1,631 research outputs found

    Auralization of a Supersonic Business Jet Using Advanced Takeoff Procedures

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    Recent NASA studies of a supersonic business jet airplane indicated that advanced takeoff procedures could be used to reduce noise at the lateral sideline location to a level at which Chapter 4 noise certification requirements could be met. The studies were conducted with the NASA Aircraft Noise Prediction Program, using an analytical model of the airframe and its engines. The advanced procedure consists of a higher-speed climbout and a programmed thrust lapse in which the engine thrust is automatically and gradually reduced immediately after the runway obstacle is cleared. In this paper, the authors utilize the results of the most recent study as the basis of an auralization of the predicted noise. Modifications to the NASA Auralization Framework necessary for that process are described. The auralizations are used to demonstrate differences between standard and advanced takeoff pro ond those that may be observed through comparison of integrated noise metrics

    Magnitude of Drug-Drug Interactions in Special Populations

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    Drug-drug interactions (DDIs) are one of the most frequent causes of adverse drug reactions or loss of treatment efficacy. The risk of DDIs increases with polypharmacy and is therefore of particular concern in individuals likely to present comorbidities (i.e., elderly or obese individuals). These special populations, and the population of pregnant women, are characterized by physiological changes that can impact drug pharmacokinetics and consequently the magnitude of DDIs. This review compiles existing DDI studies in elderly, obese, and pregnant populations that include a control group without the condition of interest. The impact of physiological changes on the magnitude of DDIs was then analyzed by comparing the exposure of a medication in presence and absence of an interacting drug for the special population relative to the control population. Aging does not alter the magnitude of DDIs as the related physiological changes impact the victim and perpetrator drugs to a similar extent, regardless of their elimination pathway. Conversely, the magnitude of DDIs can be changed in obese individuals or pregnant women, as these conditions impact drugs to different extents depending on their metabolic pathway

    HIV-1 Tat alters neuronal intrinsic excitability

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    Objective: In HIV+ individuals, the virus enters the central nervous system and invades innate immune cells, producing important changes that result in neurological deficits. We aimed to determine whether HIV plays a direct role in neuronal excitability. Of the HIV peptides, Tat is secreted and acts in other cells. In order to examine whether the HIV Tat can modify neuronal excitability, we exposed primary murine hippocampal neurons to that peptide, and tested its effects on the intrinsic membrane properties, 4 and 24 h after exposure. Results: The exposure of hippocampal pyramidal neurons to Tat for 4 h did not alter intrinsic membrane properties. However, we found a strong increase in intrinsic excitability, characterized by increase of the slope (Gain) of the input-output function, in cells treated with Tat for 24 h. Nevertheless, Tat treatment for 24 h did not alter the resting membrane potential, input resistance, rheobase and action potential threshold. Thus, neuronal adaptability to Tat exposure for 24 h is not applicable to basic neuronal properties. A restricted but significant effect on coupling the inputs to the outputs may have implications to our knowledge of Tat biophysical firing capability, and its involvement in neuronal hyperexcitability in neuroHIV

    Recomendações técnicas para o uso agrícola do composto de lixo urbano no Estado de São Paulo.

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    Por que proceder a compostagem dos resíduos sólidos urbanos? Qual é a composição do lixo urbano brasileiro e paulista? Por que utilizar composto de lixo urbano na agricultura? Que efeitos pode-se esperar nas propriedades dos solos? Quais as características, maturidade e composição requeridas de compostos de lixo urbano para o seu uso na agricultura? Existe alguma legislação para o uso agrícola do composto de lixo urbano? Base científica dos índices do composto.Situação do cinturão verde de São Paulo.O risco ambiental seria apenas devido a metais pesados contidos nos resíduos sólidos? E a questão dos patógenos e outros componentes orgânicos não oferece risco à saúde das pessoas? É possível haver sanilização do solo pela aplicação do composto?Onde, quando e quanto de composto de lixo urbano deve-se aplicar nas principais culturas do Estado de São Paulo? Em síntese, que cuidados ou restrições devem ser observados para o uso agrícola do composto?bitstream/CNPTIA/9962/1/circtec3.pdfAcesso em: 28 maio 2008

    Chemical Stability of α-Tocopherol in Colloidal Lipid Particles with Various Morphologies

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    Colloidal lipid particles (CLPs) are promising encapsulation systems for lipophilic bioactives, such as oil-soluble antioxidants that are applied in food and pharmaceutical formulations. Currently, there is no clear consensus regarding the relation between particle structure and the chemical stability of such bioactives. Using α-tocopherol as a model antioxidant, it is shown that emulsifier type (Tween 20 or 40, or sodium caseinate) and lipid composition (tripalmitin, tricaprylin, or combinations thereof) modulated particle morphology and antioxidant stability. The emulsifier affects particle shape, with the polysorbates facilitating tripalmitin crystallization into highly ordered lath-like particles, and sodium caseinate resulting in less ordered spherical particles. The fastest degradation of α-tocopherol is observed in tripalmitin-based CLPs, which may be attributed to its expulsion to the particle surface induced by lipid crystallization. This effect is stronger in CLPs stabilized by Tween 40, which may act as a template for crystallization. This work not only shows how the architecture of CLPs can be controlled through the type of lipid and emulsifier used, but also gives evidence that lipid crystallization does not necessarily protect entrapped lipophilic bioactives, which is an important clue for encapsulation system design. Practical Applications: Interest in enriching food and pharmaceutical products with lipophilic bioactives such as antioxidants through encapsulation in lipid particles is growing rapidly. This research suggests that for efficient encapsulation, the particle architecture plays an important role; to tailor this, the contribution of both the lipid carrier and the emulsifier needs to be considered.</p

    Adaptive-Attentive Geolocalization From Few Queries: A Hybrid Approach

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    We tackle the task of cross-domain visual geo-localization, where the goal is to geo-localize a given query image against a database of geo-tagged images, in the case where the query and the database belong to different visual domains. In particular, at training time, we consider having access to only few unlabeled queries from the target domain. To adapt our deep neural network to the database distribution, we rely on a 2-fold domain adaptation technique, based on a hybrid generative-discriminative approach. To further enhance the architecture, and to ensure robustness across domains, we employ a novel attention layer that can easily be plugged into existing architectures. Through a large number of experiments, we show that this adaptive-attentive approach makes the model robust to large domain shifts, such as unseen cities or weather conditions. Finally, we propose a new large-scale dataset for cross-domain visual geo-localization, called SVOX

    Impact of Obesity on the Drug-Drug Interaction Between Dolutegravir and Rifampicin or Any Other Strong Inducers

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    BACKGROUND: Obesity is increasingly prevalent among people with HIV. Obesity can impact drug pharmacokinetics and consequently the magnitude of drug-drug interactions (DDIs) and, thus, the related recommendations for dose adjustment. Virtual clinical DDI studies were conducted using physiologically based pharmacokinetic (PBPK) modeling to compare the magnitude of the DDI between dolutegravir and rifampicin in nonobese, obese, and morbidly obese individuals. METHODS: Each DDI scenario included a cohort of virtual individuals (50% female) between 20 and 50 years of age. Drug models for dolutegravir and rifampicin were verified against clinical observed data. The verified models were used to simulate the concurrent administration of rifampicin (600 mg) at steady state with dolutegravir (50 mg) administered twice daily in normal-weight (BMI 18.5-30 kg/m(2)), obese (BMI 30-40 kg/m(2)), and morbidly obese (BMI 40-50 kg/m(2)) individuals. RESULTS: Rifampicin was predicted to decrease dolutegravir area under the curve (AUC) by 72% in obese and 77% in morbidly obese vs 68% in nonobese individuals; however, dolutegravir trough concentrations were reduced to a similar extent (83% and 85% vs 85%). Twice-daily dolutegravir with rifampicin resulted in trough concentrations always above the protein-adjusted 90% inhibitory concentration for all BMI groups and above the 300 ng/mL threshold in a similar proportion for all BMI groups. CONCLUSIONS: The combined effect of obesity and induction by rifampicin was predicted to further decrease dolutegravir exposure but not the minimal concentration at the end of the dosing interval. Thus, dolutegravir 50 mg twice daily with rifampicin can be used in individuals with a high BMI up to 50 kg/m(2)

    Photolysis of tertiary amines in the presence of CO2: the paths to formic acid, α-amino acids, and 1,2-diamines

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    The photolysis of triethylamine (1a) in the presence of carbon dioxide leads to the hydrogenation of CO2, the α-C-C coupling of triethylamine (1a), and the CO2-insertion into the α-C-H σ-bond of amine 1a. This reaction is proposed to proceed through the radical ion pair [R3N·+·CO2·-] generated by the photoionization of amine 1a and the electron capture by CO2. The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and stereoselective α-C-C coupling of 1a by enhancing the production of α-dialkylamino radicals and the isomerization of N,N,N',N'-tetraethylbutane-2,3-diamine (4a)
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