Wandering breathers and self-trapping in weakly coupled nonlinear chains: classical counterpart of macroscopic tunneling quantum dynamics

We present analytical and numerical studies of phase-coherent dynamics of intrinsically localized excitations (breathers) in a system of two weakly coupled nonlinear oscillator chains. We show that there are two qualitatively different dynamical regimes of the coupled breathers, either immovable or slowly-moving: the periodic transverse translation (wandering) of low-amplitude breather between the chains, and the one-chain-localization of high-amplitude breather. These two modes of coupled nonlinear excitations, which involve large number of anharmonic oscillators, can be mapped onto two solutions of a single pendulum equation, detached by a separatrix mode. We also study two-chain breathers, which can be considered as bound states of discrete breathers with different symmetry and center locations in the coupled chains, and bifurcation of the anti-phase two-chain breather into the one-chain one. Delocalizing transition of 1D breather in 2D system of a large number of parallel coupled nonlinear chains is described, in which the breather, initially excited in a given chain, abruptly spreads its vibration energy in the whole 2D system upon decreasing breather frequency or amplitude below the threshold one. The threshold breather frequency is above the cut off phonon frequency in 2D system, and the threshold breather amplitude scales as square root of the inter-chain coupling constant. Delocalizing transition of discrete vibrational breather in 2D and 3D systems of coupled nonlinear chains has an analogy with delocalizing transition for Bose-Einstein condensates in 2D and 3D optical lattices.Comment: 33 pages, 16 figure

Spatial Interpolants

We propose Splinter, a new technique for proving properties of heap-manipulating programs that marries (1) a new separation logic-based analysis for heap reasoning with (2) an interpolation-based technique for refining heap-shape invariants with data invariants. Splinter is property directed, precise, and produces counterexample traces when a property does not hold. Using the novel notion of spatial interpolants modulo theories, Splinter can infer complex invariants over general recursive predicates, e.g., of the form all elements in a linked list are even or a binary tree is sorted. Furthermore, we treat interpolation as a black box, which gives us the freedom to encode data manipulation in any suitable theory for a given program (e.g., bit vectors, arrays, or linear arithmetic), so that our technique immediately benefits from any future advances in SMT solving and interpolation.Comment: Short version published in ESOP 201

Limiting phase trajectories and the origin of energy localization in nonlinear oscillatory chains

We demonstrate that the modulation instability of the zone boundary mode in a finite (periodic) Fermi-Pasta-Ulam chain is the necessary but not sufficient condition for the efficient energy transfer by localized excitations. This transfer results from the exclusion of complete energy exchange between spatially different parts of the chain, and the excitation level corresponding to that turns out to be twice more than threshold of zone boundary mode's instability. To obtain this result one needs in far going extension of the beating concept to a wide class of finite oscillatory chains. In turn, such an extension leads to description of energy exchange and transition to energy localization and transfer in terms of 'effective particles' and Limiting Phase Trajectories. The 'effective particles' appear naturally when the frequency spectrum crowding ensures the resonance interaction between zone boundary and two nearby nonlinear normal modes, but there are no additional resonances. We show that the Limiting Phase Trajectories corresponding to the most intensive energy exchange between 'effective particles' can be considered as an alternative to Nonlinear Normal Modes, which describe the stationary process

Beyond reachability: Shape abstraction in the presence of pointer arithmetic

Abstract. Previous shape analysis algorithms use a memory model where the heap is composed of discrete nodes that can be accessed only via access paths built from variables and field names, an assumption that is violated by pointer arithmetic. In this paper we show how this assumption can be removed, and pointer arithmetic embraced, by using an analysis based on separation logic. We describe an abstract domain whose elements are certain separation logic formulae, and an abstraction mechanism that automatically transits between a low-level RAM view of memory and a higher, fictional, view that abstracts from the representation of nodes and multiword linked-lists as certain configurations of the RAM. A widening operator is used to accelerate the analysis. We report experimental results obtained from running our analysis on a number of classic algorithms for dynamic memory management.

Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: A seven case series

Background: Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. Objectives: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. Methods: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. Results: Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. Conclusions: ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling

Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma

<p>Abstract</p> <p>Background</p> <p>Peroxiredoxin 6 (<it>PRDX6</it>) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the <it>PRDX6 </it>gene to uncover common variants, and tested association with ALI following major trauma.</p> <p>Methods</p> <p>To examine the extent of variation in the <it>PRDX6 </it>gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma), which uncovered 80 SNPs. <it>In silico </it>modeling was performed using Patrocles and Transcriptional Element Search System (TESS). Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma.</p> <p>Results</p> <p>Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using <it>in silico </it>modeling. Chi²analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses.</p> <p>Conclusions</p> <p>This study revealed novel SNPs within the <it>PRDX6 </it>gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of <it>PRDX6 </it>genetic variation in other diseases, where oxidative stress is suspected.</p

Оценка влияния хронической боли на функциональный и физический статус пациентов старших возрастных групп

Objective: to assess the structure and influence of chronic pain (CP) on the functional status of patients with geriatric syndromes.Patients and methods. The study included 370 geriatric patients who were divided into two groups. Group A included 300 patients (mean age 75.1±8.25 years) with CP, and group B – 70 subjects of comparable age (75.1±7.75 years) without CP. All study participants were found to have polymorbidity: the Charlson index was 5.55±1.59 points in group A and 5.56±1.64 points in group B (p=0.963). All patients underwent a comprehensive geriatric assessment (CGE) to determine the functional status and diagnose geriatric syndromes.Results and discussion. According to the CGE data, senile asthenia syndrome was detected in 127 (42.3%) patients with CP and in 20 (28.6%) patients without CP (p=0.035). The average number of geriatric syndromes in group A was 7.06±2.68, in group B – 5.2±1.8 (p&lt;0.001).Group A patients differed from those without CP in a significantly higher degree of dependence in daily life (Bartel index) and a lower score on the Physical Performance Battery.Conclusion. Patients with CP have poorer physical functioning and a greater degree of dependence on others in their daily life. When planning the most effective complex strategies for the treatment and prevention of CP exacerbations, it is necessary to take into account the functional status of elderly patients. Цель исследования – оценка структуры и влияния хронической боли (ХБ) на функциональный статус пациентов с гериатрическими синдромами.Пациенты и методы. В исследование включено 370 гериатрических пациентов, которые были распределены в две группы. В группу А вошли 300 больных (средний возраст 75,1±8,25 года) с ХБ, а в группу В – 70 лиц сопоставимого возраста (75,1±7,75 года) без ХБ. У всех участников исследования выявлена полиморбидность: индекс Charlson составил 5,55±1,59 балла в группе А и 5,56±1,64 балла в группе В (р=0,963). Всем пациентам проводилась комплексная гериатрическая оценка (КГО) для определения функционального статуса и диагностики гериатрических синдромов.Результаты и обсуждение. По данным КГО синдром старческой астении выявлен у 127 (42,3%) пациентов с ХБ и у 20 (28,6%) без ХБ (р=0,035). Среднее число гериатрических синдромов в группе А равнялось 7,06±2,68, в группе В – 5,2±1,8 (р&lt;0,001).Пациенты группы А отличались от лиц без ХБ существенно большей степенью зависимости в повседневной жизни (индекс Бартел) и более низким баллом батареи тестов физического функционирования.Заключение. У пациентов с ХБ установлены худшее физическое функционирование и большая степень зависимости от окружающих в повседневной жизни. При планировании наиболее эффективных комплексных стратегий лечения и предупреждения обострений ХБ необходимо учитывать функциональный статус пожилых пациентов