Antonio Gonzalez Cruz - Academia.edu (original) (raw)

Papers by Antonio Gonzalez Cruz

Movement Disorders, Aug 15, 2010

Among nonmotor symptoms observed in Parkinson's disease (PD) dysfunction in the visual system, in... more Among nonmotor symptoms observed in Parkinson's disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyrus (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD.

Javma J Am Vet Med Assoc, 2007

To determine characteristics, incidence rate, and possible associations with selected demographic... more To determine characteristics, incidence rate, and possible associations with selected demographic characteristics of catastrophic musculoskeletal injuries (CMIs) in Thoroughbred racehorses. 76 Thoroughbreds with CMIs. Incidence rates of CMIs during racing or training were calculated with number of CMIs as the numerator and overall numbers of races or training events during 2004 and 2005 as the denominators. Exact 95% confidence intervals were calculated. Associations between incidence and dichotomous exposure factors, nominal factors, and ordinal factors were determined. Only univariable associations were examined. 76 horses were euthanized because of CMI and represented 2.36 and 1.69 deaths/1,000 racing starts in 2004 and 2005, respectively. Of these, 57 were euthanized within 60 days before or after a race, which yielded a point incidence of 1.05/1,000 racing starts and 0.39/1,000 training starts. Incidence rate of CMIs at 2 Ontario racetracks was similar to that at other North American racetracks. A cumulative death rate of 1 to 2 deaths/wk should be considered typical when designing prevention strategies and offers a baseline value for measuring improvement.

A Weblab is an experiment operated remotely via internet. Besides the strictly technical aspects ... more A Weblab is an experiment operated remotely via internet. Besides the strictly technical aspects of such an experiment, which may contribute for the learning of Chemical Engineering fundamentals, there is another important feedback when teams of students of two different countries are working together: the Weblab turns into an intercultural experience, enhancing the communication skills of the students. A Weblab between Universidade Federal de São Carlos (DEQ/UFSCar) and the Ecole Nationale Supérieurs d'Ingénieurs en Arts Chimiques et Technologiques (ENSIACET) is presented in this work. A mass transfer experiment in a bench scale reactor (agitated and aerated) had to be studied by heterogeneous teams, thus emulating challenges that will be common in future work environments. In order to perform the experiment, students in Brazil and in France were gathered into groups. The students had to make decisions about the procedure to drive the experiments. All the students were able to control the equipment, no matter where they physically were. Students communicated using video conference software. The students and teachers opinions on this experience were very positive. This methodology is an important contribution to the formation of engineers in a world integrated by modern communication technologies.

Biophysical journal, 2015

Pulmonary surfactant (PS) is an essential complex of lipids and specific proteins synthesized in ... more Pulmonary surfactant (PS) is an essential complex of lipids and specific proteins synthesized in alveolar type II pneumocytes, where it is assembled and stored intracellularly as multilayered organelles known as lamellar bodies (LBs). Once secreted upon physiological stimulation, LBs maintain a densely packed structure in the form of lamellar body-like particles (LBPs), which are efficiently transferred into the alveolar air-water interface, lowering surface tension to avoid lung collapse at end-expiration. In this work, the structural organization of membranes in LBs and LBPs freshly secreted by primary cultures of rat ATII cells has been compared with that of native lung surfactant membranes isolated from porcine bronchoalveolar lavage. PS assembles in LBs as crystalline-like highly ordered structures, with a highly packed and dehydrated state, which is maintained at supraphysiological temperatures. This relatively ordered/packed state is retained in secreted LBPs. The micro- and ...

The Journal of Lipid Research, Nov 1, 2008

The assessment of new therapeutic strategies to cure surfactant-associated lung disorders would g... more The assessment of new therapeutic strategies to cure surfactant-associated lung disorders would greatly benefit from assay systems allowing routine evaluations of surfactant functions. We present a method to measure surfactant adsorption kinetics into interfacial air-liquid interfaces based on fluorescence microplate readers. The principle of measurement is simple, robust, and reproducible: Wells of a microtiter plate contain an aqueous solution of a light-absorbing agent. Fluorescence is excited and collected from the top of the wells so that fluorescently labeled surfactant injected into the bulk can be detected only once adsorbed into the air-liquid interface. Mass transfer from the bulk to the interface is achieved by orbital shaking implemented in the plate reader instrument. The method has been tested and validated by using phospholipids or surfactants of different origins, by using albumin as surfactant inhibitor, and by comparison of results with Wilhelmy balance measurements. The method is suited for implementation in high-throughput screening routines for conditions affecting, or improving, surfactant film formation. In contrast to surface tension measurements, our method gives a direct readout of the amount of surfactant adsorbing into the interface, including the functionally important amount of material firmly associating with the interfacial film.-Ravasio, A., A. Cruz, J. Pérez-Gil, and T. Haller. High-throughput evaluation of pulmonary surfactant adsorption and surface film formation. J. Lipid Res. 2008Res. . 49: 2479Res. -2488 Supplementary key words air-liquid interface • fluorescence • lamellar bodies • lung • microplate • surface tension

Biochemistry Usa, Jul 1, 1998

Pulmonary surfactant-associated protein B (SP-B) has been isolated from porcine lungs and reconst... more Pulmonary surfactant-associated protein B (SP-B) has been isolated from porcine lungs and reconstituted in bilayers of dipalmitoylphosphatidylcholine (DPPC) or egg yolk phosphatidylcholine (PC) to characterize the extent of insertion of the protein into phospholipid bilayers. The parameters for the interaction of SP-B with DPPC or PC using different reconstitution protocols have been estimated from the changes induced in the fluorescence emission spectrum of the single protein tryptophan. All the different reconstituted SP-B-phospholipid preparations studied had similar K d values for the binding of the protein to the lipids, on the order of a few micromolar. The depth of penetration of SP-B into phospholipid bilayers has been estimated by the parallax method, which compares the relative efficiencies of quenching of the protein fluorescence by a shallow or a deeper spin-labeled phospholipid probe. SP-B tryptophan was found to be located 10-13 Å from the center of bilayers, which is consistent with a superficial location of SP-B in phosphatidylcholine membranes. Parallax experiments, as well as resonance energy transfer from SP-B tryptophan to an acceptor probe located in the center of the bilayer, indicate that there are significant differences in the extent of insertion of the protein, depending on the method of reconstitution. SP-B reconstituted from lipid/protein mixtures in organic solvents is inserted more deeply in PC or DPPC bilayers than the protein reconstituted by addition to preformed phospholipid vesicles. These differences in the extent of insertion lead to qualitative and quantitative differences in the effect of the protein on the mobility of the phospholipid acyl chains, as studied by spin-label electron spin resonance (ESR) spectroscopy, and could represent different functional stages in the surfactant cycle.

Biophysical Journal, Jul 31, 1996

Pulmonary surfactant, a lipid-protein complex, secreted into the fluid lining of lungs prevents a... more Pulmonary surfactant, a lipid-protein complex, secreted into the fluid lining of lungs prevents alveolar collapse at low lung volumes. Pulmonary surfactant protein C (SP-C), an acylated, hydrophobic, a-helical peptide, enhances the surface activity of pulmonary surfactant lipids. Fluorescein-labeled SP-C (F-SP-C) (3, 6, 12 wt%) in dipalmitoylphosphatidylcholine (DPPC), and DPPC:dipalmitoylphosphatidylglycerol (DPPG) [DPPC:DPPG 7:3 mol/mol] in spread monolayers was studied by epifluorescence microscopy. Mass spectrometry of F-SP-C indicated that the protein is partially deacylated and labeled with 1 mol fluorescein/1 mol protein. The protein partitioned into the fluid, or liquid expanded, phase. Increasing amounts of F-SP-C in DPPC or DPPC:DPPG monolayers decreased the size and total amounts of the condensed phase at all surface pressures. Calcium (1.6 mM) increased the amount of the condensed phase in monolayers of DPPC:DPPG but not of DPPC alone, and such monolayers were also perturbed by F-SP-C. The study indicates that SP-C perturbs the packing of neutral and anionic phospholipid monolayers even when the latter systems are condensed by calcium, indicating that interactions between SP-C and the lipids are predominantly hydrophobic in nature.

American Journal of Veterinary Research, Nov 3, 2008

To characterize the microstructure of subchondral bone (SCB) plate and trabecular bone (TBB) of t... more To characterize the microstructure of subchondral bone (SCB) plate and trabecular bone (TBB) of the distopalmar aspect of the condyles of third metacarpal bones (MC3s) from Thoroughbred racehorses at 2 different stages of SCB disease via micro-computed tomography (CT). 12 pairs of MC3s from Thoroughbred racehorses euthanized for various reasons. MC3s were collected from horses with mild (n = 6) or severe (6) SCB disease, as determined via micro-CT. Cubic (6 x 6 x 6-cm) specimens of SCB plate and TBB were cut from the palmar aspect of condyles and sagittal ridges and examined with 3-dimensional micro-CT. For each specimen, apparent bone mineral density (aBMD), true BMD (tBMD), bone volume fraction (BVF), trabecular thickness (TBT), trabecular separation (TBS), and connectivity (CN) were calculated. Condyles had higher aBMD, tBMD, BVF, and TBT and lower TBS than did the sagittal ridge. In bone specimens with mild SCB changes, SCB plate had higher aBMD, TBT, and CN and lower TBS than did TBB. In bone specimens with severe SCB disease, TBB had higher aBMD and TMD and lower TBS than it did in bone specimens with mild disease, and values were similar to those for SCB plate in bone specimens with severe disease. The microstructure of SCB of the distopalmar aspect of metacarpal condyles of horses varied according to the severity of changes identified via micro-CT. With mild SCB disease, sclerosis existed in the SCB plate of the condyles; with severe disease, sclerosis also invaded condylar TBB.

Chemical Engineering Research and Design, 2015

ABSTRACT Despite being well established, a major limitation remains in ethanol fermentation proce... more ABSTRACT Despite being well established, a major limitation remains in ethanol fermentation processes: the presence of ethanol inhibits yeast activity, affecting the cell growth rate and, consequently, the ethanol production rate. For this reason, low ethanol concentrations of around 8-9% v.v−1 are reached at the end of the fermentation, hence requiring the consumption of a significant amount of energy for recovery of the fermentation product, while generating large amounts of vinasse. This situation requires the use of large fermentation tanks in order to achieve satisfactory ethanol production. Additionally, due to the large amount of heat generated by the fermentation processes, the temperature control of industrial fermentation tanks is a great challenge in tropical regions such as Brazil. The goal of the present study was to analyze the influence of operating variables on the performance of ethanol stripping at bench and pilot scales, using carbon dioxide as the carrier gas, and to propose a model describing the changes in ethanol mass and solution temperature during the stripping process. Bench scale experiments were conducted using a 5-L bubble column filled with 10% v.v−1 hydroalcoholic solution, and the pilot scale experiments were performed using a 95-L column filled with industrial fermented wine without yeast. A factorial design was applied to identify the most important operating variables for the following stripping performance parameters: entrainment factor, concentration factor, and temperature reduction factor. The results showed that both temperature and entrainment factor were positively influenced by initial solution temperature and specific CO2 flow rate, and negatively affected by height-to-diameter ratio. The temperature of the carbon dioxide did not affect either of these performance parameters. The simulation results revealed that the stripping model accurately described the decreases in ethanol mass and solution temperature during the stripping operation, with good agreement between the experimental and simulated data, and errors less than 5% in most cases.

KyaTera is an optical high speed, packet network (Gigabit Ethernet). KyaTera Network was created ... more KyaTera is an optical high speed, packet network (Gigabit Ethernet). KyaTera Network was created to gather competences and laboratorial resources that are necessary to develop science, technologies, and applications of the future Internet, in the state of So Paulo, Brazil. Its mission is to create a collaborative environment based on a Fiber-to-the-Lab network for mobilizing firms, institutes of research, universities, and funding agencies to develop technological innovations and to generate scientific knowledge. A Weblab is an experiment remotely operated via Internet. In this work, we present Weblab experiments that were performed collaboratively between undergraduate students of the Laboratory of Development and Automation of Biochemical Process (LaDABio) of the Chemical Engineering Department of the Universidade Federal de So Carlos (DEQ/UFSCar) and of the Center for Chemical Systems Engineering (CESQ) of the Chemical Engineering Department of the Escola Politcnica da Universida...

Anais do XX Congresso Brasileiro de Engenharia Química, 2015

RESUMO -Na fermentação alcoólica, o fenômeno da inibição pelo produto limita a concentração de et... more RESUMO -Na fermentação alcoólica, o fenômeno da inibição pelo produto limita a concentração de etanol no vinho ao redor de 10 ºGL, o que resulta em grande volume de vinhaça (ca. 12 L vinhaça /L etanol ) e alto consumo de vapor na etapa de destilação (ca. 2,5 kg vapor /L etanol ). Tecnologias para remover etanol do vinho vêm sendo estudadas. Exemplo é a operação de arraste de etanol por um gás, que além da remoção de etanol, provoca também a redução da temperatura do meio reacional devido à sua vaporização. Este fato é vantajoso, pois o controle da temperatura nas dornas industriais é um fator de difícil solução por envolver grandes volumes. Neste contexto, o arraste de etanol por gás pode ser utilizado tanto no controle da concentração de etanol e na redução da temperatura do meio fermentativo, como pode ser utilizado após a fermentação para a extração de etanol do vinho, sendo uma alternativa à destilação, reduzindo o consumo de vapor da planta. Neste trabalho, avaliou-se o arraste de etanol do vinho delevedurado por CO 2 (gerado no próprio processo industrial) em dorna de 95 L. Um planejamento fatorial foi utilizado para avaliar a influência das variáveis, temperatura inicial do vinho (T o ) e vazão específica de CO 2 (ΦCO2) nos parâmetros de desempenho: Fator de Arraste (F A ), Fator de Concentração (F C ) e Fator de Redução de Temperatura (F T ). Observou-se que o F A e o F T foram influenciados positivamente pelas variáveis T o e ΦCO2 enquanto o F C foi influenciado negativamente, apenas pela variável T o .

RESUMO -A operação de esgotamento (stripping) consiste na passagem de um gás insolúvel através de... more RESUMO -A operação de esgotamento (stripping) consiste na passagem de um gás insolúvel através de uma solução, da qual são retirados compostos voláteis, que vaporizam e são transferidos para a fase gasosa. Uma possível aplicação desta operação é durante a fermentação alcoólica, promovendo a retirada contínua do etanol presente no caldo e minimizando assim, a ocorrência de inibição do crescimento celular e da produção de etanol. Além disso, a retirada de compostos voláteis provoca uma diminuição da temperatura da solução, fato este que pode ser empregado para o controle da temperatura da dorna de fermentação. O objetivo deste trabalho foi a proposição de um modelo para prever a variação da massa de etanol e a temperatura do sistema durante uma operação de stripping. O modelo consiste em um sistema de Equações Diferenciais Ordinárias provenientes de balanços de massa para a água e etanol e do balanço de energia do sistema. Utilizou-se o Método de Runge-Kutta de 4 a Ordem como técnica de resolução, empregando-se um passo de integração no tempo de 0,1 h. Comparando-se os resultados obtidos da simulação com aqueles obtidos experimentalmente observou-se desvios de até 10% para a massa de etanol e de 20% para a temperatura da solução. As diferenças encontradas devem-se a ocorrência de arraste mecânico das moléculas de etanol e água, fenômeno conhecido como sublação, não previsto pelo modelo puramente termodinâmico.

RESUMO -Apesar de consagrada, a produção de etanol via fermentação alcoólica apresenta uma limita... more RESUMO -Apesar de consagrada, a produção de etanol via fermentação alcoólica apresenta uma limitação: em concentrações acima de 10°GL, a presença de etanol inibe o crescimento da levedura e consequentemente a obtenção do produto. Para superar a inibição é necessária a retirada do etanol do caldo simultaneamente à produção, de maneira a evitar que a concentração alcance valores inibitórios para o crescimento celular. Neste contexto, a operação de esgotamento (stripping) surge como uma alternativa promissora. Em vista disso, o objetivo deste trabalho foi avaliar as influências de diferentes variáveis de operação na retirada de etanol de uma solução hidroalcoólica, empregando-se dióxido de carbono como gás de arraste. Utilizou-se um planejamento fatorial completo para verificar as influências das variáveis temperatura inicial da solução hidroalcoólica (T SOL,0 ), vazão específica do gás (Φ GÁS ), temperatura do gás (T GÁS ) do gás de arraste e relação altura-diâmetro da dorna (h/D) nos seguintes parâmetros de desempenho: Fator de Arraste (F A ), Fator de Concentração (F C ) e Fator de Variação de Temperatura (F T ). Verificou-se que de um modo geral, T GÁS não exerceu influência significativa sobre nenhum dos parâmetros avaliados. Além disso, observou-se que os efeitos de T SOL,0 , Φ GÁS sobre F T e F A foram positivos e o efeito de h/D, negativo. Quanto à influência das variáveis independentes no Fator de Concentração (F C ), nenhuma delas apresentou efeito significativo de forma isolada.

European Journal of Pharmaceutics and Biopharmaceutics, 2015

To consider the lung as a target for drug delivery and to optimise strategies directed at the pul... more To consider the lung as a target for drug delivery and to optimise strategies directed at the pulmonary route, it is essential to consider the role of pulmonary surfactant, a thin lipid-protein film lining the respiratory surface of mammalian lungs. Membrane-based surfactant multilayers are essential for reducing the surface tension at the respiratory air-liquid interface to minimise the work of breathing. Different components of surfactant are also responsible for facilitating the removal of potentially pathological entities such as microorganisms, allergens or environmental pollutants and particles. Upon inhalation, drugs or nanoparticles first contact the surfactant layer, and these interactions critically affect their lifetime and fate in the airways. This review summarises the current knowledge on the possible role and effects of the pulmonary surfactant system in drug delivery strategies. It also summarises the evidence that suggests that pulmonary surfactant is far from being an insuperable barrier and could be used as an efficient shuttle for delivering hydrophobic and hydrophilic compounds deep into the lung and the organism.

Computer Aided Chemical Engineering, 2009

Saccharomyces cerevisiae biomass is still one of the most important biotechnological products in ... more Saccharomyces cerevisiae biomass is still one of the most important biotechnological products in the world, mainly in the form of baker's yeast. Costs of substrates have an important position in the overall economics of baker's yeast production, which is usually run in fed-batch bioreactors. In this context, the maximization of biomass yields, aiming at the highest achievable volumetric productivity is a driving force for improving the control of the process. Classical model-based control strategies for this process, however, face difficulties due to the inherent variability of this system: microorganisms have a complex growth dynamics, lumped in very simplified growth models; raw materials are variable and may be not traceable; the system response depends on non-controlled previous process stages, such as strain selection and inoculum preparation. Hence, the possibility of using feedback information from in situ sensors for re-tuning control parameters is an important issue to ensure sub-optimal performances, at least. A capacitance sensor is a device that can monitor cell concentration on-line. In fed-batch cultivations, the feed rate and correlated inputs can be controlled by systems coupled with softsensors that infer the state of the system from on-line measurements of primary variables. Several estimation techniques have been proposed in the literature, and among them the gas balance technique is widely used. The specific respiration rate (qO2), the specific carbon dioxide production rate (qCO2), and the respiratory quotient (RQ) are the main variables determined from the gas balance. Values of RQ for complete oxidation of some carbon sources to carbon dioxide and water are found in the literature. For the baker's yeast production process growing in glucose, a value of RQ close to unity indicates the preponderance of the aerobic route. The capacitance sensor, after calibration, may provide information about cellular growth and viability: the capacitance of the medium is linearly proportional to viable cell concentration. In this work, the signal of capacitance sensor and the RQ value are coupled to a fuzzy algorithm in order to control the glucose feed rate during baker's yeast aerobic cultivation.

Computer Aided Chemical Engineering, 2012

An integrated first and second generation ethanol production plant was simulated and optimized in... more An integrated first and second generation ethanol production plant was simulated and optimized in an equation-oriented process simulator. Two optimization methods were used: ipopt, a deterministic algorithm, and PSO, a stochastic one. The optimization of cash flow and of ethanol production was carried out for three different pretreatments. PSO was able to solve the optimization problems, while ipopt did not converge. The objective functions exhibited opposite behavior, i.e. ethanol maximization leaded to lower cash flows for the considered economic scenario.

Computer Aided Chemical Engineering, 2009

ABSTRACT The complexity of biological processes turns infeasible the development of detailed, str... more ABSTRACT The complexity of biological processes turns infeasible the development of detailed, structured phenomenological models of the cultivation of microorganisms in bioreactors. Therefore, cause-effect relations between on-line measurements and the state variables that are important for the optimal operation of industrial fermenters are sometimes hard to ascertain. In this context, data pre-treatment techniques are useful for control and fault detection. Among them, principal component analysis (PCA) has an important role. This work presents a case study of the application of this technique during real experiments, where the enzyme penicillin G acylase (PGA) was being produced by Bacillus megaterium. PGA hydrolyzes penicillin G to yield 6-aminopenicilanic acid (6-APA) and phenyl acetic acid. 6-APA is an important substrate, used to produce semi-synthetic P-lactam antibiotics. The algorithm was implemented for on-line detection of deviations from the desired process behavior. The experiments were carried out in a 2-liter bioreactor (Applikon®) operated in batch and fed-batch mode in different experimental conditions. A static PCA model was initially developed for the process, and its results are presented here. Hotteling's T2 was the discrimination criterion employed in this multivariable problem, and the method showed a high sensibility for fault detection in all real cases that were studied.

European journal of medicinal chemistry, Jan 30, 2014

The development of peptide fusion inhibitors based on short synthetic peptides represents a promi... more The development of peptide fusion inhibitors based on short synthetic peptides represents a promising option in the fight against HIV-1 infection, especially in individuals infected with multiresistant HIV-1 strains. GBV-C has the beneficial effect of retarding the progression of AIDS in people who are co-infected with both the GBV-C and HIV viruses. In previous works, the E1(22-39) GBV-C sequence (E1P8lin) was found to be capable of inhibiting the interaction of HIV-1 FP with bilayers and its cyclic analogue (E1P8cyc) showed a higher anti-HIV-1 activity. In the present work, in an attempt to gain a better understanding of the interaction of E1P8 peptides with HIV-1 FP, we analyzed direct interactions between peptides at the molecular level. Our results support that E1P8cyc might be more potent at blocking HIV-1 entry than E1P8lin as a consequence of the structure induced in the complex formed with HIV-1 FP, which is able to modify the conformation adopted by this functional domain ...

Energy & Fuels, 2014

ABSTRACT In alcoholic fermentation processes, ethanol is the main component that is toxic to yeas... more ABSTRACT In alcoholic fermentation processes, ethanol is the main component that is toxic to yeast because it acts as a noncompetitive inhibitor of metabolism. One way of overcoming the inhibition effect on yeast is to extract the ethanol from the broth during the fermentation. The present work evaluates ethanol production by extractive batch fermentation using CO2 as a stripping gas. Investigation was first made of the influence of specific CO2 flow rate (ϕ) and solution temperature on ethanol stripping. The best results, in terms of ethanol removal, were obtained at 2.0 vvm and 34.0 °C. Modeling of conventional and extractive ethanol fermentation was then performed considering cell growth, substrate consumption, ethanol production, and the entrainment of ethanol and water using first-order equations. The hybrid Andrews-Levenspiel model was able to describe the kinetics of the conventional fermentation process, and a model proposed here could accurately predict the behavior of the extractive fermentation. In all the extractive fermentations, there was faster substrate uptake and earlier substrate exhaustion, compared to the conventional fermentation. Extractive fermentation, with stripping initiated after 3 h at an ethanol concentration of 43.3 g·L-1, resulted in an ethanol productivity (in g·L-1·h-1) that was around 25% higher, and finished about 2 h earlier, compared to the control fermentation.

Movement Disorders, Aug 15, 2010

Among nonmotor symptoms observed in Parkinson's disease (PD) dysfunction in the visual system, in... more Among nonmotor symptoms observed in Parkinson's disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyrus (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD.

Javma J Am Vet Med Assoc, 2007

To determine characteristics, incidence rate, and possible associations with selected demographic... more To determine characteristics, incidence rate, and possible associations with selected demographic characteristics of catastrophic musculoskeletal injuries (CMIs) in Thoroughbred racehorses. 76 Thoroughbreds with CMIs. Incidence rates of CMIs during racing or training were calculated with number of CMIs as the numerator and overall numbers of races or training events during 2004 and 2005 as the denominators. Exact 95% confidence intervals were calculated. Associations between incidence and dichotomous exposure factors, nominal factors, and ordinal factors were determined. Only univariable associations were examined. 76 horses were euthanized because of CMI and represented 2.36 and 1.69 deaths/1,000 racing starts in 2004 and 2005, respectively. Of these, 57 were euthanized within 60 days before or after a race, which yielded a point incidence of 1.05/1,000 racing starts and 0.39/1,000 training starts. Incidence rate of CMIs at 2 Ontario racetracks was similar to that at other North American racetracks. A cumulative death rate of 1 to 2 deaths/wk should be considered typical when designing prevention strategies and offers a baseline value for measuring improvement.

A Weblab is an experiment operated remotely via internet. Besides the strictly technical aspects ... more A Weblab is an experiment operated remotely via internet. Besides the strictly technical aspects of such an experiment, which may contribute for the learning of Chemical Engineering fundamentals, there is another important feedback when teams of students of two different countries are working together: the Weblab turns into an intercultural experience, enhancing the communication skills of the students. A Weblab between Universidade Federal de São Carlos (DEQ/UFSCar) and the Ecole Nationale Supérieurs d'Ingénieurs en Arts Chimiques et Technologiques (ENSIACET) is presented in this work. A mass transfer experiment in a bench scale reactor (agitated and aerated) had to be studied by heterogeneous teams, thus emulating challenges that will be common in future work environments. In order to perform the experiment, students in Brazil and in France were gathered into groups. The students had to make decisions about the procedure to drive the experiments. All the students were able to control the equipment, no matter where they physically were. Students communicated using video conference software. The students and teachers opinions on this experience were very positive. This methodology is an important contribution to the formation of engineers in a world integrated by modern communication technologies.

Biophysical journal, 2015

Pulmonary surfactant (PS) is an essential complex of lipids and specific proteins synthesized in ... more Pulmonary surfactant (PS) is an essential complex of lipids and specific proteins synthesized in alveolar type II pneumocytes, where it is assembled and stored intracellularly as multilayered organelles known as lamellar bodies (LBs). Once secreted upon physiological stimulation, LBs maintain a densely packed structure in the form of lamellar body-like particles (LBPs), which are efficiently transferred into the alveolar air-water interface, lowering surface tension to avoid lung collapse at end-expiration. In this work, the structural organization of membranes in LBs and LBPs freshly secreted by primary cultures of rat ATII cells has been compared with that of native lung surfactant membranes isolated from porcine bronchoalveolar lavage. PS assembles in LBs as crystalline-like highly ordered structures, with a highly packed and dehydrated state, which is maintained at supraphysiological temperatures. This relatively ordered/packed state is retained in secreted LBPs. The micro- and ...

The Journal of Lipid Research, Nov 1, 2008

The assessment of new therapeutic strategies to cure surfactant-associated lung disorders would g... more The assessment of new therapeutic strategies to cure surfactant-associated lung disorders would greatly benefit from assay systems allowing routine evaluations of surfactant functions. We present a method to measure surfactant adsorption kinetics into interfacial air-liquid interfaces based on fluorescence microplate readers. The principle of measurement is simple, robust, and reproducible: Wells of a microtiter plate contain an aqueous solution of a light-absorbing agent. Fluorescence is excited and collected from the top of the wells so that fluorescently labeled surfactant injected into the bulk can be detected only once adsorbed into the air-liquid interface. Mass transfer from the bulk to the interface is achieved by orbital shaking implemented in the plate reader instrument. The method has been tested and validated by using phospholipids or surfactants of different origins, by using albumin as surfactant inhibitor, and by comparison of results with Wilhelmy balance measurements. The method is suited for implementation in high-throughput screening routines for conditions affecting, or improving, surfactant film formation. In contrast to surface tension measurements, our method gives a direct readout of the amount of surfactant adsorbing into the interface, including the functionally important amount of material firmly associating with the interfacial film.-Ravasio, A., A. Cruz, J. Pérez-Gil, and T. Haller. High-throughput evaluation of pulmonary surfactant adsorption and surface film formation. J. Lipid Res. 2008Res. . 49: 2479Res. -2488 Supplementary key words air-liquid interface • fluorescence • lamellar bodies • lung • microplate • surface tension

Biochemistry Usa, Jul 1, 1998

Pulmonary surfactant-associated protein B (SP-B) has been isolated from porcine lungs and reconst... more Pulmonary surfactant-associated protein B (SP-B) has been isolated from porcine lungs and reconstituted in bilayers of dipalmitoylphosphatidylcholine (DPPC) or egg yolk phosphatidylcholine (PC) to characterize the extent of insertion of the protein into phospholipid bilayers. The parameters for the interaction of SP-B with DPPC or PC using different reconstitution protocols have been estimated from the changes induced in the fluorescence emission spectrum of the single protein tryptophan. All the different reconstituted SP-B-phospholipid preparations studied had similar K d values for the binding of the protein to the lipids, on the order of a few micromolar. The depth of penetration of SP-B into phospholipid bilayers has been estimated by the parallax method, which compares the relative efficiencies of quenching of the protein fluorescence by a shallow or a deeper spin-labeled phospholipid probe. SP-B tryptophan was found to be located 10-13 Å from the center of bilayers, which is consistent with a superficial location of SP-B in phosphatidylcholine membranes. Parallax experiments, as well as resonance energy transfer from SP-B tryptophan to an acceptor probe located in the center of the bilayer, indicate that there are significant differences in the extent of insertion of the protein, depending on the method of reconstitution. SP-B reconstituted from lipid/protein mixtures in organic solvents is inserted more deeply in PC or DPPC bilayers than the protein reconstituted by addition to preformed phospholipid vesicles. These differences in the extent of insertion lead to qualitative and quantitative differences in the effect of the protein on the mobility of the phospholipid acyl chains, as studied by spin-label electron spin resonance (ESR) spectroscopy, and could represent different functional stages in the surfactant cycle.

Biophysical Journal, Jul 31, 1996

Pulmonary surfactant, a lipid-protein complex, secreted into the fluid lining of lungs prevents a... more Pulmonary surfactant, a lipid-protein complex, secreted into the fluid lining of lungs prevents alveolar collapse at low lung volumes. Pulmonary surfactant protein C (SP-C), an acylated, hydrophobic, a-helical peptide, enhances the surface activity of pulmonary surfactant lipids. Fluorescein-labeled SP-C (F-SP-C) (3, 6, 12 wt%) in dipalmitoylphosphatidylcholine (DPPC), and DPPC:dipalmitoylphosphatidylglycerol (DPPG) [DPPC:DPPG 7:3 mol/mol] in spread monolayers was studied by epifluorescence microscopy. Mass spectrometry of F-SP-C indicated that the protein is partially deacylated and labeled with 1 mol fluorescein/1 mol protein. The protein partitioned into the fluid, or liquid expanded, phase. Increasing amounts of F-SP-C in DPPC or DPPC:DPPG monolayers decreased the size and total amounts of the condensed phase at all surface pressures. Calcium (1.6 mM) increased the amount of the condensed phase in monolayers of DPPC:DPPG but not of DPPC alone, and such monolayers were also perturbed by F-SP-C. The study indicates that SP-C perturbs the packing of neutral and anionic phospholipid monolayers even when the latter systems are condensed by calcium, indicating that interactions between SP-C and the lipids are predominantly hydrophobic in nature.

American Journal of Veterinary Research, Nov 3, 2008

To characterize the microstructure of subchondral bone (SCB) plate and trabecular bone (TBB) of t... more To characterize the microstructure of subchondral bone (SCB) plate and trabecular bone (TBB) of the distopalmar aspect of the condyles of third metacarpal bones (MC3s) from Thoroughbred racehorses at 2 different stages of SCB disease via micro-computed tomography (CT). 12 pairs of MC3s from Thoroughbred racehorses euthanized for various reasons. MC3s were collected from horses with mild (n = 6) or severe (6) SCB disease, as determined via micro-CT. Cubic (6 x 6 x 6-cm) specimens of SCB plate and TBB were cut from the palmar aspect of condyles and sagittal ridges and examined with 3-dimensional micro-CT. For each specimen, apparent bone mineral density (aBMD), true BMD (tBMD), bone volume fraction (BVF), trabecular thickness (TBT), trabecular separation (TBS), and connectivity (CN) were calculated. Condyles had higher aBMD, tBMD, BVF, and TBT and lower TBS than did the sagittal ridge. In bone specimens with mild SCB changes, SCB plate had higher aBMD, TBT, and CN and lower TBS than did TBB. In bone specimens with severe SCB disease, TBB had higher aBMD and TMD and lower TBS than it did in bone specimens with mild disease, and values were similar to those for SCB plate in bone specimens with severe disease. The microstructure of SCB of the distopalmar aspect of metacarpal condyles of horses varied according to the severity of changes identified via micro-CT. With mild SCB disease, sclerosis existed in the SCB plate of the condyles; with severe disease, sclerosis also invaded condylar TBB.

Chemical Engineering Research and Design, 2015

ABSTRACT Despite being well established, a major limitation remains in ethanol fermentation proce... more ABSTRACT Despite being well established, a major limitation remains in ethanol fermentation processes: the presence of ethanol inhibits yeast activity, affecting the cell growth rate and, consequently, the ethanol production rate. For this reason, low ethanol concentrations of around 8-9% v.v−1 are reached at the end of the fermentation, hence requiring the consumption of a significant amount of energy for recovery of the fermentation product, while generating large amounts of vinasse. This situation requires the use of large fermentation tanks in order to achieve satisfactory ethanol production. Additionally, due to the large amount of heat generated by the fermentation processes, the temperature control of industrial fermentation tanks is a great challenge in tropical regions such as Brazil. The goal of the present study was to analyze the influence of operating variables on the performance of ethanol stripping at bench and pilot scales, using carbon dioxide as the carrier gas, and to propose a model describing the changes in ethanol mass and solution temperature during the stripping process. Bench scale experiments were conducted using a 5-L bubble column filled with 10% v.v−1 hydroalcoholic solution, and the pilot scale experiments were performed using a 95-L column filled with industrial fermented wine without yeast. A factorial design was applied to identify the most important operating variables for the following stripping performance parameters: entrainment factor, concentration factor, and temperature reduction factor. The results showed that both temperature and entrainment factor were positively influenced by initial solution temperature and specific CO2 flow rate, and negatively affected by height-to-diameter ratio. The temperature of the carbon dioxide did not affect either of these performance parameters. The simulation results revealed that the stripping model accurately described the decreases in ethanol mass and solution temperature during the stripping operation, with good agreement between the experimental and simulated data, and errors less than 5% in most cases.

KyaTera is an optical high speed, packet network (Gigabit Ethernet). KyaTera Network was created ... more KyaTera is an optical high speed, packet network (Gigabit Ethernet). KyaTera Network was created to gather competences and laboratorial resources that are necessary to develop science, technologies, and applications of the future Internet, in the state of So Paulo, Brazil. Its mission is to create a collaborative environment based on a Fiber-to-the-Lab network for mobilizing firms, institutes of research, universities, and funding agencies to develop technological innovations and to generate scientific knowledge. A Weblab is an experiment remotely operated via Internet. In this work, we present Weblab experiments that were performed collaboratively between undergraduate students of the Laboratory of Development and Automation of Biochemical Process (LaDABio) of the Chemical Engineering Department of the Universidade Federal de So Carlos (DEQ/UFSCar) and of the Center for Chemical Systems Engineering (CESQ) of the Chemical Engineering Department of the Escola Politcnica da Universida...

Anais do XX Congresso Brasileiro de Engenharia Química, 2015

RESUMO -Na fermentação alcoólica, o fenômeno da inibição pelo produto limita a concentração de et... more RESUMO -Na fermentação alcoólica, o fenômeno da inibição pelo produto limita a concentração de etanol no vinho ao redor de 10 ºGL, o que resulta em grande volume de vinhaça (ca. 12 L vinhaça /L etanol ) e alto consumo de vapor na etapa de destilação (ca. 2,5 kg vapor /L etanol ). Tecnologias para remover etanol do vinho vêm sendo estudadas. Exemplo é a operação de arraste de etanol por um gás, que além da remoção de etanol, provoca também a redução da temperatura do meio reacional devido à sua vaporização. Este fato é vantajoso, pois o controle da temperatura nas dornas industriais é um fator de difícil solução por envolver grandes volumes. Neste contexto, o arraste de etanol por gás pode ser utilizado tanto no controle da concentração de etanol e na redução da temperatura do meio fermentativo, como pode ser utilizado após a fermentação para a extração de etanol do vinho, sendo uma alternativa à destilação, reduzindo o consumo de vapor da planta. Neste trabalho, avaliou-se o arraste de etanol do vinho delevedurado por CO 2 (gerado no próprio processo industrial) em dorna de 95 L. Um planejamento fatorial foi utilizado para avaliar a influência das variáveis, temperatura inicial do vinho (T o ) e vazão específica de CO 2 (ΦCO2) nos parâmetros de desempenho: Fator de Arraste (F A ), Fator de Concentração (F C ) e Fator de Redução de Temperatura (F T ). Observou-se que o F A e o F T foram influenciados positivamente pelas variáveis T o e ΦCO2 enquanto o F C foi influenciado negativamente, apenas pela variável T o .

RESUMO -A operação de esgotamento (stripping) consiste na passagem de um gás insolúvel através de... more RESUMO -A operação de esgotamento (stripping) consiste na passagem de um gás insolúvel através de uma solução, da qual são retirados compostos voláteis, que vaporizam e são transferidos para a fase gasosa. Uma possível aplicação desta operação é durante a fermentação alcoólica, promovendo a retirada contínua do etanol presente no caldo e minimizando assim, a ocorrência de inibição do crescimento celular e da produção de etanol. Além disso, a retirada de compostos voláteis provoca uma diminuição da temperatura da solução, fato este que pode ser empregado para o controle da temperatura da dorna de fermentação. O objetivo deste trabalho foi a proposição de um modelo para prever a variação da massa de etanol e a temperatura do sistema durante uma operação de stripping. O modelo consiste em um sistema de Equações Diferenciais Ordinárias provenientes de balanços de massa para a água e etanol e do balanço de energia do sistema. Utilizou-se o Método de Runge-Kutta de 4 a Ordem como técnica de resolução, empregando-se um passo de integração no tempo de 0,1 h. Comparando-se os resultados obtidos da simulação com aqueles obtidos experimentalmente observou-se desvios de até 10% para a massa de etanol e de 20% para a temperatura da solução. As diferenças encontradas devem-se a ocorrência de arraste mecânico das moléculas de etanol e água, fenômeno conhecido como sublação, não previsto pelo modelo puramente termodinâmico.

RESUMO -Apesar de consagrada, a produção de etanol via fermentação alcoólica apresenta uma limita... more RESUMO -Apesar de consagrada, a produção de etanol via fermentação alcoólica apresenta uma limitação: em concentrações acima de 10°GL, a presença de etanol inibe o crescimento da levedura e consequentemente a obtenção do produto. Para superar a inibição é necessária a retirada do etanol do caldo simultaneamente à produção, de maneira a evitar que a concentração alcance valores inibitórios para o crescimento celular. Neste contexto, a operação de esgotamento (stripping) surge como uma alternativa promissora. Em vista disso, o objetivo deste trabalho foi avaliar as influências de diferentes variáveis de operação na retirada de etanol de uma solução hidroalcoólica, empregando-se dióxido de carbono como gás de arraste. Utilizou-se um planejamento fatorial completo para verificar as influências das variáveis temperatura inicial da solução hidroalcoólica (T SOL,0 ), vazão específica do gás (Φ GÁS ), temperatura do gás (T GÁS ) do gás de arraste e relação altura-diâmetro da dorna (h/D) nos seguintes parâmetros de desempenho: Fator de Arraste (F A ), Fator de Concentração (F C ) e Fator de Variação de Temperatura (F T ). Verificou-se que de um modo geral, T GÁS não exerceu influência significativa sobre nenhum dos parâmetros avaliados. Além disso, observou-se que os efeitos de T SOL,0 , Φ GÁS sobre F T e F A foram positivos e o efeito de h/D, negativo. Quanto à influência das variáveis independentes no Fator de Concentração (F C ), nenhuma delas apresentou efeito significativo de forma isolada.

European Journal of Pharmaceutics and Biopharmaceutics, 2015

To consider the lung as a target for drug delivery and to optimise strategies directed at the pul... more To consider the lung as a target for drug delivery and to optimise strategies directed at the pulmonary route, it is essential to consider the role of pulmonary surfactant, a thin lipid-protein film lining the respiratory surface of mammalian lungs. Membrane-based surfactant multilayers are essential for reducing the surface tension at the respiratory air-liquid interface to minimise the work of breathing. Different components of surfactant are also responsible for facilitating the removal of potentially pathological entities such as microorganisms, allergens or environmental pollutants and particles. Upon inhalation, drugs or nanoparticles first contact the surfactant layer, and these interactions critically affect their lifetime and fate in the airways. This review summarises the current knowledge on the possible role and effects of the pulmonary surfactant system in drug delivery strategies. It also summarises the evidence that suggests that pulmonary surfactant is far from being an insuperable barrier and could be used as an efficient shuttle for delivering hydrophobic and hydrophilic compounds deep into the lung and the organism.

Computer Aided Chemical Engineering, 2009

Saccharomyces cerevisiae biomass is still one of the most important biotechnological products in ... more Saccharomyces cerevisiae biomass is still one of the most important biotechnological products in the world, mainly in the form of baker's yeast. Costs of substrates have an important position in the overall economics of baker's yeast production, which is usually run in fed-batch bioreactors. In this context, the maximization of biomass yields, aiming at the highest achievable volumetric productivity is a driving force for improving the control of the process. Classical model-based control strategies for this process, however, face difficulties due to the inherent variability of this system: microorganisms have a complex growth dynamics, lumped in very simplified growth models; raw materials are variable and may be not traceable; the system response depends on non-controlled previous process stages, such as strain selection and inoculum preparation. Hence, the possibility of using feedback information from in situ sensors for re-tuning control parameters is an important issue to ensure sub-optimal performances, at least. A capacitance sensor is a device that can monitor cell concentration on-line. In fed-batch cultivations, the feed rate and correlated inputs can be controlled by systems coupled with softsensors that infer the state of the system from on-line measurements of primary variables. Several estimation techniques have been proposed in the literature, and among them the gas balance technique is widely used. The specific respiration rate (qO2), the specific carbon dioxide production rate (qCO2), and the respiratory quotient (RQ) are the main variables determined from the gas balance. Values of RQ for complete oxidation of some carbon sources to carbon dioxide and water are found in the literature. For the baker's yeast production process growing in glucose, a value of RQ close to unity indicates the preponderance of the aerobic route. The capacitance sensor, after calibration, may provide information about cellular growth and viability: the capacitance of the medium is linearly proportional to viable cell concentration. In this work, the signal of capacitance sensor and the RQ value are coupled to a fuzzy algorithm in order to control the glucose feed rate during baker's yeast aerobic cultivation.

Computer Aided Chemical Engineering, 2012

An integrated first and second generation ethanol production plant was simulated and optimized in... more An integrated first and second generation ethanol production plant was simulated and optimized in an equation-oriented process simulator. Two optimization methods were used: ipopt, a deterministic algorithm, and PSO, a stochastic one. The optimization of cash flow and of ethanol production was carried out for three different pretreatments. PSO was able to solve the optimization problems, while ipopt did not converge. The objective functions exhibited opposite behavior, i.e. ethanol maximization leaded to lower cash flows for the considered economic scenario.

Computer Aided Chemical Engineering, 2009

ABSTRACT The complexity of biological processes turns infeasible the development of detailed, str... more ABSTRACT The complexity of biological processes turns infeasible the development of detailed, structured phenomenological models of the cultivation of microorganisms in bioreactors. Therefore, cause-effect relations between on-line measurements and the state variables that are important for the optimal operation of industrial fermenters are sometimes hard to ascertain. In this context, data pre-treatment techniques are useful for control and fault detection. Among them, principal component analysis (PCA) has an important role. This work presents a case study of the application of this technique during real experiments, where the enzyme penicillin G acylase (PGA) was being produced by Bacillus megaterium. PGA hydrolyzes penicillin G to yield 6-aminopenicilanic acid (6-APA) and phenyl acetic acid. 6-APA is an important substrate, used to produce semi-synthetic P-lactam antibiotics. The algorithm was implemented for on-line detection of deviations from the desired process behavior. The experiments were carried out in a 2-liter bioreactor (Applikon®) operated in batch and fed-batch mode in different experimental conditions. A static PCA model was initially developed for the process, and its results are presented here. Hotteling's T2 was the discrimination criterion employed in this multivariable problem, and the method showed a high sensibility for fault detection in all real cases that were studied.

European journal of medicinal chemistry, Jan 30, 2014

The development of peptide fusion inhibitors based on short synthetic peptides represents a promi... more The development of peptide fusion inhibitors based on short synthetic peptides represents a promising option in the fight against HIV-1 infection, especially in individuals infected with multiresistant HIV-1 strains. GBV-C has the beneficial effect of retarding the progression of AIDS in people who are co-infected with both the GBV-C and HIV viruses. In previous works, the E1(22-39) GBV-C sequence (E1P8lin) was found to be capable of inhibiting the interaction of HIV-1 FP with bilayers and its cyclic analogue (E1P8cyc) showed a higher anti-HIV-1 activity. In the present work, in an attempt to gain a better understanding of the interaction of E1P8 peptides with HIV-1 FP, we analyzed direct interactions between peptides at the molecular level. Our results support that E1P8cyc might be more potent at blocking HIV-1 entry than E1P8lin as a consequence of the structure induced in the complex formed with HIV-1 FP, which is able to modify the conformation adopted by this functional domain ...

Energy & Fuels, 2014

ABSTRACT In alcoholic fermentation processes, ethanol is the main component that is toxic to yeas... more ABSTRACT In alcoholic fermentation processes, ethanol is the main component that is toxic to yeast because it acts as a noncompetitive inhibitor of metabolism. One way of overcoming the inhibition effect on yeast is to extract the ethanol from the broth during the fermentation. The present work evaluates ethanol production by extractive batch fermentation using CO2 as a stripping gas. Investigation was first made of the influence of specific CO2 flow rate (ϕ) and solution temperature on ethanol stripping. The best results, in terms of ethanol removal, were obtained at 2.0 vvm and 34.0 °C. Modeling of conventional and extractive ethanol fermentation was then performed considering cell growth, substrate consumption, ethanol production, and the entrainment of ethanol and water using first-order equations. The hybrid Andrews-Levenspiel model was able to describe the kinetics of the conventional fermentation process, and a model proposed here could accurately predict the behavior of the extractive fermentation. In all the extractive fermentations, there was faster substrate uptake and earlier substrate exhaustion, compared to the conventional fermentation. Extractive fermentation, with stripping initiated after 3 h at an ethanol concentration of 43.3 g·L-1, resulted in an ethanol productivity (in g·L-1·h-1) that was around 25% higher, and finished about 2 h earlier, compared to the control fermentation.