Backward Reachability of Array-based Systems by SMT solving: Termination and Invariant Synthesis

The safety of infinite state systems can be checked by a backward reachability procedure. For certain classes of systems, it is possible to prove the termination of the procedure and hence conclude the decidability of the safety problem. Although backward reachability is property-directed, it can unnecessarily explore (large) portions of the state space of a system which are not required to verify the safety property under consideration. To avoid this, invariants can be used to dramatically prune the search space. Indeed, the problem is to guess such appropriate invariants. In this paper, we present a fully declarative and symbolic approach to the mechanization of backward reachability of infinite state systems manipulating arrays by Satisfiability Modulo Theories solving. Theories are used to specify the topology and the data manipulated by the system. We identify sufficient conditions on the theories to ensure the termination of backward reachability and we show the completeness of a method for invariant synthesis (obtained as the dual of backward reachability), again, under suitable hypotheses on the theories. We also present a pragmatic approach to interleave invariant synthesis and backward reachability so that a fix-point for the set of backward reachable states is more easily obtained. Finally, we discuss heuristics that allow us to derive an implementation of the techniques in the model checker MCMT, showing remarkable speed-ups on a significant set of safety problems extracted from a variety of sources.Comment: Accepted for publication in Logical Methods in Computer Scienc

Quantifier-Free Interpolation of a Theory of Arrays

The use of interpolants in model checking is becoming an enabling technology to allow fast and robust verification of hardware and software. The application of encodings based on the theory of arrays, however, is limited by the impossibility of deriving quantifier- free interpolants in general. In this paper, we show that it is possible to obtain quantifier-free interpolants for a Skolemized version of the extensional theory of arrays. We prove this in two ways: (1) non-constructively, by using the model theoretic notion of amalgamation, which is known to be equivalent to admit quantifier-free interpolation for universal theories; and (2) constructively, by designing an interpolating procedure, based on solving equations between array updates. (Interestingly, rewriting techniques are used in the key steps of the solver and its proof of correctness.) To the best of our knowledge, this is the first successful attempt of computing quantifier- free interpolants for a variant of the theory of arrays with extensionality

Creation of museums as strategy for preservation of the fossil heritage of Araripe sedimentary basin in Pernambuco, NE, Brazil

O Araripe pernambucano tem excelentes exposições de rochas da Formação Santana, Bacia Sedimentar do Araripe (PE, CE e PI), reconhecida internacionalmente pelos fósseis de vertebrados, preservados em concreções, considerados entre os mais importantes do supercontinente Gondwana (110 Ma). Embora a região tenha excelente potencial para coleta e estudos paleontológicos, facilitada pela extração a céu aberto da gipsita (Polo Gesseiro do Araripe), não existem ações de preservação do patrimônio fossilífero. Dado a vocação mineira e o potencial paleontológico, a região torna-se relevante para desenvolvimento de programas, projetos e ações que promovam os recursos naturais para uso educacional, turístico, inclusão social e sustentabilidade. Propõe-se a criação de museus paleontológicos nos municípios do Araripe pernambucano, como estratégia de uso sustentável desses recursos para geração de cultura e renda para a região, ao mesmo tempo em que se preserva para as gerações futuras a “memória paleobiológica da Terra”, retratada nos nossos fósseis.The Araripe Basin portion located in the Pernambuco state of Brazil has excellent Santana Formation outcrops. This internationally known unit has provided some of the most important concretion preserved vertebrate fossils of the Lower Cretaceous (~110 Ma) Gondwana. Although this region has its potential for fossil collecting eased by the gypsum extraction in surface mines (known as the ‘Araripe Plast Pole’), there are currently no fossil Patrimony preservation actions in the area. Given both the mining and paleontological potentials of these localities it is relevant to develop programmes, projects, and measures to promote its natural resources for educational, touristic, social, and sustainable porpuses. Here we propose the creation of paleontological museums in some of the Araripe municipalities within the Pernambuco state. These museums will be strategic for the sustainability of these resources to generate culture and profit for this region. These museums will also preserve the ‘Earth’s paleobiological memory’ by protecting our fossils for future generations.Agradecemos ao Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil/CNPq, pela bolsa de produtividade de pesquisa 303071/2014-1 e o projeto de pesquisa 401748/2010, a Pró-reitora de Extensão- PROEXT-UFPE e a FUNCULTURA, Processo 0756/2014. Sinceros agradecimentos também são devidos a prefeitura do Munícipio de Exu, ao Departamento Nacional de Produção Mineral-DNPM e ao Sindicato da Indústria do Gesso de Pernambuco/SINDUGESSO, pelo apoio no desenvolvimento da pesquisa.info:eu-repo/semantics/publishedVersio

Visuospatial exploration and art therapy intervention in patients with Parkinson's disease: an exploratory therapeutic protocol

Abstract Though abnormalities of visuospatial function occur in Parkinson's disease, the impact of such deficits on functional independence and psychological wellbeing has been historically under- recognized, and effective treatments for this impairment are unknown. These symptoms can be encountered at any stage of the disease, affecting many activities of daily living, and negatively influencing mood, self-efficacy, independence, and overall quality of life. Furthermore, visuospatial dysfunction has been recently linked to gait impairment and falls, symptoms that are known to be poor prognostic factors. Here, we aim to present an original modality of neurorehabilitation designed to address visuospatial dysfunction and related symptoms in Parkinson's disease, known as "Art Therapy". Art creation relies on sophisticated neurologic mechanisms including shape recognition, motion perception, sensory-motor integration, abstraction, and eye-hand coordination. Furthermore, art therapy may enable subjects with disability to understand their emotions and express them through artistic creation and creative thinking, thus promoting self-awareness, relaxation, confidence and self-efficacy. The potential impact of this intervention on visuospatial dysfunction will be assessed by means of combined clinical, behavioral, gait kinematic, neuroimaging and eye tracking analyses. Potential favorable outcomes may drive further trials validating this novel paradigm of neurorehabilitation

Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae

Interleukin (IL)-23 is a heterodimeric cytokine that shares the identical p40 subunit as IL-12 but exhibits a unique p19 subunit similar to IL-12 p35. IL-12/23 p40, interferon γ (IFN-γ), and IL-17 are critical for host defense against Klebsiella pneumoniae. In vitro, K. pneumoniae–pulsed dendritic cell culture supernatants elicit T cell IL-17 production in a IL-23–dependent manner. However, the importance of IL-23 during in vivo pulmonary challenge is unknown. We show that IL-12/23 p40–deficient mice are exquisitely sensitive to intrapulmonary K. pneumoniae inoculation and that IL-23 p19−/−, IL-17R−/−, and IL-12 p35−/− mice also show increased susceptibility to infection. p40−/− mice fail to generate pulmonary IFN-γ, IL-17, or IL-17F responses to infection, whereas p35−/− mice show normal IL-17 and IL-17F induction but reduced IFN-γ. Lung IL-17 and IL-17F production in p19−/− mice was dramatically reduced, and this strain showed substantial mortality from a sublethal dose of bacteria (103 CFU), despite normal IFN-γ induction. Administration of IL-17 restored bacterial control in p19−/− mice and to a lesser degree in p40−/− mice, suggesting an additional host defense requirement for IFN-γ in this strain. Together, these data demonstrate independent requirements for IL-12 and IL-23 in pulmonary host defense against K. pneumoniae, the former of which is required for IFN-γ expression and the latter of which is required for IL-17 production

Non-L\'evy mobility patterns of Mexican Me'Phaa peasants searching for fuelwood

We measured mobility patterns that describe walking trajectories of individual Me'Phaa peasants searching and collecting fuelwood in the forests of "La Monta\~na de Guerrero" in Mexico. These one-day excursions typically follow a mixed pattern of nearly-constant steps when individuals displace from their homes towards potential collecting sites and a mixed pattern of steps of different lengths when actually searching for fallen wood in the forest. Displacements in the searching phase seem not to be compatible with L\'evy flights described by power-laws with optimal scaling exponents. These findings however can be interpreted in the light of deterministic searching on heavily degraded landscapes where the interaction of the individuals with their scarce environment produces alternative searching strategies than the expected L\'evy flights. These results have important implications for future management and restoration of degraded forests and the improvement of the ecological services they may provide to their inhabitants.Comment: 15 pages, 4 figures. First version submitted to Human Ecology. The final publication will be available at http://www.springerlink.co

Regulator of G-protein signaling 5 (RGS5) protein: a novel marker of cancer vasculature elicited and sustained by the tumor’s proangiogenic microenvironment

We previously identified regulator of G-protein signaling 5 (RGS5) among several genes expressed by tumor-derived endothelial cells (EC). In this study, we provide the first in vivo/ex vivo evidence of RGS5 protein in the vasculature of ovarian carcinoma clinical specimens and its absence in human ovaries. Consistent with this, we show higher amounts of Rgs5 transcript in EC isolated from human cancers (as opposed to normal tissues) and demonstrate that expression is sustained by a milieu of factors typical of the proangiogenic tumor environment, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Supporting these findings, we show elevated levels of Rgs5 mRNA in the stroma from strongly (as opposed to weakly) angiogenic ovarian carcinoma xenografts and accordingly, we also show more of the protein associated to the abnormal vasculature. RGS5 protein predominantly colocalizes with the endothelium expressing platelet/endothelial cell adhesion molecule-1 (PECAM-1/CD31) and to a much lesser extent with perivascular/mural cells expressing platelet-derived growth factor receptor-beta (PDGFR-β) or alpha smooth muscle actin (αSMA). To toughen the relevance of the findings, we demonstrate RGS5 in the blood vessels of other cancer models endowed with a proangiogenic environment, such as human melanoma and renal carcinoma xenografts; to the contrary, it was undetectable in the vasculature of normal mouse tissues. RGS5 expression by the cancer vasculature triggered and retained by the proangiogenic microenvironment supports its exploitation as a novel biomarker and opens the path to explore new possibilities of therapeutic intervention aimed at targeting tumor blood vessels

Determination of the serine palmitoyl transferase inhibitor Myriocin by electrospray and Q-trap mass spectrometry

Myriocin, is a potent inhibitor of serine-palmitoyl-transferase, the \ufb01rst and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure Myriocin in minute specimens of animal tissue. The chemical analog 14-OH-Myriocin is used as the internal standard. The two molecules are extracted from the tissue homogenate by solid-phase extraction, separated by gradient reverse-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole. Detection is accomplished by Multiple Reaction Monitoring, employing the most representative transitions: 400@104 and 402@104 for Myriocin and 14-OH-Myriocin, respectively. The typical LoD and LLoQ of the optimized method are 0.9 pmoles/mL (approx. 0.016 pmoles injected) and 2.3 pmoles/mL, respectively, and the method is linear up to 250 pmoles/mL range (r2= 0.9996). The intra-and between-day repeatability affords a CV% 64 7.0. Applications included quantification of Myriocin in mouse lungs after 24 hrs from administration of ~4 nmoles by intra-trachea delivery. Measured levels ranged from 4.11 (median; 2.3-7.4 IQR, n=4) to 11.7 (median; 7.6-22.7 IQR, n=6) pmoles/lung depending on the different formulations used. Myriocin was also measured in retinas of mice treated by intravitreal injection and ranged from 0.045 (<LoD) to 0.35 pmoles/retina

Parameterized Verification of Systems with Global Synchronization and Guards

Inspired by distributed applications that use consensus or other agreement protocols for global coordination, we define a new computational model for parameterized systems that is based on a general global synchronization primitive and allows for global transition guards. Our model generalizes many existing models in the literature, including broadcast protocols and guarded protocols. We show that reachability properties are decidable for systems without guards, and give sufficient conditions under which they remain decidable in the presence of guards. Furthermore, we investigate cutoffs for reachability properties and provide sufficient conditions for small cutoffs in a number of cases that are inspired by our target applications.Comment: Accepted at CAV 202