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

An aquaporin 4 antisense oligonucleotide loaded, brain targeted nanoparticulate system design

Aquaporins (AQPs), members of the water-channel protein family, are highly expressed in brain tissue especially in astrocytic end-feet. They are important players for water hemostasis during development of cytotoxic as well as vasogenic edema. Increased expression of AQPs is important in pathophysiology of neurological diseases such as neuroinflammation and ischemia. Unfortunately, there are a few pharmacological inhibitors of AQP4 with several side effects limiting their translation as a drug for use in clinical conditions. Another therapeutic approach is using antisense oligonucleotides (ASOs) to block AQP4 activity. These are short, synthetic, modified nucleic acids that bind RNA to modulate its function. However, they cannot pass the blood brain barrier (BBB). To overcome this obstacle we designed a nanoparticulate system made up of chitosan nanoparticles surface modified with PEG and conjugated with monoclonal anti transferrin receptor-1 antibody via streptavidin-biotin binding. The nanocarrier system could be targeted to the transferrin receptor-1 at the brain endothelial capillaries through monoclonal antibodies. It is hypothesized that the nanoparticles could pass the BBB via receptor mediated transcytosis and reach brain parenchyma. Particle size, zeta potential, loading capacity and release profiles of nanoparticles were investigated. It was observed that all types of chitosau (CS) nanoparticles had positive zeta potential values and nanoparticle particle size distribution varied between 100 and 800 nm. The association efficiency of ASOs into the nanoparticles was between 80–97% and the release profiles of the nanoparticles exhibited an initial burst effect followed by a controlled release. The results showed that the designed chitosan based nanocarriers could be a promising carrier system to transport nucleic acid based drugs to brain parenchymaThis study is supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project Number: 110S460)S

In Vivo FRET Imaging to Predict the Risk Associated with Hepatic Accumulation of Squalene-Based Prodrug Nanoparticles.

Förster resonance energy transfer (FRET) is used here for the first time to monitor the in vivo fate of nanoparticles made of the squalene-gemcitabine prodrug and two novel derivatives of squalene with the cyanine dyes 5.5 and 7.5, which behave as efficient FRET pair in the NIR region. Following intravenous administration, nanoparticles initially accumulate in the liver, then they show loss of their integrity within 2 h and clearance of the squalene bioconjugates is observed within 24 h. Such awareness is a key prerequisite before introduction into clinical settings.journal article2018 Feb2017 11 30importedSupporting information : librement accessible sur le site de l'éditeur

MULTICUBE: Multi-objective design space exploration of multi-core architectures

n/

Presentation of the 9th Edition of the Model Checking Contest.

International audience; The Model Checking Contest (MCC) is an annual competition of software tools for model checking. Tools must process an increasing benchmark gathered from the whole community and may participate in various examinations: state space generation, computation of global properties, computation of some upper bounds in the model, evaluation of reachability formulas, evaluation of CTL formulas, and evaluation of LTL formulas.For each examination and each model instance, participating tools are provided with up to 3600 s and 16 gigabyte of memory. Then, tool answers are analyzed and confronted to the results produced by other competing tools to detect diverging answers (which are quite rare at this stage of the competition, and lead to penalties).For each examination, golden, silver, and bronze medals are attributed to the three best tools. CPU usage and memory consumption are reported, which is also valuable information for tool developers

A Portuguese East Indiaman from the 1502-1503 Fleet of Vasco da Gama off Al Hallaniyah Island, Oman: An interim report

Two Portuguese naus from Vasco da Gama's second voyage to India, left behind to disrupt maritime trade between India and the Red Sea, were wrecked in May 1503 off the north-eastern coast of Al Hallaniyah Island, Oman. The ships, Esmeralda and São Pedro, had been commanded by da Gama's maternal uncles, Vicente and Brás Sodré, respectively. A detailed study and scientific analysis of an artefact assemblage recovered during archaeological excavations conducted in Al Hallaniyah in 2013 and 2014 confirms the location of an early 16th-century Portuguese wreck-site, initially discovered in 1998. Esmeralda is proposed as the probable source of the remaining, un-salved wreckage

Применение метода контрольных возмущений для определения характерных узлов присоединения комплексной нагрузки при расчетах динамической устойчивости

Рассматривается влияние способа замещения комплексной нагрузки на характер электромеханических переходных процессов в электрических системах (ЭС) от действия больших возмущений. Показано, что установить общие рекомендации относительно способа замещения нагрузки в сложных ЭС затруднительно. Предлагается для опреде­ления характерных узлов нагрузки, оказывающих существенное влияние на характер динамического перехода, применять известный метод контрольных возмущений. Приводятся результаты сравнительных расчетов с использованием предлагаемой методики