Isolation and characterization of sodium 2-fluoroacetate from Mascagnia rigida using chromatography and infrared spectroscopy

Sodium monofluoroacetate was first identified in Dichapetalum cymosum, a South African plant that can cause livestock poisoning and death. After, several other plants also showed to contain this toxin, which leads to the "sudden death". Mascagnia rigida, a well identified poisonous plant, commonly found in northeast of Brazil also cause sudden death in cattle, which shows clinical signs similar to those produced by the ingestion of plants that contain monofluoroacetate. Our aim was to identify the toxic compound present in the aqueous extract of M. rigida. For this purpose, the dried and milled plant was extracted; the extract was lyophilized and submitted to successive chromatographic process, until the desired purity of the active compound was achieved. The study of this material by planar chromatography and by infrared spectrometry indicated that the toxin can be a mixture of mono, di and trifluoroacetate. (C) 2012 Elsevier Ltd. All rights reserved.

Evaluation of cytotoxic, genotoxic and antigenotoxic potential of Solanum lycocarpum fruits glicoalkaloid extract in V79 cells

Solanum lycocarpum St.-Hil (Solanaceae) is a hairy shrub or small much-branched tree of the Brazilian Cerrado, popularly known as "fruit-of-wolf". Considering that the induction of chromosomal mutations is involved in the process of carcinogenesis, and that S. lycocatpum is often used in folk medicine, it becomes relevant to study its effect on genetic material. In this sense, the aim of present study was to determine the possible cytotoxic, genotoxic and antigenotoxic potentials of S. lycocarpum fruits glycoalkaloid extract (SL) in Chinese hamster lung fibroblasts (V79 cells). The cytotoxicity was evaluated by the colony forming assay, apoptosis and necrosis assay. Trypan blue exclusion dye method and mitotic index. Genotoxic and antigenotoxic potential were evaluated by comet and chromosomal aberrations assays. Four concentrations of SL (4, 8, 16 and 32 mu g/mL) were used for the evaluation of its genotoxic potential. The DNA damage-inducing agent methyl methanesulfonate (MMS, 221 mu g/mL) was utilized in combination with extract to evaluate a possible protective effect. The results showed that SL was cytotoxic at concentrations above 32 mu g/mL by the colony forming assay. For apoptosis and necrosis assay, the concentration of 64 mu g/mL of SL showed statistically significant increase in cell death by apoptosis and necrosis, while the concentrations of 128 and 256 mu g/mL of SL demonstrated statistically significant increase in cell death by necrosis, compared with the control group. Analysis of cell viability by Trypan blue exclusion indicated >96% viability for treatments with concentrations up to 32 mu g/mL of SL No significant differences in MI were observed between cultures treated with different concentrations of 51 (4, 8, 16 and 32 mu g/mL) alone or in combination with MMS and the negative control, indicating that these treatments were not cytotoxic. The comet and chromosomal aberrations assays revealed that SL does not display genotoxic activity. Moreover, the different concentrations of SL showed protective effect against both genomic and chromosomal damages induced by MMS. (C) 2012 Elsevier Ltd. All rights reserved.

Progetto e realizzazione del sistema di gestione autonoma del volo e controllo in remoto per un velivolo UAV ad ala rotante

This PhD thesis presents the results, achieved at the Aerospace Engineering Department Laboratories of the University of Bologna, concerning the development of a small scale Rotary wing UAVs (RUAVs). In the first part of the work, a mission simulation environment for rotary wing UAVs was developed, as main outcome of the University of Bologna partnership in the CAPECON program (an EU funded research program aimed at studying the UAVs civil applications and economic effectiveness of the potential configuration solutions). The results achieved in cooperation with DLR (German Aerospace Centre) and with an helicopter industrial partners will be described. In the second part of the work, the set-up of a real small scale rotary wing platform was performed. The work was carried out following a series of subsequent logical steps from hardware selection and set-up to final autonomous flight tests. This thesis will focus mainly on the RUAV avionics package set-up, on the onboard software development and final experimental tests. The setup of the electronic package allowed recording of helicopter responses to pilot commands and provided deep insight into the small scale rotorcraft dynamics, facilitating the development of helicopter models and control systems in a Hardware In the Loop (HIL) simulator. A neested PI velocity controller1 was implemented on the onboard computer and autonomous flight tests were performed. Comparison between HIL simulation and experimental results showed good agreement.

Creazione e sviluppo di un sistema di controllo in tempo reale per un sistema fuel cell

The control of a proton exchange membrane fuel cell system (PEM FC) for domestic heat and power supply requires extensive control measures to handle the complicated process. Highly dynamic and non linear behavior, increase drastically the difficulties to find the optimal design and control strategies. The objective is to design, implement and commission a controller for the entire fuel cell system. The fuel cell process and the control system are engineered simultaneously; therefore there is no access to the process hardware during the control system development. Therefore the method of choice was a model based design approach, following the rapid control prototyping (RCP) methodology. The fuel cell system is simulated using a fuel cell library which allowed thermodynamic calculations. In the course of the development the process model is continuously adapted to the real system. The controller application is designed and developed in parallel and thereby tested and verified against the process model. Furthermore, after the commissioning of the real system, the process model can be also better identified and parameterized utilizing measurement data to perform optimization procedures. The process model and the controller application are implemented in Simulink using Mathworks` Real Time Workshop (RTW) and the xPC development suite for MiL (model-in-theloop) and HiL (hardware-in-the-loop) testing. It is possible to completely develop, verify and validate the controller application without depending on the real fuel cell system, which is not available for testing during the development process. The fuel cell system can be immediately taken into operation after connecting the controller to the process.

Modellazione multibody di veicoli ferroviari: sviluppo ed implementazione di modelli innovativi per l'analisi del contatto ruota - rotaia

The wheel - rail contact analysis plays a fundamental role in the multibody modeling of railway vehicles. A good contact model must provide an accurate description of the global contact phenomena (contact forces and torques, number and position of the contact points) and of the local contact phenomena (position and shape of the contact patch, stresses and displacements). The model has also to assure high numerical efficiency (in order to be implemented directly online within multibody models) and a good compatibility with commercial multibody software (Simpack Rail, Adams Rail). The wheel - rail contact problem has been discussed by several authors and many models can be found in the literature. The contact models can be subdivided into two different categories: the global models and the local (or differential) models. Currently, as regards the global models, the main approaches to the problem are the so - called rigid contact formulation and the semi – elastic contact description. The rigid approach considers the wheel and the rail as rigid bodies. The contact is imposed by means of constraint equations and the contact points are detected during the dynamic simulation by solving the nonlinear algebraic differential equations associated to the constrained multibody system. Indentation between the bodies is not permitted and the normal contact forces are calculated through the Lagrange multipliers. Finally the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces respectively. Also the semi - elastic approach considers the wheel and the rail as rigid bodies. However in this case no kinematic constraints are imposed and the indentation between the bodies is permitted. The contact points are detected by means of approximated procedures (based on look - up tables and simplifying hypotheses on the problem geometry). The normal contact forces are calculated as a function of the indentation while, as in the rigid approach, the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces. Both the described multibody approaches are computationally very efficient but their generality and accuracy turn out to be often insufficient because the physical hypotheses behind these theories are too restrictive and, in many circumstances, unverified. In order to obtain a complete description of the contact phenomena, local (or differential) contact models are needed. In other words wheel and rail have to be considered elastic bodies governed by the Navier’s equations and the contact has to be described by suitable analytical contact conditions. The contact between elastic bodies has been widely studied in literature both in the general case and in the rolling case. Many procedures based on variational inequalities, FEM techniques and convex optimization have been developed. This kind of approach assures high generality and accuracy but still needs very large computational costs and memory consumption. Due to the high computational load and memory consumption, referring to the current state of the art, the integration between multibody and differential modeling is almost absent in literature especially in the railway field. However this integration is very important because only the differential modeling allows an accurate analysis of the contact problem (in terms of contact forces and torques, position and shape of the contact patch, stresses and displacements) while the multibody modeling is the standard in the study of the railway dynamics. In this thesis some innovative wheel – rail contact models developed during the Ph. D. activity will be described. Concerning the global models, two new models belonging to the semi – elastic approach will be presented; the models satisfy the following specifics: 1) the models have to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the models have to consider generic railway tracks and generic wheel and rail profiles 3) the models have to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the models have to evaluate the number and the position of the contact points and, for each point, the contact forces and torques 4) the models have to be implementable directly online within the multibody models without look - up tables 5) the models have to assure computation times comparable with those of commercial multibody software (Simpack Rail, Adams Rail) and compatible with RT and HIL applications 6) the models have to be compatible with commercial multibody software (Simpack Rail, Adams Rail). The most innovative aspect of the new global contact models regards the detection of the contact points. In particular both the models aim to reduce the algebraic problem dimension by means of suitable analytical techniques. This kind of reduction allows to obtain an high numerical efficiency that makes possible the online implementation of the new procedure and the achievement of performance comparable with those of commercial multibody software. At the same time the analytical approach assures high accuracy and generality. Concerning the local (or differential) contact models, one new model satisfying the following specifics will be presented: 1) the model has to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the model has to consider generic railway tracks and generic wheel and rail profiles 3) the model has to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the model has to able to calculate both the global contact variables (contact forces and torques) and the local contact variables (position and shape of the contact patch, stresses and displacements) 4) the model has to be implementable directly online within the multibody models 5) the model has to assure high numerical efficiency and a reduced memory consumption in order to achieve a good integration between multibody and differential modeling (the base for the local contact models) 6) the model has to be compatible with commercial multibody software (Simpack Rail, Adams Rail). In this case the most innovative aspects of the new local contact model regard the contact modeling (by means of suitable analytical conditions) and the implementation of the numerical algorithms needed to solve the discrete problem arising from the discretization of the original continuum problem. Moreover, during the development of the local model, the achievement of a good compromise between accuracy and efficiency turned out to be very important to obtain a good integration between multibody and differential modeling. At this point the contact models has been inserted within a 3D multibody model of a railway vehicle to obtain a complete model of the wagon. The railway vehicle chosen as benchmark is the Manchester Wagon the physical and geometrical characteristics of which are easily available in the literature. The model of the whole railway vehicle (multibody model and contact model) has been implemented in the Matlab/Simulink environment. The multibody model has been implemented in SimMechanics, a Matlab toolbox specifically designed for multibody dynamics, while, as regards the contact models, the CS – functions have been used; this particular Matlab architecture allows to efficiently connect the Matlab/Simulink and the C/C++ environment. The 3D multibody model of the same vehicle (this time equipped with a standard contact model based on the semi - elastic approach) has been then implemented also in Simpack Rail, a commercial multibody software for railway vehicles widely tested and validated. Finally numerical simulations of the vehicle dynamics have been carried out on many different railway tracks with the aim of evaluating the performances of the whole model. The comparison between the results obtained by the Matlab/ Simulink model and those obtained by the Simpack Rail model has allowed an accurate and reliable validation of the new contact models. In conclusion to this brief introduction to my Ph. D. thesis, we would like to thank Trenitalia and the Regione Toscana for the support provided during all the Ph. D. activity. Moreover we would also like to thank the INTEC GmbH, the society the develops the software Simpack Rail, with which we are currently working together to develop innovative toolboxes specifically designed for the wheel rail contact analysis.

Sviluppo di modelli motore e veicolo per l'analisi di strategie di controllo in applicazioni Software e Hardware In the Loop

This work describes the development of a simulation tool which allows the simulation of the Internal Combustion Engine (ICE), the transmission and the vehicle dynamics. It is a control oriented simulation tool, designed in order to perform both off-line (Software In the Loop) and on-line (Hardware In the Loop) simulation. In the first case the simulation tool can be used in order to optimize Engine Control Unit strategies (as far as regard, for example, the fuel consumption or the performance of the engine), while in the second case it can be used in order to test the control system. In recent years the use of HIL simulations has proved to be very useful in developing and testing of control systems. Hardware In the Loop simulation is a technology where the actual vehicles, engines or other components are replaced by a real time simulation, based on a mathematical model and running in a real time processor. The processor reads ECU (Engine Control Unit) output signals which would normally feed the actuators and, by using mathematical models, provides the signals which would be produced by the actual sensors. The simulation tool, fully designed within Simulink, includes the possibility to simulate the only engine, the transmission and vehicle dynamics and the engine along with the vehicle and transmission dynamics, allowing in this case to evaluate the performance and the operating conditions of the Internal Combustion Engine, once it is installed on a given vehicle. Furthermore the simulation tool includes different level of complexity, since it is possible to use, for example, either a zero-dimensional or a one-dimensional model of the intake system (in this case only for off-line application, because of the higher computational effort). Given these preliminary remarks, an important goal of this work is the development of a simulation environment that can be easily adapted to different engine types (single- or multi-cylinder, four-stroke or two-stroke, diesel or gasoline) and transmission architecture without reprogramming. Also, the same simulation tool can be rapidly configured both for off-line and real-time application. The Matlab-Simulink environment has been adopted to achieve such objectives, since its graphical programming interface allows building flexible and reconfigurable models, and real-time simulation is possible with standard, off-the-shelf software and hardware platforms (such as dSPACE systems).

Development of control-oriented models of Dual Clutch Transmission systems

A control-oriented model of a Dual Clutch Transmission was developed for real-time Hardware In the Loop (HIL) applications, to support model-based development of the DCT controller. The model is an innovative attempt to reproduce the fast dynamics of the actuation system while maintaining a step size large enough for real-time applications. The model comprehends a detailed physical description of hydraulic circuit, clutches, synchronizers and gears, and simplified vehicle and internal combustion engine sub-models. As the oil circulating in the system has a large bulk modulus, the pressure dynamics are very fast, possibly causing instability in a real-time simulation; the same challenge involves the servo valves dynamics, due to the very small masses of the moving elements. Therefore, the hydraulic circuit model has been modified and simplified without losing physical validity, in order to adapt it to the real-time simulation requirements. The results of offline simulations have been compared to on-board measurements to verify the validity of the developed model, that was then implemented in a HIL system and connected to the TCU (Transmission Control Unit). Several tests have been performed: electrical failure tests on sensors and actuators, hydraulic and mechanical failure tests on hydraulic valves, clutches and synchronizers, and application tests comprehending all the main features of the control performed by the TCU. Being based on physical laws, in every condition the model simulates a plausible reaction of the system. The first intensive use of the HIL application led to the validation of the new safety strategies implemented inside the TCU software. A test automation procedure has been developed to permit the execution of a pattern of tests without the interaction of the user; fully repeatable tests can be performed for non-regression verification, allowing the testing of new software releases in fully automatic mode.

Modello 0-dimensionale di motore a combustione interna e veicolo per applicazioni real-time

La presenta tesi ha come obiettivo la modellazione, tramite il software Matlab Simulink, di un motore a combustione interna ad accensione comandata nelle sue parti fondamentali ed il relativo veicolo. Le parti modellate inerenti al gruppo termico sono quelle di produzione coppia, il sistema di aspirazione con un modello statico e uno dinamico ed, infine, il sistema di scarico. Per quanto riguarda la parte veicolo si implementa la dinamica della driveline e quella longitudinale del mezzo stesso. Il simulatore deve essere costituito da un layout modulare e ha come ipotesi fondamentale quella di poter lavorare in real-time, quindi si utilizza un modello zero-dimensionale e con valori costanti all'interno di un singolo ciclo motore. In conclusione, viene mostrato come implementare il modello in un sistema SIL per poterne testare il funzionamento in tempo reale e visualizzare i risultati da esso prodotti.

Evoluzione di un sistema di automazione della guida di motoveicoli per test su banco a rulli

Evoluzione di un sistema Hardware in the Loop per l'automazione della guida di motoveicoli su banco a rulli. Questo sistema HIL, simulando un certo tipo di condizioni, permette di svolgere test su strategia centralina, implementate per il controllo motore.

Modellazione zero-dimensionale del motopropulsore per applicazioni real-time

Descrizione del lavoro svolto nella modellazione zero-dimensionale e ai valori medi di un motopropulsore. Lo scopo finale del modello è un funzionamento HIL.

Prolonged amelioration of acute lung allograft rejection by sequential overexpression of human interleukin-10 and hepatocyte growth factor in rats

The effect of prolonged electroporation-mediated human interleukin-10 (hIL-10) overexpression 24 hours before transplantation, combined with sequential human hepatocyte growth factor (HGF) overexpression into skeletal muscle on day 5, on rat lung allograft rejection was evaluated. Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Gene transfer into skeletal muscle was enhanced by electroporation. Three groups were studied: group I animals (n = 5) received 2.5 μg pCIK-hIL-10 (hIL-10/CMV [cytomegalovirus] early promoter enhancer) on day -1 and 80 μg pCIK-HGF (HGF/CMV early promoter enhancer) on day 5. Group II animals (n = 4) received 2.5 μg pCIK-hIL-10 and pUbC-hIL-10 (hIL-10/pUbC promoter) on day -1. Control group III animals (n = 4) were treated by sham electroporation on days -1 and 5. All animals received daily nontherapeutic intraperitoneal dose of cyclosporin A (2.5 mg/kg) and were sacrificed on day 15. Graft oxygenation and allograft rejection were evaluated. Significant differences were found between study groups in graft oxygenation (Pao(2)) (P = .0028; group I vs. groups II and III, P < .01 each). Pao(2) was low in group II (31 ± 1 mm Hg) and in group III controls (34 ± 10 mm Hg), without statistically significant difference between these 2 groups (P = .54). In contrast, in group I, Pao(2) of recipients sequentially transduced with IL-10 and HGF plasmids was much improved, with 112 ± 39 mm Hg (vs. groups II and III; P < .01 each), paralleled by reduced vascular and bronchial rejection (group I vs. groups II and III, P < .021 each). Sequential overexpression of anti-inflammatory cytokine IL-10, followed by sequential and overlapping HGF overexpression on day 5, preserves lung function and reduces acute lung allograft rejection up to day 15 post transplant as compared to prolonged IL-10 overexpression alone.

Prolonged amelioration of acute lung allograft rejection by overexpression of human interleukin-10 under control of a long acting ubiquitin C promoter in rats

BACKGROUND: The prolonged effect of electroporation-mediated human interleukin-10 (hIL-10) overexpression in skeletal muscle under the control of the constitutional polyubiquitin C promoter (pUb hIL-10) on rat lung allograft rejection was evaluated. METHODS: Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Either 2.5 mug pCIK hIL-10 (hIL-10/cytomegalovirus early promoter enhancer) alone (Group I/sacrifice Day 5 and II/sacrifice Day 10) or in combination with 2.5 mug pUb hIL-10 (hIL-10/UbC promoter; Group III/sacrifice Day 10) were injected into the tibialis anterior muscle of the recipient, followed by electroporation 24 hours before transplantation. Animals in Control Groups IV and V without gene transfer were euthanized on Day 5 and 10, respectively. All animals received a daily non-therapeutic dose of cyclosporine A (2.5 mg/kg). RESULTS: In Control Group IV, complete rejection (median A3B3) was noted on Day 5 with a Pao(2) of 43 +/- 9 mm Hg. In recipients of Control Group V, measurement of gas exchange on Day 10 and rejection grading was impossible because of complete destruction of the allograft. Group I animals on Day 5 (233 +/- 123 mm Hg; p = 0.02 vs Group IV) and Group II animals on Day 10 (150 +/- 139 mm Hg; p = 0.15 vs Group IV) demonstrated improved graft function. Graft function in Group III was further improved on Day 10 (299 +/- 123 mm Hg; p = 0.002 vs Group IV; p = 0.05 vs Group II; p = 0.36 vs Group I). Rejection was significantly reduced in Group III (median, A2B2) compared with Group II (median, A4B3; p < 0.05). CONCLUSIONS: Interleukin-10 overexpression under control of the constitutive ubiquitin C promoter ameliorates acute rejection and preserves lung graft function for a prolonged time.

Electroporation-mediated interleukin-10 overexpression in skeletal muscle reduces acute rejection in rat cardiac allografts

OBJECTIVES: Human interleukin 10 (hIL-10) may reduce acute rejection after organ transplantation. Our previous data shows that electroporation-mediated transfer of plasmid DNA to peripheral muscle enhances gene transduction dramatically. This study was designed to investigate the effect of electroporation-mediated overexpression of hIL-10 on acute rejection of cardiac allografts in the rat. METHODS: The study was designed to evaluate the effect of hIL-10 gene transfer on (a) early rejection pattern and (b) graft survival. Gene transfer was achieved by intramuscular (i.m.) injection into the tibialis anterior muscle of Fischer (F344) male recipients followed by electroporation 24 h prior to transplantation. Heterotopic cardiac transplantation was performed from male Brown Norway rat to F344. Four groups were studied (n = 6). Treated animals in groups B1 and B2 received 2.5 microg of pCIK hIL-10 and control animals in groups A1 and A2 distilled water. Graft function was assessed by daily palpation. Animals from group A1 were sacrificed at the cessation of the heart beat of the graft and those in group B1 were sacrificed at day 7; blood was taken for ELISA measurement of hIL-10 and tissue for myeloperoxidase (MPO) measurement and histological assessment. To evaluate graft survival, groups A2 and B2 were sacrificed at cessation of the heart beat of the graft. RESULTS: Histological examination revealed severe rejection (IIIB-IV) in group A1 in contrast to low to moderate rejection (IA-IIIA) in group B1 (p = 0.02). MPO activity was significantly lower in group B1 compared to group A1 (18 +/- 7 vs. 32 +/- 14 mU/mg protein, p = 0.05). Serum hIL-10 levels were 46 +/- 13 pg/ml in group B1 vs. 0 pg/ml in group A1. At day 7 all heart allografts in the treated groups B1 and B2 were beating, whereas they stopped beating at 5 +/- 2 days in groups A1 and A2 vs. 14 +/- 2 days in group B2 (p = 0.0012). CONCLUSIONS: Electroporation-mediated intramuscular overexpression of hIL-10 reduces acute rejection and improves survival of heterotopic heart allografts in rats. This study demonstrates that peripheral overexpression of specific genes in skeletal muscle may reduce acute rejection after whole organ transplantation.

Development of Hardware-In-the-Loop Simulation System for Hybrid Electric Vehicle Study

The development of embedded control systems for a Hybrid Electric Vehicle (HEV) is a challenging task due to the multidisciplinary nature of HEV powertrain and its complex structures. Hardware-In-the-Loop (HIL) simulation provides an open and convenient environment for the modeling, prototyping, testing and analyzing HEV control systems. This thesis focuses on the development of such a HIL system for the hybrid electric vehicle study. The hardware architecture of the HIL system, including dSPACE eDrive HIL simulator, MicroAutoBox II and MotoTron Engine Control Module (ECM), is introduced. Software used in the system includes dSPACE Real-Time Interface (RTI) blockset, Automotive Simulation Models (ASM), Matlab/Simulink/Stateflow, Real-time Workshop, ControlDesk Next Generation, ModelDesk and MotoHawk/MotoTune. A case study of the development of control systems for a single shaft parallel hybrid electric vehicle is presented to summarize the functionality of this HIL system.

Trans-Himalayan

This Trans-Himalayan tale unites two narratives, an historical account of scholarly thinking regarding linguistic phylogeny in eastern Eurasia alongside a reconstruction of the ethnolinguistic prehistory of eastern Eurasia based on linguistic and human population genetic phylogeography. The first story traces the tale of transformation in thought regarding language relationships in eastern Eurasia from Tibeto-Burman to Trans-Himalayan. The path is strewn with defunct family trees such as Indo-Chinese, Sino-Tibetan, Sino-Himalayan and Sino-Kiranti. In the heyday of racism in scholarship, Social Darwinism coloured both language typology and the phylogenetic models of language relationship in eastern Eurasia. Its influential role in the perpetuation of the Indo-Chinese model is generally left untold. The second narrative presents a conjectural reconstruction of the ethnolinguistic prehistory of eastern Eurasia based on possible correlations between genes and language communities. In so doing, biological ancestry and linguistic affinity are meticulously distinguished, a distinction which the language typologists of yore sought to blur, although the independence of language and race was stressed time and again by prominent historical linguists.