Muscle transformation of the sartorius muscle in a canine model: clinical impact for electrodynamic graciloplasty as a "neosphincter"

PURPOSE: Transformation of fast-twitching skeletal muscles to slow-twitching, slowly fatigable muscles has become of clinical interest in the recent past. Transposition and transformation of the gracilis muscle to use it as a substitute for a resected or defected anal sphincter (graciloplasty) have been reported as achieving promising results in the treatment of fecal incontinence caused by sphincter defects or following abdominoperineal anorectal excision for cancer. METHOD: This experimental study used a canine model and the sartorius muscle to evaluate the functional efficiency of two different configurations of the muscle loop to compare the presently applied transformation program (8 weeks) with a shorter (5 weeks) protocol. In six beagle dogs, both sartorius muscles were wrapped around two stomas, either in an alpha fashion or in the so-called split-sling technique. Muscle transformation was achieved by controlled neuromuscular stimulation either during eight (Program A) or five weeks (Program B). After completion of the transformation period, the function of the muscle slings was evaluated by manometry, and histomorphologic evaluation of the sartorius muscles was performed. RESULTS: It was shown that muscle transformation led to a slowly fatigable muscle that made it possible to perform continuos (tetanic) contraction, regardless of the configuration or the duration of the transformation. Median pressures created by these muscles also did not differ significantly. In accordance with these functional findings, the histologic evaluation showed the typical, significant increase of Type I fibers in both muscle slings and following both transformation protocols. Although the decrease of fast-twitching Type II fibers was more pronounced following the conventional (8 weeks) program, this finding did not influence the functional results. CONCLUSIONS: Results of our experiment indicate the possibility for using a shorter transformation protocol for transformation of the gracilis muscle during graciloplasty in the clinical setting. Furthermore, the efficacy and safety of the modified (split-sling) wrap technique was demonstrated.     

滚球半径法确定瓦斯抽放泵站放空管合理安置区域

为了确定瓦斯抽放泵站放空管合理安置区域。在滚球半径法推算原理的基础上,利用几何知识,使用AutoCAD绘图软件绘制瓦斯抽放泵站放空管合理安置区域,而非传统方法的若干公式计算。AutoCAD绘图软件作图的方法避免了《GB 50057-2010建筑物防雷设计规范》附录D中传统方法繁琐的计算。确定瓦斯抽放泵站放空管合理安置区域作图法直观、简单、清晰、明了,简化了瓦斯抽放泵站防雷设计工作。为科学合理确定瓦斯抽放泵站放空管位置提供了依据。     

Effects of Catalyst Activity Profiles on the Operating Conditions of an Industrial Polymerization Reactor

The aim of this paper is to analyze how different catalyst activity profiles influence the operating strategies of industrial polymerization reactors. Since the catalyst activity profiles may change considerably in the range of the residence-time of the reactor, the properties of the produced polymer powder are the averages of ones produced by catalyst particles with various activities. Hence, the residence-time distribution of the polymer phase has an effect on the product properties as well. Based on these phenomena a new method is proposed to transform information from laboratory reactor into a form which can be used to estimate the operation condition of industrial reactor. The whole approach is demonstrated in case of the production of high-density polyethylene.     

Heterogeneous Labour Markets in a Microsimulation–AGE Model: Application to Welfare Reform in Germany

Labour market reforms that are designed to stimulate labour supply at the lower end of the wage distribution can never be precisely restricted to the target group. Spillovers to and feedback from other segments of the labour market are unavoidable and may counteract the direct effects of the reform. An adequate representation of heterogeneous labour markets becomes therefore an important issue for the assessment of reforms. We analyse the possible interactions between labour market segments in a combined, consistent microsimulation–AGE model with a flexible representation of substitution possibilities and different mechanisms of wage determination. We look at a stylised reform and find labour-demand cross-price elasticities between the low and medium skilled to be the main drivers of the results. Interaction with the high-skilled segment is less pronounced.      

Discrete Working Time Choice in an Applied General Equilibrium Model

We present a model that integrates the discrete working time choice of heterogenous households into a general equilibrium setting where wages are determined by sectoral bargaining between firms and trade unions. The model is calibrated to German micro and macro data. We then use it to analyse a stylised policy reform designed to stimulate labour supply. JEL Code: D58, J22, J51 An erratum to this article can be found at     

A mixed disulfide bond in bacterial glutathione transferase: functional and evolutionary implications

BACKGROUND: Glutathione S-transferases (GSTs) are a multifunctional group of enzymes, widely distributed in aerobic organisms, that have a critical role in the cellular detoxification process. Unlike their mammalian counterparts, bacterial GSTs often catalyze quite specific reactions, suggesting that their roles in bacteria might be different. The GST from Proteus mirabilis (PmGST B1-1) is known to bind certain antibiotics tightly and reduce the antimicrobial activity of beta-lactam drugs. Hence, bacterial GSTs may play a part in bacterial resistance towards antibiotics and are the subject of intense interest. RESULTS: Here we present the structure of a bacterial GST, PmGST B1-1, which has been determined from two different crystal forms. The enzyme adopts the canonical GST fold although it shares less than 20% sequence identity with GSTs from higher organisms. The most surprising aspect of the structure is the observation that the substrate, glutathione, is covalently bound to Cys 10 of the enzyme. In addition, the highly structurally conserved N-terminal domain is found to have an additional beta strand. CONCLUSIONS: The crystal structure of PmGST B1-1 has highlighted the importance of a cysteine residue in the catalytic cycle. Sequence analyses suggest that a number of other GSTs share this property, leading us to propose a new class of GSTs - the beta class. The data suggest that the in vivo role of the beta class GSTs could be as metabolic or redox enzymes rather than conjugating enzymes. Compelling evidence is presented that the theta class of GSTs evolved from an ancestral member of the thioredoxin superfamily.     

Stepwise transplantation of an active site loop between heat-labile enterotoxins LT-II and LT-I and characterization of the obtained hybrid toxins

Members of the cholera toxin family, including Escherichia coli heat- labile enterotoxins LT-I and LT-II, catalyze the covalent modification of intracellular proteins by transfer of ADP-ribose from NAD to a specific arginine of the target protein. The ADP-ribosylating activity of these toxins is located in the A-subunit, for which LT-I and LT-II share a 63% sequence identity. The flexible loop in LT-I, ranging from residue 47 to 56, closes over the active site cleft. Previous studies have shown that point mutations in this loop have dramatic effects on the activity of LT-I. Yet, in LT-II the sequence of the equivalent loop differs at four positions from LT-I. Therefore five mutants of the active site loop were created by a stepwise replacement of the loop sequence in LT-I with virtually all the corresponding residues in LT- II. Since we discovered that LT-II had no activity versus the artificial substrate diethylamino-benzylidine-aminoguanidine (DEABAG) while LT-I does, our active site mutants most likely probe the NAD binding, not the arginine binding region of the active site. The five hybrid toxins obtained (Q49A, F52N, V53T, Q49V/F52N and Q49V/F52N/V53T) show (i) great differences in holotoxin assembly efficiency; (ii) decreased cytotoxicity in Chinese hamster ovary cells; and (iii) increased in vitro enzymatic activity compared with wild type LT-I. Specifically, the three mutants containing the F52N substitution display a greater Vmax for NAD than wild type LT-I. The enzymatic activity of the V53T mutant is significantly higher than that of wild type LT-I. Apparently this subtle variation at position 53 is beneficial, in contrast to several other substitutions at position 53 which previously had been shown to be deleterious for activity. The most striking result of this study is that the active site loop of LT- I, despite great sensitivity for point mutations, can essentially be replaced by the active site loop of LT-II, yielding an active 'hybrid enzyme' as well as 'hybrid toxin'.      

Envisioning human-robot coordination in future operations

Developers of autonomous capabilities underestimate the need for coordination with human team members when their automata are deployed into complex operational settings. Automata are brittle as literal minded agents and there is a basic asymmetry in coordinative competencies between people and automata. The new capabilities of robotic systems raise new questions about how to support coordination. This paper presents a series of issues that demand innovation to achieve human-robot coordination (HRC). These include supporting people in their roles as problem holder and as robotic handler, overcoming ambiguities in remote perception, avoiding coordination surprises by better tools to see into future robotic activities and contingencies, and responsibility in human-robot teams.     

Relevance of aquatic biodegradation tests for predicting degradation of polymeric materials during biological solid waste treatment

L. A. Clark and D. Watson's (1991) tripartite model groups the symptoms of depression and anxiety into 3 components: nonspecific symptoms of general distress, which do not distinguish depression and anxiety; physiologic arousal, which is relatively unique to anxiety; and anhedonia (or low positive affect), which is unique to depression. Structural equation modeling was used to test this model with self-report data from 3 different samples: outpatients seeking treatment for mood disorder, anxiety disorder, or both (n = 483) outpatients seeking treatment for substance abuse (n = 453), and college students (n = 516). The tripartite model did not fit any of the sample covariance matrices, because the nonspecific symptoms of depression and anxiety could not be adequately represented by a single General Distress factor. An alternative model, in which the Anhedonia and Nonspecific Depression factors loaded on a second-order Depression factor, while the Somatic Arousal and Nonspecific Anxiety factors loaded on a second-order Anxiety factor, produced an excellent fit in all the groups. The Nonspecific Depression and Nonspecific Anxiety factors were the most valid and specific indicators of depression and anxiety, respectively. Anhedonia and Somatic Arousal were significantly less valid measures of depression and anxiety. The implications of these findings are discussed.