Efficient Emptiness Check for Timed B\"uchi Automata (Extended version)

The B\"uchi non-emptiness problem for timed automata refers to deciding if a given automaton has an infinite non-Zeno run satisfying the B\"uchi accepting condition. The standard solution to this problem involves adding an auxiliary clock to take care of the non-Zenoness. In this paper, it is shown that this simple transformation may sometimes result in an exponential blowup. A construction avoiding this blowup is proposed. It is also shown that in many cases, non-Zenoness can be ascertained without extra construction. An on-the-fly algorithm for the non-emptiness problem, using non-Zenoness construction only when required, is proposed. Experiments carried out with a prototype implementation of the algorithm are reported.Comment: Published in the Special Issue on Computer Aided Verification - CAV 2010; Formal Methods in System Design, 201

Lazy Abstraction-Based Controller Synthesis

We present lazy abstraction-based controller synthesis (ABCS) for continuous-time nonlinear dynamical systems against reach-avoid and safety specifications. State-of-the-art multi-layered ABCS pre-computes multiple finite-state abstractions of varying granularity and applies reactive synthesis to the coarsest abstraction whenever feasible, but adaptively considers finer abstractions when necessary. Lazy ABCS improves this technique by constructing abstractions on demand. Our insight is that the abstract transition relation only needs to be locally computed for a small set of frontier states at the precision currently required by the synthesis algorithm. We show that lazy ABCS can significantly outperform previous multi-layered ABCS algorithms: on standard benchmarks, lazy ABCS is more than 4 times faster

Reversible brain edema associated to flow diverter stent procedures: a retrospective single-center study to evaluate frequency, clinical evolution, and possible mechanism

Background Hemorrhage and ischemia after flow diverter stent (FDS) procedures for intracranial aneurysms are the most common complications and have been extensively described. Temporary brain edema (TBE) is an unknown complication that could be associated with particular FDS procedures. Objective To estimate the frequency, clinical presentation, imaging findings, and possible mechanisms associating TBE with FDS. Methods Unruptured aneurysms treated with FDS implantation performed in our service from June 2015 to March 2018 were reviewed. Medical antecedents, endovascular procedure, clinical assessments before and after treatment, aneurysm characteristics, and image records were collected. Artery diameters of patients in whom TEB developed were also calculated to investigate any correlation between TBE and anatomic descriptors. Results A total of 179 FDS procedures in 176 patients were reviewed. Six patients (3.4%) presented with symptomatic TBE, and all TBE patients had undergone FDS implantation from the middle cerebral artery (MCA) to the internal carotid artery (ICA). A Pearson product-moment correlation coefficient (PPCC) found smaller MCA diameters and MCA/ICA ratios in these 6 patients (respectively PPCC = −0.619, P < 0.04; PPCC = −0.647, P < 0.03). Hemorrhagic and ischemic complications were less frequent than TBE (2.3% and 1.1% vs. 3.4%). Conclusions TBE was more frequent than ischemic or hemorrhagic complications after FDS in this study. TBE seemed to be associated with a particular FDS positioning in small arteries, inducing flow changes and disruption of the blood–brain barrier

Evidence of Toxoplasma gondii in rodents from Bangladesh

Rodents contribute to the life cycle of the protozoan parasite Toxoplasma gondii as an intermediate host and key prey animal of cats, the definitive host. As there is limited scientific knowledge available about the incidence and prevalence of T. gondii in commensal rodents in many Asian countries, we tested rodents from a commercial rice mill and eight local villages in Bangladesh for the presence of T. gondii DNA using rodent brain material preserved in ethanol. Overall, 10 of 296 (3.4%) rodent samples tested positive for Toxoplasma DNA. Our results indicate that rodents present in food production and food storage facilities may carry T. gondii

Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV(mac239)

BACKGROUND: The 5' untranslated region (UTR) or leader sequence of simian immunodeficiency virus (SIV(mac239)) is multifunctional and harbors the regulatory elements for viral replication, persistence, gene translation, expression, and the packaging and dimerization of viral genomic RNA (vRNA). We have constructed a series of deletions in the SIV(mac239 )leader sequence in order to determine the involvement of this region in both the packaging and dimerization of viral genomic RNA. We also assessed the impact of these deletions upon viral infectiousness, replication kinetics and gene expression in cell lines and monkey peripheral blood mononuclear cells (PBMC). RESULTS: Regions on both sides of the major splice donor (SD) were found to be necessary for the efficiency and specificity of viral genome packaging. However, stem-loop1 is critical for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the initiation site of SIV-Gag have additive effects on RNA packaging and contribute to a lesser degree to RNA dimerization. The targeted disruption of structures on both sides of the SD also severely impacts viral infectiousness, gene expression and replication in both CEMx174 cells and rhesus PBMC. CONCLUSION: In the leader region of SIV(mac239), stem-loop1 functions as the primary determinant for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the translational initiation site of SIV-Gag are classified as secondary determinants and play a role in dimerization. Collectively, these data signify a linkage between the primary encapsidation determinant of SIV(mac239 )and RNA dimerization

Multiple geographic origins of commensalism and complex dispersal history of black rats

The Black Rat (Rattus rattus) spread out of Asia to become one of the world's worst agricultural and urban pests, and a reservoir or vector of numerous zoonotic diseases, including the devastating plague. Despite the global scale and inestimable cost of their impacts on both human livelihoods and natural ecosystems, little is known of the global genetic diversity of Black Rats, the timing and directions of their historical dispersals, and the risks associated with contemporary movements. We surveyed mitochondrial DNA of Black Rats collected across their global range as a first step towards obtaining an historical genetic perspective on this socioeconomically important group of rodents. We found a strong phylogeographic pattern with well-differentiated lineages of Black Rats native to South Asia, the Himalayan region, southern Indochina, and northern Indochina to East Asia, and a diversification that probably commenced in the early Middle Pleistocene. We also identified two other currently recognised species of Rattus as potential derivatives of a paraphyletic R. rattus. Three of the four phylogenetic lineage units within R. rattus show clear genetic signatures of major population expansion in prehistoric times, and the distribution of particular haplogroups mirrors archaeologically and historically documented patterns of human dispersal and trade. Commensalism clearly arose multiple times in R. rattus and in widely separated geographic regions, and this may account for apparent regionalism in their associated pathogens. Our findings represent an important step towards deeper understanding the complex and influential relationship that has developed between Black Rats and humans, and invite a thorough re-examination of host-pathogen associations among Black Rats.Ken P. Aplin...Stephen C. Donnellan, Jeremy Austin...Julien Soubrier...Alan Coope

Multiple Geographic Origins of Commensalism and Complex Dispersal History of Black Rats

The Black Rat (Rattus rattus) spread out of Asia to become one of the world's worst agricultural and urban pests, and a reservoir or vector of numerous zoonotic diseases, including the devastating plague. Despite the global scale and inestimable cost of their impacts on both human livelihoods and natural ecosystems, little is known of the global genetic diversity of Black Rats, the timing and directions of their historical dispersals, and the risks associated with contemporary movements. We surveyed mitochondrial DNA of Black Rats collected across their global range as a first step towards obtaining an historical genetic perspective on this socioeconomically important group of rodents. We found a strong phylogeographic pattern with well-differentiated lineages of Black Rats native to South Asia, the Himalayan region, southern Indochina, and northern Indochina to East Asia, and a diversification that probably commenced in the early Middle Pleistocene. We also identified two other currently recognised species of Rattus as potential derivatives of a paraphyletic R. rattus. Three of the four phylogenetic lineage units within R. rattus show clear genetic signatures of major population expansion in prehistoric times, and the distribution of particular haplogroups mirrors archaeologically and historically documented patterns of human dispersal and trade. Commensalism clearly arose multiple times in R. rattus and in widely separated geographic regions, and this may account for apparent regionalism in their associated pathogens. Our findings represent an important step towards deeper understanding the complex and influential relationship that has developed between Black Rats and humans, and invite a thorough re-examination of host-pathogen associations among Black Rats

Preliminary assessment of the genetic population structure of the enigmatic species Laonastes aenigmamus (Rodentia: Diatomyidae)

Described in 2005, Laonastes aenigmamus is the only species of Diatomyidae. The known distribution of this rodent encompasses only the rugged mountains of the Khammouan karst in central Lao People's Democratic Republic. We used a sample of 52 specimens to survey population structure by sequencing 887 base pairs of the cytochrome-b gene. The overall haplotype diversity was low (0.789 ± 0.039 SD), with 14 haplotypes identified, whereas the nucleotide diversity was high (0.015 ± 0.008 SD). Phylogenetic and haplotypic network reconstructions revealed 3 well-supported and rather divergent lineages with mutational steps ranging from 28 to 32. Identified haplotype groups correspond to localities, suggesting that populations of L. aenigmamus are geographically structured. Mismatch distributions suggest population stability. An exact test for population differentiation confirms a significant level of differentiation. Taking into account human pressure increasingly threatening this ecosystem, we provide preliminary insights on the genetically discrete population structure of this enigmatic mammal species. © American 2011 Society of Mammalogists