Permian non-marine bivalves of the Falkland Islands and their palaeoenvironmental significance

We describe the occurrence of non-marine bivalves in exposures of the Middle Permian (Capitanian) Brenton Loch Formation on the southern shore of Choiseul Sound, East Falklands. The bivalves are associated with ichnofossils and were collected from a bed in the upper part of the formation, within a 25 cm thick interval of dark siltstones and mudstones with planar lamination, overlain by massive sandstones. The shells are articulated, with the valves either splayed open or closed. At the top of the succession, mudstone beds nearly 1.5 m above the bivalve-bearing layers yielded well-preserved Glossopteris sp. cf. G. communis leaf fossils. The closed articulated condition of some shells indicates preservation under high sedimentation rates with low residence time of bioclasts at the sediment/water interface. However, the presence of specimens with splayed shells is usually correlated to the slow decay of the shell ligament in oxygen-deficient bottom waters. The presence of complete carbonized leaves of Glossopteris associated with the bivalve-bearing levels also suggests a possibly dysoxic-anoxic bottom environment. Overall, our data suggest that the bivalves were preserved by abrupt burial, possibly by distal sediment flows into a Brenton Loch lake, and may represent autochthonous to parautochthonous fossil accumulations. The shells resemble those of anthracosiids and are herein assigned to Palaeanodonta sp. aff. P. dubia, a species also found in the Permian succession of the Karoo Basin, South Africa. Our results confirm that (a) the true distributions in space and time of all Permian non-marine (freshwater) bivalves are not yet well known, and (b) there is no evidence for marine conditions in the upper part of the Brenton Loch Formation.

Comparison of zooplankton community structure between impacted and non-impacted areas of Paranagua Bay Estuarine Complex, south Brazil

We analysed the seasonal distribution of the zooplankton community in an anthropogenically impacted area (Paranagua Bay) and a non-impacted area (Laranjeiras Bay) of the Paranagua Bay Estuarine Complex. Large phytoplankton (>50 mu m) and zooplankton were collected every two months, between August 2003 and June 2004. The phytoplankton community was numerically dominated by diatoms (78%) and dinoflagellates (19%). Zooplankton abundance varied between 670 and 100,716 individuals m(-3), with a dominance of copepods, mainly the calanoids Acartia lilljeborgii, Acartia tonsa and Pseudodiaptomus acutus. A clear seasonal pattern was observed: copepods were significantly more abundant during the rainy than in the dry season. Significant differences in abundance between the two bays were detected only for cirripede larvae, which were more abundant in Paranagua Bay. This lack of difference between the two areas was probably a consequence of the water circulation along the estuary, which may have diluted and dispersed the pollutants from Paranagua Bay to other areas of the estuary.

Strong Coupling Isotropization of Non-Abelian Plasmas Simplified

We study the isotropization of a homogeneous, strongly coupled, non-Abelian plasma by means of its gravity dual. We compare the time evolution of a large number of initially anisotropic states as determined, on the one hand, by the full nonlinear Einstein's equations and, on the other, by the Einstein's equations linearized around the final equilibrium state. The linear approximation works remarkably well even for states that exhibit large anisotropies. For example, it predicts with a 20% accuracy the isotropization time, which is of the order of t(iso) less than or similar to 1/T, with T the final equilibrium temperature. We comment on possible extensions to less symmetric situations.

Clinical characteristics and possible phenotypes of an adult severe asthma population

Background: Currently, there are no studies of well-characterized severe asthmatics in Brazil. We aimed to study a population of severe treated asthmatics still uncontrolled to characterize them and define possible phenotypes. Methods: Descriptive cross-sectional outpatient study of severe asthmatics, evaluating functional and inflammatory markers, health-related quality of life, anxiety and depression symptoms, clinical control status, and characteristics related to atopy, age of asthma onset, induced sputum eosinophil levels, and airflow limitation. We also grouped the subgroups characteristics to identify phenotypes. The study is registered on ClinicalTrial.gov NCT 01089322. Results: From 128 eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion criteria. The cohort was comprised of 85% women, frequently with a body mass index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had significant higher asthma onset (19 y.a.) and twice level of induced sputum eosinophil. Late-onset patients had significantly less atopy (57%) and higher levels of induced sputum eosinophils. Non-eosinophilics had lower levels of inflammatory markers. Patients with airflow limitation had more intensive care unit admissions (56%) and 1.5 times more airway resistance. Subgroups characteristics identified a priori four well-characterized phenotypes, with 55% presenting sputum eosinophilia. Conclusion: Our data emphasize the high burden of disease, the persistence of inflammation and the existence of clinical possible phenotypes population sharing common features with published cohorts. Despite the necessity of further investigation into pathogenic mechanisms, this study with clinically difficult patient group may help to improve future asthma care. (C) 2011 Elsevier Ltd. All rights reserved.

Forum: social network for the surveillance and prevention of workplace accidents

In 2008, academic researchers and public service officials created a university extension studies platform based on online and on-site meetings denominated "Work-Related Accidents Forum: Analysis, Prevention, and Other Relevant Aspects. Its aim was to help public agents and social partners to propagate a systemic approach that would be helpful in the surveillance and prevention of work-related accidents. This article describes and analyses such a platform. Online access is free and structured to: support dissemination of updated concepts; support on-site meetings and capacity to build educational activities; and keep a permanent space for debate among the registered participants. The desired result is the propagation of a social-technical-systemic view of work-related accidents that replaces the current traditional view that emphasizes human error and results in blaming the victims. The Forum uses an educational approach known as permanent health education, which is based on the experience and needs of workers and encourages debate among participants. The forum adopts a problematizing pedagogy that starts from the requirements and experiences of the social actors and stimulates support and discussions among them in line with an ongoing health educational approach. The current challenge is to turn the platform into a social networking website in order to broaden its links with society.

Computational framework to support integration of biomolecular and clinical data within a translational approach

Background The use of the knowledge produced by sciences to promote human health is the main goal of translational medicine. To make it feasible we need computational methods to handle the large amount of information that arises from bench to bedside and to deal with its heterogeneity. A computational challenge that must be faced is to promote the integration of clinical, socio-demographic and biological data. In this effort, ontologies play an essential role as a powerful artifact for knowledge representation. Chado is a modular ontology-oriented database model that gained popularity due to its robustness and flexibility as a generic platform to store biological data; however it lacks supporting representation of clinical and socio-demographic information. Results We have implemented an extension of Chado – the Clinical Module - to allow the representation of this kind of information. Our approach consists of a framework for data integration through the use of a common reference ontology. The design of this framework has four levels: data level, to store the data; semantic level, to integrate and standardize the data by the use of ontologies; application level, to manage clinical databases, ontologies and data integration process; and web interface level, to allow interaction between the user and the system. The clinical module was built based on the Entity-Attribute-Value (EAV) model. We also proposed a methodology to migrate data from legacy clinical databases to the integrative framework. A Chado instance was initialized using a relational database management system. The Clinical Module was implemented and the framework was loaded using data from a factual clinical research database. Clinical and demographic data as well as biomaterial data were obtained from patients with tumors of head and neck. We implemented the IPTrans tool that is a complete environment for data migration, which comprises: the construction of a model to describe the legacy clinical data, based on an ontology; the Extraction, Transformation and Load (ETL) process to extract the data from the source clinical database and load it in the Clinical Module of Chado; the development of a web tool and a Bridge Layer to adapt the web tool to Chado, as well as other applications. Conclusions Open-source computational solutions currently available for translational science does not have a model to represent biomolecular information and also are not integrated with the existing bioinformatics tools. On the other hand, existing genomic data models do not represent clinical patient data. A framework was developed to support translational research by integrating biomolecular information coming from different “omics” technologies with patient’s clinical and socio-demographic data. This framework should present some features: flexibility, compression and robustness. The experiments accomplished from a use case demonstrated that the proposed system meets requirements of flexibility and robustness, leading to the desired integration. The Clinical Module can be accessed in http://dcm.ffclrp.usp.br/caib/pg=iptrans webcite.

Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus

Background Oxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the CYBA gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O2•- (-675 T → A in CYBA, unregistered) and in glutathione metabolism (-129 C → T in GCLC [rs17883901] and -65 T → C in GPX3 [rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients. Methods 401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m2 (n = 136) and were genotyped. Results No differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying CYBA genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying GCLC genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (p = 0.0082). Logistic regression analysis identified the presence of at least one A allele of the CYBA SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, p = 0.0354) and the presence of at least one T allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, p = 0.0068). Conclusions The functional SNPs CYBA -675 T → A and GCLC rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.

Assessment of functional capacity of the elderly associated with the risk for pressure ulcer

OBJECTIVE: To characterize the elderly with physical limitations; to assess functional capacity as it relates to physical mobility, cognitive status and level of functional independence in activities of daily living, and to relate functional capacity to the risk for pressure ulcers. METHODS: A quantitative cross-sectional approach, conducted in households in the city of João Pessoa (PB) with seniors who presented physical limitation. Fifty-one elderly were investigated in a two-stage cluster sampling design. RESULTS: There was evidence of impairments in functional capacity of the elderly aged 80 years or more, with more severe physical limitations, cognitive impairment and a higher level of dependency for activities. Significant differences were observed between the level of functional independence in performing activities of daily living and the risk of pressure ulcers. CONCLUSION: This study allowed for the identification of the elderly in functional decline and at risk for developing pressure ulcers, supporting the implementation of preventive actions at the household level.

Identification of Drosophila heart-specific Cis-Regulatory Modules under Hox control

Cardiac morphogenesis is a complex process governed by evolutionarily conserved transcription factors and signaling molecules. The Drosophila cardiac tube is linear, made of 52 pairs of cardiomyocytes (CMs), which express specific transcription factor genes that have human homologues implicated in Congenital Heart Diseases (CHDs) (NKX2-5, GATA4 and TBX5). The Drosophila cardiac tube is linear and composed of a rostral portion named aorta and a caudal one called heart, distinguished by morphological and functional differences controlled by Hox genes, key regulators of axial patterning. Overexpression and inactivation of the Hox gene abdominal-A (abd-A), which is expressed exclusively in the heart, revealed that abd-A controls heart identity. The aim of our work is to isolate the heart-specific cisregulatory sequences of abd-A direct target genes, the realizator genes granting heart identity. In each segment of the heart, four pairs of cardiomyocytes (CMs) express tinman (tin), homologous to NKX2-5, and acquire strong contractile and automatic rhythmic activities. By tyramide amplified FISH, we found that seven genes, encoding ion channels, pumps or transporters, are specifically expressed in the Tin-CMs of the heart. We initially used online available tools to identify their heart-specific cisregutatory modules by looking for Conserved Non-coding Sequences containing clusters of binding sites for various cardiac transcription factors, including Hox proteins. Based on these data we generated several reporter gene constructs and transgenic embryos, but none of them showed reporter gene expression in the heart. In order to identify additional abd-A target genes, we performed microarray experiments comparing the transcriptomes of aorta versus heart and identified 144 genes overexpressed in the heart. In order to find the heart-specific cis-regulatory regions of these target genes we developed a new bioinformatic approach where prediction is based on pattern matching and ordered statistics. We first retrieved Conserved Noncoding Sequences from the alignment between the D.melanogaster and D.pseudobscura genomes. We scored for combinations of conserved occurrences of ABD-A, ABD-B, TIN, PNR, dMEF2, MADS box, T-box and E-box sites and we ranked these results based on two independent strategies. On one hand we ranked the putative cis-regulatory sequences according to best scored ABD-A biding sites, on the other hand we scored according to conservation of binding sites. We integrated and ranked again the two lists obtained independently to produce a final rank. We generated nGFP reporter construct flies for in vivo validation. We identified three 1kblong heart-specific enhancers. By in vivo and in vitro experiments we are determining whether they are direct abd-A targets, demonstrating the role of a Hox gene in the realization of heart identity. The identified abd-A direct target genes may be targets also of the NKX2-5, GATA4 and/or TBX5 homologues tin, pannier and Doc genes, respectively. The identification of sequences coregulated by a Hox protein and the homologues of transcription factors causing CHDs, will provide a mean to test whether these factors function as Hox cofactors granting cardiac specificity to Hox proteins, increasing our knowledge on the molecular mechanisms underlying CHDs. Finally, it may be investigated whether these Hox targets are involved in CHDs.

Mathematical models of cognitive processes

The research activity carried out during the PhD course was focused on the development of mathematical models of some cognitive processes and their validation by means of data present in literature, with a double aim: i) to achieve a better interpretation and explanation of the great amount of data obtained on these processes from different methodologies (electrophysiological recordings on animals, neuropsychological, psychophysical and neuroimaging studies in humans), ii) to exploit model predictions and results to guide future research and experiments. In particular, the research activity has been focused on two different projects: 1) the first one concerns the development of neural oscillators networks, in order to investigate the mechanisms of synchronization of the neural oscillatory activity during cognitive processes, such as object recognition, memory, language, attention; 2) the second one concerns the mathematical modelling of multisensory integration processes (e.g. visual-acoustic), which occur in several cortical and subcortical regions (in particular in a subcortical structure named Superior Colliculus (SC)), and which are fundamental for orienting motor and attentive responses to external world stimuli. This activity has been realized in collaboration with the Center for Studies and Researches in Cognitive Neuroscience of the University of Bologna (in Cesena) and the Department of Neurobiology and Anatomy of the Wake Forest University School of Medicine (NC, USA). PART 1. Objects representation in a number of cognitive functions, like perception and recognition, foresees distribute processes in different cortical areas. One of the main neurophysiological question concerns how the correlation between these disparate areas is realized, in order to succeed in grouping together the characteristics of the same object (binding problem) and in maintaining segregated the properties belonging to different objects simultaneously present (segmentation problem). Different theories have been proposed to address these questions (Barlow, 1972). One of the most influential theory is the so called “assembly coding”, postulated by Singer (2003), according to which 1) an object is well described by a few fundamental properties, processing in different and distributed cortical areas; 2) the recognition of the object would be realized by means of the simultaneously activation of the cortical areas representing its different features; 3) groups of properties belonging to different objects would be kept separated in the time domain. In Chapter 1.1 and in Chapter 1.2 we present two neural network models for object recognition, based on the “assembly coding” hypothesis. These models are networks of Wilson-Cowan oscillators which exploit: i) two high-level “Gestalt Rules” (the similarity and previous knowledge rules), to realize the functional link between elements of different cortical areas representing properties of the same object (binding problem); 2) the synchronization of the neural oscillatory activity in the γ-band (30-100Hz), to segregate in time the representations of different objects simultaneously present (segmentation problem). These models are able to recognize and reconstruct multiple simultaneous external objects, even in difficult case (some wrong or lacking features, shared features, superimposed noise). In Chapter 1.3 the previous models are extended to realize a semantic memory, in which sensory-motor representations of objects are linked with words. To this aim, the network, previously developed, devoted to the representation of objects as a collection of sensory-motor features, is reciprocally linked with a second network devoted to the representation of words (lexical network) Synapses linking the two networks are trained via a time-dependent Hebbian rule, during a training period in which individual objects are presented together with the corresponding words. Simulation results demonstrate that, during the retrieval phase, the network can deal with the simultaneous presence of objects (from sensory-motor inputs) and words (from linguistic inputs), can correctly associate objects with words and segment objects even in the presence of incomplete information. Moreover, the network can realize some semantic links among words representing objects with some shared features. These results support the idea that semantic memory can be described as an integrated process, whose content is retrieved by the co-activation of different multimodal regions. In perspective, extended versions of this model may be used to test conceptual theories, and to provide a quantitative assessment of existing data (for instance concerning patients with neural deficits). PART 2. The ability of the brain to integrate information from different sensory channels is fundamental to perception of the external world (Stein et al, 1993). It is well documented that a number of extraprimary areas have neurons capable of such a task; one of the best known of these is the superior colliculus (SC). This midbrain structure receives auditory, visual and somatosensory inputs from different subcortical and cortical areas, and is involved in the control of orientation to external events (Wallace et al, 1993). SC neurons respond to each of these sensory inputs separately, but is also capable of integrating them (Stein et al, 1993) so that the response to the combined multisensory stimuli is greater than that to the individual component stimuli (enhancement). This enhancement is proportionately greater if the modality-specific paired stimuli are weaker (the principle of inverse effectiveness). Several studies have shown that the capability of SC neurons to engage in multisensory integration requires inputs from cortex; primarily the anterior ectosylvian sulcus (AES), but also the rostral lateral suprasylvian sulcus (rLS). If these cortical inputs are deactivated the response of SC neurons to cross-modal stimulation is no different from that evoked by the most effective of its individual component stimuli (Jiang et al 2001). This phenomenon can be better understood through mathematical models. The use of mathematical models and neural networks can place the mass of data that has been accumulated about this phenomenon and its underlying circuitry into a coherent theoretical structure. In Chapter 2.1 a simple neural network model of this structure is presented; this model is able to reproduce a large number of SC behaviours like multisensory enhancement, multisensory and unisensory depression, inverse effectiveness. In Chapter 2.2 this model was improved by incorporating more neurophysiological knowledge about the neural circuitry underlying SC multisensory integration, in order to suggest possible physiological mechanisms through which it is effected. This endeavour was realized in collaboration with Professor B.E. Stein and Doctor B. Rowland during the 6 months-period spent at the Department of Neurobiology and Anatomy of the Wake Forest University School of Medicine (NC, USA), within the Marco Polo Project. The model includes four distinct unisensory areas that are devoted to a topological representation of external stimuli. Two of them represent subregions of the AES (i.e., FAES, an auditory area, and AEV, a visual area) and send descending inputs to the ipsilateral SC; the other two represent subcortical areas (one auditory and one visual) projecting ascending inputs to the same SC. Different competitive mechanisms, realized by means of population of interneurons, are used in the model to reproduce the different behaviour of SC neurons in conditions of cortical activation and deactivation. The model, with a single set of parameters, is able to mimic the behaviour of SC multisensory neurons in response to very different stimulus conditions (multisensory enhancement, inverse effectiveness, within- and cross-modal suppression of spatially disparate stimuli), with cortex functional and cortex deactivated, and with a particular type of membrane receptors (NMDA receptors) active or inhibited. All these results agree with the data reported in Jiang et al. (2001) and in Binns and Salt (1996). The model suggests that non-linearities in neural responses and synaptic (excitatory and inhibitory) connections can explain the fundamental aspects of multisensory integration, and provides a biologically plausible hypothesis about the underlying circuitry.

Numerical investigation of turbulent/non-turbulent interface

The subject of this work is the diffusion of turbulence in a non-turbulent flow. Such phenomenon can be found in almost every practical case of turbulent flow: all types of shear flows (wakes, jet, boundary layers) present some boundary between turbulence and the non-turbulent surround; all transients from a laminar flow to turbulence must account for turbulent diffusion; mixing of flows often involve the injection of a turbulent solution in a non-turbulent fluid. The mechanism of what Phillips defined as “the erosion by turbulence of the underlying non-turbulent flow”, is called entrainment. It is usually considered to operate on two scales with different mechanics. The small scale nibbling, which is the entrainment of fluid by viscous diffusion of turbulence, and the large scale engulfment, which entraps large volume of flow to be “digested” subsequently by viscous diffusion. The exact role of each of them in the overall entrainment rate is still not well understood, as it is the interplay between these two mechanics of diffusion. It is anyway accepted that the entrainment rate scales with large properties of the flow, while is not understood how the large scale inertial behavior can affect an intrinsically viscous phenomenon as diffusion of vorticity. In the present work we will address then the problem of turbulent diffusion through pseudo-spectral DNS simulations of the interface between a volume of decaying turbulence and quiescent flow. Such simulations will give us first hand measures of velocity, vorticity and strains fields at the interface; moreover the framework of unforced decaying turbulence will permit to study both spatial and temporal evolution of such fields. The analysis will evidence that for this kind of flows the overall production of enstrophy , i.e. the square of vorticity omega^2 , is dominated near the interface by the local inertial transport of “fresh vorticity” coming from the turbulent flow. Viscous diffusion instead plays a major role in enstrophy production in the outbound of the interface, where the nibbling process is dominant. The data from our simulation seems to confirm the theory of an inertially stirred viscous phenomenon proposed by others authors before and provides new data about the inertial diffusion of turbulence across the interface.

Web advertising. Le comunicazioni commerciali on-line.

La tesi ha ad oggetto lo studio e l’approfondimento delle forme di promozione commerciale presenti in Rete caratterizzate, più che da una normale evoluzione, da continue metamorfosi che ridefiniscono ogni giorno il concetto di pubblicità. L’intento è quello di analizzare il quadro giuridico applicabile alla pubblicità via Web, a fronte della varità di forme e di modalità che essa può assumere. Nel lavoro vengono passate in rassegna le caratteristiche che differenziano la pubblicità commerciale on-line rispetto a quella tradizionale; tra le quali, particolare rilievo assume la capacità d’istaurare una relazione – diretta e non mediata – tra impresa e consumatore. Nel prosieguo viene affrontato il problema dell’individuazione, stante il carattere a-territoriale della Rete, della legge applicabile al web advertising, per poi passare ad una ricognizione delle norme europee ed italiane in materia, senza trascurare quelle emanate in sede di autodisciplina. Ampio spazio è dedicato, infine, all’esame delle diverse e più recenti tecniche di promozione pubblicitaria, di cui sono messi in evidenza gli aspetti tecnico-informatici, imprescindibili ai fini di una corretta valutazione del tema giuridico. In particolare, vengono approfonditi il servizio di posizionamento a pagamento offerto dai principali motori di ricerca (keywords advertising) e gli strumenti di tracciamento dei “comportamenti” on-line degli utenti, che consentono la realizzazione di campagne pubblicitarie mirate (on-line behavioural advertising). Il Web, infatti, non offre più soltanto la possibilità di superare barriere spaziali, linguistiche o temporali e di ampliare la propria sfera di notorietà, ma anche di raggiungere l’utente “interessato” e, pertanto, potenziale acquirente. Di queste nuove realtà pubblicitarie vengono vagliati gli aspetti più critici ed esaminata la disciplina giuridica eventualmente applicabile anche alla luce delle principali decisioni giurisprudenziali nazionali ed europee in materia, nonché delle esperienze giuridiche nord-americane e di tipo autoregolamentare.

Functional characterization of modified vaccinia virus Ankara-encoded anti-apoptotic proteins

Candidate vaccines based on the highly attenuated orthopoxvirus strain MVA are tested against various infectious and cancer diseases and, more profound, vaccines based on wildtype and recombinant viruses have been found safe and immunogenic in clinical trials. Compared to conventional vaccine strains, MVA lacks many functional genes for potentially important regulators of virus-host interactions. However, some gene functions responsible for counteraction of cellular antiviral pathways are still conserved in the genome of MVA and the inhibition of apoptosis seems to be one important mechanism, the virus is still able to interact with.rnrnVaccinia viruses encode several proteins which prevent the induction of virus-induced apoptosis. The vaccinia virus anti-apoptotic protein F1 was shown to counteract the activation of the mitochondrial pathway of apoptosis in a highly effective manner. Another vaccinia virus protein, N1, like F1 shows structural and functional similarity to members of the cellular anti-apoptotic bcl-2 family and was also shown to inhibit apoptosis. The vaccinia virus early protein E3 inhibits programmed cell death by binding to and sequestration of dsRNA molecules, normally inducing cellular antiviral pathways also driving the induction of apoptosis. All three anti-apoptotic genes were functionally analyzed during this work.rn

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.