Acute supra-therapeutic oral terbutaline administration has no ergogenic effect in non-asthmatic athletes.

This study aimed to investigate the effects on a possible improvement in aerobic and anaerobic performance of oral terbutaline (TER) at a supra-therapeutic dose in 7 healthy competitive male athletes. On day 1, ventilatory threshold, maximum oxygen uptake [Formula: see text] and corresponding power output were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3, 8 mg of TER or placebo were orally administered in a double-blind process to athletes who rested for 3 h, and then performed a battery of tests including a force-velocity exercise test, running sprint and a maximal endurance cycling test at Δ50 % (50 % between VT and [Formula: see text]). Lactatemia, anaerobic parameters and endurance performance ([Formula: see text] and time until exhaustion) were raised during the corresponding tests. We found that TER administration did not improve any of the parameters of aerobic performance (p > 0.05). In addition, no change in [Formula: see text] kinetic parameters was found with TER compared to placebo (p > 0.05). Moreover, no enhancement of the force-velocity relationship was observed during sprint exercises after TER intake (p > 0.05) and, on the contrary, maximal strength decreased significantly after TER intake (p < 0.05) but maximal power remained unchanged (p > 0.05). In conclusion, oral acute administration of TER at a supra-therapeutic dose seems to be without any relevant ergogenic effect on anaerobic and aerobic performances in healthy athletes. However, all participants experienced adverse side effects such as tremors.

Manganese uptake and redistribution in soybean as affected by glyphosate

Detrimental effects of glyphosate on plant mineral nutrition have been reported in the literature, particularly on Mn uptake and redistribution. However, in most of the experiments conducted so far glyphosate-susceptible plants were used. Effects of glyphosate on Mn absorption kinetics, accumulation, and distribution within the plant, as well as soybean response to Mn as affected by glyphosate were studied in three experiments. In the first experiment, in nutrient solution, the effect of glyphosate on soybean Mn uptake kinetic parameters (Imax, Km and Cmin) was determined. In a second experiment, also in nutrient solution, differential Mn accumulation and distribution were studied for a conventional soybean cultivar and its near-isogenic glyphosate-resistant counterpart as affected by glyphosate. In a third experiment, response of glyphosate-resistant soybean cultivars to Mn application was studied in the presence of glyphosate, in pots with Mn-deficient soil. Maximum Mn influx (Imax) was higher in the herbicide-resistant (GR) cultivar than in its conventional counterpart. Glyphosate applied to nutrient solution at low rates decreased Km and Cmin. A few days after herbicide treatment, RR soybean plants developed yellowish leaves, a symptom which, in the field, could be misinterpreted as Mn deficiency, but herbicide application had no effect on Mn uptake or distribution within the plant. In the soil experiment, soybean Mn uptake was increased by Mn application, with no effect of glyphosate. Under greenhouse conditions, there was no evidence of deleterious effects of glyphosate on Mn absorption, accumulation and distribution in the plant and on soybean cultivars response to Mn application.

Accuracy in the experimental calorimetric study of the crystallization kinetics and predicitve transformation diagrams: Application to a Ga-Te amorphous alloy

The uncertainties inherent to experimental differential scanning calorimetric data are evaluated. A new procedure is developed to perform the kinetic analysis of continuous heating calorimetric data when the heat capacity of the sample changes during the crystallization. The accuracy of isothermal calorimetric data is analyzed in terms of the peak-to-peak noise of the calorimetric signal and base line drift typical of differential scanning calorimetry equipment. Their influence in the evaluation of the kinetic parameters is discussed. An empirical construction of the time-temperature and temperature heating rate transformation diagrams, grounded on the kinetic parameters, is presented. The method is applied to the kinetic study of the primary crystallization of Te in an amorphous alloy of nominal composition Ga20Te80, obtained by rapid solidification.

Lack of Enantioselectivity in the SULT1A3-catalyzed Sulfoconjugation of Normetanephrine Enantiomers: An In Vitro and Computational Study.

(1R)-Normetanephrine is the natural stereoisomeric substrate for sulfotransferase 1A3 (SULT1A3)-catalyzed sulfonation. Nothing appears known on the enantioselectivity of the reaction despite its potential significance in the metabolism of adrenergic amines and in clinical biochemistry. We confronted the kinetic parameters of the sulfoconjugation of synthetic (1R)-normetanephrine and (1S)-normetanephrine by recombinant human SULT1A3 to a docking model of each normetanephrine enantiomer with SULT1A3 and the 3'-phosphoadenosine-5'-phosphosulfate cofactor on the basis of molecular modeling and molecular dynamics simulations of the stability of the complexes. The K(M) , V(max) , and k(cat) values for the sulfonation of (1R)-normetanephrine, (1S)-normetanephrine, and racemic normetanephrine were similar. In silico models were consistent with these findings as they showed that the binding modes of the two enantiomers were almost identical. In conclusion, SULT1A3 is not substrate-enantioselective toward normetanephrine, an unexpected finding explainable by a mutual adaptability between the ligands and SULT1A3 through an "induced-fit model" in the catalytic pocket. Chirality, 00:000-000, 2012.© 2012 Wiley Periodicals, Inc.

Characterization of surface functional groups present on laboratory-generated and ambient aerosol particles by means of heterogeneous titration reactions

A Knudsen flow reactor has been used to quantify surface functional groups on aerosols collected in the field. This technique is based on a heterogeneous titration reaction between a probe gas and a specific functional group on the particle surface. In the first part of this work, the reactivity of different probe gases on laboratory-generated aerosols (limonene SOA, Pb(NO3)2, Cd(NO3)2) and diesel reference soot (SRM 2975) has been studied. Five probe gases have been selected for the quantitative determination of important functional groups: N(CH3)3 (for the titration of acidic sites), NH2OH (for carbonyl functions), CF3COOH and HCl (for basic sites of different strength), and O3 (for oxidizable groups). The second part describes a field campaign that has been undertaken in several bus depots in Switzerland, where ambient fine and ultrafine particles were collected on suitable filters and quantitatively investigated using the Knudsen flow reactor. Results point to important differences in the surface reactivity of ambient particles, depending on the sampling site and season. The particle surface appears to be multi-functional, with the simultaneous presence of antagonistic functional groups which do not undergo internal chemical reactions, such as acid-base neutralization. Results also indicate that the surface of ambient particles was characterized by a high density of carbonyl functions (reactivity towards NH2OH probe in the range 0.26-6 formal molecular monolayers) and a low density of acidic sites (reactivity towards N(CH3)3 probe in the range 0.01-0.20 formal molecular monolayer). Kinetic parameters point to fast redox reactions (uptake coefficient ?0>10-3 for O3 probe) and slow acid-base reactions (?0<10-4 for N(CH3)3 probe) on the particle surface. [Authors]

MM-GBSA binding free energy decomposition and T cell receptor engineering.

Recognition by the T-cell receptor (TCR) of immunogenic peptides (p) presented by class I major histocompatibility complexes (MHC) is the key event in the immune response against virus infected cells or tumor cells. The major determinant of T cell activation is the affinity of the TCR for the peptide-MHC complex, though kinetic parameters are also important. A study of the 2C TCR/SIYR/H-2Kb system using a binding free energy decomposition (BFED) based on the MM-GBSA approach had been performed to assess the performance of the approach on this system. The results showed that the TCR-p-MHC BFED including entropic terms provides a detailed and reliable description of the energetics of the interaction (Zoete and Michielin, 2007). Based on these results, we have developed a new approach to design sequence modifications for a TCR recognizing the human leukocyte antigen (HLA)-A2 restricted tumor epitope NY-ESO-1. NY-ESO-1 is a cancer testis antigen expressed not only in melanoma, but also on several other types of cancers. It has been observed at high frequencies in melanoma patients with unusually positive clinical outcome and, therefore, represents an interesting target for adoptive transfer with modified TCR. Sequence modifications of TCR potentially increasing the affinity for this epitope have been proposed and tested in vitro. T cells expressing some of the proposed TCR mutants showed better T cell functionality, with improved killing of peptide-loaded T2 cells and better proliferative capacity compared to the wild type TCR expressing cells. These results open the door of rational TCR design for adoptive transfer cancer therapy.

Comment on “Dynamics of thermal growth of silicon oxide films on Si”

The paper commented on here R. M. C. de Almeida, S. Gonçalves, I. J. R. Baumvol and F. C. Stedile Phys. Rev. B 61 12992 (2000) claims that the Deal and Grove model of oxidation is unable to describe the kinetics in the thin oxide regime due to two main simplifications: (a) the steady-state assumption and (b) the abrupt Si∕SiO2 interface assumption. Although reasonably good fits are obtained without these simplifications, it will be shown that the values of the kinetic parameters are not reliable and that the solutions given for different partial pressures are erroneous. Finally, it will be shown that the correct solution of their model is unable to predict the oxidation rate enhancement observed in the thin oxide regime and that the predicted width of the interface compatible with the Deal and Grove rate constants is too large

T cell receptor-ligand interactions: a conformational preequilibrium or an induced fit.

Kinetic parameters of T cell receptor (TCR) interactions with its ligand have been proposed to control T cell activation. Analysis of kinetic data obtained has so far produced conflicting insights; here, we offer a consideration of this problem. As a model system, association and dissociation of a soluble TCR (sT1) and its specific ligand, an azidobenzoic acid derivative of the peptide SYIPSAEK-(ABA)I (residues 252-260 from Plasmodium berghei circumsporozoite protein), bound to class I MHC H-2K(d)-encoded molecule (MHCp) were studied by surface plasmon resonance. The association time courses exhibited biphasic patterns. The fast and dominant phase was assigned to ligand association with the major fraction of TCR molecules, whereas the slow component was attributed to the presence of traces of TCR dimers. The association rate constant derived for the fast phase, assuming a reversible, single-step reaction mechanism, was relatively slow and markedly temperature-dependent, decreasing from 7.0 x 10(3) at 25 degrees C to 1.8 x 10(2) M(-1).s(-1) at 4 degrees C. Hence, it is suggested that these observed slow rate constants are the result of unresolved elementary steps of the process. Indeed, our analysis of the kinetic data shows that the time courses of TCR-MHCp interaction fit well to two different, yet closely related mechanisms, where an induced fit or a preequilibrium of two unbound TCR conformers are operational. These mechanisms may provide a rationale for the reported conformational flexibility of the TCR and its unusual ligand recognition properties, which combine high specificity with considerable crossreactivity.

Rasvaisten ja öljyisten jätevesien biologisen puhdistuksen mallinnus

Työn kirjallisuusosassa on tarkasteltu rasvaistenjätevesien puhdistuksessa käytettyjä perinteisiä käsittelymenetelmiä ja ultrasuodatusta. Perinteisiä rasvaisten jätevesien käsittelymenetelmiä ovat muun muassalaskeutus, flotaatio, hydrosykloni, pisarakoon kasvattaminen suodatus sekä biologinen käsittely. Lisäksi happohydrolyysia voidaan soveltaa edellä mainittujen menetelmien esikäsittelynä. Perinteisten puhdistusmenetelmien käyttöä rajoittavatniiden tehottomuus emulgoituneen ja liukoisen öljyn poistossa. Tämä sekä kiristyneet päästövaatimukset ja kalvotekniikan nopea kehittyminen ovat lisänneet kiinnostusta kalvotekniikkaan. Työn soveltavassa osassa on tarkasteltu rasvojen mahdollisesti aiheuttamia ongelmia Porvoon jalostamon kemiallisessa ja biologisessa puhdistuksessa. Rasvaisia jätevesiä muodostuu biodieselin valmistuksessa, jossa rasvoja käytetään syöttöaineena. Vertailtaessa jalostamon vesilaitoksen nykyisiä olosuhteita ja rasvojen käsittelyn vaatimia olosuhteita havaitaan, että optimiolosuhteet ovat melko lähellä toisiaan ja rasvaisten jätevesien mukana tulevat fosfori-, typpi- ja COD-kuormat melko pieniä. Suurimmat mahdolliset rasvojen aiheuttamat ongelmat syntyvät aktiivilietelaitoksella, jossa kevyt pinnalle nouseva rasva nostaa mukanaan lietettä. Rasvat ja rasvahapot myös lisäävät rihmamaisten bakteerien kasvua, joiden runsas esiintyminen aiheuttaa huonosti laskeutuvaa lietettä, eli paisuntalietettä. Rasvaisten vesien aiheuttamaa kuormitusta aktiivilieteprosessiin on tarkasteltu Activated sludge Model No. 3:n ja bio-P fosforin poisto moduuliin pohjautuvan Excel-taulukkolaskentamallin avulla. Pohjana työssä on käytetty Tuomo Hillin vuonna 2002 diplomityönä tekemää taulukkolaskentamallia. Työssä on esitelty kaikki mallin kannalta oleelliset yhtälöt ja parametrit. Tämän tutkimuksen perusteella mallin käytettävyyttä rajoittaa se, että sitä ei ole kalibroitu Porvoon jalostamolle. Kalibroimattomalla mallilla voidaan saada vain suuntaa antavia tuloksia.

Implisiittisen kalibroinnin soveltamismahdollisuudet kemiantekniikassa

Työn taustalla oli tavoite parantaa erään teollisuusprosessin toimintaa ja sen tuottoa mallintamalla reaktiovaiheen alussa tapahtuvan välituotteen muodostumisen reaktiokinetiikka sekä perinteisellä tavalla että implisiittisellä kalibroinnilla. Toisena tavoitteena oli selvittää, kuinka implisiittistä kalibrointia voidaan yleisemmin hyödyntää kemiantekniikassa. Implisiittinen kalibrointi on menetelmä, jolla voidaan ratkaista jonkin teoreettisen mallin parametrit suoraan epäsuorasta mittausdatasta (esimerkiksi spektreistä) lähes kokonaan ilman off-line analyysejä. Tämän työn kirjallisuusosassa on esitetty implisiittisen kalibroinnin toimintaperiaate sekä lyhyesti FTIR-spektrometrian perusteita. Työn kokeellisessa osassa on estimoitu tutkitun välituotteen muodostumisen kineettiset parametrit sekä tavanomaisella parametriestimoinnilla että implisiittisellä kalibroinnilla. Lisäksi kokeellisessa osassa on selvitetty lyhyesti tutkitun prosessin FTIR-spektrien lämpötilariippuvuuksia ja esitetty neljä mahdollista uutta sovelluskohdetta implisiittiselle kalibroinnille. Tavanomaisella parametriestimoinnilla saatiin estimoitua varsin yksiselitteiset arvot kineettisille parametreille. Myös mallin sovitus koedataan on hyvä kolmessa kokeessa viidestä. Parametriestimointi implisiittisellä kalibroinnilla onnistui lupaavasti vaikka tulokset eivät ole aivan niin hyviä kuin tavanomaisessa parametriestimoinnissa. Parhaat tulokset implisiittisessä kalibroinnissa saavutettiin suoralla kalibrointitavalla GRR (Generalized Ridge Regression)-kalibrointimenetelmää käyttämällä.

Structure-Based, Rational Design of T Cell Receptors.

Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce T cell receptor (TCR) modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction with peptides (p) bound to major histocompatibility complexes (MHC). Using the well-characterized 2C TCR/SIYR/H-2K(b) structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. Fifty-four percent of the designed sequence replacements exhibited improved pMHC binding as compared to the native TCR, with up to 150-fold increase in affinity, while preserving specificity. Genetically engineered CD8(+) T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity, K D = ∼1 - 5 μM. Beyond the affinity threshold at K D < 1 μM we observed an attenuation in cellular function, in line with the "half-life" model of T cell activation. Our computer-aided protein-engineering approach requires the 3D-structure of the TCR-pMHC complex of interest, which can be obtained from X-ray crystallography. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes when experimental data is not available. Since the accuracy of the models depends on the prediction of the TCR orientation over pMHC, we have complemented the approach with a simplified rigid method to predict this orientation and successfully assessed it using all non-redundant TCR-pMHC crystal structures available. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of stage IV melanoma.

Modeling reaction kinetics and mass transfer in ozonation in water solutions

This dissertation is based on four articles dealing with modeling of ozonation. The literature part of this considers some models for hydrodynamics in bubble column simulation. A literature review of methods for obtaining mass transfer coefficients is presented. The methods presented to obtain mass transfer are general models and can be applied to any gas-liquid system. Ozonation reaction models and methods for obtaining stoichiometric coefficients and reaction rate coefficients for ozonation reactions are discussed in the final section of the literature part. In the first article, ozone gas-liquid mass transfer into water in a bubble column was investigated for different pH values. A more general method for estimation of mass transfer and Henry’s coefficient was developed from the Beltrán method. The ozone volumetric mass transfer coefficient and the Henry’s coefficient were determined simultaneously by parameter estimation using a nonlinear optimization method. A minor dependence of the Henry’s law constant on pH was detected at the pH range 4 - 9. In the second article, a new method using the axial dispersion model for estimation of ozone self-decomposition kinetics in a semi-batch bubble column reactor was developed. The reaction rate coefficients for literature equations of ozone decomposition and the gas phase dispersion coefficient were estimated and compared with the literature data. The reaction order in the pH range 7-10 with respect to ozone 1.12 and 0.51 the hydroxyl ion were obtained, which is in good agreement with literature. The model parameters were determined by parameter estimation using a nonlinear optimization method. Sensitivity analysis was conducted using object function method to obtain information about the reliability and identifiability of the estimated parameters. In the third article, the reaction rate coefficients and the stoichiometric coefficients in the reaction of ozone with the model component p-nitrophenol were estimated at low pH of water using nonlinear optimization. A novel method for estimation of multireaction model parameters in ozonation was developed. In this method the concentration of unknown intermediate compounds is presented as a residual COD (chemical oxygen demand) calculated from the measured COD and the theoretical COD for the known species. The decomposition rate of p-nitrophenol on the pathway producing hydroquinone was found to be about two times faster than the p-nitrophenol decomposition rate on the pathway producing 4- nitrocatechol. In the fourth article, the reaction kinetics of p-nitrophenol ozonation was studied in a bubble column at pH 2. Using the new reaction kinetic model presented in the previous article, the reaction kinetic parameters, rate coefficients, and stoichiometric coefficients as well as the mass transfer coefficient were estimated with nonlinear estimation. The decomposition rate of pnitrophenol was found to be equal both on the pathway producing hydroquinone and on the path way producing 4-nitrocathecol. Comparison of the rate coefficients with the case at initial pH 5 indicates that the p-nitrophenol degradation producing 4- nitrocathecol is more selective towards molecular ozone than the reaction producing hydroquinone. The identifiability and reliability of the estimated parameters were analyzed with the Marcov chain Monte Carlo (MCMC) method. @All rights reserved. No part of the publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the author.

Desenvolvimento e aplicação de células eletroquímicas em camada delgada

Theoretical and practical aspects concerning construction and use of a thin layer electrochemical cell are presented. Construction was realized by a simple technic and geometry was optimized in order to minimize the problems of electrical resistance. A well known redox system was studied ((Fe(III)(CN)6(3-)/Fe(II)(CN) 6(4-)) using two experimental methods, cyclic voltammetry and pulse chronopotentiometry. A numerical integration based-program was developed to calculate the voltammetric current in case of nernstian and non-nernstian behaviours and a diffusional model was used to treat the chronopotentiometric data. Thermodynamic (potential, concentration) and kinetic parameters (diffusion coefficient) were successfully determined for the redox system studied in this work.

Caracterização de catalisadores Cu/CeO2/Al2O3 por redução a temperatura programada e atividade para oxidação de CO

The kinetic parameters for the CO oxidation reaction using copper/alumina-modified ceria as catalysts were determined. The catalysts with different concentrations of the metals were prepared using impregnation methods. In addition, the reduction-oxidation behaviour of the catalysts were investigated by temperature-programmed reduction. The activity results show that the mechanism for CO oxidation is bifunctional : oxygen is activated on the anionic vacancies of ceria surface, while carbon monoxide is adsorbed preferentially on the higher oxidation copper site. Therefore, the reaction occurs on the interfacial active centers. Temperatures-programmed Reduction patterns show a higher disperdion when cerium oxide is present.

O eletrólito suporte e suas múltiplas funções em processos de eletrodo

The aim of this work is to present the principal properties and applications of supporting electrolytes (SE) to students, teachers and researchers interested in electrode processes. Different aspects are discussed including the importance of SE in maintaining constant the activity coefficients and the diffusion coefficients and reducing the transport number of electroactive species. Its effect on the electrochemical kinetic parameters is also presented.