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481.
V De Gennaro Colonna G Rossoni M Bernareggi EE Müller F Berti 《Canadian Metallurgical Quarterly》1997,42(11):1165-1172
The development of new chemotherapy for the treatment of tuberculosis has three major objectives: first, the development of faster-acting drugs to shorten the duration of treatment; second, the development of novel antimicrobials to counter the emergence of bacteria resistant to current therapies; and, third, the development of chemotherapeutics that specifically target dormant bacilli to treat the one-third of the world's population latently infected with tubercle bacilli. Strategies based upon optimizing the inhibition of known targets require an extensive knowledge of the detailed mechanism of action of current antimycobacterial agents. For many agents such as isoniazid, ethambutol, rifampin, and pyrazinamide such knowledge is now available. Strategies based upon the identification of novel targets will necessitate the identification of biochemical pathways specific to mycobacteria and related organisms. Many unique metabolic processes occur during the biosynthesis of mycobacterial cell wall components, and some attractive new targets have emerged. The development of targets specific to latency will require a detailed picture of the metabolism and biochemical pathways occurring in dormant bacilli. Recent evidence suggests that anaerobic metabolic pathways may operate in dormant bacilli, and the enzymes involved in such pathways may also provide significant new targets for intervention. The combination of the mycobacterial genome sequence that is anticipated to become available this year with an improved understanding of the unique metabolic processes that define mycobacteria as a genus offers the greatest hope for the elimination of one of mankind's oldest enemies. 相似文献
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Michaela Stickney Colleen Hickey Roland Hoerr 《Lakes & Reservoirs: Research and Management》2001,6(3):217-223
Lake Champlain is the sixth largest freshwater lake in the USA. Lake Champlain’s watershed is shared by Vermont and New York in the USA, and Quebec in Canada. The lake’s remarkable drainage area to surface area ratio is 19:1. More than 600 000 people live in the Lake Champlain basin and millions visit each year. The lake’s relatively healthy natural resources sustain a thriving economy. The three most challenging environmental issues facing the Lake Champlain basin are reducing phosphorus pollution, preventing toxic contaminants from entering the lake and managing invasive aquatic species that are not native that threaten native flora and fauna. To effectively address these issues, the Lake Champlain Basin Program (LCBP) believes that all decisions about the lake must be based on accurate, ongoing scientific research and that citizen involvement and inter‐jurisdictional cooperation is vital. The programme has worked hard to identify all citizens and organizations that have a stake in Lake Champlain and draw them into a cooperative, sustainable management process. A 1990 Act of Congress (Public Law 101‐596) established a coordinated framework to study and understand the diverse systems of Lake Champlain and its basin in order to develop a comprehensive management plan to protect and restore lake and watershed resources. A 31‐member multi‐stakeholder board was established to develop the plan, a process that took 5 years and included numerous public meetings. Today, a Steering Committee oversees the implementation of the plan and the activities of the LCBP. 相似文献
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Gabriel Molas Marc Bocquet Julien Buckley Helen Grampeix Marc Gly Jean-Philippe Colonna Christophe Licitra Nvine Rochat Thomas Veyront Xavier Garros Franois Martin Pierre Brianceau Vincent Vidal Cosimo Bongiorno Salvatore Lombardo Barbara De Salvo Simon Deleonibus 《Solid-state electronics》2007,51(11-12):1540
In this paper, we evaluate the potentialities of hafnium-aluminates (HfAlO) materials as possible candidates for the interpoly dielectrics of future Flash memory devices. HfAlO layers of different thicknesses and compositions are integrated in single-layers and in Oxide/HfAlO/Oxide (OHO) triple-layer stacks, and analyzed in terms of coupling and insulating capabilities. We demonstrate that increasing the Hf content allows reducing the leakage current at high voltages but it results in a stronger leakage current at low voltages. We also show that once normalized in electric fields, the leakage current characteristics are independent of the high-k thickness. The electron conduction modes in these materials, at different temperatures, are also investigated. The activation energy increases with the Hf concentration in the HfAlO alloy, resulting in a higher leakage current at elevated temperatures. Finally, it is demonstrated that the conduction in triple-layer stacks is limited by a Poole–Frenkel conduction in the high-k layers, while the trap contribution in the case of single-layers becomes dominant when the HfAlO layer is thicker than 8 nm. 相似文献
488.
Hee Jin Michaela Jeong Gyeongseok Lee Minjeong Kim Youngjo Yoo Hyun Jin Kim Jaeho Cho Yun-Sil Lee Hyukjin Lee 《Advanced functional materials》2023,33(7):2209432
Pulmonary fibrosis is a chronic and irreversible lung disease with limited therapeutic regimens. Advances in elucidating the pathophysiological mechanism and discovering novel therapeutic interventions are still in urgent need. Here, the engineered lipid nanoparticles (LNPs) are developed for delivering RNA therapeutics to the lungs. Three different types of LNPs (native, cationic, and ligand incorporated) are optimized to facilitate the pulmonary delivery of RNAs. Among them, the mannose incorporated LNPs (Mannose LNPs) outperform the others and show efficient delivery of siRNAs down-regulating the epithelial-mesenchymal transition (EMT) associated protein, G2 and S phase-expressed protein 1 (GTSE1). Treatment with the mannose LNPs confirms a significant decrease in collagen accumulation and EMT-related proteins in the fibrosis animal models and provides functional recovery from pulmonary fibrosis. This approach demonstrates that engineered LNPs can facilitate the delivery of RNA therapeutics to the lungs and potentially open a new regimen of treatment for pulmonary fibrosis. 相似文献
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Donna Elizabeth Sunny Elke Hammer Till Ittermann Elisabeth Luise Krüger Stephanie Hübner Michaela Friederike Hartmann Stefan Alexander Wudy Uwe Vlker Matthias Heckmann 《International journal of molecular sciences》2021,22(12)
Oxygen causes white matter damage in preterm infants and male sex is a major risk factor for poor neurological outcome, which speculates the role of steroid hormones in sex-based differences. Preterm birth is accompanied by a drop in 17β-estradiol (E2) and progesterone along with increased levels of fetal zone steroids (FZS). We performed a sex-based analysis on the FZS concentration differences in urine samples collected from preterm and term infants. We show that, in preterm urine samples, the total concentration of FZS, and in particular the 16α-OH-DHEA concentration, is significantly higher in ill female infants as compared to males. Since we previously identified Nup133 as a novel target protein affected by hyperoxia, here we studied the effect of FZS, allopregnanolone (Allo) and E2 on differentiation and Nup133 signaling using mouse-derived primary oligodendrocyte progenitor cells (OPCs). We show that the steroids could reverse the effect of hyperoxia-mediated downregulation of Nup133 in cultured male OPCs. The addition of FZS and E2 protected cells from oxidative stress. However, E2, in presence of 16α-OH-DHEA, showed a negative effect on male cells. These results assert the importance of sex-based differences and their potential implications in preterm stress response. 相似文献