Incremental Branching Programs

We propose a new model of restricted branching programs specific to solving GEN problems, which we call incremental branching programs. We show that syntactic incremental branching programs capture previously studied models of computation for the problem GEN, namely marking machines (Cook, S.A. in J. Comput. Syst. Sci. 9(3):308–316, 1974) and Poon’s extension (Proc. of the 34th IEEE Symp. on the Foundations of Computer Science, pp. 218–227, 1993) of jumping automata on graphs (Cook, S.A., Rackoff, C.W. in SIAM J. Comput. 9:636–652, 1980). We then prove exponential size lower bounds for our syntactic incremental model, and for some other variants of branching program computation for GEN. We further show that nondeterministic syntactic incremental branching programs are provably stronger than their deterministic counterpart when solving a natural NL-complete GEN sub-problem. It remains open if syntactic incremental branching programs are as powerful as unrestricted branching programs for GEN problems. A preliminary version of this paper appears as (Gál, A., Koucky, M., McKenzie, P., Incremental branching programs, in Proc. of the 2006 Computer Science in Russia Conference CSR06. Lecture Notes in Computer Science, vol. 3967, pp. 178–190, 2006). A. Gal supported in part by NSF Grant CCF-0430695 and an Alfred P. Sloan Research Fellowship. M. Koucky did part of this work while being a postdoctoral fellow at McGill University, Canada and at CWI, Amsterdam, Netherlands. Supported in part by NWO vici project 2004–2009, project No. 1M0021620808 of MŠMT ČR, grants 201/07/P276, 201/05/0124 of GA ČR, and Institutional Research Plan No. AV0Z10190503. P. McKenzie supported by the NSERC of Canada and the (Québec) FQRNT.     

A Dynamic Network Oligopoly Model with Transportation Costs,Product Differentiation,and Quality Competition

This paper develops a new dynamic model of Cournot–Nash oligopolistic competition that includes production and transportation costs, product differentiation, and quality levels in a network framework. The production costs capture the total quality cost, which, in turn, can also represent the R&D cost. We first present the equilibrium version and derive alternative variational inequality formulations. We then construct the projected dynamical systems model, which provides a continuous-time evolution of the firms’ product shipments and product quality levels, and whose set of stationary points coincides with the set of solutions to the variational inequality problem. We establish stability analysis results using a monotonicity approach and construct a discrete-time version of the continuous-time adjustment process, which yields an algorithm, with closed form expressions at each iteration. The algorithm is then utilized to compute solutions to several numerical examples. The framework can serve as the foundation for the modeling and analysis of competition among firms in industries ranging from food to pharmaceuticals to durable goods and high tech products, as well as Internet services, where quality and product differentiation are seminal.     

基于去极化电流子谱线的油纸绝缘老化评估

去极化电流能够很好表征油纸绝缘系统介质响应过程.本文对去极化电流内部弛豫特性进行研究,引入子谱线和子谱线能量这两个新特征量,探讨子谱线能量与绝缘老化状况的关系,进而研究子谱线与油纸绝缘成分的对应关系,从而得到油纸绝缘老化的判别方法.研究结果表明子谱线能量对老化变化灵敏,它随绝缘水平的降低而显著增加;绝缘油的状态与小时间常数子谱线相关;绝缘纸的状态与大时间常数子谱线相关.因此,去极化电流子谱线及其能量可重点作为绝缘诊断的判据,其为准确评估油纸绝缘老化状态提供一种可靠有力的分析手段.     

STUDIES ON YEAST ESTERASE

An esterase (carboxylic acid hydrolase EC 3 1.1.1.) has been prepared from Saccharomyces cerevisiae. This esterase is active at pH 4.4 and, though it is unstable in solution, it can be maintained in an active form either by lyophilization or by coupling to an affinity gel. At pH 4.4, yeast esterase can hydrolyse between 20 and 40% of the esters commonly present in beer, and it is capable of synthesizing ethyl acetate from ethanol and acetic acid in a simple buffered solution without the provision of a co-factor. Different yeast strains yield different amounts of esterase, and there appears to be a positive correlation between the ability of the yeast to form esterase and the level of esters present in fermentations accomplished by that yeast.     

Critical Review on Fatty Acid-Based Food and Nutraceuticals as Supporting Therapy in Cancer

Fatty acids have an important place in both biological and nutritional contexts and, from a clinical point of view, they have known consequences for diseases’ onset and development, including cancer. The use of fatty acid-based food and nutraceuticals to support cancer therapy is a multidisciplinary subject, involving molecular and clinical research. Knowledge regarding polyunsaturated fatty acids essentiality/oxidizability and the role of lipogenesis-desaturase pathways for cell growth, as well as oxidative reactivity in cancer cells, are discussed, since they can drive the choice of fatty acids using their multiple roles to support antitumoral drug activity. The central role of membrane fatty acid composition is highlighted for the application of membrane lipid therapy. As fatty acids are also known as biomarkers of cancer onset and progression, the personalization of the fatty acid-based therapy is also possible, taking into account other important factors such as formulation, bioavailability and the distribution of the supplementation. A holistic approach emerges combining nutra- and pharma-strategies in an appropriate manner, to develop further knowledge and applications in cancer therapy.     

Progression and Dissemination of Pulmonary Mycobacterium Avium Infection in a Susceptible Immunocompetent Mouse Model

Pulmonary infections caused by the group of nontuberculosis mycobacteria (NTM), Mycobacterium avium complex (MAC), are a growing public health concern with incidence and mortality steadily increasing globally. Granulomatous inflammation is the hallmark of MAC lung infection, yet reliable correlates of disease progression, susceptibility, and resolution are poorly defined. Unlike widely used inbred mouse strains, mice that carry the mutant allele at the genetic locus sst1 develop human-like pulmonary tuberculosis featuring well-organized caseating granulomas. We characterized pulmonary temporospatial outcomes of intranasal and left intrabronchial M. avium spp. hominissuis (M.av) induced pneumonia in B6.Sst1S mice, which carries the sst1 mutant allele. We utilized traditional semi-quantitative histomorphological evaluation, in combination with fluorescent multiplex immunohistochemistry (fmIHC), whole slide imaging, and quantitative digital image analysis. Followingintrabronchiolar infection with the laboratory M.av strain 101, the B6.Sst1S pulmonary lesions progressed 12–16 weeks post infection (wpi), with plateauing and/or resolving disease by 21 wpi. Caseating granulomas were not observed during the study. Disease progression from 12–16 wpi was associated with increased acid-fast bacilli, area of secondary granulomatous pneumonia lesions, and Arg1+ and double positive iNOS+/Arg1+ macrophages. Compared to B6 WT, at 16 wpi, B6.Sst1S lungs exhibited an increased area of acid-fast bacilli, larger secondary lesions with greater Arg1+ and double positive iNOS+/Arg1+ macrophages, and reduced T cell density. This morphomolecular analysis of histologic correlates of disease progression in B6.Sst1S could serve as a platform for assessment of medical countermeasures against NTM infection.     

Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination

Dysfunctional mitochondria are linked to several neurodegenerative diseases. Metabolic defects, a symptom which can result from dysfunctional mitochondria, are also present in spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, the most frequent, dominantly inherited neurodegenerative ataxia worldwide. Mitochondrial dysfunction has been reported for several neurodegenerative disorders and ataxin-3 is known to deubiquitinylate parkin, a key protein required for canonical mitophagy. In this study, we analyzed mitochondrial function and mitophagy in a patient-derived SCA3 cell model. Human fibroblast lines isolated from SCA3 patients were immortalized and characterized. SCA3 patient fibroblasts revealed circular, ring-shaped mitochondria and featured reduced OXPHOS complexes, ATP production and cell viability. We show that wildtype ataxin-3 deubiquitinates VDAC1 (voltage-dependent anion channel 1), a member of the mitochondrial permeability transition pore and a parkin substrate. In SCA3 patients, VDAC1 deubiquitination and parkin recruitment to the depolarized mitochondria is inhibited. Increased p62-linked mitophagy, autophagosome formation and autophagy is observed under disease conditions, which is in line with mitochondrial fission. SCA3 fibroblast lines demonstrated a mitochondrial phenotype and dysregulation of parkin-VDAC1-mediated mitophagy, thereby promoting mitochondrial quality control via alternative pathways.     

The Effect of High and Variable Glucose on the Viability of Endothelial Cells Co-Cultured with Smooth Muscle Cells

Diabetes mellitus causes endothelial dysfunction. The aim of this study was to investigate the effect of normal (5 mmol/L), high (20 mmol/L), and fluctuating (5 and 20 mmol/L changed every day) glucose concentration in the culture medium on the viability of human umbilical vein endothelial cells (HUVECs) co-cultured with human umbilical artery smooth muscle cells (HUASMCs). The cultures were conducted on semi-permeable flat polysulfone (PSU) fibronectin-coated membranes immobilized in self-made inserts. The insert contained either HUVECs on a single membrane or HUASMCs and HUVECs on two membranes close to each other. Cultures were conducted for 7 or 14 days. Apoptosis, mitochondrial potential, and the production of reactive oxygen species and lactate by HUVECs were investigated. The results indicate that fluctuations in glucose concentration have a stronger negative effect on HUVECs viability than constant high glucose concentration. High and fluctuating glucose concentrations slow down cell proliferation compared to the culture carried out in the medium with normal glucose concentration. In conclusion, HUASMCs affect the viability of HUVECs when both types of cells are co-cultured in medium with normal or variable glucose concentration.     

Early Postoperative Immunothrombosis of Bioprosthetic Mitral Valve and Left Atrium: A Case Report

A 72-year-old female patient with mixed rheumatic mitral valve disease and persistent atrial fibrillation underwent mitral valve replacement and suffered from a combined thrombosis of the bioprosthetic valve and the left atrium as soon as 2 days post operation. The patient immediately underwent repeated valve replacement and left atrial thrombectomy. Yet, four days later the patient died due to the recurrent prosthetic valve and left atrial thrombosis which both resulted in an extremely low cardiac output. In this patient’s case, the thrombosis was notable for the resistance to anticoagulant therapy as well as for aggressive neutrophil infiltration and release of neutrophil extracellular traps (NETs) within the clot, as demonstrated by immunostaining. The reasons behind these phenomena remained unclear, as no signs of sepsis or contamination of the BHV were documented, although the patient was diagnosed with inherited thrombophilia that could impede the fibrinolysis. The described case highlights the hazard of immunothrombosis upon valve replacement and elucidates its mechanisms in this surgical setting.