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

NAP1 Modulates Binding of Linker Histone H1 to Chromatin and Induces an Extended Chromatin Fiber Conformation

NAP1 (nucleosome assembly protein 1) is a histone chaperone that has been described to bind predominantly to the histone H2A·H2B dimer in the cell during shuttling of histones into the nucleus, nucleosome assembly/remodeling, and transcription. Here it was examined how NAP1 interacts with chromatin fibers isolated from HeLa cells. NAP1 induced a reversible change toward an extended fiber conformation as demonstrated by sedimentation velocity ultracentrifugation experiments. This transition was due to the removal of the linker histone H1. The H2A·H2B dimer remained stably bound to the native fiber fragments and to fibers devoid of linker histone H1. This was in contrast to mononucleosome substrates, which displayed a NAP1-induced removal of a single H2A·H2B dimer from the core particle. The effect of NAP1 on the chromatin fiber structure was examined by scanning/atomic force microscopy. A quantitative image analysis of ∼36,000 nucleosomes revealed an increase of the average internucleosomal distance from 22.3 ± 0.4 to 27.6 ± 0.6 nm, whereas the overall fiber structure was preserved. This change reflects the disintegration of the chromatosome due to binding of H1 to NAP1 as chromatin fibers stripped from H1 showed an average nucleosome distance of 27.4 ± 0.8 nm. The findings suggest a possible role of NAP1 in chromatin remodeling processes involved in transcription and replication by modulating the local linker histone content

Effect of Nb and Ti micro-additives and thermo-mechanical treatment of high-manganese steels with aluminium and silicon on their microstructure and mechanical properties

The r esults are based on two experimental high-manganese X98MnAlSiNbTi24-11 and X105MnAlSi24-11 steels subjected to thermo-mechanical treatment by hot-rolling on a semi-industrial processing line. The paper presents the results of diffraction and structural studies using scanning and transmission electron microscopy showing the role of Nb and Ti micro-additives in shaping high strength properties of high-manganese austenitic-ferritic steels with complex carbides. The performed investigations of two experimental steels allow to explain how the change cooling conditions after thermo-mechanical treatment of the analysed steels affects the change of their microstructure and mechanical properties. The obtained results allow assessing the impact of both the chemical composition and the applied thermo-mechanical treatment technology on the structural effects of strengthening of the newly developed steels

Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.

Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention

Concurrent Computing with Shared Replicated Memory

The behavioural theory of concurrent systems states that any concurrent system can be captured by a behaviourally equivalent concurrent Abstract State Machine (cASM). While the theory in general assumes shared locations, it remains valid, if different agents can only interact via messages, i.e. sharing is restricted to mailboxes. There may even be a strict separation between memory managing agents and other agents that can only access the shared memory by sending query and update requests to the memory agents. This article is dedicated to an investigation of replicated data that is maintained by a memory management subsystem, whereas the replication neither appears in the requests nor in the corresponding answers. We show how the behaviour of a concurrent system with such a memory management can be specified using concurrent communicating ASMs. We provide several refinements of a high-level ground model addressing different replication policies and internal messaging between data centres. For all these refinements we analyse their effects on the runs such that decisions concerning the degree of consistency can be consciously made.Comment: 23 page

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

Śródnaczyniowa implantacja stentgraftów aortalnych : 5 lat doświadczeń

Background: Presentation of own experience in the field of endovascular treatment of aneurysms and aortal wall damage, as well as comparison of the value of angio-CT and dimensioning angiography imaging of aneurysms in the aspect of qualification for aortal stentgraft implantation procedures. Material/Method: 133 patients (11 females and 121 males) aged 23 - 82 years underwent endovascular stentgraft implantation procedures preformed as treatment for aortal aneurysms, delaminations and posttraumatic damage of the aortal wall. The treated patients were classified as belonging to groups II (35.5%), III (55%) and IV (9.5%) according to ASA. Qualification for endovascular surgery was based on angio-CT and dimensioning angiography. Results: 21 stentgrafts were implanted into the thoracic and 113 into the abdominal aorta. There was no necessity of perioperative removal of the prosthesis in any case. The overall rate of postoperative complications was 9.7 %. The duration of the surgery ranged from 30 to 120 min. Conclusions: Implantation of aortal stentgrafts is a safe method of treatment for aortal aneurysms, delaminations and ruptures. It as also a life-saving procedure in damage of the aortal wall due to trauma. Computed tomography is an essential imaging modality in the diagnostics of aortal abnormalities. Owing to 3D reconstructions of CT images, the aortal anatomy and the exact site of aortal wall damage can be identified. This is very important for correct selection of the stentgraft parameters and makes it possible to resign from dimensioning angiography

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