1,513 research outputs found

    Modelling short channel mosfets for use in VLSI

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    In an investigation of metal oxide semiconductor field effect transistor (MOFSET) devices, a one-dimensional mathematical model of device dynamics was prepared, from which an accurate and computationally efficient drain current expression could be derived for subsequent parameter extraction. While a critical review revealed weaknesses in existing 1-D models (Pao-Sah, Pierret-Shields, Brews, and Van de Wiele), this new model in contrast was found to allow all the charge distributions to be continuous, to retain the inversion layer structure, and to include the contribution of current from the pinched-off part of the device. The model allows the source and drain to operate in different regimes. Numerical algorithms used for the evaluation of surface potentials in the various models are presented

    Comparative study of the potential of poly(2-ethyl-2-oxazoline) as carrier in the formulation of amorphous solid dispersions of poorly soluble drugs

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    Despite the fact that solid dispersions are gaining momentum, the number of polymers that have been used as a carrier during the past 50 years is rather limited. Recently, the poly(2-alkyl-2-oxazoline) (PAOx) polymer class profiled itself as a versatile platform for a wide variety of applications in drug delivery, including their use as amorphous solid dispersion (ASD) carrier. The aim of this study was to investigate the potential of poly(2-ethyl-2-oxazoline) (PEtOx) by applying a benchmark approach with well-known, commercially available carriers (ie. polyvinylpyrrolidone (PVP) K30, poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) 64 and hydro-xypropylmethylcellulose (HPMC)). For this purpose, itraconazole (ITC) and fenofibrate (FFB) were selected as poorly water-soluble model drugs. The four polymers were compared by establishing their supersaturation maintaining potential and by investigating their capability as carrier for ASDs with high drug loadings. Spray drying, as well as hot melt extrusion and cryo-milling were implemented as ASD manufacturing technologies for comparative evaluation. For each manufacturing technique, the formulations with the highest possible drug loadings were tested with respect to in vitro drug release kinetics. This study indicates that PEtOx is able to maintain supersaturation of the drugs to a similar extent as the commercially available polymers and that ASDs with comparable drug loadings can be manufactured. The results of the in vitro dissolution tests reveal that high drug release can be obtained for PEtOx formulations. Overall, proof-of-concept is provided for the potential of PEtOx for drug formulation purposes

    Deux carnets et une orthographe : genèse, publication et lecture de William Shakespeare

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    L’édition de référence de William Shakespeare, en 1937, augmenta l’œuvre de 1864 de nombreux inédits, certains longs et importants, donnés pour « chapitres » détachés par Hugo du manuscrit. Elle suggérait ainsi une genèse par assemblage, en vue de la publication, de « panneaux » à l’origine indépendants les uns des autres. William Shakespeare fut dès lors considéré comme « somme » philosophique relevant de l’histoire des idées. Deux carnets et une variante orthographique du manuscrit (Shakspeare/Shakespeare) infirment cette hypothèse, déplacent de plus d’un semestre le début de la rédaction, montrent une genèse comparable à celle des trois recueils poétiques précédents, permettent la reconstitution d’un noyau initial entièrement rédigé à la fin du printemps 1863, et conduisent à une autre lecture. Celle d’une représentation unifiée des activités de l’esprit telles qu’elles s’exercent dans la double situation humaine, permanente entre la nature et Dieu et progressive dans l’histoire.The 1937 standard edition of William Shakespeare enriched the 1864 work with many unpublished texts, some long and important, given as “chapters” that Hugo had removed from the manuscript. This edition thus proposed a patchwork genesis, for the publication of a grouping of originally separate “panels. From then on William Shakespeare was considered a philosophical compendium belonging to the history of ideas. Two notebooks and a spelling variant in the manuscript (Shakspeare/Shakespeare) disprove this hypothesis. They postpone the beginning of the writing for more than a semester, show a genesis similar to the three previous poetry books, and make possible the reconstitution of an initial nucleus entirely written at the end of Spring 1863, thus leading to a different reading. A reading of a representation unifying the activities of the mind such as they come into play in a twofold human situation : permanent between God and Nature and progressive in History.Die Referenzausgabe von William Shakespeare von 1937 vermehrte das Werk von 1864 um zahlreiche unveröffentliche Schriftstücke, manche lang und wichtig, die als « Kapitel », durch Hugo vom Manuskript getrennt, wiedergegeben werden. Hinsichtlich der Publikation suggeriert sie daher eine Genese durch Zusammenfügung von « Bildern », die ursprünglich unabhängig voneinander waren. William Shakespeare wurde seitdem als philosophische « Summe », der Ideengschichte zugehörig, angesehen. Zwei Notizhefte und eine orthographische Variante des Manuskripts (Shakspeare/Shakespeare) entkräften diese Hypothese, und verschieben den Anfang der Niederschrift um mehr als ein Semester. Sie zeigen eine Genese, vergleichbar mit jener der drei vorherigen Poesiesammlungen, was die Rekonstitution eines gemeinsamen Ausgangspunkts — Ende Frühjahr 1863 — erlaubt und zu einer anderen Lektüre führt – nämlich jener einer vereinheitlichten Darstellung von geistigen Tätigkeiten, wie sie sich in der zweifachen Situation des Menschen manifestieren, beständig zwischen Natur und Gott und in der Geschichte vorwärtsschreitend.La edición de consulta de William Shakespeare, en 1937, añadió a la obra de 1864 numerosos inéditos, entre ellos algunos extensos e importantes, considerados como capítulos, extraídos por el propio Hugo del manuscrito. Sugería también una génesis constituida de montajes –en vista a la publicación– de “paneles” originalmente independientes unos de otros. Esto llevó a que William Shakespeare fuera catalogada como una “suma” filosófica integrada en la historia de las ideas. Dos libretas y una variante ortográfica del manuscrito (Shakspeare/Shakespeare) vienen a desmentir esta hipótesis, desplazando de más de un semestre el comienzo de la redacción, revelando una génesis comparable a la de las tres recopilaciones poéticas precedentes, permitiendo la reconstitución de un núcleo inicial enteramente redactado a finales de la primavera de 1863 e induciendo a una lectura diferente : la de una representación unificada de las actividades espirituales, tales como se ejercen en la doble situación humana, permanente entre la naturaleza y Dios y progresiva en la historia.A edição de referência de William Shakespeare, 1937, aumentou o livro de 1864 com muitos inéditos, um alguns longos e importantes, apresentados como "capítulos" destacados por Hugo do manuscrito. Assim, ela sugeria uma génese que teria consistido na associação, para fins de publicação, de "painéis" originalmente independentes uns dos outros. William Shakespeare foi desde logo considerado como uma "suma" filosófica relevante para a história das ideias. No entanto, dois cadernos e uma variante de ortografia do manuscrito (Shakspeare/Shakespeare) bastam para invalidar esta hipótese, deslocando em mais de um semestre o início da redacção, revelando uma génese similar à de três colectâneas poéticas precedentes, permitindo a reconstituição de um núcleo inicial escrito inteiramente no final da Primavera de 1863 e proporcionando uma nova leitura. A saber, uma representação unificada das atividades do espírito, tais como se exercem numa situação humana dupla, permanente entre a natureza e Deus e progressiva na história.L’edizione di riferimento di William Shakespeare del 1937 arricchì l’opera del 1864 di numerosi inediti, alcuni lunghi e importanti, considerati come “capitoli” che Hugo avrebbe rimosso dal manoscritto. Si suggeriva così una genesi per assemblaggio, in vista della pubblicazione dei “pannelli” che erano all’origine indipendenti uno dall’altro. William Shakespeare fu da quel momento considerato come “somma” filosofica, pertinente alla storia delle idee. Due quaderni e una variante ortografica del manoscritto (Shakspeare/Shakespeare) infirmano questa ipotesi, spostano di più di un semestre l’inizio della redazione, mostrano una genesi simile a quella di tre raccolte poetiche precedenti, permettono la ricostituzione di un nucleo iniziale interamente redatto alla fine della primavera 1863, e portano ad un’altra lettura : una rappresentazione unificata delle attività dello spirito che si esplicano nella doppia condizione umana, permanente tra la natura e Dio e progressiva nella storia

    Kekcekça ? (IV, 6, 2) ou Editer Les Misérables - A propos de la nouvelle édition de la Pléiade (établie par Henri Scepi, avec la collaboration de Dominique Moncond’huy, Gallimard, 2018)

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    Recension publiée en ligne: http://www.groupugo.univ-paris-diderot.fr/Groupugo/Textes_et_documents/Rosa_CR_Mis_2018.ht

    Visual responses of neurons in the middle temporal area of new World Monkeys after lesions of striate cortex

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    In primates, lesions of striate cortex (V1) result in scotomas in which only rudimentary visual abilities remain. These aspects of vision that survive V1 lesions have been attributed to direct thalamic pathways to extrastriate areas, including the middle temporal area (MT). However, studies in New World monkeys and humans have questioned this interpretation, suggesting that remnants of V1 are responsible for both the activation of MT and residual vision. We studied the visual responses of neurons in area MT in New World marmoset monkeys in the weeks after lesions of V1. The extent of the scotoma in each case was estimated by mapping the receptive fields of cells located near the lesion border and by histological reconstruction. Two response types were observed among the cells located in the part of MT that corresponds, in visuotopic coordinates, to the lesioned part of V1. Many neurons (62%) had receptive fields that were displaced relative to their expected location, so that they represented the visual field immediately surrounding the scotoma. This may be a consequence of a process analogous to the reorganization of the V1 map after retinal lesions. However, another 20% of the cells had receptive fields centered inside the scotoma. Most of these neurons were strongly direction-selective, similar to normal MT cells. These results show that MT cells differ in their responses to lesioning of V1 and that only a subpopulation of MT neurons can be reasonably linked to residual vision and blindsight

    Oral Delivery of Double-Stranded RNAs and siRNAs Induces RNAi Effects in the Potato/Tomato Psyllid, Bactericerca cockerelli

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    The potato/tomato psyllid, Bactericerca cockerelli (B. cockerelli), and the Asian citrus psyllid, Diaphorina citri (D. citri), are very important plant pests, but they are also vectors of phloem-limited bacteria that are associated with two devastating plant diseases. B. cockerelli is the vector of Candidatus Liberibacter psyllaurous (solanacearum), which is associated with zebra chip disease of potatoes, and D. citri is the vector of Ca. Liberibacter asiaticus, which is associated with the Huanglongbing (citrus greening) disease that currently threatens the entire Florida citrus industry. Here we used EST sequence information from D. citri to identify potential targets for RNA interference in B. cockerelli. We targeted ubiquitously expressed and gut-abundant mRNAs via injection and oral acquisition of double-stranded RNAs and siRNAs and were able to induce mortality in recipient psyllids. We also showed knockdown of target mRNAs, and that oral acquisition resulted primarily in mRNA knockdown in the psyllid gut. Concurrent with gene knockdown was the accumulation of target specific ∼ 21 nucleotide siRNAs for an abundant mRNA for BC-Actin. These results showed that RNAi can be a powerful tool for gene function studies in psyllids, and give support for continued efforts for investigating RNAi approaches as possible tools for psyllid and plant disease control

    Real-time detection of riboflavin production by Lactobacillus plantarum strains and tracking of their gastrointestinal survival and functionality in vitro and in vivo using mCherry labeling

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    Some strains of lactic acid bacteria (LAB) produce riboflavin, a water-soluble vitamin of the B complex, essential for human beings. Here, we have evaluated riboflavin (B2 vitamin) production by five Lactobacillus plantarum strains isolated from chicha, a traditional maize-based fermented alcoholic beverage from north-western Argentina and their isogenic riboflavin-overproducing derivatives previously selected using roseoflavin. A direct fluorescence spectroscopic detection method to quantify riboflavin production in bacterial culture supernatants has been tested. Comparison of the efficiency for riboflavin fluorescence quantification with and without prior HPLC fractionation showed that the developed method is a rapid and easy test for selection of B2 vitamin-producing strains. In addition, it can be used for quantitative detection of the vitamin production in real time during bacterial growth. On the basis of this and previous analyses, the L. plantarum M5MA1-B2 riboflavin overproducer was selected for in vitro and in vivo studies after being fluorescently labeled by transfer of the pRCR12 plasmid, which encodes the mCherry protein. The labeling did not affect negatively the growth, the riboflavin production nor the adhesion of the strain to Caco-2 cells. Thus, L. plantarum M5MA1-B2[pRCR12] was evaluated for its survival under digestive tract stresses in the presence of microbiota in the dynamic multistage BFBL gut model and in a murine model. After exposure to both models, M5MA1-B2[pRCR12] could be recovered and detected by the pink color of the colonies. The results indicated a satisfactory resistance of the strain to gastric and intestinal stress conditions but a low colonization capability observed both in vitro and in vivo. Overall, L. plantarum M5MA1-B2 could be proposed as a probiotic strain for the development of functional foods.Fil: Mohedano, Mari Luz. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: Hernández Recio, Sara. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: Yépez, Alba. Universidad de Valencia; EspañaFil: Requena, Teresa. Consejo Superior de Investigaciones Científicas. Instituto de Investigación en Ciencias de la Alimentación; EspañaFil: Martínez Cuesta, M. Carmen. Consejo Superior de Investigaciones Científicas. Instituto de Investigación en Ciencias de la Alimentación; EspañaFil: Peláez, Carmen. Consejo Superior de Investigaciones Científicas. Instituto de Investigación en Ciencias de la Alimentación; EspañaFil: Russo, Pasquale. Università di Foggia; ItaliaFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Spano, Giuseppe. Università di Foggia; ItaliaFil: Aznar, Rosa. Universidad de Valencia; España. Consejo Superior de Investigaciones Científicas. Instituto de Agroquímica y Tecnología de Alimentos; EspañaFil: López, Paloma. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; Españ

    Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial

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    Objectives. Evaluation of pharmacokinetics and pharmacodynamics of darunavir and etravirine among HIV-1–infected, treatment-experienced adults from GRACE, by sex and race. Methods. Patients received darunavir/ritonavir 600/100mg twice daily plus other antiretrovirals, which could include etravirine 200mg twice daily. Population pharmacokinetics for darunavir and etravirine were determined over 48 weeks and relationships assessed with virologic response and safety. Rich sampling for darunavir, etravirine, and ritonavir was collected in a substudy at weeks 4, 24, and 48. Results. Pharmacokinetics were estimated in 376 patients for darunavir and 190 patients for etravirine. Median darunavir AUC12h and C0h were 60,642ng·h/mL and 3624ng/mL, respectively; and for etravirine were 4183ng · h/mL and 280ng/mL, respectively. There were no differences in darunavir or etravirine AUC12h or C0h by sex or race. Age, body weight, or use of etravirine did not affect darunavir exposure. No relationships were seen between darunavir pharmacokinetics and efficacy or safety. Patients with etravirine exposure in the lowest quartile generally had lower response rates. Rich sampling showed no time-dependent relationship for darunavir, etravirine, or ritonavir exposure over 48 weeks. Conclusions. Population pharmacokinetics showed no relevant differences in darunavir or etravirine exposure by assessed covariates. Lower etravirine exposures were associated with lower response rates

    Making Primarily Professional Terms More Comprehensible to the Lay Audience

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    Certain texts, such as clinical reports and clinical trial records, are written by professionals for professionals while being increasingly accessed by lay people. To improve the comprehensibility of such documents to the lay audience, we conducted a pilot study to analyze terms used primarily by health professionals, and explore ways to make them more comprehensible to lay people
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