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Christophe, Thierry,Jackson, Mary,Jeon, Hee Kyoung,Fenistein, Denis,Contreras-Dominguez, Monica,Kim, Jaeseung,Genovesio, Auguste,Carralot, Jean-Philippe,Ewann, Fanny,Kim, Eun Hye,Lee, Sae Yeon,Kang, S Public Library of Science 2009 PLoS pathogens Vol.5 No.10
<▼1><P>A critical feature of <I>Mycobacterium tuberculosis</I>, the causative agent of human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing the intracellular tubercle bacilli is a key requirement for efficient tuberculosis treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques and lack of validated targets. Here, we present the development of a phenotypic cell-based assay that uses automated confocal fluorescence microscopy for high throughput screening of chemicals that interfere with the replication of <I>M. tuberculosis</I> within macrophages. Screening a library of 57,000 small molecules led to the identification of 135 active compounds with potent intracellular anti-mycobacterial efficacy and no host cell toxicity. Among these, the dinitrobenzamide derivatives (DNB) showed high activity against <I>M. tuberculosis</I>, including extensively drug resistant (XDR) strains. More importantly, we demonstrate that incubation of <I>M. tuberculosis</I> with DNB inhibited the formation of both lipoarabinomannan and arabinogalactan, attributable to the inhibition of decaprenyl-phospho-arabinose synthesis catalyzed by the decaprenyl-phosphoribose 2′ epimerase DprE1/DprE2. Inhibition of this new target will likely contribute to new therapeutic solutions against emerging XDR-TB. Beyond validating the high throughput/content screening approach, our results open new avenues for finding the next generation of antimicrobials.</P></▼1><▼2><P><B>Author Summary</B></P><P>Tuberculosis is still a major threat to global health. The disease in humans is caused by a bacterium, <I>Mycobacterium tuberculosis</I>, and treatment of an infected individual requires more than six months of chemotherapy. Because such a long course of treatment is required, compliance is low, which can result in the development of multidrug resistant strains (MDR-TB) and even extremely resistant strains (XDR-TB). Identifying new drug targets and potential lead therapeutic compounds are needed to combat MDR-XDR-TB. We developed a new type of assay based on the visualization of mycobacterium replication within host cells and applied it for the search of compounds that are able to chase the pathogen from its hideout. As a result, we found 20 new series of drug candidates that are effective against the bacilli in its hiding place, potentially addressing a crucial aspect in the resilience of the disease. We also showed that one series of compounds acts by inhibiting a key enzyme required for the synthesis of an essential component from the mycobacterial cell wall that is not targeted by any of the commercially available antituberculosis drugs. Altogether, our results pave the way for development of the next generation of antibacterial agents.</P></▼2>
Effect of DC Power on the Structural and the Electrical Properties of B-ion-doped ZnO Films
Christophe Avis,Se Hwan Kim,Ji Ho Hur,Sung Jun Hong,Jin Jang 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.55 No.1
We fabricated zinc-oxide (ZnO) thin films by DC sputtering at various DC powers after which the films were doped with boron ions. With increasing DC power, the crystalline quality improved, the Hall mobility increased and the sheet resistance decreased. DC-sputtered samples showed an increase in Hall mobility from 2.44 to 18.6 cm2/Vs and a decrease in the resistivity from 75.8 to 5.26 mΩ·cm when the DC current was increased from 0.3 A to 1.5 A. We fabricated zinc-oxide (ZnO) thin films by DC sputtering at various DC powers after which the films were doped with boron ions. With increasing DC power, the crystalline quality improved, the Hall mobility increased and the sheet resistance decreased. DC-sputtered samples showed an increase in Hall mobility from 2.44 to 18.6 cm2/Vs and a decrease in the resistivity from 75.8 to 5.26 mΩ·cm when the DC current was increased from 0.3 A to 1.5 A.
B-Ion Doping Effect in ZnO Thin-Films
Christophe Avis,김세환,김가현,홍성준,Youn Duck Nam,Ji Ho Hur,장진 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.1
We studied the effect of boron ion doping on the properties of zinc oxide (ZnO) thin-film. Xray diffraction (XRD) and Raman intensities were analyzed to see the change in the structural property and the Hall effect was measured to have an insight into the carrier concentration and the Hall mobility for the B-ion doped ZnO films. A doped ZnO film exhibited a sheet resistance of ∼0.9 kohm/square and a Hall mobility of ∼22 cm<SUP>2</SUP>/Vs. Therefore, B doping can be used to modify the conductivity of the ZnO.
Christophe, Thierry,Ewann, Fanny,Jeon, Hee Kyoung,Cechetto, Jonathan,Brodin, Priscille Future Science 2010 Future medicinal chemistry Vol.2 No.8
<P>Macrophages are reservoirs for replicating mycobacterium during tuberculosis (TB) infections. In this study, small molecules to be developed as anti-tubercular treatments were investigated for their ability to kill intracellular bacteria in in vitro macrophage models. High-content imaging technologies offer a high-throughput method to quantify a drug's ability to inhibit Mycobacterium tuberculosis intracellular invasion and multiplication in host cells. Dedicated image analysis enables the automated quantification of infected macrophages, and compounds that inhibit mycobacteria proliferation can be tested using this method. Furthermore, the implementation of the assay in 384-well microtiter plates combined with automated image acquisition and analysis allows large-scale screening of compound libraries in M. tuberculosis-infected macrophages. Here we describe a high-throughput and high-content workflow and detail its utility for the development of new TB drugs.</P>
Management of Biliopancreatic Limb Bleeding after Roux-en-Y Gastric Bypass: A Case Report
Christophe Riquoir,Luis Antonio Díaz,David Chiliquinga,Roberto Candia,Fernando Pimentel,Alex Arenas 대한소화기내시경학회 2021 Clinical Endoscopy Vol.54 No.5
The Roux-en-Y gastric bypass is one of the most extensive surgical treatments for obesity. The treatment of upper gastrointestinalbleeding after Roux-en-Y gastric bypass is complex due to the difficulty of accessing the excluded gastric antrum and duodenal bulb. There is no consensus regarding the management of this complication. While various techniques have been described to accessthe biliopancreatic limb, double-balloon enteroscopy is the most commonly used. If double-balloon enteroscopy is unavailable, apediatric colonoscope may be used as an alternative; however, its use in such cases has not been described. We report the case of a50-year-old male patient who underwent gastric bypass 13 years ago and was admitted for a second episode of upper gastrointestinalbleeding. The initial approach using upper endoscopy, colonoscopy, and abdominal computed tomography angiography did notreveal the cause of gastrointestinal hemorrhage; therefore, an endoscopic study of the biliopancreatic limb was performed using apediatric colonoscope. A Forrest Ib ulcer was found in the duodenal bulb, and endoscopic therapy was administered. The evolutionwas found to be satisfactory.
Determining terminal concession durations in seaports
Christophe Theys,Theo Notteboom 인하대학교 정석물류통상연구원 2010 JOURNAL OF INTERNATIONAL LOGISTICS AND TRADE Vol.8 No.1
The awarding of terminals to private operators is considered a prime task of landlord port authorities. Yet, terminal concessions in seaports have only recently gained interest in academic circles. The awarding process poses a complex set of managerial challenges to port authorities, one of the key issues being the determination of the duration of the concession. Despite the importance of the duration of terminal concessions in seaports, the issue has not received much attention in academic circles. Factors impacting on the duration of contracts, leases or concessions have, however, been studied extensively in other research areas, such as agriculture, coal contracts, franchising and natural gas, This paper uses insights from these academic studies to obtain a better understanding of the impact of concession duration on the stakeholders involved and relates them to empirical evidence on concession length in European seaports. The paper then proposes a classification scheme for the exogenous determination of concession duration, based on techniques developed for Public-Private-Partnerships in large infrastructure projects. In the last section the paper discusses the importance of concession durations to various stakeholders in seaports and illustrates these principles using a case study.