Topological Calculus of Looping Sequences

Il Calculus of Looping Sequences (CLS) permette la descrizione dei sistemi biologici e della loro evoluzione. Nell'ambito del lavoro di tesi e' stata sviluppata una estensione del CLS, chiamata Topological CLS (TCLS), dove ad ogni oggetto del sistema biologico sono associate una precisa posizione e dimensione nello spazio. Gli oggetti possono muoversi autonomamente e l'applicabilita' delle regole di riscrittura, che modellano le reazioni tra gli elementi, puo' essere determinata dalle posizioni degli oggetti coinvolti. Infine, alle regole di riscrittura e' associato un parametro che ne specifica la velocita' di reazione. Il Topological CLS e' stato quindi utilizzato per modellare due esempi di sistemi biologici: il processo di mitosi e il quorum-sensing

Formal Modelling and Simulation of Biological Systems with Spatiality

In Systems Biology, spatial modelling allows an accurate description of phenomena whose behaviour is influenced by the spatial arrangement of the elements. In this thesis, we present various modelling formalisms with spatial features, each using a different abstraction level of the real space. From the formalisms with the most abstract notion of space, to the most concrete, we formally define the MIM Calculus with compartments, the Spatial P systems, and the Spatial CLS. Each formalism is suitable for the description of different kinds of systems, which call for the use of different space modelling abstractions. We present models of various real-world systems which benefit from the ability to precisely describe space-dependent behaviours. We define the MIM Calculus, inspired by Molecular Interaction Maps, a graphical notation for bioregulatory networks. The MIM Calculus provides high-level operators with a direct biological meaning, which are used to describe the interaction capabilities of the elements of such systems. Its spatial extension includes the most abstract notion of space, namely it only allows the modelling of compartments. Such a feature allows distinguishing only the abstract position where an element is, identified by the name of the compartment. Subsequently, we propose a spatial extension to the membrane computing formalism P systems. In this case, we follow a more precise approach to spatial modelling, by embedding membranes and objects in a two-dimensional discrete space. Some objects of a Spatial P system can be declared as mutually exclusive objects, with the constraint that each position can accommodate at most one of them. The distinction between ordinary and mutually exclusive objects can be thought of as an abstraction on the size of the objects. We study the computational complexity of the formalism and the problem of efficient simulation of some kinds of models. Finally, we present the Spatial Calculus of Looping Sequences (Spatial CLS), which is an extension of the Calculus of Looping Sequences (CLS), a formalism geared towards the modelling of cellular systems. In this case, models are based on two/three dimensional continuous space, and allow an accurate description of the motion of the elements, and of their size. In particular, Spatial CLS allows the description of the space occupied by elements and membranes, which can change their sizes dynamically as the system evolves. Space conflicts which may occur can be resolved by performing a rearrangement of elements and membranes. As example applications of the calculus we present a model of cell proliferation, and a model of the quorum sensing process in Pseudomonas aeruginosa

SWITCHGRASS CULTIVATION ON RECLAIMED M INELAND W ITH SOME AMENDMENTS

Reclaimed mining rocks can be potential lands for biofuel feedstock production. Minelands are considered marginal because they often have low organic matter contents and adverse soil physical and chemical characteristics. Establishing perennial grasses such as switchgrass (Panicum virgatum L.) on these lands can be an economically viable option to produce cellulosic biomass with the addition of biological agents such as fertilizers, cinder and sewage sludge

Lazy Security Controllers

A security controller follows the execution of a target to identify and prevent security violations. Eective controllers proactively observe a full execution of a target and, in case of a security violation, either interrupt or modify its original behaviour. Beyond the theoretical aspects, the assumption that a controller can observe the entire execution of its target might be restrictive in several practical cases. In this paper we dene lazy controllers, a category of security controllers which can schedule observation points over the target execution. Finding an optimal scheduling strategy is non-trivial in general. Indeed, a lazy controller could miss security-sensitive observations. Also, we propose synthesis strategies applicable to (i) non-deterministic targets with non-instantaneous actions, (ii) probabilistic targets modelled as Discrete Time Markov Chains and (iii) stochastic targets modelled as Continuous Time Markov Chains. In each case we give an analytical characterization of the probability that the lazy controller misses the detection of a violation

The M. tuberculosis Phosphate-Binding Lipoproteins PstS1 and PstS3 Induce Th1 and Th17 Responses That Are Not Associated with Protection against M. tuberculosis Infection

The M. tuberculosis phosphate-binding transporter lipoproteins PstS1 and PstS3 were good immunogens inducing CD8+ T-cell activation and both Th1 and Th17 immunity in mice. However, this antigen-specific immunity, even when amplified by administration of the protein with the adjuvant LTK63 or by the DNA priming/protein boosting regimen, was not able to contain M. tuberculosis replication in the lungs of infected mice. The lack of protection might be ascribed with the scarce/absent capacity of PstS1/PstS3 antigens to modulate the IFN-γ response elicited by M. tuberculosis infection during which, however, PstS1-specific IL-17 secreting cells were generated in both unvaccinated and BCG-vaccinated mice. In spite of a lack of protection by PstS1/PstS3 immunizations, our results do show that PstS1 is able to induce IL-17 response upon M. tuberculosis infection which is of interest in the study of anti-M. tuberculosis immunity and as potential immunomodulator in combined vaccines

Acetaldehyde and parkinsonism: role of CYP450 2E1.

The present review update the relationship between acetaldehyde (ACE) and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly. We have indicated that ACE is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide (DAS) and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine (DA) neurons of rodent Substantia Nigra (SN), but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout (KO) mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the SN induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. ACE is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson's disease (PD) patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and P

Cord cross-sectional area at foramen magnum as a correlate of disability in amyotrophic lateral sclerosis

Spinal cord atrophy is one of the hallmarks of amyotrophic lateral sclerosis (ALS); however, it is not routinely assessed in routine clinical practice. In the present study, we evaluated whether spinal cord cross-sectional area measured at the foramen magnum level using a magnetic resonance imaging head scan represents a clinically meaningful measure to be added to the whole-brain volume assessment. Using an active surface approach, we measured the cord area at the foramen magnum and brain parenchymal fraction on T1-weighted three-dimensional spoiled gradient recalled head scans in two groups of subjects: 23 patients with ALS (males/females, 13/10; mean\u2009\ub1\u2009standard deviation [SD] age 61.7\u2009\ub1\u200910.3 years; median ALS Functional Rating Scale-Revised score 39, range 27-46) and 18 age- and sex-matched healthy volunteers (mean\u2009\ub1\u2009SD age 55.7\u2009\ub1\u200910.2 years). Spinal cord area at the foramen magnum was significantly less in patients than in control subjects and was significantly correlated with disability as measured with the ALS Functional Rating Scale-Revised (\u3c1\u2009=\u20090.593, p\u2009<\u2009 0.005). This correlation remained significant after taking into account inter-individual differences in brain parenchymal fraction (\u3c1\u2009=\u20090.684, p\u2009<\u2009 0.001). Our data show that spinal cord area at the foramen magnum correlates with disability in ALS independently of whole-brain atrophy, thus indicating its potential as a disease biomarker

Different MRI patterns in MS worsening after stopping fingolimod

Objective To analyze MRI images in patients with MS who experienced worsening of neurologic status (WNS) after stopping fingolimod (FTY).MethodsIn this retrospective study, demographic, clinical, and radiologic data of patients with MS who experienced WNS after stopping FTY were retrospectively collected. We introduced the "\u3b4Expanded Disability Status Scale (EDSS)-ratio" to identify patients who, after FTY withdrawal, showed an inflammatory flare-up exceeding the highest lifetime disease activity level. Patients with \u3b4EDSS-ratio > 1 were enrolled in the study.ResultsEight patients were identified. The mean (SD) age of the 8 (7 female) patients was 35.3 (4.9) years. The mean FTY treatment duration was 3.1 (0.8) years. The mean FTY discontinuation-WNS interval was 4 (0.9) months. The 4 patients with \u3b4EDSS-ratio 65 2 developed severe monophasic WNS (EDSS score above 8.5), characterized by clinical features and MRI findings not typical of MS, which we classified as "tumefactive demyelination pattern" (TDL) and "Punctuated pattern" (PL). Conversely, patients whose \u3b4EDSS-ratio was between 1 and 2 had clinical features and brain MRI compatible with a more typical, even if aggressive, MS relapse. In patients with TDL and PL, the flare-up of inflammatory activity led to severe tissue damage resulting in T2 but also T1 lesion volume increase at 6-month follow-up.ConclusionsPeculiar MRI features (TDL and PL), different from a typical MS flare-up, might occur in some patients who experienced WNS after stopping FTY. Further studies, also involving immunologic biomarkers, are necessary to investigate TDL or PL pathophysiology

Analysing the effect of land use and vegetation cover on soil infiltration in three contrasting environments in Northeast Spain

Este estudio presenta el análisis conjunto de la información obtenida a partir de 195 ensayos de infiltración en el campo, que fueron realizados mediante dispositivos de doble anillo. Los experimentos se realizaron en 20 situaciones contrastadas de usos del suelo, los cuales se encuentran distribuidos en tres contextos geográficos (costa NE de Cataluña, monte bajo del sector central del valle del Ebro y montaña media de la vertiente Sur del Pirineo central). El objetivo de esta investigación es determinar los factores más importantes que explican la variabilidad de la infiltración: uso del suelo, tipo de cubierta vegetal, características del suelo y del substrato rocoso, humedad del suelo y altitud. El análisis de los datos se realizó mediante la comparación de las variables a partir de distintos métodos estadísticos: test de correlación lineal bivariada, ANOVA y comparaciones múltiples de Bonferroni. Los resultados muestran que la variabilidad de la infiltración está principalmente asociada al tipo de uso del suelo, siendo el factor más determinante. El tipo de cubierta vegetal se mostró como el segundo factor en importancia, mientras la humedad del suelo no presentó correlación con la infiltración. La interpretación de estos resultados sugiere que las características de las áreas de estudio son más determinantes que las variaciones temporales del estado hídrico del suelo, aunque la humedad pueda tener un grado de influencia mayor o menor en cada uso del suelo. La validez de los resultados obtenidos en este estudio está avalada porque se ha analizado un amplio espectro de escenarios de uso del suelo/cubierta vegetal, incluso teniendo en cuenta que se han comparado zonas con distintas características geográficas y geológicas. This study presents a joint analysis of the information from 195 field infiltration experiments, using double ring devices. The experiments were carried out in 20 contrasting types of land use, distributed across three geographic contexts (coast of NE Catalonia, low mountains in the central Ebro Valley and mid-height mountains from the southern range of the Central Pyrenees). The objective of this research was to determine the most important factors explaining infiltration variability: land use, type of vegetation cover, soil and bedrock characteristics, soil moisture and altitude. Data analysis was performed by comparing variables using statistical methods: bivariate lineal correlation, ANOVA and Bonferroni multiple comparison tests. Results show that infiltration variability is the most important factor and mainly linked to land use, followed by vegetation type. In contrast, soil moisture did not show any relation with infiltration. The interpretation of these results suggests that the characteristics of the study areas are more decisive than temporal variations of soil water content, although humidity can influence land use to a greater or lesser degree. The validity of the results obtained in this study is supported by the wide range of land use and land cover analysed, located in areas with different geographical and geological characteristics