improved tolerance profile of liposomal MP-LPS was associated with the preferential activation of the TLR4-TRIF pathway. Finally, in vitro studies demonstrated that stimulation with encapsulated MP-LPS reversed the polarization of M2 macrophages towards an M1 phenotype, and a phase 1 trial in healthy dogs validated its tolerance upon systemic administration up to very high doses (10µg/kg). Altogether, our results demonstrate the strong therapeutic potential of MPLPS formulated in liposomes as a systemically active anticancer agent, supporting its evaluation in patients with cancer