A Framework to Synergize Partial Order Reduction with State Interpolation

We address the problem of reasoning about interleavings in safety verification of concurrent programs. In the literature, there are two prominent techniques for pruning the search space. First, there are well-investigated trace-based methods, collectively known as "Partial Order Reduction (POR)", which operate by weakening the concept of a trace by abstracting the total order of its transitions into a partial order. Second, there is state-based interpolation where a collection of formulas can be generalized by taking into account the property to be verified. Our main contribution is a framework that synergistically combines POR with state interpolation so that the sum is more than its parts

Symbolic Partial-Order Execution for Testing Multi-Threaded Programs

We describe a technique for systematic testing of multi-threaded programs. We combine Quasi-Optimal Partial-Order Reduction, a state-of-the-art technique that tackles path explosion due to interleaving non-determinism, with symbolic execution to handle data non-determinism. Our technique iteratively and exhaustively finds all executions of the program. It represents program executions using partial orders and finds the next execution using an underlying unfolding semantics. We avoid the exploration of redundant program traces using cutoff events. We implemented our technique as an extension of KLEE and evaluated it on a set of large multi-threaded C programs. Our experiments found several previously undiscovered bugs and undefined behaviors in memcached and GNU sort, showing that the new method is capable of finding bugs in industrial-size benchmarks.Comment: Extended version of a paper presented at CAV'2

Changes in insulin like growth factors, myostatin and vascular endothelial growth factor in rat musculus latissimus dorsi by poly 3-hydroxybutyrate implants

The present study aimed at researching the synergistic effect between an ectopic bone substitute and surrounding muscle tissue. To describe this effect, changes of insulin like growth factors (IGF1, IGF2), myostatin (GDF8) and vascular endothelial growth factor (VEGF) mRNA content of 12 Wistar-King rats musculus latissimus dorsi with implanted poly-3-hydroxybutyrate (PHB) scaffold were examined after 6 and 12 weeks. At each time interval six rats were killed and implants and surrounding tissues prepared for genetic evaluation. Eight rats without any implants served as controls. RNAwas extracted from homogenized muscle tissue and reverse transcribed. Changes in mRNA content were measured by Real-Time PCR using specific primers for IGF1, IGF2, GDF8 and VEGF. Comparing the level of VEGF mRNA in muscle after 6 and 12 weeks to the controls, we could assess a significant increase of VEGF gene expression (

Time to onset of cannabidiol (CBD) treatment effect in Lennox-Gastaut syndrome: Analysis from two randomized controlled trials

OBJECTIVE: To estimate time to onset of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]), we conducted post hoc analyses of data from two randomized, placebo-controlled, Phase 3 trials, GWPCARE3 (NCT02224560) and GWPCARE4 (NCT02224690), of patients with Lennox-Gastaut syndrome. METHODS: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex, 100 mg/ml oral solution) at 10 mg/kg/day (CBD10; GWPCARE3) or 20 mg/kg/day (CBD20; both trials) or placebo for 14 weeks. Treatment started at 2.5 mg/kg/day for all groups and reached 10 mg/kg/day on Day 7 and 20 mg/kg/day (CBD20 and matching placebo only) on Day 11. Percentage change from baseline in drop seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. RESULTS: Overall, 235 patients received CBD (CBD10 [GWPCARE3 only], n = 67; CBD20 [pooled GWPCARE3&4], n = 168) and 161 received placebo. Mean (range) age was 15.3 years (2.6-48.0). Patients had previously discontinued a median (range) of six (0-28) antiepileptic drugs (AEDs) and were currently taking a median of three (0-5) AEDs. Differences in drop seizure reduction between placebo and CBD emerged during the titration period and became nominally significant by Day 6 (p = .008) for pooled CBD treatment groups. Separation between placebo and CBD in ≥50% responder rate emerged by Day 6. Onset of the first reported AE occurred during the titration period in 45% of patients (CBD10, 46%; CBD20, 52%; placebo, 38%). In patients with AEs, resolution occurred within 4 weeks of onset in 53% of placebo and 39% of CBD patients and by end of study in 63% of placebo and 61% of CBD patients. SIGNIFICANCE: Treatment effect (efficacy and AEs) of CBD may occur within 1 week of starting treatment. Although AEs lasted longer for CBD than placebo, most resolved within the 14-week period

Optimal dynamic partial order reduction

Stateless model checking is a powerful technique for program verification, which however suffers from an exponential growth in the number of explored executions. A successful technique for reducing this number, while still maintaining complete coverage, is Dynamic Partial Order Reduction (DPOR). We present a new DPOR algorithm, which is the first to be provably optimal in that it always explores the minimal number of executions. It is based on a novel class of sets, called source sets, which replace the role of persistent sets in previous algorithms. First, we show how to modify an existing DPOR algorithm to work with source sets, resulting in an efficient and simple to implement algorithm. Second, we extend this algorithm with a novel mechanism, called wakeup trees, that allows to achieve optimality. We have implemented both algorithms in a stateless model checking tool for Erlang programs. Experiments show that source sets significantly increase the performance and that wakeup trees incur only a small overhead in both time and space

The Lantern Vol. 16, No. 2, December 1947

• A Little Light • Traitor\u27s Son • The Comeback • Wolf-Dog • Lucky Harry • Security or Progress • To Tell a Story • Endless • What Purpose, Life? • I Would Not Say • Adult Farewell • Springtime Fields • M.W. Armstronghttps://digitalcommons.ursinus.edu/lantern/1044/thumbnail.jp

INFLUENCE ALLOGENEIC MESENCHYMAL STEM CELLS IN PERITONEAL MACROPHAGES OKSYHENZALEZHNYY METABOLISM MICE S57BL / 6

Дослідження проводили на самцях мишей C57BL/6 масою 20–22 г віком 2–3 місяці. Алогенні МСК отримували культивуванням первинного матеріалу, що був виділений з кісткового мозку мишей С57BL/6. Культивування клітин проводили  у середовищі DMEM з додаванням 20 % фетальної сироватки бичків (FBS) та 1 % суміші антибіотика-антимікотика (Sigma, USA) за 37°С, 100 % вологості і 5 % СО2.Мишам С57BL/6 внутрішньом’язово інокулювали клітинну суспензію метастатичної карциноми легень Льюїс (LLC) у концентрації 1×106/0,1 мл розчину Хенкса. На 8-му добу після інокуляції пухлинних клітин групі тварин вводили  внутрішньовенно алогенні МСК в концентрації 1,25×104 на тварину. Після цього було сформовано такі групи тварин: 1-ша включала інтактних тварин (контроль), 2-га включала тварин, яким вводили тільки  алогенні мезенхімальні стовбурові клітини (MSC), 3-тя включала тварин, яким вводили суспензію метастатичної карциноми легень Льюїс (LLC), 4-та – тварини, яким вводили суспензію метастатичної карциноми легень Льюїс  і  алогенні МСК (LLC+ MSC).Для визначення оксигензалежної біоцидності перитонеальних макрофагів  застосовували спонтанний та стимулювальний НСТ-тест.Встановлено, що введення  алогенних МСК чинить вплив на оксигензалежний метаболізм перитонеальних макрофагів у мишей С57BL/6. Застосування алогенних МСК забезпечує вірогідне зниження метаболічної активності перитонеальних макрофагів  у мишей С57BL/6 з показником  стимуляції  -12% , що вказує  на відсутність функціонального резерву клітин. Встановлено вірогідне зниження метаболічної активності перитонеальних макрофагів  у мишей С57BL/6 з перещепленою карциномою легень Льюїс з показником  стимуляції  -30% , що вказує  на відсутність функціонального резерву клітин.  Введення алогенних МСК призводить до  вірогідного  незначного підвищення метаболічної активності перитонеальних макрофагів  у мишей С57BL/6 з перещепленою карциномою легень Льюїс із показником  стимуляції –  8% , що вказує  на наявність функціонального резерву клітин.Исследования проводили на самцах мышей C57BL/6 массой 20–22 г в возрасте 2–3 месяца. Аллогенные МСК получали культивированием первичного материала, который был выделен из костного мозга мышей С57BL/6. Культивирование клеток проводили в среде DMEM с добавлением 20% фетальной сыворотки бычков (FBS) и 1% смеси антибиотика-антимикотика (Sigma, USA) при 37 °С, 100% влажности и 5% СО2.Мышам С57BL/6 внутримышечно вводили клеточную суспензию метастатической карциномы легких Льюис (LLC) в концентрации 1×106/0,1 мл раствора Хэнкса. На 8-е сутки после инокуляции опухолевых клеток группе животных вводили внутривенно аллогенные МСК в концентрации 1,25×104 на животное. После этого было сформировано следующие группы животных: 1-я включала интактных животных (контроль), 2-я включала животных, которым вводили только аллогенные мезенхимальные стволовые клетки (МСК), 3-я включала животных, которым вводили суспензию метастатической карциномы легких Льюис (LLC), 4-я – животные, которым вводили суспензию метастатической карциномы легких Льюис и аллогенные МСК (LLC + MSC).Для определения оксигензависимой биоцидности перитонеальных макрофагов применяли спонтанный и стимулированный НСТ-тест.Установлено, что введение аллогенных МСК оказывает влияние на оксигензависимый метаболизм перитонеальных макрофагов у мышей С57BL/6. Применение аллогенных МСК обеспечивает достоверное снижение метаболической активности перитонеальных макрофагов у мышей С57BL/6 с показателем стимуляции -12%, что указывает на отсутствие функционального резерва клеток. Установлено достоверное снижение метаболической активности перитонеальных макрофагов у мышей С57BL/6 с первитой карциномой легких Льюис с показателем стимуляции  -30%, что указывает на отсутствие функционального резерва клеток. Введение аллогенных МСК приводит к достоверному незначительного повышению метаболической активности перитонеальных макрофагов у мышей С57BL / 6 с перевитой карциномой легких Льюис с показателем стимуляции – 8%, что указывает на наличие функционального резерва клеток.The study was conducted on male mice C57BL/6 weighing 20-22 g aged 2-3 months. Receiving allogeneic MSCs cultivation of primary material that was isolated from the bone marrow of mice C57BL/6. Cultivation of cells was carried out in DMEM medium with addition of 20% fetal bovis serum (FBS) and 1% antibiotic-antimycotics (Sigma, USA) at 37 °C, 100% humidity and 5% CO2.It was inoculated intramuscularly cell suspension metastatic Lewis lung carcinoma (LLC) in a concentration 1×106/0.1 ml Hanks to mice C57BL/6. On the 8th day after tumor cell inoculation it was administered intravenously allogeneic MSCs in a concentration 1,25×104  to 4th  group of animals. After that was formed following groups of animals: 1st included intact animals (control), 2nd – included animals which was administered only allogeneic mesenchymal stem cells (MSC), 3rd  – included animals which was administered suspension metastatic Lewis lung carcinoma (LLC ),  4th  group  – which was administered suspension metastatic Lewis lung carcinoma and allogeneic MSCs (LLC + MSC).Spontaneous and stimulated oxidative metabolism of peritoneal macrophages were established  in NBT-test.It was established that administration  allogeneic MSCs   influence on  oxidative metabolism of peritoneal macrophages in mice C57BL/6. The use of allogeneic MSCs provides a probable decrease metabolic activity of peritoneal macrophages in miceC57BL/6 with stimulation  index -12%. It was indicate  that  cells lose of functional reserve. In mice with  Lewis lung carcinoma ( 3rd  group of animals)  metabolic activity of peritoneal macrophages in mice C57BL/6   was decreased  with stimulation  index  -30% like  indicating a losek of cells. functional reserve.Allogeneic MSCs application in mice C57BL/6 perescheplenoyu Lewis lung carcinoma is lead to a slight increase metabolic activity of peritoneal macrophages   with stimulation  index  8%, which indicates the presence of cells functional reserve

Virulence of Oomycete Pathogens from \u3cem\u3ePhragmites australis\u3c/em\u3e-Invaded and Noninvaded Soils to Seedlings of Wetland Plant Species

Soil pathogens affect plant community structure and function through negative plant-soil feedbacks that may contribute to the invasiveness of non-native plant species. Our understanding of these pathogen-induced soil feedbacks has relied largely on observations of the collective impact of the soil biota on plant populations, with few observations of accompanying changes in populations of specific soil pathogens and their impacts on invasive and noninvasive species. As a result, the roles of specific soil pathogens in plant invasions remain unknown. In this study, we examine the diversity and virulence of soil oomycete pathogens in freshwater wetland soils invaded by non-native Phragmites australis (European common reed) to better understand the potential for soil pathogen communities to impact a range of native and non-native species and influence invasiveness. We isolated oomycetes from four sites over a 2-year period, collecting nearly 500 isolates belonging to 36 different species. These sites were dominated by species of Pythium, many of which decreased seedling survival of a range of native and invasive plants. Despite any clear host specialization, many of the Pythium species were differentially virulent to the native and non-native plant species tested. Isolates from invaded and noninvaded soils were equally virulent to given individual plant species, and no apparent differences in susceptibility were observed between the collective groups of native and non-native plant species

Convulsive status epilepticus management in adults and children: Report of the Working Group of the Polish Society of Epileptology

Introduction The Working Group was established at the initiative of the General Board of the Polish Society of Epileptology (PSE) to develop an expert position on the treatment of convulsive status epilepticus (SE) in adults and children in Poland. Generalized convulsive SE is the most common form and also represents the greatest threat to life, highlighting the importance of the choice of appropriate therapeutic treatment. Aim of guideline We present the therapeutic options separately for treatment during the early preclinical (>5–30min), established (30–60min), and refractory (>60min) SE phases. This division is based on time and response to AEDs, and indicates a practical approach based on pathophysiological data. Results Benzodiazepines (BZD) are the first-line drugs. In cases of ineffective first-line treatment and persistence of the seizure, the use of second-line treatment: phenytoin, valproic acid or phenobarbital is required. SE that persists after the administration of benzodiazepines and phenytoin or another second-line AED at appropriate doses is defined as refractory and drug resistant and requires treatment in the intensive care unit (ICU). EEG monitoring is essential during therapy at this stage. Anesthesia is typically continued for an initial period of 24h followed by a slow reversal and is re-established if seizures recur. Anesthesia is usually administered either to the level of the “burst suppression pattern” or to obtain the “EEG suppression” pattern. Conclusions Experts agree that close and early cooperation with a neurologist and anesthetist aiming to reduce the risk of pharmacoresistant cases is an extremely important factor in the treatment of patients with SE. This report has educational, practical and organizational aspects, outlining a standard plan for SE management in Poland that will improve therapeutic efficacy

A symbolic algorithm for the synthesis of bounded Petri nets

This paper presents an algorithm for the synthesis of bounded Petri nets from transition systems. A bounded Petri net is always provided in case it exists. Otherwise, the events are split into several transitions to guarantee the synthesis of a Petri net with bisimilar behavior. The algorithm uses symbolic representations of multisets of states to efficiently generate all the minimal regions. The algorithm has been implemented in a tool. Experimental results show a significant net reduction when compared with approaches for the synthesis of safe Petri nets.Peer ReviewedPostprint (author's final draft