79 research outputs found

    Optimal Design of a Trickle Bed Reactor for Light Fuel Oxidative Desulfurization based on Experiments and Modelling

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    YesIn this work, the performance of oxidative desulfurization (ODS) of dibenzothiophene (DBT) in light gas oil (LGO) is evaluated with a homemade manganese oxide (MnO2/γ-Al2O3) catalyst. The catalyst is prepared by Incipient Wetness Impregnation (IWI) method with air under moderate operating conditions. The effect of different reaction parameters such as reaction temperature, liquid hour space velocity and initial concentration of DBT are also investigated experimentally. Developing a detailed and a validated trickle bed reactor (TBR) process model that can be employed for design and optimization of the ODS process, it is important to develop kinetic models for the relevant reactions with high accuracy. Best kinetic model for the ODS process taking into account hydrodynamic factors (mainly, catalyst effectiveness factor, catalyst wetting efficiency and internal diffusion) and the physical properties affecting the oxidation process is developed utilizing data from pilot plant experiments. An optimization technique based upon the minimization of the sum of the squared error between the experimental and predicted composition of oxidation process is used to determine the best parameters of the kinetic models. The predicted product conversion showed very good agreement with the experimental data for a wide range of the operating condition with absolute average errors less than 5%

    Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

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    BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents

    Real-time visualization of heterotrimeric G protein Gq activation in living cells

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    Contains fulltext : 97296.pdf (publisher's version ) (Open Access)BACKGROUND: Gq is a heterotrimeric G protein that plays an important role in numerous physiological processes. To delineate the molecular mechanisms and kinetics of signalling through this protein, its activation should be measurable in single living cells. Recently, fluorescence resonance energy transfer (FRET) sensors have been developed for this purpose. RESULTS: In this paper, we describe the development of an improved FRET-based Gq activity sensor that consists of a yellow fluorescent protein (YFP)-tagged Ggamma2 subunit and a Galphaq subunit with an inserted monomeric Turquoise (mTurquoise), the best cyan fluorescent protein variant currently available. This sensor enabled us to determine, for the first time, the kon (2/s) of Gq activation. In addition, we found that the guanine nucleotide exchange factor p63RhoGEF has a profound effect on the number of Gq proteins that become active upon stimulation of endogenous histamine H1 receptors. The sensor was also used to measure ligand-independent activation of the histamine H1 receptor (H1R) upon addition of a hypotonic stimulus. CONCLUSIONS: Our observations reveal that the application of a truncated mTurquoise as donor and a YFP-tagged Ggamma2 as acceptor in FRET-based Gq activity sensors substantially improves their dynamic range. This optimization enables the real-time single cell quantification of Gq signalling dynamics, the influence of accessory proteins and allows future drug screening applications by virtue of its sensitivity

    Effects of Deoxycholylglycine, a Conjugated Secondary Bile Acid, on Myogenic Tone and Agonist-Induced Contraction in Rat Resistance Arteries

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    Bile acids (BAs) regulate cardiovascular function via diverse mechanisms. Although in both health and disease serum glycine-conjugated BAs are more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT), a key determinant of systemic vascular resistance (SVR), have not been examined.Fourth-order mesenteric arteries (170-250 µm) isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to develop spontaneous constriction, i.e., MT. Deoxycholylglycine (DCG; 0.1-100 µM), a glycine-conjugated major secondary BA, induced reversible, concentration-dependent reduction of MT that was similar in endothelium-intact and -denuded arteries. DCG reduced the myogenic response to stepwise increase in pressure (20 to 100 mmHg). Neither atropine nor the combination of L-NAME (a NOS inhibitor) plus indomethacin altered DCG-mediated reduction of MT. K(+) channel blockade with glibenclamide (K(ATP)), 4-aminopyradine (K(V)), BaCl(2) (K(IR)) or tetraethylammonium (TEA, K(Ca)) were also ineffective. In Fluo-2-loaded arteries, DCG markedly reduced vascular smooth muscle cell (VSM) Ca(2+) fluorescence (∼50%). In arteries incubated with DCG, physiological salt solution (PSS) with high Ca(2+) (4 mM) restored myogenic response. DCG reduced vascular tone and VSM cytoplasmic Ca(2+) responses (∼50%) of phenylephrine (PE)- and Ang II-treated arteries, but did not affect KCl-induced vasoconstriction.In rat mesenteric resistance arteries DCG reduces pressure- and agonist-induced vasoconstriction and VSM cytoplasmic Ca(2+) responses, independent of muscarinic receptor, NO or K(+) channel activation. We conclude that BAs alter vasomotor responses, an effect favoring reduced SVR. These findings are likely pertinent to vascular dysfunction in cirrhosis and other conditions associated with elevated serum BAs

    Stroke genetics informs drug discovery and risk prediction across ancestries

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    Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

    Identificación de micobacterias no tuberculosas en pacientes VIH/SIDA por métodos convencionales y de fracciones de ácidos micólicos

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    &nbsp;Las micobacterias no tuberculosas son pat&oacute;genos oportunistas capaces de producir infecciones pulmonares y extrapulmonares.&nbsp;El &nbsp;aumento &nbsp;de &nbsp;su &nbsp; &nbsp;incidencia &nbsp;se &nbsp;ha &nbsp;acelerado &nbsp;despu&eacute;s &nbsp;de &nbsp;la &nbsp;aparici&oacute;n &nbsp;del &nbsp;S&iacute;ndrome &nbsp;de &nbsp;Inmunodeficiencia &nbsp;Adquirida &nbsp;(SIDA). &nbsp;En &nbsp;este&nbsp;trabajo se estudiaron 40 cepas aisladas de pacientes infectados por el Virus de Inmunodeficiencia Humana, A los aislamientos con signifi-caci&oacute;n patog&eacute;nica se le aplic&oacute; el estudio de los patrones de las fracciones de &aacute;cidos mic&oacute;licos. Los resultados fueron: 9 Mycobacterium&nbsp;avium, 8 Mycobacterium fortuitum, 4 Mycobacterium flavescens, 4 Mycobacterium smegmatis, 3 Mycobacterium marinum, 4 Mycobacte-rium gastri, 2 Mycobacterium gordonae, 2 Mycobacterium chelonae, 1 Mycobacterium xenopi, 1 Mycobacterium phlei, 1 Mycobacterium&nbsp;triviale, y 1 Mycobacterium malmoense. S&oacute;lo 5 de estas cepas estaban asociadas a cuadros cl&iacute;nicos: 2 Mycobacterium avium (micobacte-riosis diseminada y renal respectivamente), 1 Mycobacterium gordonae (lesiones en piel), 1 Mycobacterium fortuitum (linfadenitis sub-maxilar), 1 Mycobacterium malmoense (linfadenitis submaxilar). Las especies m&aacute;s frecuentemente aisladas fueron M. avium y M. fortui-tum acorde con lo revisado en la literatura. La aplicaci&oacute;n simult&aacute;nea de las t&eacute;cnicas convencionales y el estudio de las fracciones de &aacute;ci-dos mic&oacute;licos ha permitido obtener resultados m&aacute;s confiables por lo que recomendamos su aplicaci&oacute;n en estos estudios.&nbsp

    Modelación matemática de la hidrodesintegración de fracciones de petróleo utilizando uno a seis lumps

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    The mathematical modeling of hydrocracking reaction of petroleum fractions was carried out considering a pseudohomogeneous phase. The discrete description was used to represent the kinetic of the reactions. Oneto 6 lumps of pseudocompounds with different reaction routes were used. Data from the oil hydrocarbon hydrocracking of literature were used to obtain the mathematical model parameters. Modeling more than one group or lump was done by automatic successive approach solving the system of equations starting with one lump, then two, then three, and so on, checking that the material balance is satisfied in each case. Findings showed concordance between the models and the experimental data, highlighting the use of six lumps, from whose description it is possible to determine the composition of the hydrocracking products in a detailed and reliable way.Se realizó la modelación matemática de la reacción de hidrodesintegración de fracciones de petróleo considerando una fase pseudohomogénea. Se empleó la descripción discreta para representar la cinética de las reacciones. Se utilizaron de uno hasta seis grupos de pseudocomponentes o lumps con diferentes rutas de reacción. Se utilizaron datos de la literatura de la hidrodesintegración de hidrocarburos de petróleo para obtener los parámetros de los modelos matemáticos. Para el modelo de más de un grupo o lump se utilizó la aproximación sucesiva automática, resolviendo el sistema de ecuaciones comenzando con un lump, dos, o tres y así sucesivamente, verificando que siempre se cumpliera el balance de materia. Se encontró buena concordancia entre el modelo y los datos experimentales para las aproximaciones utilizadas, destacando el uso de seis lumps, a partir de cuya descripción es posible determinar la composición de los productos de hidrodesintegración de una forma detallada y confiable

    Modelación matemática de un reactor de tanque agitado con catalizador disperso para la obtención de metil oleato a partir de trioleína

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    The mathematical modeling of a three-phase reactor with dispersed phase catalyst for production of methyl oleate was carried out. Mass balances were used at the reactor level as well as the fluid-catalyst interphase to represent the operation system. The effect of type, particle size and catalyst concentration, as well as space-time and arrangement of reactors in series were examined. The purity of the triglyceride in the feeding was also investigated. The factors that most affected the reactor behavior quantitatively were the concentration of the catalyst, and its type, as well as the series arrangement of two reactors at constant space-timeSe realizó la modelación matemática de un reactor trifásico con catalizador en fase dispersa para la producción de metil oleato. Se uti-lizaron balances de materia a nivel reactor, así como entre fase fluida-catalizador para representar la operación del sistema. Se investigó el efecto del tipo, tamaño de partícula y concentración del catalizador, así como espacio-tiempo y arreglo de reactores en serie. Asimismo, se investigó sobre la pureza del triglicérido en la alimentación. Los factores que más afectaron cuantitativamente el desempeño del reactor fueron la concentración del catalizador, su tipo y el arreglo en serie de dos reactores a espacio-tiempo constante
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