41 research outputs found

    Rapid Evaluation in Whole Blood Culture of Regimens for XDR-TB Containing PNU-100480 (Sutezolid), TMC207, PA-824, SQ109, and Pyrazinamide

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    There presently is no rapid method to assess the bactericidal activity of new regimens for tuberculosis. This study examined PNU-100480, TMC207, PA-824, SQ109, and pyrazinamide, singly and in various combinations, against intracellular M. tuberculosis, using whole blood culture (WBA). The addition of 1,25-dihydroxy vitamin D facilitated detection of the activity of TMC207 in the 3-day cultures. Pyrazinamide failed to show significant activity against a PZA-resistant strain (M. bovis BCG), and was not further considered. Low, mid, and high therapeutic concentrations of each remaining drug were tested individually and in a paired checkerboard fashion. Observed bactericidal activity was compared to that predicted by the sum of the effects of individual drugs. Combinations of PNU-100480, TMC207, and SQ109 were fully additive, whereas those including PA-824 were less than additive or antagonistic. The cumulative activities of 2, 3, and 4 drug combinations were predicted based on the observed concentration-activity relationship, published pharmacokinetic data, and, for PNU-100480, published WBA data after oral dosing. The most active regimens, including PNU-100480, TMC207, and SQ109, were predicted to have cumulative activity comparable to standard TB therapy. Further testing of regimens including these compounds is warranted. Measurement of whole blood bactericidal activity can accelerate the development of novel TB regimens

    Secondary structure of rhBMP-2 in a protective biopolymeric carrier material

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    Efficient delivery of growth factors is one of the great challenges of tissue engineering. Polyelectrolyte multilayer films (PEM) made of biopolymers have recently emerged as an interesting carrier for delivering recombinant human bone morphogenetic protein 2 (rhBMP-2 noted here BMP-2) to cells in a matrix-bound manner. We recently showed that PEM made of poly(l-lysine) and hyaluronan (PLL/HA) can retain high and tunable quantities of BMP-2 and can deliver it to cells to induce their differentiation in osteoblasts. Here, we investigate quantitatively by Fourier transform infrared spectroscopy (FTIR) the secondary structure of BMP-2 in solution as well as trapped in a biopolymeric thin film. We reveal that the major structural elements of BMP-2 in solution are intramolecular β-sheets and unordered structures as well as α-helices. Furthermore, we studied the secondary structure of rhBMP-2 trapped in hydrated films and in dry films since drying is an important step for future applications of these bioactive films onto orthopedic biomaterials. We demonstrate that the structural elements were preserved when BMP-2 was trapped in the biopolymeric film in hydrated conditions and, to a lesser extent, in dry state. Importantly, its bioactivity was maintained after drying of the film. Our results appear highly promising for future applications of these films as coatings of biomedical materials, to deliver bioactive proteins while preserving their bioactivity upon storage in dry state.This work was supported by the French Ministry of Research through an ANR-EmergenceBIO grant (ANR-09-EBIO-012-01), by the European Commission (FP7 program) via a European Research Council starting grant (BIOMIM, GA 259370), and by GRAVIT (081012_FIBIOS). C.P. is grafetul to IUF for financial support

    Hydration of polysaccharide hyaluronan observed by IR spectrometry. I: Preliminary experiments and band assignments

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    Microstructure and texture analysis of narrow copper line versus widths and annealing for reliability improvement

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    International audienceIn this article, we focus on the possible influence of interconnect Cu microstructure on electromigration phenomenon. First three annealing conditions were applied on interconnects. Microstructure and texture of copper were characterized by Electron BackScattered Diffraction (EBSD). Then electromigration tests have been carried out on 70 and 150 nm line widths of 45 nm node technology. In both cases no significant difference was observed in term of reliability performance versus annealing conditions. On the contrary large difference is observed on Electron BackScattered Diffraction results. Then, a statistical approach was used to investigate local microstructure and texture of copper for 150 nm line width. The results underline that morphological parameters of copper can vary versus annealing conditions but lead to similar reliability performances. We can thus conclude that these parameters are not in relationship with electromigration phenomena in these interconnects. On the other hand, high amount of misorientation has been highlighted as responsible of early failures. (C) 2010 Elsevier B.V. All rights reserved

    Gap fill enhancement with medium acid electrolyte for the 45nm node and below

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    International audienceCopper damascene interconnects technologies have introduced the use of electroplating in semiconductor. Several specific issues were brought by this typical application such as the necessity to plate in very narrow features and on large substrates while keeping electrical contacts on the edges. For this, sulfate based acidic solution coupled with additives allowing superfill behavior were introduced. Since the introduction of 200mm wafers, acidity of the bath was chosen as a compromise between transport efficiency and sufficient resistivity to ensure good plating uniformity on large diameters. Going to sub 65nm technologies, so called "1ow acid" electrolytes are supposed to reach their limits. In order to enhance the gap fill properties, medium acid electrolytes are being evaluated. In this study, the performances of such electrolytes are examined, first using coupons to evaluate the deposition kinetics compared to a low acid one. In order to have a first cross evaluation of their performances in integration, electrical tests are realized on 45nm node technology 300mm wafers
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