Programmed Evolution for Optimization of Orthogonal Metabolic Output in Bacteria

Science.gov (United States)

Eckdahl, Todd T.; Campbell, A. Malcolm; Heyer, Laurie J.; Poet, Jeffrey L.; Blauch, David N.; Snyder, Nicole L.; Atchley, Dustin T.; Baker, Erich J.; Brown, Micah; Brunner, Elizabeth C.; Callen, Sean A.; Campbell, Jesse S.; Carr, Caleb J.; Carr, David R.; Chadinha, Spencer A.; Chester, Grace I.; Chester, Josh; Clarkson, Ben R.; Cochran, Kelly E.; Doherty, Shannon E.; Doyle, Catherine; Dwyer, Sarah; Edlin, Linnea M.; Evans, Rebecca A.; Fluharty, Taylor; Frederick, Janna; Galeota-Sprung, Jonah; Gammon, Betsy L.; Grieshaber, Brandon; Gronniger, Jessica; Gutteridge, Katelyn; Henningsen, Joel; Isom, Bradley; Itell, Hannah L.; Keffeler, Erica C.; Lantz, Andrew J.; Lim, Jonathan N.; McGuire, Erin P.; Moore, Alexander K.; Morton, Jerrad; Nakano, Meredith; Pearson, Sara A.; Perkins, Virginia; Parrish, Phoebe; Pierson, Claire E.; Polpityaarachchige, Sachith; Quaney, Michael J.; Slattery, Abagael; Smith, Kathryn E.; Spell, Jackson; Spencer, Morgan; Taye, Telavive; Trueblood, Kamay; Vrana, Caroline J.; Whitesides, E. Tucker

2015-01-01

Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields – evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy

Optimization of multiple performance characteristics in turning using Taguchi’s quality loss function: An experimental investigation

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Tanmaya Mohanty

2013-06-01

Full Text Available Cutting force and chip reduction coefficient is the important index of machinability as it determines the power consumption and amount of energy invested in machining actions. It is primarily influenced by process parameters like cutting speed, feed and depth of cut. This paper presents the application of Taguchi’s parameter design to optimize the parameters for individual responses. For multi-response optimization, Taguchi’s quality loss function approach is proposed. In the present investigation, optimal values of cutting speed, feed and depth of cut are determined to minimize cutting force and chip reduction coefficient during orthogonal turning. The effectiveness of the proposed methodology is illustrated through an experimental investigation in turning mild steel workpiece using high speed steel tool.

Process planning optimization on turning machine tool using a hybrid genetic algorithm with local search approach

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Yuliang Su

2015-04-01

Full Text Available A turning machine tool is a kind of new type of machine tool that is equipped with more than one spindle and turret. The distinctive simultaneous and parallel processing abilities of turning machine tool increase the complexity of process planning. The operations would not only be sequenced and satisfy precedence constraints, but also should be scheduled with multiple objectives such as minimizing machining cost, maximizing utilization of turning machine tool, and so on. To solve this problem, a hybrid genetic algorithm was proposed to generate optimal process plans based on a mixed 0-1 integer programming model. An operation precedence graph is used to represent precedence constraints and help generate a feasible initial population of hybrid genetic algorithm. Encoding strategy based on data structure was developed to represent process plans digitally in order to form the solution space. In addition, a local search approach for optimizing the assignments of available turrets would be added to incorporate scheduling with process planning. A real-world case is used to prove that the proposed approach could avoid infeasible solutions and effectively generate a global optimal process plan.

Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

NARCIS (Netherlands)

Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

2000-01-01

The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

A mathematical framework for yield (vs. rate) optimization in constraint-based modeling and applications in metabolic engineering.

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Klamt, Steffen; Müller, Stefan; Regensburger, Georg; Zanghellini, Jürgen

2018-02-07

The optimization of metabolic rates (as linear objective functions) represents the methodical core of flux-balance analysis techniques which have become a standard tool for the study of genome-scale metabolic models. Besides (growth and synthesis) rates, metabolic yields are key parameters for the characterization of biochemical transformation processes, especially in the context of biotechnological applications. However, yields are ratios of rates, and hence the optimization of yields (as nonlinear objective functions) under arbitrary linear constraints is not possible with current flux-balance analysis techniques. Despite the fundamental importance of yields in constraint-based modeling, a comprehensive mathematical framework for yield optimization is still missing. We present a mathematical theory that allows one to systematically compute and analyze yield-optimal solutions of metabolic models under arbitrary linear constraints. In particular, we formulate yield optimization as a linear-fractional program. For practical computations, we transform the linear-fractional yield optimization problem to a (higher-dimensional) linear problem. Its solutions determine the solutions of the original problem and can be used to predict yield-optimal flux distributions in genome-scale metabolic models. For the theoretical analysis, we consider the linear-fractional problem directly. Most importantly, we show that the yield-optimal solution set (like the rate-optimal solution set) is determined by (yield-optimal) elementary flux vectors of the underlying metabolic model. However, yield- and rate-optimal solutions may differ from each other, and hence optimal (biomass or product) yields are not necessarily obtained at solutions with optimal (growth or synthesis) rates. Moreover, we discuss phase planes/production envelopes and yield spaces, in particular, we prove that yield spaces are convex and provide algorithms for their computation. We illustrate our findings by a small

Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering.

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Liu, Yang; Liu, Ye; Wang, Meng

2017-01-01

The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors.

Minimum-fuel turning climbout and descent guidance of transport jets

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Neuman, F.; Kreindler, E.

1983-01-01

The complete flightpath optimization problem for minimum fuel consumption from takeoff to landing including the initial and final turns from and to the runway heading is solved. However, only the initial and final segments which contain the turns are treated, since the straight-line climbout, cruise, and descent problems have already been solved. The paths are derived by generating fields of extremals, using the necessary conditions of optimal control together with singular arcs and state constraints. Results show that the speed profiles for straight flight and turning flight are essentially identical except for the final horizontal accelerating or decelerating turns. The optimal turns require no abrupt maneuvers, and an approximation of the optimal turns could be easily integrated with present straight-line climb-cruise-descent fuel-optimization algorithms. Climbout at the optimal IAS rather than the 250-knot terminal-area speed limit would save 36 lb of fuel for the 727-100 aircraft.

Multiobjective Optimization of Turning Cutting Parameters for J-Steel Material

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Adel T. Abbas

2016-01-01

Full Text Available This paper presents a multiobjective optimization study of cutting parameters in turning operation for a heat-treated alloy steel material (J-Steel with Vickers hardness in the range of HV 365–395 using uncoated, unlubricated Tungsten-Carbide tools. The primary aim is to identify proper settings of the cutting parameters (cutting speed, feed rate, and depth of cut that lead to reasonable compromises between good surface quality and high material removal rate. Thorough exploration of the range of cutting parameters was conducted via a five-level full-factorial experimental matrix of samples and the Pareto trade-off frontier is identified. The trade-off among the objectives was observed to have a “knee” shape, in which certain settings for the cutting parameters can achieve both good surface quality and high material removal rate within certain limits. However, improving one of the objectives beyond these limits can only happen at the expense of a large compromise in the other objective. An alternative approach for identifying the trade-off frontier was also tested via multiobjective implementation of the Efficient Global Optimization (m-EGO algorithm. The m-EGO algorithm was successful in identifying two points within the good range of the trade-off frontier with 36% fewer experimental samples.

Turn over management and optimization of Shangdong nuclear power plant

International Nuclear Information System (INIS)

Zheng Tong

2014-01-01

After the equipments' installation is completed, the system will carry out commissioning tests. After commissioning work is completed, the system will be transferred to temporary operation. The plant buildings and structures will be transferred to operation for management and maintenance after civil work. The turn over work is an important part of the transfer from construction to operation. The article describes the significance of the nuclear power plant turn over work, turn over organization and management mode, the workflow of system turn over from construction to commissioning (TOP), turn over form commissioning to operation (TOTO), house hand over (HHO), building hand over (BHO) of Shandong Haiyang nuclear power plant, and analyze the current lack and future improvements of turn over work. Shandong Haiyang nuclear power plant will usher in the peak period of turn over work in 2013, fully aware of the importance of the turn over work, will play a key role in the long-term stable operation of the unit. (author)

Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

DEFF Research Database (Denmark)

Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup

2016-01-01

Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches...... for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

Multi objective optimization model for minimizing production cost and environmental impact in CNC turning process

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Widhiarso, Wahyu; Rosyidi, Cucuk Nur

2018-02-01

Minimizing production cost in a manufacturing company will increase the profit of the company. The cutting parameters will affect total processing time which then will affect the production cost of machining process. Besides affecting the production cost and processing time, the cutting parameters will also affect the environment. An optimization model is needed to determine the optimum cutting parameters. In this paper, we develop an optimization model to minimize the production cost and the environmental impact in CNC turning process. The model is used a multi objective optimization. Cutting speed and feed rate are served as the decision variables. Constraints considered are cutting speed, feed rate, cutting force, output power, and surface roughness. The environmental impact is converted from the environmental burden by using eco-indicator 99. Numerical example is given to show the implementation of the model and solved using OptQuest of Oracle Crystal Ball software. The results of optimization indicate that the model can be used to optimize the cutting parameters to minimize the production cost and the environmental impact.

Optimization of a blueprint for in vitro glycolysis by metabolic real-time analysis

NARCIS (Netherlands)

Bujara, Matthias; Schümperli, Michael; Pellaux, René; Heinemann, Matthias; Panke, Sven

Recruiting complex metabolic reaction networks for chemical synthesis has attracted considerable attention but frequently requires optimization of network composition and dynamics to reach sufficient productivity. As a design framework to predict optimal levels for all enzymes in the network is

Application of dragonfly algorithm for optimal performance analysis of process parameters in turn-mill operations- A case study

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Vikram, K. Arun; Ratnam, Ch; Lakshmi, VVK; Kumar, A. Sunny; Ramakanth, RT

2018-02-01

Meta-heuristic multi-response optimization methods are widely in use to solve multi-objective problems to obtain Pareto optimal solutions during optimization. This work focuses on optimal multi-response evaluation of process parameters in generating responses like surface roughness (Ra), surface hardness (H) and tool vibration displacement amplitude (Vib) while performing operations like tangential and orthogonal turn-mill processes on A-axis Computer Numerical Control vertical milling center. Process parameters like tool speed, feed rate and depth of cut are considered as process parameters machined over brass material under dry condition with high speed steel end milling cutters using Taguchi design of experiments (DOE). Meta-heuristic like Dragonfly algorithm is used to optimize the multi-objectives like ‘Ra’, ‘H’ and ‘Vib’ to identify the optimal multi-response process parameters combination. Later, the results thus obtained from multi-objective dragonfly algorithm (MODA) are compared with another multi-response optimization technique Viz. Grey relational analysis (GRA).

Optimal decoding and information transmission in Hodgkin-Huxley neurons under metabolic cost constraints.

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Kostal, Lubomir; Kobayashi, Ryota

2015-10-01

Information theory quantifies the ultimate limits on reliable information transfer by means of the channel capacity. However, the channel capacity is known to be an asymptotic quantity, assuming unlimited metabolic cost and computational power. We investigate a single-compartment Hodgkin-Huxley type neuronal model under the spike-rate coding scheme and address how the metabolic cost and the decoding complexity affects the optimal information transmission. We find that the sub-threshold stimulation regime, although attaining the smallest capacity, allows for the most efficient balance between the information transmission and the metabolic cost. Furthermore, we determine post-synaptic firing rate histograms that are optimal from the information-theoretic point of view, which enables the comparison of our results with experimental data. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

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Vijayaraghava T S Rao

Full Text Available Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination. Here, we directly compare the metabolic profiles of oligodendrocytes derived from adult rat brain with oligodendrocytes newly differentiated in vitro from oligodendrocyte progenitor cells obtained from the post natal rat brain, under both optimal culture and metabolic stress (low/no glucose conditions. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Our findings indicate that under optimal conditions, adult rat oligodendrocytes preferentially use glycolysis whereas newly differentiated post natal rat oligodendrocytes, and the oligodendrocyte progenitor cells from which they are derived, mainly utilize oxidative phosphorylation to produce ATP. Metabolic stress increases the rate of ATP production via oxidative phosphorylation and significantly reduces glycolysis in adult oligodendrocytes. The rate of ATP production was relatively unchanged in newly differentiated post natal oligodendrocytes under these stress conditions, while it was significantly reduced in oligodendrocyte progenitor cells. Our study indicates that both age and maturation influence the metabolic profile under optimal and stressed conditions, emphasizing the need to consider these variables for in vitro studies that aim to model adult human disease.

13C metabolic flux analysis: optimal design of isotopic labeling experiments.

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Antoniewicz, Maciek R

2013-12-01

Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Turn-Based War Chess Model and Its Search Algorithm per Turn

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Hai Nan

2016-01-01

Full Text Available War chess gaming has so far received insufficient attention but is a significant component of turn-based strategy games (TBS and is studied in this paper. First, a common game model is proposed through various existing war chess types. Based on the model, we propose a theory frame involving combinational optimization on the one hand and game tree search on the other hand. We also discuss a key problem, namely, that the number of the branching factors of each turn in the game tree is huge. Then, we propose two algorithms for searching in one turn to solve the problem: (1 enumeration by order; (2 enumeration by recursion. The main difference between these two is the permutation method used: the former uses the dictionary sequence method, while the latter uses the recursive permutation method. Finally, we prove that both of these algorithms are optimal, and we analyze the difference between their efficiencies. An important factor is the total time taken for the unit to expand until it achieves its reachable position. The factor, which is the total number of expansions that each unit makes in its reachable position, is set. The conclusion proposed is in terms of this factor: Enumeration by recursion is better than enumeration by order in all situations.

Optimization of lysine metabolism in Corynebacterium glutamicum

DEFF Research Database (Denmark)

Rytter, Jakob Vang

,000,000 tons. The aim of this project is to optimize the yield of lysine in C. glutamicum using metabolic engineering strategies. According to a genome scale model of C. glutamicum, theoretically there is much room for increasing the lysine yield (Kjeldsen and Nielsen 2009). Lysine synthesis requires NADPH......Commercial pig and poultry production use the essential amino acid lysine as a feed additive with the purpose of optimizing the feed utilization. Lysine is produced by a fermentation process involving either Corynebacterium glutamicum or Escherichia coli. The global annual production is around 1...... the project intends to eliminate. PGI catalyzes the conversion of alpha-D-glucose-6-phosphate to fructose-6-phosphate just downstream of the branch in the glycolysis, but it also catalyzes the reverse reaction. It is unknown whether up- or down-regulation of the pgi is required to increase the flux through...

Simulation Modeling to Compare High-Throughput, Low-Iteration Optimization Strategies for Metabolic Engineering.

Science.gov (United States)

Heinsch, Stephen C; Das, Siba R; Smanski, Michael J

2018-01-01

Increasing the final titer of a multi-gene metabolic pathway can be viewed as a multivariate optimization problem. While numerous multivariate optimization algorithms exist, few are specifically designed to accommodate the constraints posed by genetic engineering workflows. We present a strategy for optimizing expression levels across an arbitrary number of genes that requires few design-build-test iterations. We compare the performance of several optimization algorithms on a series of simulated expression landscapes. We show that optimal experimental design parameters depend on the degree of landscape ruggedness. This work provides a theoretical framework for designing and executing numerical optimization on multi-gene systems.

Sequential metabolic phases as a means to optimize cellular output in a constant environment.

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Palinkas, Aljoscha; Bulik, Sascha; Bockmayr, Alexander; Holzhütter, Hermann-Georg

2015-01-01

Temporal changes of gene expression are a well-known regulatory feature of all cells, which is commonly perceived as a strategy to adapt the proteome to varying external conditions. However, temporal (rhythmic and non-rhythmic) changes of gene expression are also observed under virtually constant external conditions. Here we hypothesize that such changes are a means to render the synthesis of the metabolic output more efficient than under conditions of constant gene activities. In order to substantiate this hypothesis, we used a flux-balance model of the cellular metabolism. The total time span spent on the production of a given set of target metabolites was split into a series of shorter time intervals (metabolic phases) during which only selected groups of metabolic genes are active. The related flux distributions were calculated under the constraint that genes can be either active or inactive whereby the amount of protein related to an active gene is only controlled by the number of active genes: the lower the number of active genes the more protein can be allocated to the enzymes carrying non-zero fluxes. This concept of a predominantly protein-limited efficiency of gene expression clearly differs from other concepts resting on the assumption of an optimal gene regulation capable of allocating to all enzymes and transporters just that fraction of protein necessary to prevent rate limitation. Applying this concept to a simplified metabolic network of the central carbon metabolism with glucose or lactate as alternative substrates, we demonstrate that switching between optimally chosen stationary flux modes comprising different sets of active genes allows producing a demanded amount of target metabolites in a significantly shorter time than by a single optimal flux mode at fixed gene activities. Our model-based findings suggest that temporal expression of metabolic genes can be advantageous even under conditions of constant external substrate supply.

Multi-response optimization of process parameters using Taguchi method and grey relational analysis during turning AA 7075/SiC composite in dry and spray cooling environments

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P. C. Mishra

2015-09-01

Full Text Available Turning experiments were carried out on AA 7075/SiC composite workpiece in dry and spray cooling environments based on L16 Taguchi design of experiments. Multiple performance optimization of process parameters was performed using grey relational analysis. The performance characteristics considered were average surface roughness, cutting tool temperature and material removal rate. Uncoated carbide inserts were used for machining the workpiece in a high speed precision lathe. A grey relational grade obtained from grey relational analysis was used to optimize the process parameters. Optimal combination of process parameters was then determined by the Taguchi method using the grey relational grade as the performance index. Experimental results indicated that the turning in spray cooling environment was beneficial compared to that in dry environment for the quality response characteristics under consideration. Analysis of variance showed that feed was the most significant parameter for the multiple performance characteristics during turning in both the environments.

Identification of metabolic system parameters using global optimization methods

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Gatzke Edward P

2006-01-01

Full Text Available Abstract Background The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. Methods and results Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. Conclusion The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.

Taguchi Optimization of Cutting Parameters in Turning AISI 1020 MS with M2 HSS Tool

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Sonowal, Dharindom; Sarma, Dhrupad; Bakul Barua, Parimal; Nath, Thuleswar

2017-08-01

In this paper the effect of three cutting parameters viz. Spindle speed, Feed and Depth of Cut on surface roughness of AISI 1020 mild steel bar in turning was investigated and optimized to obtain minimum surface roughness. All the experiments are conducted on HMT LB25 lathe machine using M2 HSS cutting tool. Ranges of parameters of interest have been decided through some preliminary experimentation (One Factor At a Time experiments). Finally a combined experiment has been carried out using Taguchi’s L27 Orthogonal Array (OA) to study the main effect and interaction effect of the all three parameters. The experimental results were analyzed with raw data ANOVA (Analysis of Variance) and S/N data (Signal to Noise ratio) ANOVA. Results show that Spindle speed, Feed and Depth of Cut have significant effects on both mean and variation of surface roughness in turning AISI 1020 mild steel. Mild two factors interactions are observed among the aforesaid factors with significant effects only on the mean of the output variable. From the Taguchi parameter optimization the optimum factor combination is found to be 630 rpm spindle speed, 0.05 mm/rev feed and 1.25 mm depth of cut with estimated surface roughness 2.358 ± 0.970 µm. A confirmatory experiment was conducted with the optimum factor combination to verify the results. In the confirmatory experiment the average value of surface roughness is found to be 2.408 µm which is well within the range (0.418 µm to 4.299 µm) predicted for confirmatory experiment.

Factors Affecting Optimal Surface Roughness of AISI 4140 Steel in Turning Operation Using Taguchi Experiment

Science.gov (United States)

Novareza, O.; Sulistiyarini, D. H.; Wiradmoko, R.

2018-02-01

This paper presents the result of using Taguchi method in turning process of medium carbon steel of AISI 4140. The primary concern is to find the optimal surface roughness after turning process. The taguchi method is used to get a combination of factors and factor levels in order to get the optimum surface roughness level. Four important factors with three levels were used in experiment based on Taguchi method. A number of 27 experiments were carried out during the research and analysed using analysis of variance (ANOVA) method. The result of surface finish was determined in Ra type surface roughness. The depth of cut was found to be the most important factors for reducing the surface roughness of AISI 4140 steel. On the contrary, the other important factors i.e. spindle speed and rake side angle of the tool were proven to be less factors that affecting the surface finish. It is interesting to see the effect of coolant composition that gained the second important factors to reduce the roughness. It may need further research to explain this result.

Effects of catecholamines on rat myocardial metabolism. II. Influence of catecholamines on 32p-incorporation into rat myocardial adenylic nucleotides and their turn-over.

Science.gov (United States)

Merouze, P; Gaudemer, Y; Gautheron, D

1975-01-01

1. The influence of catecholamines (adrenaline and noradrenaline) on 32Pi incorporation into intracellular phosphate and adenylic nucleotides has been studied on rat myocardium slices; consequently, the turn-over of nucleotides could be determined and compared under the influence of these two hormones. 2. In order to specify the site of action of these catecholamines, several inhibitors and activators of energetic metabolism were included in the incubation medium: 3'5'-AMP, caffein, ouabain, oligomycin, rotenone + antimycin. 3. Both catecholamines favour Pi exchanges between intra and extracellular spaces; ATP turn-over is greatly increased, while ADP turn-over is slightly decreased, and 32P-incorporation into ADP is increased. 4. 3'5'-AMP and caffein are without effect on Pi penetration; however, caffein increases catecholamine effects on this penetration. ATP turn-over is slightly increased by 3'5'-AMP or caffein. 5. Ouabain decreases ATP turn-over but does not prevent the adrenaline induced acceleration. Inhibitors of oxidative phosphorylation and electron transport decrease ATP-turn-over severely; this inhibition is not released by catecholamines. 6. It is concluded that the catecholamine effects observed are dependent on the oxidative phosphorylations process. The increase of Pi exchange by catecholamines may be related to the increase of extracellular space and cation translocations we observed with the hormones.

STATISTICAL APPROACH FOR MULTI CRITERIA OPTIMIZATION OF CUTTING PARAMETERS OF TURNING ON HEAT TREATED BERYLLIUM COPPER ALLOY

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K. DEVAKI DEVI

2017-08-01

Full Text Available In machining operations, achieving desired performance features of the machined product, is really a challenging job. Because, these quality features are highly correlated and are expected to be influenced directly or indirectly by the direct effect of process parameters or their interactive effects. This paper presents effective method and to determine optimal machining parameters in a turning operation on heat treated Beryllium copper alloy to minimize the surface roughness, cutting forces and work tool interface temperature along with the maximization of metal removal rate. The scope of this work is extended to Multi Objective Optimization. Response Surface Methodology is opted for preparing the design matrix, generating ANOVA, and optimization. A powerful model would be obtained with high accuracy to analyse the effect of each parameter on the output. The input parameters considered in this work are cutting speed, feed, depth of cut, work material (Annealed and Hardened and tool material (CBN and HSS.

Effect of type and percentage of reinforcement for optimization of the cutting force in turning of Aluminium matrix nanocomposites using response surface methodologies

Energy Technology Data Exchange (ETDEWEB)

Priyadarshi, Devinder [DAV Institute of Engineering and Technology, Jalandhar (India); Sharma, Rajesh Kumar [Institute of Technology, Hamirpur (India)

2016-03-15

Aluminium matrix composites (AMCs) now hold a significant share of raw materials in many applications. It is of prime importance to study the machinability of such composites so as to enhance their applicability. Sufficient work has been done for studying the machining of AMCs with particle reinforcements of micron range. This paper presents the study of AMCs with particle reinforcement of under micron range i.e. nanoparticles. This paper brings out the results of an experimental investigation of type and weight percent of nanoparticles on the tangential cutting force during turning operation. SiC, Gr and SiC-Gr (in equal proportions) were used with Al-6061 alloy as the matrix phase. The results indicate that composites with SiC require greater cutting force followed by hybrid and then Gr. Increase in the weight percent also significantly affected the magnitude of cutting force. RSM was used first to design and analyze the experiments and then to optimize the turning process and obtain optimal conditions of weight and type of reinforcements for turning operation.

Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

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Carlos Pozo

Full Text Available Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study

Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

Science.gov (United States)

Pozo, Carlos; Guillén-Gosálbez, Gonzalo; Sorribas, Albert; Jiménez, Laureano

2012-01-01

Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the

Mathematical simulation and optimization of cutting mode in turning of workpieces made of nickel-based heat-resistant alloy

Science.gov (United States)

Bogoljubova, M. N.; Afonasov, A. I.; Kozlov, B. N.; Shavdurov, D. E.

2018-05-01

A predictive simulation technique of optimal cutting modes in the turning of workpieces made of nickel-based heat-resistant alloys, different from the well-known ones, is proposed. The impact of various factors on the cutting process with the purpose of determining optimal parameters of machining in concordance with certain effectiveness criteria is analyzed in the paper. A mathematical model of optimization, algorithms and computer programmes, visual graphical forms reflecting dependences of the effectiveness criteria – productivity, net cost, and tool life on parameters of the technological process - have been worked out. A nonlinear model for multidimensional functions, “solution of the equation with multiple unknowns”, “a coordinate descent method” and heuristic algorithms are accepted to solve the problem of optimization of cutting mode parameters. Research shows that in machining of workpieces made from heat-resistant alloy AISI N07263, the highest possible productivity will be achieved with the following parameters: cutting speed v = 22.1 m/min., feed rate s=0.26 mm/rev; tool life T = 18 min.; net cost – 2.45 per hour.

Comparative Assessment of Cutting Inserts and Optimization during Hard Turning: Taguchi-Based Grey Relational Analysis

Science.gov (United States)

Venkata Subbaiah, K.; Raju, Ch.; Suresh, Ch.

2017-08-01

The present study aims to compare the conventional cutting inserts with wiper cutting inserts during the hard turning of AISI 4340 steel at different workpiece hardness. Type of insert, hardness, cutting speed, feed, and depth of cut are taken as process parameters. Taguchi’s L18 orthogonal array was used to conduct the experimental tests. Parametric analysis carried in order to know the influence of each process parameter on the three important Surface Roughness Characteristics (Ra, Rz, and Rt) and Material Removal Rate. Taguchi based Grey Relational Analysis (GRA) used to optimize the process parameters for individual response and multi-response outputs. Additionally, the analysis of variance (ANOVA) is also applied to identify the most significant factor.

ANN Surface Roughness Optimization of AZ61 Magnesium Alloy Finish Turning: Minimum Machining Times at Prime Machining Costs

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Adel Taha Abbas

2018-05-01

Full Text Available Magnesium alloys are widely used in aerospace vehicles and modern cars, due to their rapid machinability at high cutting speeds. A novel Edgeworth–Pareto optimization of an artificial neural network (ANN is presented in this paper for surface roughness (Ra prediction of one component in computer numerical control (CNC turning over minimal machining time (Tm and at prime machining costs (C. An ANN is built in the Matlab programming environment, based on a 4-12-3 multi-layer perceptron (MLP, to predict Ra, Tm, and C, in relation to cutting speed, vc, depth of cut, ap, and feed per revolution, fr. For the first time, a profile of an AZ61 alloy workpiece after finish turning is constructed using an ANN for the range of experimental values vc, ap, and fr. The global minimum length of a three-dimensional estimation vector was defined with the following coordinates: Ra = 0.087 μm, Tm = 0.358 min/cm3, C = $8.2973. Likewise, the corresponding finish-turning parameters were also estimated: cutting speed vc = 250 m/min, cutting depth ap = 1.0 mm, and feed per revolution fr = 0.08 mm/rev. The ANN model achieved a reliable prediction accuracy of ±1.35% for surface roughness.

Optimization on Turning Parameters of 15-5PH Stainless Steel Using Taguchi Based Grey Approach and Topsis

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Palanisamy D.

2016-09-01

Full Text Available The machinability and the process parameter optimization of turning operation for 15-5 Precipitation Hardening (PH stainless steel have been investigated based on the Taguchi based grey approach and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS. An L27 orthogonal array was selected for planning the experiment. Cutting speed, depth of cut and feed rate were considered as input process parameters. Cutting force (Fz and surface roughness (Ra were considered as the performance measures. These performance measures were optimized for the improvement of machinability quality of product. A comparison is made between the multi-criteria decision making tools. Grey Relational Analysis (GRA and TOPSIS are used to confirm and prove the similarity. To determine the influence of process parameters, Analysis of Variance (ANOVA is employed. The end results of experimental investigation proved that the machining performance can be enhanced effectively with the assistance of the proposed approaches.

Enzyme allocation problems in kinetic metabolic networks: Optimal solutions are elementary flux modes

Czech Academy of Sciences Publication Activity Database

Müller, Stefan; Regensburger, G.; Steuer, Ralf

2014-01-01

Roč. 347, APR 2014 (2014), s. 182-190 ISSN 0022-5193 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : metabolic optimization * enzyme kinetics * oriented matroid * elementary vector * conformal sum Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.116, year: 2014

Artificial Promoters for Metabolic Optimization

DEFF Research Database (Denmark)

Jensen, Peter Ruhdal; Hammer, Karin

1998-01-01

In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms...

ANN Surface Roughness Optimization of AZ61 Magnesium Alloy Finish Turning: Minimum Machining Times at Prime Machining Costs.

Science.gov (United States)

Abbas, Adel Taha; Pimenov, Danil Yurievich; Erdakov, Ivan Nikolaevich; Taha, Mohamed Adel; Soliman, Mahmoud Sayed; El Rayes, Magdy Mostafa

2018-05-16

Magnesium alloys are widely used in aerospace vehicles and modern cars, due to their rapid machinability at high cutting speeds. A novel Edgeworth⁻Pareto optimization of an artificial neural network (ANN) is presented in this paper for surface roughness ( Ra ) prediction of one component in computer numerical control (CNC) turning over minimal machining time ( T m ) and at prime machining costs ( C ). An ANN is built in the Matlab programming environment, based on a 4-12-3 multi-layer perceptron (MLP), to predict Ra , T m , and C , in relation to cutting speed, v c , depth of cut, a p , and feed per revolution, f r . For the first time, a profile of an AZ61 alloy workpiece after finish turning is constructed using an ANN for the range of experimental values v c , a p , and f r . The global minimum length of a three-dimensional estimation vector was defined with the following coordinates: Ra = 0.087 μm, T m = 0.358 min/cm³, C = $8.2973. Likewise, the corresponding finish-turning parameters were also estimated: cutting speed v c = 250 m/min, cutting depth a p = 1.0 mm, and feed per revolution f r = 0.08 mm/rev. The ANN model achieved a reliable prediction accuracy of ±1.35% for surface roughness.

A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories

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Amanda K. Fisher

2014-08-01

Full Text Available Microbial cell factories (MCFs are of considerable interest to convert low value renewable substrates to biofuels and high value chemicals. This review highlights the progress of computational models for the rational design of an MCF to produce a target bio-commodity. In particular, the rational design of an MCF involves: (i product selection, (ii de novo biosynthetic pathway identification (i.e., rational, heterologous, or artificial, (iii MCF chassis selection, (iv enzyme engineering of promiscuity to enable the formation of new products, and (v metabolic engineering to ensure optimal use of the pathway by the MCF host. Computational tools such as (i de novo biosynthetic pathway builders, (ii docking, (iii molecular dynamics (MD and steered MD (SMD, and (iv genome-scale metabolic flux modeling all play critical roles in the rational design of an MCF. Genome-scale metabolic flux models are of considerable use to the design process since they can reveal metabolic capabilities of MCF hosts. These can be used for host selection as well as optimizing precursors and cofactors of artificial de novo biosynthetic pathways. In addition, recent advances in genome-scale modeling have enabled the derivation of metabolic engineering strategies, which can be implemented using the genomic tools reviewed here as well.

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

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Monique E. Francois

2017-10-01

Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

Science.gov (United States)

Francois, Monique E; Gillen, Jenna B; Little, Jonathan P

2017-01-01

Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT) have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Optimization of cutting parameters in CNC turning of stainless steel 304 with TiAlN nano coated carbide cutting tool

Science.gov (United States)

Durga Prasada Rao, V.; Harsha, N.; Raghu Ram, N. S.; Navya Geethika, V.

2018-02-01

In this work, turning was performed to optimize the surface finish or roughness (Ra) of stainless steel 304 with uncoated and coated carbide tools under dry conditions. The carbide tools were coated with Titanium Aluminium Nitride (TiAlN) nano coating using Physical Vapour Deposition (PVD) method. The machining parameters, viz., cutting speed, depth of cut and feed rate which show major impact on Ra are considered during turning. The experiments are designed as per Taguchi orthogonal array and machining process is done accordingly. Then second-order regression equations have been developed on the basis of experimental results for Ra in terms of machining parameters used. Regarding the effect of machining parameters, an upward trend is observed in Ra with respect to feed rate, and as cutting speed increases the Ra value increased slightly due to chatter and vibrations. The adequacy of response variable (Ra) is tested by conducting additional experiments. The predicted Ra values are found to be a close match of their corresponding experimental values of uncoated and coated tools. The corresponding average % errors are found to be within the acceptable limits. Then the surface roughness equations of uncoated and coated tools are set as the objectives of optimization problem and are solved by using Differential Evolution (DE) algorithm. Also the tool lives of uncoated and coated tools are predicted by using Taylor’s tool life equation.

Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

Science.gov (United States)

van Riel, N A; Giuseppin, M L; Verrips, C T

2000-01-01

The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

FCC-hh turn-around cycle

CERN Document Server

Alemany Fernandez, Reyes; Bartmann, Wolfgang; Buffat, Xavier; Niemi, Arto; Schulte, Daniel; Solfaroli Camillocci, Matteo; Stoel, Linda

2016-01-01

The turn-around cycle time of a collider is defined as the time spent between the end of stable beams and the start of the next stable beams period, and its calculation is of fundamental importance. On one side it is a crucial ingredient for the computation of the optimal time spent in luminosity production, which defines the integrated luminosity per fill or store. On the other side, combined with the availability and reliability of the machine, it allows to perform a detailed breakdown of the operational performance of the collider over an operational season, i.e. percentage of time in stable beams and beam in the machine with respect to down time. This paper presents a preliminary operational cycle definition for the hadron-hadron Future Circular Collider, as a base line for estimating the corresponding turn-around time. The cycle definition is based on the Large Hadron Collider (LHC) operational cycle. Two turn-around times are presented, the theoretical one and a more realistic one based on the LHC exper...

Turning the 'mustard oil bomb' into a 'cyanide bomb': aromatic glucosinolate metabolism in a specialist insect herbivore.

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Einar J Stauber

Full Text Available Plants have evolved a variety of mechanisms for dealing with insect herbivory among which chemical defense through secondary metabolites plays a prominent role. Physiological, behavioural and sensorical adaptations to these chemicals provide herbivores with selective advantages allowing them to diversify within the newly occupied ecological niche. In turn, this may influence the evolution of plant metabolism giving rise to e.g. new chemical defenses. The association of Pierid butterflies and plants of the Brassicales has been cited as an illustrative example of this adaptive process known as 'coevolutionary armsrace'. All plants of the Brassicales are defended by the glucosinolate-myrosinase system to which larvae of cabbage white butterflies and related species are biochemically adapted through a gut nitrile-specifier protein. Here, we provide evidence by metabolite profiling and enzyme assays that metabolism of benzylglucosinolate in Pieris rapae results in release of equimolar amounts of cyanide, a potent inhibitor of cellular respiration. We further demonstrate that P. rapae larvae develop on transgenic Arabidopsis plants with ectopic production of the cyanogenic glucoside dhurrin without ill effects. Metabolite analyses and fumigation experiments indicate that cyanide is detoxified by β-cyanoalanine synthase and rhodanese in the larvae. Based on these results as well as on the facts that benzylglucosinolate was one of the predominant glucosinolates in ancient Brassicales and that ancient Brassicales lack nitrilases involved in alternative pathways, we propose that the ability of Pierid species to safely handle cyanide contributed to the primary host shift from Fabales to Brassicales that occured about 75 million years ago and was followed by Pierid species diversification.

The application of microfluidic-based technologies in the cycle of metabolic engineering

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Xiaoyan Ma

2016-09-01

Full Text Available The process of metabolic engineering consists of multiple cycles of design, build, test and learn, which is typically laborious and time-consuming. To increase the efficiency and the rate of success of strain engineering, novel instrumentation must be applied. Microfluidics, the control of liquid flow in microstructures, has enabled flexible, accurate, automatic, and high-throughput manipulation of cells in liquid at picoliter to nanoliter scale. These attributes hold great promise in advancing metabolic engineering in terms of the phases of design, build, test and learn. To promote the application of microfluidic-based technologies in strain improvement, this review addressed the potentials of microfluidics and the related approaches in DNA assembly, transformation, strain screening, genotyping and phenotyping, and highlighted their adaptations for single-cell analysis. As a result, this facilitates in-depth understanding of the metabolic network, which in turn promote efficient optimization in the following cycles of strain engineering. Taken together, microfluidic-based technologies enable on-chip workflow, and could greatly accelerate the turnaround of metabolic engineering.

Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors.

Science.gov (United States)

Ramachandran, Sreekanth A; Jadhavar, Pradeep S; Miglani, Sandeep K; Singh, Manvendra P; Kalane, Deepak P; Agarwal, Anil K; Sathe, Balaji D; Mukherjee, Kakoli; Gupta, Ashu; Haldar, Srijan; Raja, Mohd; Singh, Siddhartha; Pham, Son M; Chakravarty, Sarvajit; Quinn, Kevin; Belmar, Sebastian; Alfaro, Ivan E; Higgs, Christopher; Bernales, Sebastian; Herrera, Francisco J; Rai, Roopa

2017-05-15

Signaling via the receptor tyrosine kinase CSF1R is thought to play an important role in recruitment and differentiation of tumor-associated macrophages (TAMs). TAMs play pro-tumorigenic roles, including the suppression of anti-tumor immune response, promotion of angiogenesis and tumor cell metastasis. Because of the role of this signaling pathway in the tumor microenvironment, several small molecule CSF1R kinase inhibitors are undergoing clinical evaluation for cancer therapy, either as a single agent or in combination with other cancer therapies, including immune checkpoint inhibitors. Herein we describe our lead optimization effort that resulted in the identification of a potent, cellular active and orally bioavailable bis-amide CSF1R inhibitor. Docking and biochemical analysis allowed the removal of a metabolically labile and poorly permeable methyl piperazine group from an early lead compound. Optimization led to improved metabolic stability and Caco2 permeability, which in turn resulted in good oral bioavailability in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experimental Evaluation and Optimization of Flank Wear During Turning of AISI 4340 Steel with Coated Carbide Inserts Using Different Cutting Fluids

Science.gov (United States)

Lawal, S. A.; Choudhury, I. A.; Nukman, Y.

2015-01-01

The understanding of cutting fluids performance in turning process is very important in order to improve the efficiency of the process. This efficiency can be determined based on certain process parameters such as flank wear, cutting forces developed, temperature developed at the tool chip interface, surface roughness on the work piece, etc. In this study, the objective is to determine the influence of cutting fluids on flank wear during turning of AISI 4340 with coated carbide inserts. The performances of three types of cutting fluids were compared using Taguchi experimental method. The results show that palm kernel oil based cutting fluids performed better than the other two cutting fluids in reducing flank wear. Mathematical models for cutting parameters such as cutting speed, feed rate, depth of cut and cutting fluids were obtained from regression analysis using MINITAB 14 software to predict flank wear. Experiments were conducted based on the optimized values to validate the regression equations for flank wear and 5.82 % error was obtained. The optimal cutting parameters for the flank wear using S/N ratio were 160 m/min of cutting speed (level 1), 0.18 mm/rev of feed (level 1), 1.75 mm of depth of cut (level 2) and 2.97 mm2/s palm kernel oil based cutting fluid (level 3). ANOVA shows cutting speed of 85.36 %; and feed rate 4.81 %) as significant factors.

Recent developments in turning hardened steels - A review

Science.gov (United States)

Sivaraman, V.; Prakash, S.

2017-05-01

Hard materials ranging from HRC 45 - 68 such as hardened AISI H13, AISI 4340, AISI 52100, D2 STL, D3 STEEL Steel etc., need super hard tool materials to machine. Turning of these hard materials is termed as hard turning. Hard turning makes possible direct machining of the hard materials and also eliminates the lubricant requirement and thus favoring dry machining. Hard turning is a finish turning process and hence conventional grinding is not required. Development of the new advanced super hard tool materials such as ceramic inserts, Cubic Boron Nitride, Polycrystalline Cubic Boron Nitride etc. enabled the turning of these materials. PVD and CVD methods of coating have made easier the production of single and multi layered coated tool inserts. Coatings of TiN, TiAlN, TiC, Al2O3, AlCrN over cemented carbide inserts has lead to the machining of difficult to machine materials. Advancement in the process of hard machining paved way for better surface finish, long tool life, reduced tool wear, cutting force and cutting temperatures. Micro and Nano coated carbide inserts, nanocomposite coated PCBN inserts, micro and nano CBN coated carbide inserts and similar developments have made machining of hardened steels much easier and economical. In this paper, broad literature review on turning of hardened steels including optimizing process parameters, cooling requirements, different tool materials etc., are done.

Turn by Turn Measurements at the KEK-ATF

CERN Document Server

Renier, Y; Tomas, R; Wendt, M; Eddy, N; Kubo, K; Kuroda, S; Naito, T; Okugi, T; Terunuma, N; Urakawa, J

2013-01-01

The ATF damping ring has been upgraded with new read-out electronics for the beam position monitors (BPM), capable to acquire the beam orbits on a turn-by-turn basis, as well as in a high resolution averaging mode. The new BPM system allows to improve optic corrections and to achieve an even smaller vertical emittance (<2pm). Experimental results are presented based on turn-by-turn beam orbit measurements in the ring, for estimating the β functions and dispersion along the lattice. A fast method to measure spectral line amplitude in a few turns is also presented, including the evaluation of chromaticity.

Silicon Carbide Emitter Turn-Off Thyristor

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Jun Wang

2008-01-01

Full Text Available A novel MOS-controlled SiC thyristor device, the SiC emitter turn-off thyristor (ETO is a promising technology for future high-voltage switching applications because it integrates the excellent current conduction capability of a SiC thyristor with a simple MOS-control interface. Through unity-gain turn-off, the SiC ETO also achieves excellent Safe Operation Area (SOA and faster switching speeds than silicon ETOs. The world's first 4.5-kV SiC ETO prototype shows a forward voltage drop of 4.26 V at 26.5 A/cm2 current density at room and elevated temperatures. Tested in an inductive circuit with a 2.5 kV DC link voltage and a 9.56-A load current, the SiC ETO shows a fast turn-off time of 1.63 microseconds and a low 9.88 mJ turn-off energy. The low switching loss indicates that the SiC ETO could operate at about 4 kHz if 100 W/cm2 conduction and the 100 W/cm2 turn-off losses can be removed by the thermal management system. This frequency capability is about 4 times higher than 4.5-kV-class silicon power devices. The preliminary demonstration shows that the SiC ETO is a promising candidate for high-frequency, high-voltage power conversion applications, and additional developments to optimize the device for higher voltage (>5 kV and higher frequency (10 kHz are needed.

Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling.

Science.gov (United States)

Cuperlovic-Culf, Miroslava

2018-01-11

Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies.

Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling

Science.gov (United States)

Cuperlovic-Culf, Miroslava

2018-01-01

Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies. PMID:29324649

Optimization of prosthetic foot stiffness to reduce metabolic cost and intact knee loading during below-knee amputee walking: a theoretical study.

Science.gov (United States)

Fey, Nicholas P; Klute, Glenn K; Neptune, Richard R

2012-11-01

Unilateral below-knee amputees develop abnormal gait characteristics that include bilateral asymmetries and an elevated metabolic cost relative to non-amputees. In addition, long-term prosthesis use has been linked to an increased prevalence of joint pain and osteoarthritis in the intact leg knee. To improve amputee mobility, prosthetic feet that utilize elastic energy storage and return (ESAR) have been designed, which perform important biomechanical functions such as providing body support and forward propulsion. However, the prescription of appropriate design characteristics (e.g., stiffness) is not well-defined since its influence on foot function and important in vivo biomechanical quantities such as metabolic cost and joint loading remain unclear. The design of feet that improve these quantities could provide considerable advancements in amputee care. Therefore, the purpose of this study was to couple design optimization with dynamic simulations of amputee walking to identify the optimal foot stiffness that minimizes metabolic cost and intact knee joint loading. A musculoskeletal model and distributed stiffness ESAR prosthetic foot model were developed to generate muscle-actuated forward dynamics simulations of amputee walking. Dynamic optimization was used to solve for the optimal muscle excitation patterns and foot stiffness profile that produced simulations that tracked experimental amputee walking data while minimizing metabolic cost and intact leg internal knee contact forces. Muscle and foot function were evaluated by calculating their contributions to the important walking subtasks of body support, forward propulsion and leg swing. The analyses showed that altering a nominal prosthetic foot stiffness distribution by stiffening the toe and mid-foot while making the ankle and heel less stiff improved ESAR foot performance by offloading the intact knee during early to mid-stance of the intact leg and reducing metabolic cost. The optimal design also

Turning for Ulcer Reduction (TURN) Study: An Economic Analysis.

Science.gov (United States)

Paulden, Mike; Bergstrom, Nancy; Horn, Susan D; Rapp, Mary; Stern, Anita; Barrett, Ryan; Watkiss, Michael; Krahn, Murray

2014-01-01

The Turning for Ulcer Reduction (TURN) study was a multisite, randomized controlled trial that aimed to determine the optimal frequency of turning nursing facility residents with mobility limitations who are at moderate and high risk for pressure ulcer (PrU) development. Here we present data from the economic analysis. This economic analysis aims to estimate the economic consequences for Ontario of switching from a repositioning schedule of 2-hour intervals to a schedule of 3-hour or 4-hour intervals. Costs considered in the analysis included those associated with nursing staff time spent repositioning residents and with incontinent care supplies, which included briefs, barrier cream, and washcloths. The total economic benefit of switching to 3-hour or 4-hour repositioning is estimated to be $11.05 or $16.74 per day, respectively, for every resident at moderate or high risk of developing PrUs. For a typical facility with 123 residents, 41 (33%) of whom are at moderate or high risk of developing PrUs, the total economic benefit is estimated to be $453 daily for 3-hour or $686 daily for 4-hour repositioning. For Ontario as a whole, assuming that there are 77,933 residents at 634 LTC facilities, 25,927 (33%) of whom are at moderate or high risk of developing PrUs, the total economic benefits of switching to 3-hour or 4-hour repositioning are estimated to be $286,420 or $433,913 daily, respectively, equivalent to $104.5 million or $158.4 million per year. We did not consider the savings the Ontario Ministry of Health and Long-Term Care might incur should less frequent repositioning reduce the incidence of work-related injury among nursing staff, so our findings are potentially conservative. A switch to 3-hour or 4-hour repositioning appears likely to yield substantial economic benefits to Ontario without placing residents at greater risk of developing PrUs.

Dynamic metabolic modeling of heterotrophic and mixotrophic microalgal growth on fermentative wastes.

Directory of Open Access Journals (Sweden)

Caroline Baroukh

2017-06-01

Full Text Available Microalgae are promising microorganisms for the production of numerous molecules of interest, such as pigments, proteins or triglycerides that can be turned into biofuels. Heterotrophic or mixotrophic growth on fermentative wastes represents an interesting approach to achieving higher biomass concentrations, while reducing cost and improving the environmental footprint. Fermentative wastes generally consist of a blend of diverse molecules and it is thus crucial to understand microalgal metabolism in such conditions, where switching between substrates might occur. Metabolic modeling has proven to be an efficient tool for understanding metabolism and guiding the optimization of biomass or target molecule production. Here, we focused on the metabolism of Chlorella sorokiniana growing heterotrophically and mixotrophically on acetate and butyrate. The metabolism was represented by 172 metabolic reactions. The DRUM modeling framework with a mildly relaxed quasi-steady-state assumption was used to account for the switching between substrates and the presence of light. Nine experiments were used to calibrate the model and nine experiments for the validation. The model efficiently predicted the experimental data, including the transient behavior during heterotrophic, autotrophic, mixotrophic and diauxic growth. It shows that an accurate model of metabolism can now be constructed, even in dynamic conditions, with the presence of several carbon substrates. It also opens new perspectives for the heterotrophic and mixotrophic use of microalgae, especially for biofuel production from wastes.

[The optimal cutoff value of waist-to-height ratio in Chinese: based on cardiovascular risk and metabolic disease].

Science.gov (United States)

Jia, A H; Xu, S Y; Ming, J; Zhou, J; Zhang, W C; Hao, P R; Ji, Q H

2017-11-01

Objective: Waist-to-height ratio (WHtR), a measurement of the distribution of body fat, correlated with abdominal obesity indicating that it might be a better predictor of cardiovascular risk and metabolic disease. We, therefore, evaluated optimal WHtR cutoff points according to the risk of framingham risk score (FRS) and metabolic syndrome (MS) in Chinese. Methods: The subjects were from China National Diabetes and Metabolic Disorders Survey during 2007-2008. Receiver operating characteristic analysis was used to examine the optimal cutoff values of WHtR according to the risk of FRS and MS. Results: A total of 27 820 women and 18 419 men were included in the evaluation. The average age was (45.0±13.7) years. The proportions of FRS ≥10% and MS increased with WHtR both in men and women. The cutoff points of WHtR for the risk of FRS ≥10% and MS were 0.51, 0.52 in men, and 0.52, 0.53 in women, respectively. When FRS ≥10% and MS were taken into consideration with a certain weights, the pooled cutoffs of WHtR were 0.51 in men, and 0.53 in women, respectively. By using the similar method, the optimized cutoff points were 0.52, 0.51, 0.50 for men and 0.51, 0.53, 0.54 for women in age group 20-39, 40-59 and ≥60 years, respectively. Conclusions: The optimal cutoffs of WHtR are 0.51 in men, and 0.53 in women for FRS≥10% in combination with MS indicating that this WHtR cutoff points might be used as indexes to evaluate obesity and risk of obesity-related diseases.

Early optimal parenteral nutrition and metabolic acidosis in very preterm infants.

Directory of Open Access Journals (Sweden)

Francesco Bonsante

Full Text Available It is currently recognized that an optimized nutritional approach, consisting of an early and substantial supply of protein and energy by parenteral route, may be beneficial for very low birth weight infants and recent guidelines endorse this strategy. However, the impact of the enhanced parenteral nutrition (PN on acid-basic balance has never been investigated. The aim of the present study is to assess the effect of nutrient intake on acid-base homeostasis in a large population of preterm infants on PN.This observational study described the acid-base profile of very preterm infants (≤29 week's gestation receiving PN during the first week of life. For this purpose three different cohorts of infants who received increasing (group 1 to group 3 nutritional intakes were considered. Nutrition data were recorded daily and correlated to acid-base data (pH, base excess, and lactate. The outcome measure to assess metabolic acidosis was the base excess (BE.161 infants were included. 1127 daily nutritional records and 795 blood gas data were analyzed. The three groups were different with regard to nutritional intravenous intakes. Group 3 in particular had a higher mean intake of both amino acids (3.3 ± 0.8 g/kg/d and lipids (2.8 ± 1.4 g/kg/d during the first week of life. Metabolic acidosis was more severe in the group with the highest parenteral intake of amino acids and lipids: mean BE = -8.7 ± 3.4 (group 3; -6.4 ± 3.4 (group 2; -5.1 ± 3.0 (group 1]. At the multivariate analysis the significant risk factors for metabolic acidosis were: gestational age, initial base excess, amino acid and lipid intravenous intakes.Acid-base homeostasis was influenced by the nutritional intake. Earlier and higher intravenous amino acid and lipid intakes particularly increased the risk of metabolic acidosis. The nutritional tolerance was different depending on gestational age, and the smaller infants (24-26 week's gestation displayed greater acidotic disequilibrium

Transparent lattice characterization with gated turn-by-turn data of diagnostic bunch train

Science.gov (United States)

Li, Yongjun; Cheng, Weixing; Ha, Kiman; Rainer, Robert

2017-11-01

Methods of characterization of a storage ring's lattice have traditionally been intrusive to routine operations. More importantly, the lattice seen by particles can drift with the beam current due to collective effects. To circumvent this, we have developed a novel approach for dynamically characterizing a storage ring's lattice that is transparent to operations. Our approach adopts a dedicated filling pattern which has a short, separate diagnostic bunch train (DBT). Through the use of a bunch-by-bunch feedback system, the DBT can be selectively excited on demand. Gated functionality of a beam position monitor system is capable of collecting turn-by-turn data of the DBT, from which the lattice can then be characterized after excitation. As the DBT comprises only about one percent of the total operational bunches, the effects of its excitation are negligible to users. This approach allows us to localize the distributed quadrupolar wakefields generated in the storage ring vacuum chamber during beam accumulation. While effectively transparent to operations, our approach enables us to dynamically control the beta beat and phase beat, and unobtrusively optimize performance of the National Synchrotron Light Source-II accelerator during routine operations.

N-Glycosylation optimization of recombinant antibodies in CHO cell through process and metabolic engineering

DEFF Research Database (Denmark)

Fan, Yuzhou

, analysis, control and optimization of N-glycosylation were thoroughly reviewed. In particular, how to control and optimize N-glycosylation in CHO cells was exclusively studied. The main focus of this PhD project is to find effective approaches of modulating N-glycosylation of CHO-derived recombinant...... galactose as feed additives, changing process parameters such as seeding density and cultivation duration are all demonstrated to be effective. The causal explanation of their impact on glycosylation can be various, including product, metabolism, proteome and physiology-associated mechanism. In the middle...... part of the thesis, both literature reviews and experimental applications were provided to demonstrate how to use omics data and implement systems biology to understand biological activities, especially N-glycosylation in CHO cells. In the last part of the thesis, the second strategy that apply genetic...

Noise effect in metabolic networks

International Nuclear Information System (INIS)

Zheng-Yan, Li; Zheng-Wei, Xie; Tong, Chen; Qi, Ouyang

2009-01-01

Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states. (cross-disciplinary physics and related areas of science and technology)

On the use of metabolic control analysis in the optimization of cyanobacterial biosolar cell factories.

Science.gov (United States)

Angermayr, S Andreas; Hellingwerf, Klaas J

2013-09-26

Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.

IsoDesign: a software for optimizing the design of 13C-metabolic flux analysis experiments.

Science.gov (United States)

Millard, Pierre; Sokol, Serguei; Letisse, Fabien; Portais, Jean-Charles

2014-01-01

The growing demand for (13) C-metabolic flux analysis ((13) C-MFA) in the field of metabolic engineering and systems biology is driving the need to rationalize expensive and time-consuming (13) C-labeling experiments. Experimental design is a key step in improving both the number of fluxes that can be calculated from a set of isotopic data and the precision of flux values. We present IsoDesign, a software that enables these parameters to be maximized by optimizing the isotopic composition of the label input. It can be applied to (13) C-MFA investigations using a broad panel of analytical tools (MS, MS/MS, (1) H NMR, (13) C NMR, etc.) individually or in combination. It includes a visualization module to intuitively select the optimal label input depending on the biological question to be addressed. Applications of IsoDesign are described, with an example of the entire (13) C-MFA workflow from the experimental design to the flux map including important practical considerations. IsoDesign makes the experimental design of (13) C-MFA experiments more accessible to a wider biological community. IsoDesign is distributed under an open source license at http://metasys.insa-toulouse.fr/software/isodes/ © 2013 Wiley Periodicals, Inc.

ReacKnock: identifying reaction deletion strategies for microbial strain optimization based on genome-scale metabolic network.

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Zixiang Xu

Full Text Available Gene knockout has been used as a common strategy to improve microbial strains for producing chemicals. Several algorithms are available to predict the target reactions to be deleted. Most of them apply mixed integer bi-level linear programming (MIBLP based on metabolic networks, and use duality theory to transform bi-level optimization problem of large-scale MIBLP to single-level programming. However, the validity of the transformation was not proved. Solution of MIBLP depends on the structure of inner problem. If the inner problem is continuous, Karush-Kuhn-Tucker (KKT method can be used to reformulate the MIBLP to a single-level one. We adopt KKT technique in our algorithm ReacKnock to attack the intractable problem of the solution of MIBLP, demonstrated with the genome-scale metabolic network model of E. coli for producing various chemicals such as succinate, ethanol, threonine and etc. Compared to the previous methods, our algorithm is fast, stable and reliable to find the optimal solutions for all the chemical products tested, and able to provide all the alternative deletion strategies which lead to the same industrial objective.

In silico strain optimization by adding reactions to metabolic models.

Science.gov (United States)

Correia, Sara; Rocha, Miguel

2012-07-24

Nowadays, the concerns about the environment and the needs to increase the productivity at low costs, demand for the search of new ways to produce compounds with industrial interest. Based on the increasing knowledge of biological processes, through genome sequencing projects, and high-throughput experimental techniques as well as the available computational tools, the use of microorganisms has been considered as an approach to produce desirable compounds. However, this usually requires to manipulate these organisms by genetic engineering and/ or changing the enviromental conditions to make the production of these compounds possible. In many cases, it is necessary to enrich the genetic material of those microbes with hereologous pathways from other species and consequently adding the potential to produce novel compounds. This paper introduces a new plug-in for the OptFlux Metabolic Engineering platform, aimed at finding suitable sets of reactions to add to the genomes of selected microbes (wild type strain), as well as finding complementary sets of deletions, so that the mutant becomes able to overproduce compounds with industrial interest, while preserving their viability. The necessity of adding reactions to the metabolic model arises from existing gaps in the original model or motivated by the productions of new compounds by the organism. The optimization methods used are metaheuristics such as Evolutionary Algorithms and Simulated Annealing. The usefulness of this plug-in is demonstrated by a case study, regarding the production of vanillin by the bacterium E. coli.

Optimization of surface roughness parameters in dry turning

OpenAIRE

R.A. Mahdavinejad; H. Sharifi Bidgoli

2009-01-01

Purpose: The precision of machine tools on one hand and the input setup parameters on the other hand, are strongly influenced in main output machining parameters such as stock removal, toll wear ratio and surface roughnes.Design/methodology/approach: There are a lot of input parameters which are effective in the variations of these output parameters. In CNC machines, the optimization of machining process in order to predict surface roughness is very important.Findings: From this point of view...

Modeling and multi-objective optimization of surface roughness and productivity in dry turning of AISI 52100 steel using (TiCN-TiN) coating cermet tools

OpenAIRE

Ouahid Keblouti; Lakhdar Boulanouar; Mohamed Walid Azizi; Mohamed Athmane Yallese

2017-01-01

The present work concerns an experimental study of turning with coated cermet tools with TiCN-TiN coating layer of AISI 52100 bearing steel. The main objectives are firstly focused on the effect of cutting parameters and coating material on the performances of cutting tools. Secondly, to perform a Multi-objective optimization for minimizing surface roughness (Ra) and maximizing material removal rate by desirability approach. A mathematical model was developed based on the Response Surface Met...

Sample preparation optimization in fecal metabolic profiling.

Science.gov (United States)

Deda, Olga; Chatziioannou, Anastasia Chrysovalantou; Fasoula, Stella; Palachanis, Dimitris; Raikos, Νicolaos; Theodoridis, Georgios A; Gika, Helen G

2017-03-15

Metabolomic analysis of feces can provide useful insight on the metabolic status, the health/disease state of the human/animal and the symbiosis with the gut microbiome. As a result, recently there is increased interest on the application of holistic analysis of feces for biomarker discovery. For metabolomics applications, the sample preparation process used prior to the analysis of fecal samples is of high importance, as it greatly affects the obtained metabolic profile, especially since feces, as matrix are diversifying in their physicochemical characteristics and molecular content. However there is still little information in the literature and lack of a universal approach on sample treatment for fecal metabolic profiling. The scope of the present work was to study the conditions for sample preparation of rat feces with the ultimate goal of the acquisition of comprehensive metabolic profiles either untargeted by NMR spectroscopy and GC-MS or targeted by HILIC-MS/MS. A fecal sample pooled from male and female Wistar rats was extracted under various conditions by modifying the pH value, the nature of the organic solvent and the sample weight to solvent volume ratio. It was found that the 1/2 (w f /v s ) ratio provided the highest number of metabolites under neutral and basic conditions in both untargeted profiling techniques. Concerning LC-MS profiles, neutral acetonitrile and propanol provided higher signals and wide metabolite coverage, though extraction efficiency is metabolite dependent. Copyright © 2016 Elsevier B.V. All rights reserved.

Eco-Approach and Departure System for Left-Turn Vehicles at a Fixed-Time Signalized Intersection

Directory of Open Access Journals (Sweden)

Huifu Jiang

2018-01-01

Full Text Available This research proposed an eco-approach and departure system for left-turn vehicles at a fixed-time signalized intersection. This system gives higher priority to enhancing traffic safety than improving mobility and fuel efficiency, and optimizes the entire traffic consisted of connected and automated vehicles (CAVs and conventional human-driven vehicles by providing ecological speed trajectories for left-turn CAVs. All the ecological speed trajectories are offline optimized before the implementation of system. The speed trajectory optimization is constructed in Pontryagin’s Minimum Principle structure. The before and after evaluation of the proposed system shows the percentage of vehicles that drive pass the intersection at safe speed increases by 2.14% to 45.65%, fuel consumption benefits range 0.53% to 18.44%, emission benefits range from 0.57% to 15.69%, no significant throughput benefits is observed. The proposed system significantly enhances the traffic safety and improves the fuel efficiency and emission reduction of left-turn vehicles with no adverse effect on mobility, and has a good robustness against the randomness of traffic. The investigation also indicates that the computation time of proposed system is greatly reduced compared to previous eco-driving system with online speed optimization. The computation time is up to 0.01 s. The proposed system is ready for real-time application.

The Translator's Turn: in the Cultural Turn

Institute of Scientific and Technical Information of China (English)

徐玮玮

2003-01-01

@@ Introduction: Douglas Robinson rose to the defense of the " atheoretical" American literary translator in The Translator's Turn (1991). Here, I borrowed the title from him, but I will write my paper in the thought of the translator's role in translating. In his book, Robinson argued that the literary translator embodies an integration of feeling and thought, of intuition and systematization. In analyzing the " turn" that the translator take from the source text to the target text, Robinson offered a " dialogical" model, that is the translator's dialogical engagement with the source language and with the ethic of the target language. Robinson allows for the translator to intervene, subvert, divert, even entertain, emphasizing the creative aspect of literary translation. The translation linguists, scientists, and philosophers have had their chance at translation theory; now it is time, he argued, for the literary translators to have their " turn".

Multi-objective optimization of surface roughness, cutting forces, productivity and Power consumption when turning of Inconel 718

Directory of Open Access Journals (Sweden)

Hamid Tebassi

2016-01-01

Full Text Available Nickel based super alloys are excellent for several applications and mainly in structural components submitted to high temperatures owing to their high strength to weight ratio, good corrosion resistance and metallurgical stability such as in cases of jet engine and gas turbine components. The current work presents the experimental investigations of the cutting parameters effects (cutting speed, depth of cut and feed rate on the surface roughness, cutting force components, productivity and power consumption during dry conditions in straight turning using coated carbide tool. The mathematical models for output parameters have been developed using Box-Behnken design with 15 runs and Box-Cox transformation was used for improving normality. The results of the analysis have shown that the surface finish was statistically sensitive to the feed rate and cutting speed with the contribution of 43.58% and 23.85% respectively, while depth of cut had the greatest effect on the evolution of cutting force components with the contribution of 79.87% for feed force, 66.92% for radial force and 66.26% for tangential force. Multi-objective optimization procedure allowed minimizing roughness Ra, cutting forces and power consumption and maximizing material removal rate using desirability approach.

Seeing the wood for the trees: a forest of methods for optimization and omic-network integration in metabolic modelling.

Science.gov (United States)

Vijayakumar, Supreeta; Conway, Max; Lió, Pietro; Angione, Claudio

2017-05-30

Metabolic modelling has entered a mature phase with dozens of methods and software implementations available to the practitioner and the theoretician. It is not easy for a modeller to be able to see the wood (or the forest) for the trees. Driven by this analogy, we here present a 'forest' of principal methods used for constraint-based modelling in systems biology. This provides a tree-based view of methods available to prospective modellers, also available in interactive version at http://modellingmetabolism.net, where it will be kept updated with new methods after the publication of the present manuscript. Our updated classification of existing methods and tools highlights the most promising in the different branches, with the aim to develop a vision of how existing methods could hybridize and become more complex. We then provide the first hands-on tutorial for multi-objective optimization of metabolic models in R. We finally discuss the implementation of multi-view machine learning approaches in poly-omic integration. Throughout this work, we demonstrate the optimization of trade-offs between multiple metabolic objectives, with a focus on omic data integration through machine learning. We anticipate that the combination of a survey, a perspective on multi-view machine learning and a step-by-step R tutorial should be of interest for both the beginner and the advanced user. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Optimization of surface integrity in dry hard turning using RSM

Indian Academy of Sciences (India)

This paper investigates the effect of different cutting parameters (cutting ... with coated carbide tool under different settings of cutting parameters. ... procedure of response surface methodology (RSM) to determine optimal ..... The numerical opti- .... and analysis of experiments, New Delhi, A. K. Ghosh, PHI Learning Private.

Lattice modeling and calibration with turn-by-turn orbit data

Directory of Open Access Journals (Sweden)

Xiaobiao Huang

2010-11-01

Full Text Available A new method that explores turn-by-turn beam position monitor (BPM data to calibrate lattice models of accelerators is proposed. The turn-by-turn phase space coordinates at one location of the ring are first established using data from two BPMs separated by a simple section with a known transfer matrix, such as a drift space. The phase space coordinates are then tracked with the model to predict positions at other BPMs, which can be compared to measurements. The model is adjusted to minimize the difference between the measured and predicted orbit data. BPM gains and rolls are included as fitting variables. This technique can be applied to either the entire or a section of the ring. We have tested the method experimentally on a part of the SPEAR3 ring.

Lattice modeling and calibration with turn-by-turn orbit data

Science.gov (United States)

Huang, Xiaobiao; Sebek, Jim; Martin, Don

2010-11-01

A new method that explores turn-by-turn beam position monitor (BPM) data to calibrate lattice models of accelerators is proposed. The turn-by-turn phase space coordinates at one location of the ring are first established using data from two BPMs separated by a simple section with a known transfer matrix, such as a drift space. The phase space coordinates are then tracked with the model to predict positions at other BPMs, which can be compared to measurements. The model is adjusted to minimize the difference between the measured and predicted orbit data. BPM gains and rolls are included as fitting variables. This technique can be applied to either the entire or a section of the ring. We have tested the method experimentally on a part of the SPEAR3 ring.

Urban metabolism: A review of research methodologies

International Nuclear Information System (INIS)

Zhang, Yan

2013-01-01

Urban metabolism analysis has become an important tool for the study of urban ecosystems. The problems of large metabolic throughput, low metabolic efficiency, and disordered metabolic processes are a major cause of unhealthy urban systems. In this paper, I summarize the international research on urban metabolism, and describe the progress that has been made in terms of research methodologies. I also review the methods used in accounting for and evaluating material and energy flows in urban metabolic processes, simulation of these flows using a network model, and practical applications of these methods. Based on this review of the literature, I propose directions for future research, and particularly the need to study the urban carbon metabolism because of the modern context of global climate change. Moreover, I recommend more research on the optimal regulation of urban metabolic systems. Highlights: •Urban metabolic processes can be analyzed by regarding cities as superorganisms. •Urban metabolism methods include accounting, assessment, modeling, and regulation. •Research methodologies have improved greatly since this field began in 1965. •Future research should focus on carbon metabolism and optimal regulation. -- The author reviews research progress in the field of urban metabolism, and based on her literature review, proposes directions for future research

Modelling central metabolic fluxes by constraint-based optimization reveals metabolic reprogramming of developing Solanum lycopersicum (tomato) fruit.

Science.gov (United States)

Colombié, Sophie; Nazaret, Christine; Bénard, Camille; Biais, Benoît; Mengin, Virginie; Solé, Marion; Fouillen, Laëtitia; Dieuaide-Noubhani, Martine; Mazat, Jean-Pierre; Beauvoit, Bertrand; Gibon, Yves

2015-01-01

Modelling of metabolic networks is a powerful tool to analyse the behaviour of developing plant organs, including fruits. Guided by our current understanding of heterotrophic metabolism of plant cells, a medium-scale stoichiometric model, including the balance of co-factors and energy, was constructed in order to describe metabolic shifts that occur through the nine sequential stages of Solanum lycopersicum (tomato) fruit development. The measured concentrations of the main biomass components and the accumulated metabolites in the pericarp, determined at each stage, were fitted in order to calculate, by derivation, the corresponding external fluxes. They were used as constraints to solve the model by minimizing the internal fluxes. The distribution of the calculated fluxes of central metabolism were then analysed and compared with known metabolic behaviours. For instance, the partition of the main metabolic pathways (glycolysis, pentose phosphate pathway, etc.) was relevant throughout fruit development. We also predicted a valid import of carbon and nitrogen by the fruit, as well as a consistent CO2 release. Interestingly, the energetic balance indicates that excess ATP is dissipated just before the onset of ripening, supporting the concept of the climacteric crisis. Finally, the apparent contradiction between calculated fluxes with low values compared with measured enzyme capacities suggest a complex reprogramming of the metabolic machinery during fruit development. With a powerful set of experimental data and an accurate definition of the metabolic system, this work provides important insight into the metabolic and physiological requirements of the developing tomato fruits. © 2014 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

Mimicry by asx- and ST-turns of the four main types of beta-turn in proteins.

Science.gov (United States)

Duddy, William J; Nissink, J Willem M; Allen, Frank H; Milner-White, E James

2004-11-01

Hydrogen-bonded beta-turns in proteins occur in four categories: type I (the most common), type II, type II', and type I'. Asx-turns resemble beta-turns, in that both have an NH. . .OC hydrogen bond forming a ring of 10 atoms. Serine and threonine side chains also commonly form hydrogen-bonded turns, here called ST-turns. Asx-turns and ST-turns can be categorized into four classes, based on side chain rotamers and the conformation of the central turn residue, which are geometrically equivalent to the four types of beta-turns. We propose asx- and ST-turns be named using the type I, II, I', and II' beta-turn nomenclature. Using this, the frequency of occurrence of both asx- and ST-turns is: type II' > type I > type II > type I', whereas for beta-turns it is type I > type II > type I' > type II'. Almost all type II asx-turns occur as a recently described three residue feature named an asx-nest.

Metabolic and Physiological Responses of Shiraz and Cabernet Sauvignon (Vitis vinifera L. to Near Optimal Temperatures of 25 and 35 °C

Directory of Open Access Journals (Sweden)

Uri Hochberg

2015-10-01

Full Text Available Shiraz and Cabernet Sauvignon (Cs grapevines were grown at near optimal temperatures (25 or 35 °C. Gas exchange, fluorescence, metabolic profiling and correlation based network analysis were used to characterize leaf physiology. When grown at 25 °C, the growth rate and photosynthesis of both cultivars were similar. At 35 °C Shiraz showed increased respiration, non-photochemical quenching and reductions of photosynthesis and growth. In contrast, Cs maintained relatively stable photosynthetic activity and growth regardless of the condition. In both cultivars, growth at 35 °C resulted in accumulations of secondary sugars (raffinose, fucose and ribulose and reduction of primary sugars concentration (glucose, fructose and sucrose, more noticeably in Shiraz than Cs. In spite of similar patterns of metabolic changes in response to growth at 35 °C, significant differences in important leaf antioxidants and antioxidant precursors (DHA/ascorbate, quinates, cathechins characterized the cultivar response. Correlation analysis reinforced Shiraz sensitivity to the 35 °C, showing higher number of newly formed edges at 35 °C and higher modularity in Shiraz as compared to Cs. The results suggest that the optimal growth temperatures of grapevines are cultivar dependent, and allow a first insight into the variability of the metabolic responses of grapevines under varied temperatures.

Metabolic and Physiological Responses of Shiraz and Cabernet Sauvignon (Vitis vinifera L.) to Near Optimal Temperatures of 25 and 35 °C.

Science.gov (United States)

Hochberg, Uri; Batushansky, Albert; Degu, Asfaw; Rachmilevitch, Shimon; Fait, Aaron

2015-10-14

Shiraz and Cabernet Sauvignon (Cs) grapevines were grown at near optimal temperatures (25 or 35 °C). Gas exchange, fluorescence, metabolic profiling and correlation based network analysis were used to characterize leaf physiology. When grown at 25 °C, the growth rate and photosynthesis of both cultivars were similar. At 35 °C Shiraz showed increased respiration, non-photochemical quenching and reductions of photosynthesis and growth. In contrast, Cs maintained relatively stable photosynthetic activity and growth regardless of the condition. In both cultivars, growth at 35 °C resulted in accumulations of secondary sugars (raffinose, fucose and ribulose) and reduction of primary sugars concentration (glucose, fructose and sucrose), more noticeably in Shiraz than Cs. In spite of similar patterns of metabolic changes in response to growth at 35 °C, significant differences in important leaf antioxidants and antioxidant precursors (DHA/ascorbate, quinates, cathechins) characterized the cultivar response. Correlation analysis reinforced Shiraz sensitivity to the 35 °C, showing higher number of newly formed edges at 35 °C and higher modularity in Shiraz as compared to Cs. The results suggest that the optimal growth temperatures of grapevines are cultivar dependent, and allow a first insight into the variability of the metabolic responses of grapevines under varied temperatures.

Reducing surface roughness by optimising the turning parameters

Directory of Open Access Journals (Sweden)

Senthil Kumar, K.

2013-08-01

Full Text Available Modern manufacturers worldwide look for the cheapest quality-manufactured machined components to compete in the market. Good surface quality is desired for the proper functioning of the parts produced. The surface quality is influenced by the cutting speed, feed rate, depth of cut, and many other parameters. In this paper, the Taguchi method a powerful tool to design optimisation for quality is used to find the optimal machining parameters for the turning operation. An orthogonal array, the signal-to-noise (S/N ratio, and the analysis of variance (ANOVA are employed to investigate the machining characteristics of super duplex stainless steel bars using uncoated carbide cutting tools. The effect of machining parameters on surface roughness was discovered. Confirmation tests were conducted at optimal conditions to compare the experimental results with the predicted values.

Interactions between host metabolism, immune regulation, and the gut microbiota in diet-associated obesity and metabolic dysfunction

DEFF Research Database (Denmark)

Andersen, Daniel

The increase in the prevalence of obesity and obesity-associated complications such as the metabolic syndrome is becoming a global challenge. Dietary habits and nutrient consumption modulates host homeostasis, which manifests in various diet-induced complications marked by changes in host...... metabolism and immune regulation, which are intricately linked. In addition, diet effectively shapes the gut microbiota composition and activity, which in turn interacts with the host to modulate host metabolism and immune regulation. In the three studies included in this PhD thesis, we have explored...... the impact of specific dietary components on host metabolic function, immune regulation and gut microbiota composition and activity. In the first study, we have characterized the effect of a combined high-fat and gliadin-rich diet, since dietary gliadin has been reported to be associated with intestinal...

Turning breech babies after 34 weeks: the if, how, & when of turning breech babies.

Science.gov (United States)

Cohain, Judy Slome

2007-01-01

Techniques for turning a term breech baby are 1). External cephalic version (ECV) using hands and ultrasound only; 2). Acupuncture point stimulation, by needle or moxibustion; 3). Chiropractic "Webster" technique; 4). Hypnotherapy; and 5). Special exercises. Fifty % of breech fetuses at 34 weeks will turn by themselves to head down by 38 weeks. Therefore, to be considered effective, a technique for turning breech must turn the baby and keep it turned more than 50% of the time. Only ECV with an experienced practitioner has been documented to have a greater than 50% success rate at 37 weeks; in 95% of cases the head stays down. Most women experience the fetus turning by hand as quick but very painful. "Unstable lie" is sometimes used as a baseless excuse for inducing labor after the baby turns from breech to head down. (judyslome@hotmail.com).

MiYA, an efficient machine-learning workflow in conjunction with the YeastFab assembly strategy for combinatorial optimization of heterologous metabolic pathways in Saccharomyces cerevisiae.

Science.gov (United States)

Zhou, Yikang; Li, Gang; Dong, Junkai; Xing, Xin-Hui; Dai, Junbiao; Zhang, Chong

2018-05-01

Facing boosting ability to construct combinatorial metabolic pathways, how to search the metabolic sweet spot has become the rate-limiting step. We here reported an efficient Machine-learning workflow in conjunction with YeastFab Assembly strategy (MiYA) for combinatorial optimizing the large biosynthetic genotypic space of heterologous metabolic pathways in Saccharomyces cerevisiae. Using β-carotene biosynthetic pathway as example, we first demonstrated that MiYA has the power to search only a small fraction (2-5%) of combinatorial space to precisely tune the expression level of each gene with a machine-learning algorithm of an artificial neural network (ANN) ensemble to avoid over-fitting problem when dealing with a small number of training samples. We then applied MiYA to improve the biosynthesis of violacein. Feed with initial data from a colorimetric plate-based, pre-screened pool of 24 strains producing violacein, MiYA successfully predicted, and verified experimentally, the existence of a strain that showed a 2.42-fold titer improvement in violacein production among 3125 possible designs. Furthermore, MiYA was able to largely avoid the branch pathway of violacein biosynthesis that makes deoxyviolacein, and produces very pure violacein. Together, MiYA combines the advantages of standardized building blocks and machine learning to accelerate the Design-Build-Test-Learn (DBTL) cycle for combinatorial optimization of metabolic pathways, which could significantly accelerate the development of microbial cell factories. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models.

Science.gov (United States)

Pozo, Carlos; Marín-Sanguino, Alberto; Alves, Rui; Guillén-Gosálbez, Gonzalo; Jiménez, Laureano; Sorribas, Albert

2011-08-25

Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

Directory of Open Access Journals (Sweden)

Sorribas Albert

2011-08-01

Full Text Available Abstract Background Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

On the application of response surface methodology for predicting and optimizing surface roughness and cutting forces in hard turning by PVD coated insert

Directory of Open Access Journals (Sweden)

Hessainia Zahia

2015-04-01

Full Text Available This paper focuses on the exploitation of the response surface methodology (RSM to determine optimum cutting conditions leading to minimum surface roughness and cutting force components. The technique of RSM helps to create an efficient statistical model for studying the evolution of surface roughness and cutting forces according to cutting parameters: cutting speed, feed rate and depth of cut. For this purpose, turning tests of hardened steel alloy (AISI 4140 (56 HRC were carried out using PVD – coated ceramic insert under different cutting conditions. The equations of surface roughness and cutting forces were achieved by using the experimental data and the technique of the analysis of variance (ANOVA. The obtained results are presented in terms of mean values and confidence levels. It is shown that feed rate and depth of cut are the most influential factors on surface roughness and cutting forces, respectively. In addition, it is underlined that the surface roughness is mainly related to the cutting speed, whereas depth of cut has the greatest effect on the evolution of cutting forces. The optimal machining parameters obtained in this study represent reductions about 6.88%, 3.65%, 19.05% in cutting force components (Fa, Fr, Ft, respectively. The latters are compared with the results of initial cutting parameters for machining AISI 4140 steel in the hard turning process.

The metabolic syndrome: prevalence, CHD risk, and treatment.

Science.gov (United States)

Sarti, Cinzia; Gallagher, John

2006-01-01

An increased risk of coronary heart disease (CHD) morbidity and mortality is associated with the metabolic syndrome, a condition characterized by the concomitant presence of several abnormalities, including abdominal obesity, dyslipidemia, hypertension, insulin resistance (with or without glucose intolerance or diabetes), microalbuminuria, prothrombotic, and proinflammatory states. Estimates of the prevalence of the metabolic syndrome indicate that this condition is now common and likely to increase dramatically over the coming decades, in parallel with greater rates of obesity and Type 2 diabetes. Risk factors for the metabolic syndrome are already present in obese children and adolescents. Thus, identifying and treating all affected individuals promptly and optimally are critical to ensure that this potentially challenging healthcare burden is minimized. Here, we review the prevalence of the metabolic syndrome, dyslipidemias, and CHD risk. Although changes in lifestyle are fundamental to reducing many of the CHD risk factors associated with the metabolic syndrome, pharmacologic interventions also play an important role. Retrospective subanalyses of the effects of statins on coronary event rates and lipid levels in patients with the metabolic syndrome included in clinical trials indicate that these agents are beneficial in correcting the extensive lipid abnormalities that are frequently present in these individuals. However, the optimal management of metabolic syndrome dyslipidemia will depend on the outcomes of future prospective clinical trials. This review examines the underlying causes and prevalence of the metabolic syndrome and its impact on CHD morbidity and mortality and discusses the role of statins in optimizing its management.

Metabolic interrogation as a tool to optimize chemotherapeutic regimens.

Science.gov (United States)

Sandulache, Vlad C; Chen, Yunyun; Feng, Lei; William, William N; Skinner, Heath D; Myers, Jeffrey N; Meyn, Raymond E; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A; Fuller, Clifton D; Konopleva, Marina Y; Lai, Stephen Y

2017-03-14

Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines.Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies.

A hybrid approach identifies metabolic signatures of high-producers for chinese hamster ovary clone selection and process optimization.

Science.gov (United States)

Popp, Oliver; Müller, Dirk; Didzus, Katharina; Paul, Wolfgang; Lipsmeier, Florian; Kirchner, Florian; Niklas, Jens; Mauch, Klaus; Beaucamp, Nicola

2016-09-01

In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. This requires applying appropriate methods during bioprocess development to enable meaningful characterization of CHO clones and processes. Here, we present a novel hybrid approach for supporting comprehensive characterization of metabolic clone performance. The approach combines metabolite profiling with multivariate data analysis and fluxomics to enable a data-driven mechanistic analysis of key metabolic traits associated with desired cell phenotypes. We applied the methodology to quantify and compare metabolic performance in a set of 10 recombinant CHO-K1 producer clones and a host cell line. The comprehensive characterization enabled us to derive an extended set of clone performance criteria that not only captured growth and product formation, but also incorporated information on intracellular clone physiology and on metabolic changes during the process. These criteria served to establish a quantitative clone ranking and allowed us to identify metabolic differences between high-producing CHO-K1 clones yielding comparably high product titers. Through multivariate data analysis of the combined metabolite and flux data we uncovered common metabolic traits characteristic of high-producer clones in the screening setup. This included high intracellular rates of glutamine synthesis, low cysteine uptake, reduced excretion of aspartate and glutamate, and low intracellular degradation rates of branched-chain amino acids and of histidine. Finally, the above approach was integrated into a workflow that enables standardized high-content selection of CHO producer clones in a high-throughput fashion. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic

Determination of linear optics functions from turn-by-turn data

Energy Technology Data Exchange (ETDEWEB)

Alexahin, Y; Gianfelice-Wendt, E, E-mail: alexahin@fnal.gov [Fermi National Accelerator Laboratory, P.O. Box 500, Batavia, Illinois 60510 (United States)

2011-10-15

A method for evaluation of coupled optics functions, detection of strong perturbing elements, determination of BPM calibration errors and tilts using turn-by-turn (TBT) data is presented as well as the new version of the Hamiltonian perturbation theory of betatron oscillations the method is based upon. An example of application of the considered method to the Tevatron is given.

[Metabolic acidosis].

Science.gov (United States)

Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

2016-01-01

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

Multiobjective optimization of a steering linkage

Energy Technology Data Exchange (ETDEWEB)

Sleesonsom, S.; Bureerat, S. [Sustainable and Infrastructure Research and Development Center, Dept. of Mechanical Engineering, Faculty of Engineering, Khon Kaen University, Khon Kaen (Thailand)

2016-08-15

In this paper, multi-objective optimization of a rack-and-pinion steering linkage is proposed. This steering linkage is a common mechanism used in small cars with three advantages as it is simple to construct, economical to manufacture, and compact and easy to operate. In the previous works, many researchers tried to minimize a steering error but minimization of a turning radius is somewhat ignored. As a result, a multi-objective optimization problem is assigned to simultaneously minimize a steering error and a turning radius. The design variables are linkage dimensions. The design problem is solved by the hybrid of multi-objective population-based incremental learning and differential evolution with various constraint handling schemes. The new design strategy leads to effective design of rack-and-pinion steering linkages satisfying both steering error and turning radius criteria.

Multiobjective optimization of a steering linkage

International Nuclear Information System (INIS)

Sleesonsom, S.; Bureerat, S.

2016-01-01

In this paper, multi-objective optimization of a rack-and-pinion steering linkage is proposed. This steering linkage is a common mechanism used in small cars with three advantages as it is simple to construct, economical to manufacture, and compact and easy to operate. In the previous works, many researchers tried to minimize a steering error but minimization of a turning radius is somewhat ignored. As a result, a multi-objective optimization problem is assigned to simultaneously minimize a steering error and a turning radius. The design variables are linkage dimensions. The design problem is solved by the hybrid of multi-objective population-based incremental learning and differential evolution with various constraint handling schemes. The new design strategy leads to effective design of rack-and-pinion steering linkages satisfying both steering error and turning radius criteria

Turn-around improvements

International Nuclear Information System (INIS)

Redaelli, S.; Venturini Delsolaro, W.

2012-01-01

An efficient turn-around will be an important parameter for the integrated luminosity performance at LHC in 2012, when an operation with steady beam parameters and machine configuration will be achieved at the beginning of the run. Improvements of the operational cycle were already put successfully in place after the 2010 experience but additional ways to reduce the time required to setup collisions are possible. In this paper, the 2011 turn-around performance is reviewed and the benefits of the improvements from 2010 are presented. Phases of the operational cycle when further amelioration is possible are discussed and some proposal for a faster turn-around in 2012 are outlined. (authors)

Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

Science.gov (United States)

McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

2015-09-01

Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Turns prediction : Turns prediction

OpenAIRE

Fuchs, Patrick; Etchebest, Catherine; De Brevern, Alexandre

2007-01-01

The description of protein 3D structure usually focuses on the repetitive local folds (alpha-helices and beta-sheets). The remaining class, sometimes called unordered region, has often been considered as random (one also calls it ‘random coil'). However, some interesting local folds are also highly recurrent and definitely more structured than a real random region. One of such particularly interesting motif is tight turn; this latter is characterized by few residues (3 to 5) and by the revers...

Protected Turning Movements of Noncooperative Automated Vehicles: Geometrics, Trajectories, and Saturation Flow

Directory of Open Access Journals (Sweden)

Xiaobo Liu

2018-01-01

Full Text Available This study is the first to quantify throughput (saturation flow of noncooperative automated vehicles when performing turning maneuvers, which are critical bottlenecks in arterial road networks. We first develop a constrained optimization problem based on AVs’ kinematic behavior during a protected signal phase which considers both ABS-enabled and wheels-locked braking, as well as avoiding encroaching into oncoming traffic or past the edge-of-receiving-lane. We analyze noncooperative (“defensive” behavior, in keeping with the Assured Clear Distance Ahead legal standard to which human drivers are held and AVs will likely also be for the foreseeable future. We demonstrate that, under plausible behavioral parameters, AVs appear likely to have positive impacts on throughput of turning traffic streams at intersections, in the range of +0.2% (under the most conservative circumstances to +43% for a typical turning maneuver. We demonstrate that the primary mechanism of impact of turning radius is its effect on speed, which is likely to be constrained by passenger comfort. We show heterogeneous per-lane throughput in the case of “double turn lanes.” Finally, we demonstrate limited sensitivity to crash-risk criterion, with a 4% difference arising from a change from 1 in 10,000 to 1 in 100,000,000. The paper concludes with a brief discussion of policy implications and future research needs.

A new optimized self-firing mos-thyristor device

Energy Technology Data Exchange (ETDEWEB)

Breil, M.; Sanchez, J.L.; Austin, P.; Laur, J.P.

1998-12-01

In this paper, a new integrated self-firing and controlled turn-off MOS-thyristor structure is investigated. An analytical model describing the turn-off operation and parasitic latch-up has been developed, allowing to highlight and optimize the physical and geometrical parameters acting upon main electrical characteristics. The analytical model is validated by 2D simulations using PISCES. The technological fabrication process is optimized by 2D simulations using SUPREM IV. Electrical characterization results of fabricated test structures are presented. (authors) 6 refs.

Mathematical modelling of metabolism

DEFF Research Database (Denmark)

Gombert, Andreas Karoly; Nielsen, Jens

2000-01-01

Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

Research of remote control system in turn by turn timing system

International Nuclear Information System (INIS)

Zhan Zhifeng; Xiao Yanguo; Ma Kui; Yin Zejie; Wu Xiaoyi

2003-01-01

In this paper, we introduce a remote control system which is used in a frequency dividing and time-delay module. This control system is based on client/server architecture, and RS232 serial communication protocol. This control system is used in timing system of NSRL turn by turn beam position monitor

Waist-to-Height Ratio and Triglycerides/High-Density Lipoprotein Cholesterol Were the Optimal Predictors of Metabolic Syndrome in Uighur Men and Women in Xinjiang, China.

Science.gov (United States)

Chen, Bang-Dang; Yang, Yi-Ning; Ma, Yi-Tong; Pan, Shuo; He, Chun-Hui; Liu, Fen; Ma, Xiang; Fu, Zhen-Yan; Li, Xiao-Mei; Xie, Xiang; Zheng, Ying-Ying

2015-06-01

This study aimed to identify the best single predictor of metabolic syndrome by comparing the predictive ability of various anthropometric and atherogenic parameters among a Uighur population in Xinjiang, northwest China. A total of 4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS), which was carried out from October, 2007, to March, 2010. Anthropometric data, blood pressure, serum concentration of serum total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting glucose were documented. Prevalence of metabolic syndrome and its individual components were confirmed according to International Diabetes Federation (IDF) criteria. Area under the receiver operating characteristic curve (AUC) of each variable for the presence of metabolic syndrome was compared. The sensitivity (Sen), specificity (Spe), distance in the receiver operating characteristic (ROC) curve, and cutoffs of each variable for the presence of metabolic syndrome were calculated. In all, 23.7% of men had the metabolic syndrome, whereas 40.1% of women had the metabolic syndrome in a Uighur population in Xinjiang; the prevalence of metabolic syndrome in women was significantly higher than that in men (PAUC value (AUC=0.838); it was followed by TGs/HDL-C (AUC=0.826), body mass index (BMI) (AUC=0.812), waist-to-hip ratio (WHR) (AUC=0.781), and body adiposity index (BAI) (AUC=0.709). In women, the TGs/HDL-C had the highest AUC value (AUC=0.815); it was followed by WHtR (AUC=0.780), WHR (AUC=0.730), BMI (AUC=0.719), and BAI (AUC=0.699). Similarly, among all five anthropometric and atherogenic parameters, the WHtR had the shortest ROC distance of 0.32 (Sen=85.40%, Spe=71.6%), and the optimal cutoff for WHtR was 0.55 in men. In women, TGs/HDL-C had the shortest ROC distance of 0.35 (Sen=75.29%, Spe=75.18%), and the optimal cutoff of TGs/HDL-C was 1.22. WHtR was the best predictor of metabolic

Modeling and Parameter Optimization for Surface Roughness and Residual Stress in Dry Turning Process

Directory of Open Access Journals (Sweden)

M. H. El-Axir

2017-10-01

Full Text Available The influence of some turning variables and tool overhang on surface roughness parameters and residual stress induced due to machining 6061-T6 aluminum alloy is investigated in this paper. Four input parameters (cutting speed, feed rate, depth of cut and tool overhang are considered. Tests are carried out by precision turning operation on a lathe. Design of experiment techniques, i.e. response surface methodology (RSM and Taguchi's technique have been used to accomplish the objective of the experimental study. Surface roughness parameters are measured using a portable surface roughness device while residual stresses are measured employing deflection-etching technique using electrochemical analysis. The results obtained reveal that feed and rotational speed play significant role in determining the average surface roughness. Furthermore, the depth of cut and tool overhang are less significant parameters, whereas tool overhang interacts with feed rate. The best result of surface roughness was obtained using low or medium values of overhang with low speed and /or feed rate. Minimum maximum tensile residual stress can be obtained with a combination of tool overhang of 37 mm with very low depth of cut, low rotational speed and feed rate of 0.188 mm/rev.

MTOR-Driven Metabolic Reprogramming Regulates Legionella pneumophila Intracellular Niche Homeostasis

Science.gov (United States)

Abshire, Camille F.; Roy, Craig R.

2016-01-01

Vacuolar bacterial pathogens are sheltered within unique membrane-bound organelles that expand over time to support bacterial replication. These compartments sequester bacterial molecules away from host cytosolic immunosurveillance pathways that induce antimicrobial responses. The mechanisms by which the human pulmonary pathogen Legionella pneumophila maintains niche homeostasis are poorly understood. We uncovered that the Legionella-containing vacuole (LCV) required a sustained supply of host lipids during expansion. Lipids shortage resulted in LCV rupture and initiation of a host cell death response, whereas excess of host lipids increased LCVs size and housing capacity. We found that lipids uptake from serum and de novo lipogenesis are distinct redundant supply mechanisms for membrane biogenesis in Legionella-infected macrophages. During infection, the metabolic checkpoint kinase Mechanistic Target of Rapamycin (MTOR) controlled lipogenesis through the Serum Response Element Binding Protein 1 and 2 (SREBP1/2) transcription factors. In Legionella-infected macrophages a host-driven response that required the Toll-like receptors (TLRs) adaptor protein Myeloid differentiation primary response gene 88 (Myd88) dampened MTOR signaling which in turn destabilized LCVs under serum starvation. Inactivation of the host MTOR-suppression pathway revealed that L. pneumophila sustained MTOR signaling throughout its intracellular infection cycle by a process that required the upstream regulator Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and one or more Dot/Icm effector proteins. Legionella-sustained MTOR signaling facilitated LCV expansion and inhibition of the PI3K-MTOR-SREPB1/2 axis through pharmacological or genetic interference or by activation of the host MTOR-suppression response destabilized expanding LCVs, which in turn triggered cell death of infected macrophages. Our work identified a host metabolic requirement for LCV homeostasis and demonstrated that L

Is There an Optimal Diet for Weight Management and Metabolic Health?

Science.gov (United States)

Thom, George; Lean, Mike

2017-05-01

Individuals can lose body weight and improve health status on a wide range of energy (calorie)-restricted dietary interventions. In this paper, we have reviewed the effectiveness of the most commonly utilized diets, including low-fat, low-carbohydrate, and Mediterranean approaches, in addition to commercial slimming programs, meal replacements, and newly popularized intermittent fasting diets. We also consider the role of artificial sweeteners in weight management. Low-fat diets tend to improve low-density lipoprotein cholesterol the most, while lower-carbohydrate diets may preferentially improve triglycerides and high-density lipoprotein cholesterol. However, differences between diets are marginal. Weight loss improves almost all obesity-related co-morbidities and metabolic markers, regardless of the macronutrient composition of the diet, but individuals do vary in preferences and ability to adhere to different diets. Optimizing adherence is the most important factor for weight loss success, and this is enhanced by regular professional contact and supportive behavioral change programs. Maintaining weight losses in the long term remains the biggest challenge, and is undermined by an "obesogenic" environment and biological adaptations that accompany weight loss. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Modelling of the metabolism of Zymomonas mobilis

Energy Technology Data Exchange (ETDEWEB)

Posten, C; Thoma, M

1986-01-01

In order to optimize fermentations with respect to media, reactor configuration, and control a structured model of the metabolism of Zymononas mobilis has been developed. The model is based on structure of metabolism, rate limiting steps, energy balance and metabolic elemental balances. A three-fold effect of ethanol has been observed concerning substrate-turnover, ammonia uptake and energy consumption. In addition to the metabolic view a structured cell-membrane-model should be considered.

Algorithm of axial fuel optimization based in progressive steps of turned search

International Nuclear Information System (INIS)

Martin del Campo, C.; Francois, J.L.

2003-01-01

The development of an algorithm for the axial optimization of fuel of boiling water reactors (BWR) is presented. The algorithm is based in a serial optimizations process in the one that the best solution in each stage is the starting point of the following stage. The objective function of each stage adapts to orient the search toward better values of one or two parameters leaving the rest like restrictions. Conform to it advances in those optimization stages, it is increased the fineness of the evaluation of the investigated designs. The algorithm is based on three stages, in the first one are used Genetic algorithms and in the two following Tabu Search. The objective function of the first stage it looks for to minimize the average enrichment of the one it assembles and to fulfill with the generation of specified energy for the operation cycle besides not violating none of the limits of the design base. In the following stages the objective function looks for to minimize the power factor peak (PPF) and to maximize the margin of shutdown (SDM), having as restrictions the one average enrichment obtained for the best design in the first stage and those other restrictions. The third stage, very similar to the previous one, it begins with the design of the previous stage but it carries out a search of the margin of shutdown to different exhibition steps with calculations in three dimensions (3D). An application to the case of the design of the fresh assemble for the fourth fuel reload of the Unit 1 reactor of the Laguna Verde power plant (U1-CLV) is presented. The obtained results show an advance in the handling of optimization methods and in the construction of the objective functions that should be used for the different design stages of the fuel assemblies. (Author)

Application of digital lock-in detection to Hefei Light Source turn-by-turn system

International Nuclear Information System (INIS)

Yang Yongliang; Wang Junhua; Sun Baogen; Chen Yuanbo; Zhou Zeran

2010-01-01

This paper introduces the digital lock-in detection theory and discusses its feasibility to obtain the damping rate in turn-by-turn measurement systems. Numerical simulations of this method were carried out with Matlab. Then principle presenting beam experiments were conducted on the Hefei Light Source (HLS) storage ring. The measured beta oscillation growth time is about 0.26 ms and the damping time is about 1.2 ms. Simulation and experimental results show that, the digital lock-in detection method is effective in damping rate measurement in turn-by-turn measurement systems. (authors)

Turned on/turned off

DEFF Research Database (Denmark)

Petersen, Eva Bendix

2016-01-01

position, it attempts to sense into the lived experience of being subject to, and of, turns in social theory. As a whole the paper seeks to work with and allow for multiplicity in tone, focus, researcher positioning, reader positioning, and more, to see what knowledge that does not seek confident closure......Through cacophonic story-telling, emerging from ethnographic observations from academic scenes in Australia and elsewhere, the article seeks to explore the timeliness and untimeliness of feminist knowledge production. Rather than arguing a particular point or making a claim for a particular...

Immediate Effects of Clock-Turn Strategy on the Pattern and Performance of Narrow Turning in Persons With Parkinson Disease.

Science.gov (United States)

Yang, Wen-Chieh; Hsu, Wei-Li; Wu, Ruey-Meei; Lin, Kwan-Hwa

2016-10-01

Turning difficulty is common in people with Parkinson disease (PD). The clock-turn strategy is a cognitive movement strategy to improve turning performance in people with PD despite its effects are unverified. Therefore, this study aimed to investigate the effects of the clock-turn strategy on the pattern of turning steps, turning performance, and freezing of gait during a narrow turning, and how these effects were influenced by concurrent performance of a cognitive task (dual task). Twenty-five people with PD were randomly assigned to the clock-turn or usual-turn group. Participants performed the Timed Up and Go test with and without concurrent cognitive task during the medication OFF period. The clock-turn group performed the Timed Up and Go test using the clock-turn strategy, whereas participants in the usual-turn group performed in their usual manner. Measurements were taken during the 180° turn of the Timed Up and Go test. The pattern of turning steps was evaluated by step time variability and step time asymmetry. Turning performance was evaluated by turning time and number of turning steps. The number and duration of freezing of gait were calculated by video review. The clock-turn group had lower step time variability and step time asymmetry than the usual-turn group. Furthermore, the clock-turn group turned faster with fewer freezing of gait episodes than the usual-turn group. Dual task increased the step time variability and step time asymmetry in both groups but did not affect turning performance and freezing severity. The clock-turn strategy reduces turning time and freezing of gait during turning, probably by lowering step time variability and asymmetry. Dual task compromises the effects of the clock-turn strategy, suggesting a competition for attentional resources.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A141).

Two-Scale 13C Metabolic Flux Analysis for Metabolic Engineering.

Science.gov (United States)

Ando, David; Garcia Martin, Hector

2018-01-01

Accelerating the Design-Build-Test-Learn (DBTL) cycle in synthetic biology is critical to achieving rapid and facile bioengineering of organisms for the production of, e.g., biofuels and other chemicals. The Learn phase involves using data obtained from the Test phase to inform the next Design phase. As part of the Learn phase, mathematical models of metabolic fluxes give a mechanistic level of comprehension to cellular metabolism, isolating the principle drivers of metabolic behavior from the peripheral ones, and directing future experimental designs and engineering methodologies. Furthermore, the measurement of intracellular metabolic fluxes is specifically noteworthy as providing a rapid and easy-to-understand picture of how carbon and energy flow throughout the cell. Here, we present a detailed guide to performing metabolic flux analysis in the Learn phase of the DBTL cycle, where we show how one can take the isotope labeling data from a 13 C labeling experiment and immediately turn it into a determination of cellular fluxes that points in the direction of genetic engineering strategies that will advance the metabolic engineering process.For our modeling purposes we use the Joint BioEnergy Institute (JBEI) Quantitative Metabolic Modeling (jQMM) library, which provides an open-source, python-based framework for modeling internal metabolic fluxes and making actionable predictions on how to modify cellular metabolism for specific bioengineering goals. It presents a complete toolbox for performing different types of flux analysis such as Flux Balance Analysis, 13 C Metabolic Flux Analysis, and it introduces the capability to use 13 C labeling experimental data to constrain comprehensive genome-scale models through a technique called two-scale 13 C Metabolic Flux Analysis (2S- 13 C MFA) [1]. In addition to several other capabilities, the jQMM is also able to predict the effects of knockouts using the MoMA and ROOM methodologies. The use of the jQMM library is

Metabolic and demographic feedbacks shape the emergent spatial structure and function of microbial communities.

Directory of Open Access Journals (Sweden)

Sylvie Estrela

Full Text Available Microbes are predominantly found in surface-attached and spatially structured polymicrobial communities. Within these communities, microbial cells excrete a wide range of metabolites, setting the stage for interspecific metabolic interactions. The links, however, between metabolic and ecological interactions (functional relationships, and species spatial organization (structural relationships are still poorly understood. Here, we use an individual-based modelling framework to simulate the growth of a two-species surface-attached community where food (resource is traded for detoxification (service and investigate how metabolic constraints of individual species shape the emergent structural and functional relationships of the community. We show that strong metabolic interdependence drives the emergence of mutualism, robust interspecific mixing, and increased community productivity. Specifically, we observed a striking and highly stable emergent lineage branching pattern, generating a persistent lineage mixing that was absent when the metabolic exchange was removed. These emergent community properties are driven by demographic feedbacks, such that aid from neighbouring cells directly enhances focal cell growth, which in turn feeds back to neighbour fecundity. In contrast, weak metabolic interdependence drives conflict (exploitation or competition, and in turn greater interspecific segregation. Together, these results support the idea that species structural and functional relationships represent the net balance of metabolic interdependencies.

Study on the machinability characteristics of superalloy Inconel 718 during high speed turning

International Nuclear Information System (INIS)

Thakur, D.G.; Ramamoorthy, B.; Vijayaraghavan, L.

2009-01-01

The present paper is an attempt of an experimental investigation on the machinability of superalloy, Inconel 718 during high speed turning using tungsten carbide insert (K20) tool. The effect of machining parameters on the cutting force, specific cutting pressure, cutting temperature, tool wear and surface finish criteria were investigated during the experimentation. The machining parameters have been optimized by measuring forces. The effect of machining parameters on the tool wear was examined through SEM micrographs. During high speed turning acoustic emission signal were collected and analyzed to understand the effect of cutting parameters during online. The research work findings will also provide useful economic machining solution by utilizing economical tungsten carbide tooling during high speed processing of Inconel 718, which is otherwise usually machined by costly PCD or CBN tools. The present approach and results will be helpful for understanding the machinability of Inconel 718 during high speed turning for the manufacturing engineers

DESHARKY: automatic design of metabolic pathways for optimal cell growth.

Science.gov (United States)

Rodrigo, Guillermo; Carrera, Javier; Prather, Kristala Jones; Jaramillo, Alfonso

2008-11-01

The biological solution for synthesis or remediation of organic compounds using living organisms, particularly bacteria and yeast, has been promoted because of the cost reduction with respect to the non-living chemical approach. In that way, computational frameworks can profit from the previous knowledge stored in large databases of compounds, enzymes and reactions. In addition, the cell behavior can be studied by modeling the cellular context. We have implemented a Monte Carlo algorithm (DESHARKY) that finds a metabolic pathway from a target compound by exploring a database of enzymatic reactions. DESHARKY outputs a biochemical route to the host metabolism together with its impact in the cellular context by using mathematical models of the cell resources and metabolism. Furthermore, we provide the sequence of amino acids for the enzymes involved in the route closest phylogenetically to the considered organism. We provide examples of designed metabolic pathways with their genetic load characterizations. Here, we have used Escherichia coli as host organism. In addition, our bioinformatic tool can be applied for biodegradation or biosynthesis and its performance scales with the database size. Software, a tutorial and examples are freely available and open source at http://soft.synth-bio.org/desharky.html

Optimization by record dynamics

DEFF Research Database (Denmark)

Barettin, Daniele; Sibani, Paolo

2014-01-01

Large dynamical changes in thermalizing glassy systems are triggered by trajectories crossing record sized barriers, a behavior revealing the presence of a hierarchical structure in configuration space. The observation is here turned into a novel local search optimization algorithm dubbed record...... dynamics optimization,or RDO. RDO uses the Metropolis rule to accept or reject candidate solutions depending on the value of a parameter akin to the temperature and minimizes the cost function of the problem at hand through cycles where its ‘temperature’ is raised and subsequently decreased in order......), is applied to the same problem as a benchmark. RDO and PT turn out to produce solutions of similar quality for similar numerical effort, but RDO is simpler to program and additionally yields geometrical information on the system’s configuration space which is of interest in many applications. In particular...

Computer-aided design for metabolic engineering.

Science.gov (United States)

Fernández-Castané, Alfred; Fehér, Tamás; Carbonell, Pablo; Pauthenier, Cyrille; Faulon, Jean-Loup

2014-12-20

The development and application of biotechnology-based strategies has had a great socio-economical impact and is likely to play a crucial role in the foundation of more sustainable and efficient industrial processes. Within biotechnology, metabolic engineering aims at the directed improvement of cellular properties, often with the goal of synthesizing a target chemical compound. The use of computer-aided design (CAD) tools, along with the continuously emerging advanced genetic engineering techniques have allowed metabolic engineering to broaden and streamline the process of heterologous compound-production. In this work, we review the CAD tools available for metabolic engineering with an emphasis, on retrosynthesis methodologies. Recent advances in genetic engineering strategies for pathway implementation and optimization are also reviewed as well as a range of bionalytical tools to validate in silico predictions. A case study applying retrosynthesis is presented as an experimental verification of the output from Retropath, the first complete automated computational pipeline applicable to metabolic engineering. Applying this CAD pipeline, together with genetic reassembly and optimization of culture conditions led to improved production of the plant flavonoid pinocembrin. Coupling CAD tools with advanced genetic engineering strategies and bioprocess optimization is crucial for enhanced product yields and will be of great value for the development of non-natural products through sustainable biotechnological processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Estimation and optimization of flank wear and tool lifespan in finish turning of AISI 304 stainless steel using desirability function approach

Directory of Open Access Journals (Sweden)

Lakhdar Bouzid

2018-10-01

Full Text Available The wear of cutting tools remains a major obstacle. The effects of wear are not only antagonistic at the lifespan and productivity, but also harmful with the surface quality. The present work deals with some machinability studies on flank wear, surface roughness, and lifespan in finish turning of AISI 304 stainless steel using multilayer Ti(C,N/Al2O3/TiN coated carbide inserts. The machining experiments are conducted based on the response surface methodology (RSM. Combined effects of three cutting parameters, namely cutting speed, feed rate and cutting time on the two performance outputs (i.e. VB and Ra, and combined effects of two cutting parameters, namely cutting speed and feed rate on lifespan (T, are explored employing the analysis of variance (ANOVA. The relationship between the variables and the technological parameters is determined using a quadratic regression model and optimal cutting conditions for each performance level are established through desirability function approach (DFA optimization. The results show that the flank wear is influenced principally by the cutting time and in the second level by the cutting speed. In addition, it is indicated that the cutting time is the dominant factor affecting workpiece surface roughness followed by feed rate, while lifespan is influenced by cutting speed. The optimum level of input parameters for composite desirability was found Vc1-f1-t1 for VB, Ra and Vc1-f1 for T, with a maximum percentage of error 6.38%.

Genome-scale modeling for metabolic engineering.

Science.gov (United States)

Simeonidis, Evangelos; Price, Nathan D

2015-03-01

We focus on the application of constraint-based methodologies and, more specifically, flux balance analysis in the field of metabolic engineering, and enumerate recent developments and successes of the field. We also review computational frameworks that have been developed with the express purpose of automatically selecting optimal gene deletions for achieving improved production of a chemical of interest. The application of flux balance analysis methods in rational metabolic engineering requires a metabolic network reconstruction and a corresponding in silico metabolic model for the microorganism in question. For this reason, we additionally present a brief overview of automated reconstruction techniques. Finally, we emphasize the importance of integrating metabolic networks with regulatory information-an area which we expect will become increasingly important for metabolic engineering-and present recent developments in the field of metabolic and regulatory integration.

Optimal lag in dynamical investments

OpenAIRE

Serva, M.

1998-01-01

A portfolio of different stocks and a risk-less security whose composition is dynamically maintained stable by trading shares at any time step leads to a growth of the capital with a nonrandom rate. This is the key for the theory of optimal-growth investment formulated by Kelly. In presence of transaction costs, the optimal composition changes and, more important, it turns out that the frequency of transactions must be reduced. This simple observation leads to the definition of an optimal lag...

Influence of acute normobaric hypoxia on physiological variables and lactate turn point determination in trained men.

Science.gov (United States)

Ofner, Michael; Wonisch, Manfred; Frei, Mario; Tschakert, Gerhard; Domej, Wolfgang; Kröpfl, Julia M; Hofmann, Peter

2014-12-01

The goal of this study is to evaluate the response of physiological variables to acute normobaric hypoxia compared to normoxia and its influence on the lactate turn point determination according to the three-phase model of energy supply (Phase I: metabolically balanced at muscular level; Phase II: metabolically balanced at systemic level; Phase III: not metabolically balanced) during maximal incremental exercise. Ten physically active (VO2max 3.9 [0.49] l·min(-1)), healthy men (mean age [SD]: 25.3 [4.6] yrs.), participated in the study. All participants performed two maximal cycle ergometric exercise tests under normoxic as well as hypoxic conditions (FiO2 = 14%). Blood lactate concentration, heart rate, gas exchange data, and power output at maximum and the first and the second lactate turn point (LTP1, LTP2), the heart rate turn point (HRTP) and the first and the second ventilatory turn point (VETP1, VETP2) were determined. Since in normobaric hypoxia absolute power output (P) was reduced at all reference points (max: 314 / 274 W; LTP2: 218 / 184 W; LTP1: 110 / 96 W), as well as VO2max (max: 3.90 / 3.23 l·min(-1); LTP2: 2.90 / 2.43 l·min(-1); LTP1: 1.66 / 1.52 l·min(-1)), percentages of Pmax at LTP1, LTP2, HRTP and VETP1, VETP2 were almost identical for hypoxic as well as normoxic conditions. Heart rate was significantly reduced at Pmax in hypoxia (max: 190 / 185 bpm), but no significant differences were found at submaximal control points. Blood lactate concentration was not different at maximum, and all reference points in both conditions. Respiratory exchange ratio (RER) (max: 1.28 / 1.08; LTP2: 1.13 / 0.98) and ventilatory equivalents for O2 (max: 43.4 / 34.0; LTP2: 32.1 / 25.4) and CO2 (max: 34.1 / 31.6; LTP2: 29.1 / 26.1) were significantly higher at some reference points in hypoxia. Significant correlations were found between LTP1 and VETP1 (r = 0.778; p better the performance of the athletes the higher is the effect of hypoxiaThe HRTP and LTP2 are

Turn-by-Turn and Bunch-by-Bunch Transverse Profiles of a Single Bunch in a Full Ring

International Nuclear Information System (INIS)

Kraus, R.; Fisher, A.S.

2005-01-01

The apparatus described in this paper can image the evolution of the transverse profile of a single bunch, isolated from a full PEP-II ring of 1500 bunches. Using this apparatus there are two methods of single bunch imaging; bunch-by-bunch beam profiling can image every bunch in the ring a single bunch at a time with the images of sequential bunches being in order, allowing one to see variations in beam size along a train. Turn-by-turn beam profiling images a single bunch on each successive turn it makes around the ring. This method will be useful in determining the effect that an injected bunch has on a stable bunch as the oscillations of the injected bunch damp out. Turn-by-turn imaging of the synchrotron light uses a system of lenses and mirrors to image many turns of both the major and minor axis of a single bunch across the photocathode of a gateable camera. The bunch-by-bunch method is simpler: because of a focusing mirror used in porting the light from the ring, the synchrotron light from the orbiting electrons becomes an image at a certain distance from the mirror; and since the camera does not use a lens, the photocathode is set exactly at this image distance. Bunch-by-bunch profiling has shown that in the Low Energy Ring (LER) horizontal bunch size decreases along a train. Turn-by-turn profiling has been able to image 100 turns of a single bunch on one exposure of the camera. The turn-by-turn setup has also been able to image 50 turns of the minor axis showing part of the damping process of an oscillating injected charge during a LER fill. The goal is to image the damping of oscillations of injected charge for 100 turns of both the major and minor axis throughout the damping process during trickle injection. With some changes to the apparatus this goal is within reach and will make turn-by-turn imaging a very useful tool in beam diagnostics

Metabolic Engineering VII Conference

Energy Technology Data Exchange (ETDEWEB)

Kevin Korpics

2012-12-04

The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

Supplementation of Saccharomyces cerevisiae modulates the metabolic response to lipopolysaccharide challenge in feedlot steers

Science.gov (United States)

Live yeast has the potential to serve as an alternative to the use of low-dose supplementation of antibiotics in cattle due to the ability to alter ruminant metabolism; which in turn may influence the immune response. Therefore, the objective of this study was to determine the metabolic response to ...

Beam Optics Measurements Through Turn by Turn Beam Position Data in the SLS

CERN Document Server

Zisopoulos, P; Streun, A; Ziemann, v

2013-01-01

Refined Fourier analysis of turn-by-turn (TBT) transverse position data measurements can be used for determining several beam properties of a ring, such as transverse tunes, optics functions, phases, chromatic properties and coupling. In particular, the Numerical Analysis of Fundamental Frequencies (NAFF) algorithm is used to analyse TBT data from the Swiss Light Source (SLS) storage ring in order to estimate on and off-momentum beam characteristics. Of particular interest is the potential of using the full position information within one turn in order to measure beam optics properties.

Realistic page-turning of electronic books

Science.gov (United States)

Fan, Chaoran; Li, Haisheng; Bai, Yannan

2014-01-01

The booming electronic books (e-books), as an extension to the paper book, are popular with readers. Recently, many efforts are put into the realistic page-turning simulation o f e-book to improve its reading experience. This paper presents a new 3D page-turning simulation approach, which employs piecewise time-dependent cylindrical surfaces to describe the turning page and constructs smooth transition method between time-dependent cylinders. The page-turning animation is produced by sequentially mapping the turning page into the cylinders with different radii and positions. Compared to the previous approaches, our method is able to imitate various effects efficiently and obtains more natural animation of turning page.

Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes.

Science.gov (United States)

Jeong, Hyunyoung

2010-06-01

Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.

Hummingbirds control turning velocity using body orientation and turning radius using asymmetrical wingbeat kinematics.

Science.gov (United States)

Read, Tyson J G; Segre, Paolo S; Middleton, Kevin M; Altshuler, Douglas L

2016-03-01

Turning in flight requires reorientation of force, which birds, bats and insects accomplish either by shifting body position and total force in concert or by using left-right asymmetries in wingbeat kinematics. Although both mechanisms have been observed in multiple species, it is currently unknown how each is used to control changes in trajectory. We addressed this problem by measuring body and wingbeat kinematics as hummingbirds tracked a revolving feeder, and estimating aerodynamic forces using a quasi-steady model. During arcing turns, hummingbirds symmetrically banked the stroke plane of both wings, and the body, into turns, supporting a body-dependent mechanism. However, several wingbeat asymmetries were present during turning, including a higher and flatter outer wingtip path and a lower more deviated inner wingtip path. A quasi-steady analysis of arcing turns performed with different trajectories revealed that changes in radius were associated with asymmetrical kinematics and forces, and changes in velocity were associated with symmetrical kinematics and forces. Collectively, our results indicate that both body-dependent and -independent force orientation mechanisms are available to hummingbirds, and that these kinematic strategies are used to meet the separate aerodynamic challenges posed by changes in velocity and turning radius. © 2016 The Author(s).

Natural selection and optimality

International Nuclear Information System (INIS)

Torres, J.L.

1989-01-01

It is assumed that Darwin's principle translates into optimal regimes of operation along metabolical pathways in an ecological system. Fitness is then defined in terms of the distance of a given individual's thermodynamic parameters from their optimal values. The method is illustrated testing maximum power as a criterion of merit satisfied in ATP synthesis. (author). 26 refs, 2 figs

Controlling cell-free metabolism through physiochemical perturbations.

Science.gov (United States)

Karim, Ashty S; Heggestad, Jacob T; Crowe, Samantha A; Jewett, Michael C

2018-01-01

Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of biosynthetic systems, we recently reported a new cell-free framework for pathway construction and testing. In this framework, multiple crude-cell extracts are selectively enriched with individual pathway enzymes, which are then mixed to construct full biosynthetic pathways on the time scale of a day. This rapid approach to building pathways aids in the study of metabolic pathway performance by providing a unique freedom of design to modify and control biological systems for both fundamental and applied biotechnology. The goal of this work was to demonstrate the ability to probe biosynthetic pathway performance in our cell-free framework by perturbing physiochemical conditions, using n-butanol synthesis as a model. We carried out three unique case studies. First, we demonstrated the power of our cell-free approach to maximize biosynthesis yields by mapping physiochemical landscapes using a robotic liquid-handler. This allowed us to determine that NAD and CoA are the most important factors that govern cell-free n-butanol metabolism. Second, we compared metabolic profile differences between two different approaches for building pathways from enriched lysates, heterologous expression and cell-free protein synthesis. We discover that phosphate from PEP utilization, along with other physiochemical reagents, during cell-free protein synthesis-coupled, crude-lysate metabolic system operation inhibits optimal cell-free n-butanol metabolism. Third, we show that non-phosphorylated secondary energy substrates can be used to fuel cell-free protein synthesis and n-butanol biosynthesis. Taken together, our work highlights the ease of using cell-free systems to explore

Cancer cell metabolism: one hallmark, many faces.

Science.gov (United States)

Cantor, Jason R; Sabatini, David M

2012-10-01

Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

Directory of Open Access Journals (Sweden)

Lihong Jiang

2018-06-01

Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

CONNECTION OF TURN AHEAD AND TURN BACK WITH MOTORIC ABILITIES OF THE FIFTH GRADE STUDENTS

Directory of Open Access Journals (Sweden)

Jovica Petković

2006-06-01

Full Text Available The research is done for the purpose of determination and defining of the level of connection between some motoric abilities with success in realization of programmed contents from the area of gymnastics (turn ahead and turn back. The research is done on the sample of fifty one students from the fifth grade of Elementary School, on ten motoric tests and on two specific motoric assignments – turn ahead and turn back. The results of this research clearly point that there exist the multitude of statistically important coefficients of correlation between treated motoric abilities and applied motoric assignments.

Fuzzy Linguistic Optimization on Multi-Attribute Machining

Directory of Open Access Journals (Sweden)

Tian-Syung Lan

2010-06-01

Full Text Available Most existing multi-attribute optimization researches for the modern CNC (computer numerical control turning industry were either accomplished within certain manufacturing circumstances, or achieved through numerous equipment operations. Therefore, a general deduction optimization scheme proposed is deemed to be necessary for the industry. In this paper, four parameters (cutting depth, feed rate, speed, tool nose runoff with three levels (low, medium, high are considered to optimize the multi-attribute (surface roughness, tool wear, and material removal rate finish turning. Through FAHP (Fuzzy Analytic Hierarchy Process with eighty intervals for each attribute, the weight of each attribute is evaluated from the paired comparison matrix constructed by the expert judgment. Additionally, twenty-seven fuzzy control rules using trapezoid membership function with respective to seventeen linguistic grades for each attribute are constructed. Considering thirty input and eighty output intervals, the defuzzifierion using center of gravity is thus completed. The TOPSIS (Technique for Order Preference by Similarity to Ideal Solution is moreover utilized to integrate and evaluate the multiple machining attributes for the Taguchi experiment, and thus the optimum general deduction parameters can then be received. The confirmation experiment for optimum general deduction parameters is furthermore performed on an ECOCA-3807 CNC lathe. It is shown that the attributes from the fuzzy linguistic optimization parameters are all significantly advanced comparing to those from benchmark. This paper not only proposes a general deduction optimization scheme using orthogonal array, but also contributes the satisfactory fuzzy linguistic approach for multiple CNC turning attributes with profound insight.

Optimal trading quantity integration as a basis for optimal portfolio management

Directory of Open Access Journals (Sweden)

Saša Žiković

2005-06-01

Full Text Available The author in this paper points out the reason behind calculating and using optimal trading quantity in conjunction with Markowitz’s Modern portfolio theory. In the opening part the author presents an example of calculating optimal weights using Markowitz’s Mean-Variance approach, followed by an explanation of basic logic behind optimal trading quantity. The use of optimal trading quantity is not limited to systems with Bernoulli outcome, but can also be used when trading shares, futures, options etc. Optimal trading quantity points out two often-overlooked axioms: (1 a system with negative mathematical expectancy can never be transformed in a system with positive mathematical expectancy, (2 by missing the optimal trading quantity an investor can turn a system with positive expectancy into a negative one. Optimal trading quantity is that quantity which maximizes geometric mean (growth function of a particular system. To determine the optimal trading quantity for simpler systems, with a very limited number of outcomes, a set of Kelly’s formulas is appropriate. In the conclusion the summary of the paper is presented.

Energy Demand Modeling Methodology of Key State Transitions of Turning Processes

Directory of Open Access Journals (Sweden)

Shun Jia

2017-04-01

Full Text Available Energy demand modeling of machining processes is the foundation of energy optimization. Energy demand of machining state transition is integral to the energy requirements of the machining process. However, research focus on energy modeling of state transition is scarce. To fill this gap, an energy demand modeling methodology of key state transitions of the turning process is proposed. The establishment of an energy demand model of state transition could improve the accuracy of the energy model of the machining process, which also provides an accurate model and reliable data for energy optimization of the machining process. Finally, case studies were conducted on a CK6153i CNC lathe, the results demonstrating that predictive accuracy with the proposed method is generally above 90% for the state transition cases.

CERN PS Optical Properties Measured with Turn-By-Turn Orbit Data

CERN Document Server

Bach, T; Giovannozzi, M; Hernalsteens, C; Lachaize, A; Sterbini, G; Tom´as, R; Wasef, R

2013-01-01

The performance of the CERN Proton Synchrotron (PS) has been constantly increasing over the years both in terms of beam parameters (intensity and brightness) and beam manipulations (transverse and longitudinal splitting). This implies a very good knowledge of the linear and non-linear model of the ring. In this paper we report on a detailed campaign of beam measurements based on turn-by-turn orbit data aimed at measuring the optics in several conditions as well as the resonance driving terms.

Two routes toward optimism: how agentic and communal themes in autobiographical memories guide optimism for the future.

Science.gov (United States)

Austin, Adrienne; Costabile, Kristi

2017-11-01

Autobiographical memories are particularly adaptive because they function not only to preserve the past, but also to direct our future thoughts and behaviours. Two studies were conducted to examine how communal and agentic themes of positive autobiographical memories differentially predicted the route from autobiographical memories to optimism for the future. Across two studies, results revealed that the degree to which participants focused on communal themes in their autobiographical memories predicted their experience of nostalgia. In turn, the experience of nostalgia increased participants' levels of self-esteem and in turn, optimism for the future. By contrast, the degree to which participants focused on agentic themes in their memories predicted self-esteem and optimism, operating outside the experience of nostalgia. These effects remained even after controlling for self-focused attention. Together, these studies provide greater understanding of the interrelations among autobiographical memory, self-concept, and time, and demonstrate how agency and communion operate to influence perceptions of one's future when thinking about the past.

Sandstone Turning by Abrasive Waterjet

Czech Academy of Sciences Publication Activity Database

Hlaváček, Petr; Cárach, J.; Hloch, Sergej; Vasilko, K.; Klichová, Dagmar; Klich, Jiří; Lehocká, D.

2015-01-01

Roč. 48, č. 6 (2015), s. 2489-2493 ISSN 0723-2632 R&D Projects: GA MŠk ED2.1.00/03.0082; GA MŠk(CZ) LO1406 Institutional support: RVO:68145535 Keywords : turning away from the jet * conventional turning towards the jet * sandstone * abrasive water jet Subject RIV: JQ - Machines ; Tools Impact factor: 2.386, year: 2015 http://www.springerprofessional.de/sandstone-turning-by-abrasive-waterjet/6038028.html

NetTurnP--neural network prediction of beta-turns by use of evolutionary information and predicted protein sequence features.

Directory of Open Access Journals (Sweden)

Bent Petersen

Full Text Available UNLABELLED: β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. CONCLUSION: The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences.

NetTurnP--neural network prediction of beta-turns by use of evolutionary information and predicted protein sequence features.

Science.gov (United States)

Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

2010-11-30

β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences.

Stand up, sit down, keep moving: turning circles in physical activity research?

Science.gov (United States)

Brown, W J; Bauman, A E; Owen, N

2009-02-01

This review tracks the evidence and associated recommendations and guidelines for optimal levels of physical activity for health benefit. In the 1950s, early epidemiological studies focused on the increased risk of cardiovascular disease and all-cause mortality associated with sitting at work. The period from the mid-seventies to the turn of the century saw an initial focus on the health benefits of vigorous exercise give way to mounting evidence for the benefits of moderate-intensity physical activity. As daily energy expenditure in most domains of human activity (travel, domestic and occupational work, and leisure) continues to decline, early 21st century researchers are starting to turn full circle, with a rekindling of interest in the health effects of sedentary behaviour at work, and indeed in the balance between activity and sedentariness in all aspects of daily life.

Evolutionary programming as a platform for in silico metabolic engineering

Directory of Open Access Journals (Sweden)

Förster Jochen

2005-12-01

Full Text Available Abstract Background Through genetic engineering it is possible to introduce targeted genetic changes and hereby engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, owing to the complexity of metabolic networks, both in terms of structure and regulation, it is often difficult to predict the effects of genetic modifications on the resulting phenotype. Recently genome-scale metabolic models have been compiled for several different microorganisms where structural and stoichiometric complexity is inherently accounted for. New algorithms are being developed by using genome-scale metabolic models that enable identification of gene knockout strategies for obtaining improved phenotypes. However, the problem of finding optimal gene deletion strategy is combinatorial and consequently the computational time increases exponentially with the size of the problem, and it is therefore interesting to develop new faster algorithms. Results In this study we report an evolutionary programming based method to rapidly identify gene deletion strategies for optimization of a desired phenotypic objective function. We illustrate the proposed method for two important design parameters in industrial fermentations, one linear and other non-linear, by using a genome-scale model of the yeast Saccharomyces cerevisiae. Potential metabolic engineering targets for improved production of succinic acid, glycerol and vanillin are identified and underlying flux changes for the predicted mutants are discussed. Conclusion We show that evolutionary programming enables solving large gene knockout problems in relatively short computational time. The proposed algorithm also allows the optimization of non-linear objective functions or incorporation of non-linear constraints and additionally provides a family of close to optimal solutions. The identified metabolic engineering strategies suggest that non-intuitive genetic modifications span

and γγ-turns in proteins revisited: A new set of amino acid turn-type de

Indian Academy of Sciences (India)

mine, valine, glutamic acid and alanine has decreased for β-turns. Certain new amino acid preferences were observed for both turn types and individual amino acids showed turn-type dependent positional preferences. The rationale for new amino acid preferences are discussed in the light of hydrogen bonds and other.

Balancing cellular redox metabolism in microbial electrosynthesis and electro fermentation - A chance for metabolic engineering.

Science.gov (United States)

Kracke, Frauke; Lai, Bin; Yu, Shiqin; Krömer, Jens O

2018-01-01

More and more microbes are discovered that are capable of extracellular electron transfer, a process in which they use external electrodes as electron donors or acceptors for metabolic reactions. This feature can be used to overcome cellular redox limitations and thus optimizing microbial production. The technologies, termed microbial electrosynthesis and electro-fermentation, have the potential to open novel bio-electro production platforms from sustainable energy and carbon sources. However, the performance of reported systems is currently limited by low electron transport rates between microbes and electrodes and our limited ability for targeted engineering of these systems due to remaining knowledge gaps about the underlying fundamental processes. Metabolic engineering offers many opportunities to optimize these processes, for instance by genetic engineering of pathways for electron transfer on the one hand and target product synthesis on the other hand. With this review, we summarize the status quo of knowledge and engineering attempts around chemical production in bio-electrochemical systems from a microbe perspective. Challenges associated with the introduction or enhancement of extracellular electron transfer capabilities into production hosts versus the engineering of target compound synthesis pathways in natural exoelectrogens are discussed. Recent advances of the research community in both directions are examined critically. Further, systems biology approaches, for instance using metabolic modelling, are examined for their potential to provide insight into fundamental processes and to identify targets for metabolic engineering. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

SEARCHING FOR CRITERIA IN EVALUATING THE MONOFIN SWIMMING TURN FROM THE PERSPECTIVE OF COACHING AND IMPROVING TECHNIQUE

Directory of Open Access Journals (Sweden)

Marek Rejman

2008-03-01

Full Text Available This study aims to analysise the selected kinematic parameters of the monofin swimming turn. The high complexity of performing turns is hindered by the large surface of the monofin, which disturbs control and sense of the body in water. A lack of objective data available on monofin swimming turns has resulted in field research connected with the specification of parameters needed for the evaluation of the technique. Therefore, turns observed in elite swimmers contain underlying conclusions for objective criteria, ensuring the highest level of coaching and the improving of turns in young swimmers. Six, high level, male swimmers participated in the study. The subject of the analysis was the fastest turn, from one out of three trial turns made after swimming a distance of 25 m. Images of the turns were collected from two cameras located under water in accordance with the procedures of the previous analyses of freestyle turns. The images were digitized and analysed by the SIMI®- Movement Analysis System. The interdependency of the total turn time and the remaining recorded parameters, constituted the basis for analysis of the kinematic parameters of five turn phases. The interdependency was measured using r- Pearson's correlation coefficients. The novel character of the subject covered in this study, forced interpretation of the results on the basis of turn analyses in freestyle swimming. The results allow for the creation of a diagram outlinig area of search for an effective and efficient monofin swimming turn mechanism. The activities performed from the moment of wall contact until the commencement of stroking seem to be crucial for turn improvement. A strong belief has resulted that, the correct monofin swimming turn, is more than just a simple consequence of the fastest performance of all its components. The most important criteria in evaluating the quality of the monofin swimming turn are: striving for the optimal extension of wall contact

SNS 2.1K Cold Box Turn-down Studies

International Nuclear Information System (INIS)

F. Casagrande; P.A. Gurd; D.R. Hatfield; M.P. Howell; W.H. Strong; D. Arenius; J. Creel; V. Ganni; P. Knudsen

2006-01-01

The Spallation Neutron Source (SNS) at Oak Ridge National Laboratory is nearing completion. The cold section of the Linac consists of 81 superconducting radio frequency cavities cooled to 2.1K by a 2400 watt cryogenic refrigeration system. The 2.1K cold box consists of four stages of centrifugal compressors with LN2-cooled variable speed electric motors and magnetic bearings. The cryogenic system successfully supported the Linac beam commissioning at both 4.2K and 2.1K and has been fully operational since June 2005. This paper describes the control principles utilized and the experimental results obtained for the SNS cold compressors turn-down capability to about 30% of the design flow, and possible limitation of the frequency dependent power factor of the cold compressor electric motors, which was measured for the first time during commissioning. These results helped to support the operation of the Linac over a very broad and stable cold compressor operating flow range (refrigeration capacity) and pressure. This in turn helped to optimize the cryogenic system operating parameters, minimizing the utilities and improving the system reliability and availability

Beta-and gamma-turns in proteins revisited: a new set of amino acid turn-type dependent positional preferences and potentials.

Science.gov (United States)

Guruprasad, K; Rajkumar, S

2000-06-01

The number of beta-turns in a representative set of 426 protein three-dimensional crystal structures selected from the recent Protein Data Bank has nearly doubled and the number of gamma-turns in a representative set of 320 proteins has increased over seven times since the previous analysis. Beta-turns (7153) and gamma-turns (911) extracted from these proteins were used to derive a revised set of type-dependent amino acid positional preferences and potentials. Compared with previous results, the preference for proline, methionine and tryptophan has increased and the preference for glutamine, valine, glutamic acid and alanine has decreased for beta-turns. Certain new amino acid preferences were observed for both turn types and individual amino acids showed turn-type dependent positional preferences. The rationale for new amino acid preferences are discussed in the light of hydrogen bonds and other interactions involving the turns. Where main-chain hydrogen bonds of the type NH(i + 3) --> CO(i) were not observed for some beta-turns, other main-chain hydrogen bonds or solvent interactions were observed that possibly stabilize such beta-turns. A number of unexpected isolated beta-turns with proline at i + 2 position were also observed. The NH(i + 2) --> CO(i) hydrogen bond was observed for almost all gamma-turns. Nearly 20% classic gamma-turns and 43% inverse gamma-turns are isolated turns.

Turn-by-Turn Imaging of the Transverse Beam Profile in PEP-II

Energy Technology Data Exchange (ETDEWEB)

Fisher, Alan A.; Petree, Mark; /SLAC

2006-12-18

During injection or instability, the transverse profile of an individual bunch in a storage ring can change significantly in a few turns. However, most synchrotron-light imaging techniques are not designed for this time scale. We have developed a novel diagnostic that enhances the utility of a fast gated camera by adding, inexpensively, some features of a dual-axis streak camera, in order to watch the turn-by-turn evolution of the transverse profile, in both x and y. The beam's elliptical profile is reshaped using cylindrical lenses to form a tall and narrow ellipse--essentially the projection of the full ellipse onto one transverse axis. We do this projection twice, by splitting the beam into two paths at different heights, and rotating the ellipse by 90{sup o} on one path. A rapidly rotating mirror scans these vertical ''pencils'' of light horizontally across the photocathode of the camera, which is gated for 3 ns on every Nth ring turn. A single readout of the camera captures 100 images, looking like a stroboscopic photograph of a moving object. We have observed the capture of injected charge into a bunch and the rapid change of beam size at the onset of a fast instability.

Evolutionary programming as a platform for in silico metabolic engineering

DEFF Research Database (Denmark)

Patil, Kiran Raosaheb; Rocha, Isabel; Förster, Jochen

2005-01-01

, and it is therefore interesting to develop new faster algorithms. Results In this study we report an evolutionary programming based method to rapidly identify gene deletion strategies for optimization of a desired phenotypic objective function. We illustrate the proposed method for two important design parameters...... of close to optimal solutions. The identified metabolic engineering strategies suggest that non-intuitive genetic modifications span several different pathways and may be necessary for solving challenging metabolic engineering problems....

Clinical evaluation of an automated turning bed.

Science.gov (United States)

Melland, H I; Langemo, D; Hanson, D; Olson, B; Hunter, S

1999-01-01

The purposes of this study were to assess client comfort and sleep quality, client physiologic response (skin and respiratory status), the effect on the need for caregiver assistance, and cost when using an automated turning bed. Nonexperimental, evaluative study. Twenty-four adult home or long-term care resident subjects who had a degenerative disease, spinal cord injury, stroke, cerebral palsy, or back surgery. Each subject agreed to use the automated turning bed for four weeks. Researchers completed a demographic survey and skin assessment, and assessed each subject for pressure ulcer risk and for the need of assistance of a care giver for turning before and after the four weeks of using the turning bed. Subjects rated the turning bed in terms of comfort and sleep quality. Subjects rated the turning bed as more comfortable than their own bed and expressed satisfaction at the pain relief attained when on the turning bed. While using the turning bed, there was a significant improvement in sleep quality. No skin breakdown or deterioration in respiratory status occurred. Fewer subjects required the assistance of a caregiver for turning when on the turning bed. This automated turning bed shows great promise in meeting a need for patients with limited mobility whether they are homebound or in a residential community. Future studies that further investigate use of the turning bed for postoperative back patients while still in the acute care setting are indicated. Replicative studies with a larger sample size are also indicated.

DRUM: a new framework for metabolic modeling under non-balanced growth. Application to the carbon metabolism of unicellular microalgae.

Science.gov (United States)

Baroukh, Caroline; Muñoz-Tamayo, Rafael; Steyer, Jean-Philippe; Bernard, Olivier

2014-01-01

Metabolic modeling is a powerful tool to understand, predict and optimize bioprocesses, particularly when they imply intracellular molecules of interest. Unfortunately, the use of metabolic models for time varying metabolic fluxes is hampered by the lack of experimental data required to define and calibrate the kinetic reaction rates of the metabolic pathways. For this reason, metabolic models are often used under the balanced growth hypothesis. However, for some processes such as the photoautotrophic metabolism of microalgae, the balanced-growth assumption appears to be unreasonable because of the synchronization of their circadian cycle on the daily light. Yet, understanding microalgae metabolism is necessary to optimize the production yield of bioprocesses based on this microorganism, as for example production of third-generation biofuels. In this paper, we propose DRUM, a new dynamic metabolic modeling framework that handles the non-balanced growth condition and hence accumulation of intracellular metabolites. The first stage of the approach consists in splitting the metabolic network into sub-networks describing reactions which are spatially close, and which are assumed to satisfy balanced growth condition. The left metabolites interconnecting the sub-networks behave dynamically. Then, thanks to Elementary Flux Mode analysis, each sub-network is reduced to macroscopic reactions, for which simple kinetics are assumed. Finally, an Ordinary Differential Equation system is obtained to describe substrate consumption, biomass production, products excretion and accumulation of some internal metabolites. DRUM was applied to the accumulation of lipids and carbohydrates of the microalgae Tisochrysis lutea under day/night cycles. The resulting model describes accurately experimental data obtained in day/night conditions. It efficiently predicts the accumulation and consumption of lipids and carbohydrates.

DRUM: a new framework for metabolic modeling under non-balanced growth. Application to the carbon metabolism of unicellular microalgae.

Directory of Open Access Journals (Sweden)

Caroline Baroukh

Full Text Available Metabolic modeling is a powerful tool to understand, predict and optimize bioprocesses, particularly when they imply intracellular molecules of interest. Unfortunately, the use of metabolic models for time varying metabolic fluxes is hampered by the lack of experimental data required to define and calibrate the kinetic reaction rates of the metabolic pathways. For this reason, metabolic models are often used under the balanced growth hypothesis. However, for some processes such as the photoautotrophic metabolism of microalgae, the balanced-growth assumption appears to be unreasonable because of the synchronization of their circadian cycle on the daily light. Yet, understanding microalgae metabolism is necessary to optimize the production yield of bioprocesses based on this microorganism, as for example production of third-generation biofuels. In this paper, we propose DRUM, a new dynamic metabolic modeling framework that handles the non-balanced growth condition and hence accumulation of intracellular metabolites. The first stage of the approach consists in splitting the metabolic network into sub-networks describing reactions which are spatially close, and which are assumed to satisfy balanced growth condition. The left metabolites interconnecting the sub-networks behave dynamically. Then, thanks to Elementary Flux Mode analysis, each sub-network is reduced to macroscopic reactions, for which simple kinetics are assumed. Finally, an Ordinary Differential Equation system is obtained to describe substrate consumption, biomass production, products excretion and accumulation of some internal metabolites. DRUM was applied to the accumulation of lipids and carbohydrates of the microalgae Tisochrysis lutea under day/night cycles. The resulting model describes accurately experimental data obtained in day/night conditions. It efficiently predicts the accumulation and consumption of lipids and carbohydrates.

and γγ-turns in proteins revisited: A new set of amino acid turn-type de

Indian Academy of Sciences (India)

cent Protein Data Bank has nearly doubled and the number of γ-turns in a representative set of 320 proteins has in- creased over seven times since the previous analysis. β-turns (7153) and γ-turns (911) extracted from these proteins were used to derive a revised set of type-dependent amino acid positional preferences and ...

Conformational interconversions in peptide beta-turns: analysis of turns in proteins and computational estimates of barriers.

Science.gov (United States)

Gunasekaran, K; Gomathi, L; Ramakrishnan, C; Chandrasekhar, J; Balaram, P

1998-12-18

The two most important beta-turn features in peptides and proteins are the type I and type II turns, which differ mainly in the orientation of the central peptide unit. Facile conformational interconversion is possible, in principle, by a flip of the central peptide unit. Homologous crystal structures afford an opportunity to structurally characterize both possible conformational states, thus allowing identification of sites that are potentially stereochemically mobile. A representative data set of 250 high-resolution (turns that are assigned different conformational types (type I/type II) in related structures. A total of 55 examples of beta-turns were identified as possible candidates for a stereochemically mobile site. Of the 55 examples, 45 could be classified as a potential site for interconversion between type I and type II beta-turns, while ten correspond to flips from type I' to type II' structures. As a further check, the temperature factors of the central peptide unit carbonyl oxygen atom of the 55 examples were examined. The analysis reveals that the turn assignments are indeed reliable. Examination of the secondary structures at the flanking positions of the flippable beta-turns reveals that seven examples occur in the loop region of beta-hairpins, indicating that the formation of ordered secondary structures on either side of the beta-turn does not preclude local conformational variations. In these beta-turns, Pro (11 examples), Lys (nine examples) and Ser (seven examples) were most often found at the i+1 position. Glycine was found to occur overwhelmingly at position i+2 (28 examples), while Ser (seven examples) and Asn (six examples) were amongst the most frequent residues. Activation energy barriers for the interconversion between type I and type II beta-turns were computed using the peptide models Ac-Pro-Aib-NHMe and Ac-Pro-Gly-NHMe within the framework of the AM1 semi-empirical molecular orbital procedure. In order to have a uniform basis for

NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

DEFF Research Database (Denmark)

Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

2010-01-01

is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino......β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method...... NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which...

Obesity-driven gut microbiota inflammatory pathways to metabolic syndrome

Directory of Open Access Journals (Sweden)

Luiz Henrique Agra eCavalcante-Silva

2015-11-01

Full Text Available The intimate interplay between immune system, metabolism and gut microbiota plays an important role in controlling metabolic homeostasis and possible obesity development. Obesity involves impairment of immune response affecting both innate and adaptive immunity. The main factors involved in the relationship of obesity with inflammation have not been completely elucidated. On the other hand, gut microbiota, via innate immune receptors, has emerged as one of the key factors regulating events triggering acute inflammation associated with obesity and metabolic syndrome. Inflammatory disorders lead to several signalling transduction pathways activation, inflammatory cytokine, chemokine production and cell migration, which in turn cause metabolic dysfunction. Inflamed adipose tissue, with increased macrophages infiltration, is associated with impaired preadipocyte development and differentiation to mature adipose cells, leading to ectopic lipid accumulation and insulin resistance. This review focuses on the relationship between obesity and inflammation, which is essential to understand the pathological mechanisms governing metabolic syndrome.

A New Version of Optimism for Education

Science.gov (United States)

Bojesen, Emile

2018-01-01

The primary purpose of this paper is to outline the conceptual means by which it is possible to be optimistic about education. To provide this outline I turn to Ian Hunter and David Blacker, after a brief introduction to Nietzsche's conceptions of optimism and pessimism, to show why certain forms of optimism in education are either intellectually…

Experimental investigations on the effect of process parameters with the use of minimum quantity solid lubrication in turning

Science.gov (United States)

Makhesana, Mayur A.; Patel, K. M.; Mawandiya, B. K.

2018-04-01

Turning process is a very basic process in any field of mechanical application. During turning process, most of the energy is converted into heat because of the friction between work piece and tool. Heat generation can affect the surface quality of the work piece and tool life. To reduce the heat generation, Conventional Lubrication process is used in most of the industry. Minimum quantity lubrication has been an effective alternative to improve the performance of machining process. In this present work, effort has been made to study the effect of various process parameters on the surface roughness and power consumption during turning of EN8 steel material. Result revealed the effect of depth of cut and feed on the obtained surface roughness value. Further the effect of solid lubricant has been also studied and optimization of process parameters is also done for the turning process.

Electrical Machines: Turn-to-Turn Capacitance in Formed Windings with Rectangular Cross-Section Wire

NARCIS (Netherlands)

Djukic, Nenad; Encica, L.; Paulides, Johan

2015-01-01

Calculation of turn-to-turn capacitance (Ctt) in electrical machines (EMs) with formed windings with rectangular cross-section wire is presented. Three calculation methods are used for the calculation of Ctt in case of rectangular conductors – finite element (FE) method and two previously published

Rapid Optimal Generation Algorithm for Terrain Following Trajectory Based on Optimal Control

Institute of Scientific and Technical Information of China (English)

杨剑影; 张海; 谢邦荣; 尹健

2004-01-01

Based on the optimal control theory, a 3-dimensionnal direct generation algorithm is proposed for anti-ground low altitude penetration tasks under complex terrain. By optimizing the terrain following(TF) objective function,terrain coordinate system, missile dynamic model and control vector, the TF issue is turning into the improved optimal control problem whose mathmatical model is simple and need not solve the second order terrain derivative. Simulation results prove that this method is reasonable and feasible. The TF precision is in the scope from 0.3 m to 3.0 m,and the planning time is less than 30 min. This method have the strongpionts such as rapidness, precision and has great application value.

Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects.

Science.gov (United States)

Martin, Francois-Pierre J; Rezzi, Serge; Peré-Trepat, Emma; Kamlage, Beate; Collino, Sebastiano; Leibold, Edgar; Kastler, Jürgen; Rein, Dietrich; Fay, Laurent B; Kochhar, Sunil

2009-12-01

Dietary preferences influence basal human metabolism and gut microbiome activity that in turn may have long-term health consequences. The present study reports the metabolic responses of free living subjects to a daily consumption of 40 g of dark chocolate for up to 14 days. A clinical trial was performed on a population of 30 human subjects, who were classified in low and high anxiety traits using validated psychological questionnaires. Biological fluids (urine and blood plasma) were collected during 3 test days at the beginning, midtime and at the end of a 2 week study. NMR and MS-based metabonomics were employed to study global changes in metabolism due to the chocolate consumption. Human subjects with higher anxiety trait showed a distinct metabolic profile indicative of a different energy homeostasis (lactate, citrate, succinate, trans-aconitate, urea, proline), hormonal metabolism (adrenaline, DOPA, 3-methoxy-tyrosine) and gut microbial activity (methylamines, p-cresol sulfate, hippurate). Dark chocolate reduced the urinary excretion of the stress hormone cortisol and catecholamines and partially normalized stress-related differences in energy metabolism (glycine, citrate, trans-aconitate, proline, beta-alanine) and gut microbial activities (hippurate and p-cresol sulfate). The study provides strong evidence that a daily consumption of 40 g of dark chocolate during a period of 2 weeks is sufficient to modify the metabolism of free living and healthy human subjects, as per variation of both host and gut microbial metabolism.

Scaling of Metabolic Scaling within Physical Limits

Directory of Open Access Journals (Sweden)

Douglas S. Glazier

2014-10-01

Full Text Available Both the slope and elevation of scaling relationships between log metabolic rate and log body size vary taxonomically and in relation to physiological or developmental state, ecological lifestyle and environmental conditions. Here I discuss how the recently proposed metabolic-level boundaries hypothesis (MLBH provides a useful conceptual framework for explaining and predicting much, but not all of this variation. This hypothesis is based on three major assumptions: (1 various processes related to body volume and surface area exert state-dependent effects on the scaling slope for metabolic rate in relation to body mass; (2 the elevation and slope of metabolic scaling relationships are linked; and (3 both intrinsic (anatomical, biochemical and physiological and extrinsic (ecological factors can affect metabolic scaling. According to the MLBH, the diversity of metabolic scaling relationships occurs within physical boundary limits related to body volume and surface area. Within these limits, specific metabolic scaling slopes can be predicted from the metabolic level (or scaling elevation of a species or group of species. In essence, metabolic scaling itself scales with metabolic level, which is in turn contingent on various intrinsic and extrinsic conditions operating in physiological or evolutionary time. The MLBH represents a “meta-mechanism” or collection of multiple, specific mechanisms that have contingent, state-dependent effects. As such, the MLBH is Darwinian in approach (the theory of natural selection is also meta-mechanistic, in contrast to currently influential metabolic scaling theory that is Newtonian in approach (i.e., based on unitary deterministic laws. Furthermore, the MLBH can be viewed as part of a more general theory that includes other mechanisms that may also affect metabolic scaling.

32 CFR 636.23 - Turning movements.

Science.gov (United States)

2010-07-01

... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL... movements. (a) U-turns are prohibited on all streets in the cantonment area. (b) Right-turns will be made from a position as close to the right edge or right curb of the roadway as possible. (c) Left-turns...

Turn stability in beta-hairpin peptides: Investigation of peptides containing 3:5 type I G1 bulge turns.

Science.gov (United States)

Blandl, Tamas; Cochran, Andrea G; Skelton, Nicholas J

2003-02-01

The turn-forming ability of a series of three-residue sequences was investigated by substituting them into a well-characterized beta-hairpin peptide. The starting scaffold, bhpW, is a disulfide-cyclized 10-residue peptide that folds into a stable beta-hairpin with two antiparallel strands connected by a two-residue reverse turn. Substitution of the central two residues with the three-residue test sequences leads to less stable hairpins, as judged by thiol-disulfide equilibrium measurements. However, analysis of NMR parameters indicated that each molecule retains a significant folded population, and that the type of turn adopted by the three-residue sequence is the same in all cases. The solution structure of a selected peptide with a PDG turn contained an antiparallel beta-hairpin with a 3:5 type I + G1 bulge turn. Analysis of the energetic contributions of individual turn residues in the series of peptides indicates that substitution effects have significant context dependence, limiting the predictive power of individual amino acid propensities for turn formation. The most stable and least stable sequences were also substituted into a more stable disulfide-cyclized scaffold and a linear beta-hairpin scaffold. The relative stabilities remained the same, suggesting that experimental measurements in the bhpW context are a useful way to evaluate turn stability for use in protein design projects. Moreover, these scaffolds are capable of displaying a diverse set of turns, which can be exploited for the mimicry of protein loops or for generating libraries of reverse turns.

Turning collectors for solar radiation

Science.gov (United States)

Barak, Amitzur Z.

1976-01-01

A device is provided for turning a solar collector about the polar axis so that the collector is directed toward the sun as the sun tracks the sky each day. It includes two heat-expansive elements and a shadow plate. In the morning a first expansive element is heated, expands to turn the collector to face the sun, while the second expansive element is shaded by the plate. In the afternoon the second element is heated, expands to turn the collector to face the sun, while the first is shaded by the plate.

Context-Specific Metabolic Model Extraction Based on Regularized Least Squares Optimization.

Directory of Open Access Journals (Sweden)

Semidán Robaina Estévez

Full Text Available Genome-scale metabolic models have proven highly valuable in investigating cell physiology. Recent advances include the development of methods to extract context-specific models capable of describing metabolism under more specific scenarios (e.g., cell types. Yet, none of the existing computational approaches allows for a fully automated model extraction and determination of a flux distribution independent of user-defined parameters. Here we present RegrEx, a fully automated approach that relies solely on context-specific data and ℓ1-norm regularization to extract a context-specific model and to provide a flux distribution that maximizes its correlation to data. Moreover, the publically available implementation of RegrEx was used to extract 11 context-specific human models using publicly available RNAseq expression profiles, Recon1 and also Recon2, the most recent human metabolic model. The comparison of the performance of RegrEx and its contending alternatives demonstrates that the proposed method extracts models for which both the structure, i.e., reactions included, and the flux distributions are in concordance with the employed data. These findings are supported by validation and comparison of method performance on additional data not used in context-specific model extraction. Therefore, our study sets the ground for applications of other regularization techniques in large-scale metabolic modeling.

NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

Science.gov (United States)

Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

2010-01-01

β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC  = 0.50, Qtotal = 82.1%, sensitivity  = 75.6%, PPV  = 68.8% and AUC  = 0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17 – 0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. Conclusion The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences. PMID:21152409

Numerical Optimization Algorithms and Software for Systems Biology

Energy Technology Data Exchange (ETDEWEB)

Saunders, Michael

2013-02-02

The basic aims of this work are: to develop reliable algorithms for solving optimization problems involving large stoi- chiometric matrices; to investigate cyclic dependency between metabolic and macromolecular biosynthetic networks; and to quantify the significance of thermodynamic constraints on prokaryotic metabolism.

Multiobjective flux balancing using the NISE method for metabolic network analysis.

Science.gov (United States)

Oh, Young-Gyun; Lee, Dong-Yup; Lee, Sang Yup; Park, Sunwon

2009-01-01

Flux balance analysis (FBA) is well acknowledged as an analysis tool of metabolic networks in the framework of metabolic engineering. However, FBA has a limitation for solving a multiobjective optimization problem which considers multiple conflicting objectives. In this study, we propose a novel multiobjective flux balance analysis method, which adapts the noninferior set estimation (NISE) method (Solanki et al., 1993) for multiobjective linear programming (MOLP) problems. NISE method can generate an approximation of the Pareto curve for conflicting objectives without redundant iterations of single objective optimization. Furthermore, the flux distributions at each Pareto optimal solution can be obtained for understanding the internal flux changes in the metabolic network. The functionality of this approach is shown by applying it to a genome-scale in silico model of E. coli. Multiple objectives for the poly(3-hydroxybutyrate) [P(3HB)] production are considered simultaneously, and relationships among them are identified. The Pareto curve for maximizing succinic acid production vs. maximizing biomass production is used for the in silico analysis of various combinatorial knockout strains. This proposed method accelerates the strain improvement in the metabolic engineering by reducing computation time of obtaining the Pareto curve and analysis time of flux distribution at each Pareto optimal solution. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

Predicting turns in proteins with a unified model.

Directory of Open Access Journals (Sweden)

Qi Song

Full Text Available MOTIVATION: Turns are a critical element of the structure of a protein; turns play a crucial role in loops, folds, and interactions. Current prediction methods are well developed for the prediction of individual turn types, including α-turn, β-turn, and γ-turn, etc. However, for further protein structure and function prediction it is necessary to develop a uniform model that can accurately predict all types of turns simultaneously. RESULTS: In this study, we present a novel approach, TurnP, which offers the ability to investigate all the turns in a protein based on a unified model. The main characteristics of TurnP are: (i using newly exploited features of structural evolution information (secondary structure and shape string of protein based on structure homologies, (ii considering all types of turns in a unified model, and (iii practical capability of accurate prediction of all turns simultaneously for a query. TurnP utilizes predicted secondary structures and predicted shape strings, both of which have greater accuracy, based on innovative technologies which were both developed by our group. Then, sequence and structural evolution features, which are profile of sequence, profile of secondary structures and profile of shape strings are generated by sequence and structure alignment. When TurnP was validated on a non-redundant dataset (4,107 entries by five-fold cross-validation, we achieved an accuracy of 88.8% and a sensitivity of 71.8%, which exceeded the most state-of-the-art predictors of certain type of turn. Newly determined sequences, the EVA and CASP9 datasets were used as independent tests and the results we achieved were outstanding for turn predictions and confirmed the good performance of TurnP for practical applications.

Correction of Oxygen Transport and Metabolic Disturbances in Acute Poisoning by Neurotropic Substances

Directory of Open Access Journals (Sweden)

G. A. Livanov

2007-01-01

Full Text Available Objective: to examine the capacities of pharmacological correction of impairments in oxygen-transporting systems and metabolic processes with perfluorane and cytoflavin in critically ill patients with acute intoxication with neurotropic poisons.Subjects and methods. Metabolic sequels of severe hypoxia, free radical processes, and endogenous intoxications were studied in 62 patients with the severest acute intoxication with neurotropic poisons.Results. The studies have established that hypoxia and metabolic changes lead to the development of endotoxicosis. Intensifying endotoxicosis in turn enhances hypoxic lesion. Thus, the major task of intensive care is to restore oxygen delivery and to diminish metabolic disturbances and endotoxicosis. Ways of correcting hypoxia and metabolic disturbances are considered in the severe forms of acute poisoning. 

What 'empirical turn in bioethics'?

Science.gov (United States)

Hurst, Samia

2010-10-01

Uncertainty as to how we should articulate empirical data and normative reasoning seems to underlie most difficulties regarding the 'empirical turn' in bioethics. This article examines three different ways in which we could understand 'empirical turn'. Using real facts in normative reasoning is trivial and would not represent a 'turn'. Becoming an empirical discipline through a shift to the social and neurosciences would be a turn away from normative thinking, which we should not take. Conducting empirical research to inform normative reasoning is the usual meaning given to the term 'empirical turn'. In this sense, however, the turn is incomplete. Bioethics has imported methodological tools from empirical disciplines, but too often it has not imported the standards to which researchers in these disciplines are held. Integrating empirical and normative approaches also represents true added difficulties. Addressing these issues from the standpoint of debates on the fact-value distinction can cloud very real methodological concerns by displacing the debate to a level of abstraction where they need not be apparent. Ideally, empirical research in bioethics should meet standards for empirical and normative validity similar to those used in the source disciplines for these methods, and articulate these aspects clearly and appropriately. More modestly, criteria to ensure that none of these standards are completely left aside would improve the quality of empirical bioethics research and partly clear the air of critiques addressing its theoretical justification, when its rigour in the particularly difficult context of interdisciplinarity is what should be at stake.

Constraint based modeling of metabolism allows finding metabolic cancer hallmarks and identifying personalized therapeutic windows.

Science.gov (United States)

Bordel, Sergio

2018-04-13

In order to choose optimal personalized anticancer treatments, transcriptomic data should be analyzed within the frame of biological networks. The best known human biological network (in terms of the interactions between its different components) is metabolism. Cancer cells have been known to have specific metabolic features for a long time and currently there is a growing interest in characterizing new cancer specific metabolic hallmarks. In this article it is presented a method to find personalized therapeutic windows using RNA-seq data and Genome Scale Metabolic Models. This method is implemented in the python library, pyTARG. Our predictions showed that the most anticancer selective (affecting 27 out of 34 considered cancer cell lines and only 1 out of 6 healthy mesenchymal stem cell lines) single metabolic reactions are those involved in cholesterol biosynthesis. Excluding cholesterol biosynthesis, all the considered cell lines can be selectively affected by targeting different combinations (from 1 to 5 reactions) of only 18 metabolic reactions, which suggests that a small subset of drugs or siRNAs combined in patient specific manners could be at the core of metabolism based personalized treatments.

CONNECTION OF TURN AHEAD AND TURN BACK WITH MOTORIC ABILITIES OF THE FOURTH GRADE OF HIGH SCHOOL

Directory of Open Access Journals (Sweden)

Jovica Petković

2008-08-01

Full Text Available The research is done for the purpose of determination and defining of the level of connection between some motoric abilities with success in realization of programmed contents from the area of gymnastics (turn ahead and turn back. The research is done on the sample of fifty students from the fourth grade of High School, on ten motoric tests and on two specific motoric assignments – turn ahead and turn back. The results of this research clearly point that there exist the multitude of statistically important coefficients of correlation between treated motoric abilities and applied motoric assignments.

OPTIMIZATION OF SURFACE ROUGHNESS OF AISI 304 AUSTENITIC STAINLESS STEEL IN DRY TURNING OPERATION USING TAGUCHI DESIGN METHOD

Directory of Open Access Journals (Sweden)

D. PHILIP SELVARAJ

2010-09-01

Full Text Available The present work is concentrated with the dry turning of AISI 304 Austenitic Stainless Steel (ASS. This paper presents the influence of cutting parameters like cutting speed, feed rate and depth of cut on the surface roughness of austenitic stainless steel during dry turning. A plan of experiments based on Taguchi’s technique has been used to acquire the data. An orthogonal array, the signal to noise (S/N ratio and the analysis of variance (ANOVA are employed to investigate the cutting characteristics of AISI 304 austenitic stainless steel bars using TiC and TiCN coated tungsten carbide cutting tool. Finally the confirmation tests that have been carried out to compare the predicted values with the experimental values confirm its effectiveness in the analysis of surface roughness.

The Philosophy of Turning Points

DEFF Research Database (Denmark)

Turcan, Romeo V.

2013-01-01

business and management field, the turning point is seen as a valuable unit of analysis within the research field. It is expected that this paper will encourage a dynamic scholarly conversation about the concept of turning point and how it can aid international business researchers in the development...

Heart over mind: metabolic control of white adipose tissue and liver.

Science.gov (United States)

Nakamura, Michinari; Sadoshima, Junichi

2014-12-01

Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

Next-generation genome-scale models for metabolic engineering

DEFF Research Database (Denmark)

King, Zachary A.; Lloyd, Colton J.; Feist, Adam M.

2015-01-01

Constraint-based reconstruction and analysis (COBRA) methods have become widely used tools for metabolic engineering in both academic and industrial laboratories. By employing a genome-scale in silico representation of the metabolic network of a host organism, COBRA methods can be used to predict...... examples of applying COBRA methods to strain optimization are presented and discussed. Then, an outlook is provided on the next generation of COBRA models and the new types of predictions they will enable for systems metabolic engineering....

From pathways to genomes and beyond. The metabolic engineering toolbox and its place in biofuels production

Energy Technology Data Exchange (ETDEWEB)

Liu, Leqian; Reed, Ben; Alper, Hal [Texas Univ., Austin, TX (United States). Dept. of Chemical Engineering

2011-07-01

Concerns about the availability of petroleum-derived fuels and chemicals have led to the exploration of metabolically engineered organisms as novel hosts for biofuels and chemicals production. However, the complexity inherent in metabolic and regulatory networks makes this undertaking a complex task. To address these limitations, metabolic engineering has adapted a wide-variety of tools for altering phenotypes. In this review, we will highlight traditional and recent metabolic engineering tools for optimizing cells including pathway-based, global, and genomic-enabled approaches. Specifically, we describe these tools as well as provide demonstrations of their effectiveness in optimizing biofuels production. However, each of these tools provides stepping stones towards the grand goal of biofuels production. Thus, developing methods for large-scale cellular optimization and integrative approaches are invaluable for further cell optimization. This review highlights the challenges that still must be met to accomplish this goal. (orig.)

Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise

DEFF Research Database (Denmark)

Volianitis, Stefanos; Rasmussen, Peter; Seifert, Thomas

2011-01-01

.05) following the Sal and Bicarb trials, respectively. Accordingly, the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials: from 5.8 ± 0.6 at rest to 1.7 ± 0.1 and 1.8 ± 0.2, respectively. The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis......Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose + 1/2 lactate) and metabolic acidosis appears to promote cerebral lactate uptake. However, the influence of pH on cerebral lactate uptake and, in turn, on the cerebral metabolic ratio during exercise is not known. Sodium...... during maximal exercise but that did not affect the cerebral lactate uptake and, therefore, the decrease in the cerebral metabolic ratio....

Reflector optimization for coupled liquid hydrogen moderator

International Nuclear Information System (INIS)

Kiyanagi, Y.; Iwasa, H.; Watanabe, N.; Furusaka, M.

1991-01-01

As a part of optimization studies on a coupled liquid hydrogen moderator system, the optimal thickness of the reflector, the effects of neutron absorbing liners and other beam hole/moderator on the cold-neutron-beam intensity were studied experimentally. It turns out that the optimal thickness is rather thick in this system and the existence of Cd liners around the beam extraction hole considerably reduces the cold neutron beam intensity, while the existence of other beam hole and moderator does not give an important intensity reduction. (author)

Conversion rate optimization in Finnish online businesses

OpenAIRE

Ratia, Miramaria; Ruoho, Vilma

2016-01-01

Conversion rate optimization (CRO) is an unfamiliar term to many online business owners even though it has become almost as important as search engine optimization is in e-commerce today. It is a method that is used to turn passive visitors into active users in order to improve a website’s performance. The main objective of this thesis was to find out what kinds of conversion rate optimization methods do Finnish small and medium-sized online businesses use. The thesis also studies what ar...

Prediction of beta-turns with learning machines.

Science.gov (United States)

Cai, Yu-Dong; Liu, Xiao-Jun; Li, Yi-Xue; Xu, Xue-biao; Chou, Kuo-Chen

2003-05-01

The support vector machine approach was introduced to predict the beta-turns in proteins. The overall self-consistency rate by the re-substitution test for the training or learning dataset reached 100%. Both the training dataset and independent testing dataset were taken from Chou [J. Pept. Res. 49 (1997) 120]. The success prediction rates by the jackknife test for the beta-turn subset of 455 tetrapeptides and non-beta-turn subset of 3807 tetrapeptides in the training dataset were 58.1 and 98.4%, respectively. The success rates with the independent dataset test for the beta-turn subset of 110 tetrapeptides and non-beta-turn subset of 30,231 tetrapeptides were 69.1 and 97.3%, respectively. The results obtained from this study support the conclusion that the residue-coupled effect along a tetrapeptide is important for the formation of a beta-turn.

Study on Turn-to-turn Short Circuit On一line Monitoring System for Dry一type Ai r一core Reactor

Directory of Open Access Journals (Sweden)

GAO Zi-wei

2017-04-01

Full Text Available The change of current value caused by turn-to-turn short circuit of dry-type air-core reactor is so little that failure detection is difficult to be carried out. In order to solve this problem，a new on-line monitoring system based on impedance variation of turn-to-turn short circuit is proposed. The numerical method is applied to analyze the variation of equivalent resistance and equivalent reactance when dry-type air-core reactor winding short circuit happens in different places，and the monitoring method based on harmonic analysis method and quasi- synchronization sampling method is analyzed by theory. The hardware system，which takes single-chip microcomputer as the core of data processing and logic control，completes data acquisition of voltage signal and current signal of the reactor. In the respect of software design，the impedance variation will be uploaded to the PC after it has been calculated by using the above monitoring method，and then monitoring of turn-to-turn short circuit fault will be realized. Finally，the design of on-line monitoring system is studied by testing. The research result shows that，the equivalent resistance increases and the equivalent reactance decreases when turn-to-turn short circuit occurs，and the variation of equivalent resistance is more obvious than equivalent reactance. The experiment results prove that this monitoring method is true and the on-line monitoring system is feasible.

From elementary flux modes to elementary flux vectors: Metabolic pathway analysis with arbitrary linear flux constraints

Science.gov (United States)

Klamt, Steffen; Gerstl, Matthias P.; Jungreuthmayer, Christian; Mahadevan, Radhakrishnan; Müller, Stefan

2017-01-01

Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated. These additional constraints further restrict the space of feasible flux vectors and turn the flux cone into a general flux polyhedron in which the concept of EFMs is not directly applicable anymore. For this reason, there has been a conceptual gap between EFM-based (pathway) analysis methods and linear optimization (FBA) techniques, as they operate on different geometric objects. One approach to overcome these limitations was proposed ten years ago and is based on the concept of elementary flux vectors (EFVs). Only recently has the community started to recognize the potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent the conceptual development required to generalize the idea of EFMs from flux cones to flux polyhedra. This work aims to present a concise theoretical and practical introduction to EFVs that is accessible to a broad audience. We highlight the close relationship between EFMs and EFVs and demonstrate that almost all applications of EFMs (in flux cones) are possible for EFVs (in flux polyhedra) as well. In fact, certain properties can only be studied with EFVs. Thus, we conclude that EFVs provide a powerful and unifying framework for constraint-based modeling of metabolic networks. PMID:28406903

Uric acid in metabolic syndrome: From an innocent bystander to a central player

Science.gov (United States)

Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A.; Nakagawa, Takahiko; Johnson, Richard J.

2016-01-01

Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. PMID:26703429

Injection optimization in a heavy-ion synchrotron using genetic algorithms

Energy Technology Data Exchange (ETDEWEB)

Appel, S., E-mail: s.appel@gsi.de [GSI, Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Boine-Frankenheim, O. [GSI, Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Technische Universität Darmstadt, Schlossgartenstraße 8, 64289 Darmstadt (Germany); Petrov, F. [Technische Universität Darmstadt, Schlossgartenstraße 8, 64289 Darmstadt (Germany)

2017-04-21

The control of the beam loss induced dynamic pressure is one of the most challenging problems for synchrotrons operated with high intensity beams of intermediate charge state ions. This loss-induced vacuum degradation and associated life-time reduction is one of the key intensity limiting factors. Beam loss during Multi-Turn Injection (MTI) can trigger the pressure bump instability. An optimized injection can relax the dynamic vacuum problem, but is also crucial to fill the available machine acceptance. A numerical model has been developed to describe the intensity limitation due to loss-induced vacuum degradation. In order to optimize the multi-turn injection for given initial losses, a genetic algorithm based optimization has been performed. For the SIS18 synchrotron at GSI the optimization resulted in a significant improvement of MTI performance and subsequent transmission for intense beams. A range of suitable injector brilliances for given initial loss could be defined. This information is crucial for the layout of the injector upgrade for FAIR. The effect of transverse space charge force on MTI has been included in the optimization studies.

Development process and data management of TurnSTEP, a STEP-compliant CNC system for turning

NARCIS (Netherlands)

Choi, I.; Suh, S.-H; Kim, K.; Song, M.S.; Jang, M.; Lee, B.-E.

2006-01-01

TurnSTEP is one of the earliest STEP-compliant CNC systems for turning. Based on the STEP-NC data model formalized as ISO 14649-12 and 121, it is designed to support intelligent and autonomous control of NC machines for e-manufacturing. The present paper introduces the development process and data

Time optimal paths for high speed maneuvering

Energy Technology Data Exchange (ETDEWEB)

Reister, D.B.; Lenhart, S.M.

1993-01-01

Recent theoretical results have completely solved the problem of determining the minimum length path for a vehicle with a minimum turning radius moving from an initial configuration to a final configuration. Time optimal paths for a constant speed vehicle are a subset of the minimum length paths. This paper uses the Pontryagin maximum principle to find time optimal paths for a constant speed vehicle. The time optimal paths consist of sequences of axes of circles and straight lines. The maximum principle introduces concepts (dual variables, bang-bang solutions, singular solutions, and transversality conditions) that provide important insight into the nature of the time optimal paths. We explore the properties of the optimal paths and present some experimental results for a mobile robot following an optimal path.

Optimization of IGCT for pulsed power

International Nuclear Information System (INIS)

Chen Fanglin; Tang Longgu; Chen Yongmin; Pan Xuejun

2014-01-01

In order to develop high-performance IGCT devices applied in pulse power, cathode finger layout is optimized, the finger structure is modified, minority carrier lifetime is properly controlled and gate triggering characteristics is improved. As a result of these measures, the IGCT turn -on di/dt is improved, current handling capability is enhanced and switching response speed is increased. The feasibility and validity of the optimization study on the IGCT is verified by simulation and experimental results. (authors)

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

DEFF Research Database (Denmark)

Hefzi, Hooman; Ang, Kok Siong; Hanscho, Michael

2016-01-01

Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways...

Loading pattern optimization in hexagonal geometry using PANTHER

International Nuclear Information System (INIS)

Parks, G.T.; Knight, M.P.

1996-01-01

The extension of the loading pattern optimization capability of Nuclear Electric's reactor physics code PANTHER to hexagonal geometry cores is described. The variety of search methods available and the code's performance are illustrated by an example in which three search different methods are used in turn in order to find an optimal reload design for a sample hexagonal geometry problem. (author)

The determination of optimal climate policy

International Nuclear Information System (INIS)

Aaheim, Asbjoern

2010-01-01

Analyses of the costs and benefits of climate policy, such as the Stern Review, evaluate alternative strategies to reduce greenhouse gas emissions by requiring that the cost of emission cuts in each and every year has to be covered by the associated value of avoided damage, discounted by a an exogenously chosen rate. An alternative is to optimize abatement programmes towards a stationary state, where the concentrations of greenhouse gases are stabilized and shadow prices, including the rate of discount, are determined endogenously. This paper examines the properties of optimized stabilization. It turns out that the implications for the evaluation of climate policy are substantial if compared with evaluations of the present value of costs and benefits based on exogenously chosen shadow prices. Comparisons of discounted costs and benefits tend to exaggerate the importance of the choice of discount rate, while ignoring the importance of future abatement costs, which turns out to be essential for the optimal abatement path. Numerical examples suggest that early action may be more beneficial than indicated by comparisons of costs and benefits discounted by a rate chosen on the basis of current observations. (author)

Modeling with a view to target identification in metabolic engineering: a critical evaluation of the available tools.

Science.gov (United States)

Maertens, Jo; Vanrolleghem, Peter A

2010-01-01

The state of the art tools for modeling metabolism, typically used in the domain of metabolic engineering, were reviewed. The tools considered are stoichiometric network analysis (elementary modes and extreme pathways), stoichiometric modeling (metabolic flux analysis, flux balance analysis, and carbon modeling), mechanistic and approximative modeling, cybernetic modeling, and multivariate statistics. In the context of metabolic engineering, one should be aware that the usefulness of these tools to optimize microbial metabolism for overproducing a target compound depends predominantly on the characteristic properties of that compound. Because of their shortcomings not all tools are suitable for every kind of optimization; issues like the dependence of the target compound's synthesis on severe (redox) constraints, the characteristics of its formation pathway, and the achievable/desired flux towards the target compound should play a role when choosing the optimization strategy.

Signatures of arithmetic simplicity in metabolic network architecture.

Directory of Open Access Journals (Sweden)

William J Riehl

2010-04-01

Full Text Available Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that properties similar to those predicted for the artificial chemistry hold also for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity.

Metabolic engineering tools in model cyanobacteria.

Science.gov (United States)

Carroll, Austin L; Case, Anna E; Zhang, Angela; Atsumi, Shota

2018-03-26

Developing sustainable routes for producing chemicals and fuels is one of the most important challenges in metabolic engineering. Photoautotrophic hosts are particularly attractive because of their potential to utilize light as an energy source and CO 2 as a carbon substrate through photosynthesis. Cyanobacteria are unicellular organisms capable of photosynthesis and CO 2 fixation. While engineering in heterotrophs, such as Escherichia coli, has result in a plethora of tools for strain development and hosts capable of producing valuable chemicals efficiently, these techniques are not always directly transferable to cyanobacteria. However, recent efforts have led to an increase in the scope and scale of chemicals that cyanobacteria can produce. Adaptations of important metabolic engineering tools have also been optimized to function in photoautotrophic hosts, which include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9, 13 C Metabolic Flux Analysis (MFA), and Genome-Scale Modeling (GSM). This review explores innovations in cyanobacterial metabolic engineering, and highlights how photoautotrophic metabolism has shaped their development. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Partisan Optimism and Political Bargaining

DEFF Research Database (Denmark)

Jensen, Thomas; Madum, Andreas

Partisan voters are optimistic about electoral outcomes: their estimates of the probability of electoral success for their party or candidate are substantially higher than the average among the electorate. This has large potential implications for political bargaining. Optimism about future...... electoral outcomes can make costly bargaining delay look more favorable, which may induce partisans to punish their party for agreeing to a compromise rather than waiting, for example by not turning out to vote. Therefore, party decision makers should take optimism among partisans into account when...... bargaining. In this paper we use game theoretic modeling to explore the implications of partisan optimism for political bargaining. We show that increased optimism among a partisan group leads to a stronger bargaining position for their party, but may hurt its electoral prospects. Another main finding...

Fast Turn-off Mine Transient Electromagnetic Transmitter System

Directory of Open Access Journals (Sweden)

ZHENG Xiao-Liang

2014-05-01

Full Text Available For solving problems such as short turn-off time, high linear degree of falling edge, measurement of turn-off time and influence of primary signals for transient electromagnetic transmitter, and restrictions because of the environmental conditions of underground coal mine, this thesis aims at designing a new transient electromagnetic transmitter system suitable for coal mine. Supported by damping absorption circuit, such system applies small volume, sectional transmitting coil, with features of short turn-off time, high linear degree of current falling edge. It uses the transmitter monitoring circuit, which accurately measures turn-off time and simultaneously records the current value changes after turn-off, thus to eliminate the influence of primary field as well as to restore earlier secondary field signals for reference and finally to improve the ability to detect the shallow structure. It turns out that the new system has a shorter turn-off time, a higher linear degree of current falling and more accurate data record of turn-off current.

Diagnostic performance of BMI percentiles to identify adolescents with metabolic syndrome.

Science.gov (United States)

Laurson, Kelly R; Welk, Gregory J; Eisenmann, Joey C

2014-02-01

To compare the diagnostic performance of the Centers for Disease Control and Prevention (CDC) and FITNESSGRAM (FGram) BMI standards for quantifying metabolic risk in youth. Adolescents in the NHANES (n = 3385) were measured for anthropometric variables and metabolic risk factors. BMI percentiles were calculated, and youth were categorized by weight status (using CDC and FGram thresholds). Participants were also categorized by presence or absence of metabolic syndrome. The CDC and FGram standards were compared by prevalence of metabolic abnormalities, various diagnostic criteria, and odds of metabolic syndrome. Receiver operating characteristic curves were also created to identify optimal BMI percentiles to detect metabolic syndrome. The prevalence of metabolic syndrome in obese youth was 19% to 35%, compared with <2% in the normal-weight groups. The odds of metabolic syndrome for obese boys and girls were 46 to 67 and 19 to 22 times greater, respectively, than for normal-weight youth. The receiver operating characteristic analyses identified optimal thresholds similar to the CDC standards for boys and the FGram standards for girls. Overall, BMI thresholds were more strongly associated with metabolic syndrome in boys than in girls. Both the CDC and FGram standards are predictive of metabolic syndrome. The diagnostic utility of the CDC thresholds outperformed the FGram values for boys, whereas FGram standards were slightly better thresholds for girls. The use of a common set of thresholds for school and clinical applications would provide advantages for public health and clinical research and practice.

Increasing protein stability by improving beta-turns.

Science.gov (United States)

Fu, Hailong; Grimsley, Gerald R; Razvi, Abbas; Scholtz, J Martin; Pace, C Nick

2009-11-15

Our goal was to gain a better understanding of how protein stability can be increased by improving beta-turns. We studied 22 beta-turns in nine proteins with 66-370 residues by replacing other residues with proline and glycine and measuring the stability. These two residues are statistically preferred in some beta-turn positions. We studied: Cold shock protein B (CspB), Histidine-containing phosphocarrier protein, Ubiquitin, Ribonucleases Sa2, Sa3, T1, and HI, Tryptophan synthetase alpha-subunit, and Maltose binding protein. Of the 15 single proline mutations, 11 increased stability (Average = 0.8 +/- 0.3; Range = 0.3-1.5 kcal/mol), and the stabilizing effect of double proline mutants was additive. On the basis of this and our previous work, we conclude that proteins can generally be stabilized by replacing nonproline residues with proline residues at the i + 1 position of Type I and II beta-turns and at the i position in Type II beta-turns. Other turn positions can sometimes be used if the phi angle is near -60 degrees for the residue replaced. It is important that the side chain of the residue replaced is less than 50% buried. Identical substitutions in beta-turns in related proteins give similar results. Proline substitutions increase stability mainly by decreasing the entropy of the denatured state. In contrast, the large, diverse group of proteins considered here had almost no residues in beta-turns that could be replaced by Gly to increase protein stability. Improving beta-turns by substituting Pro residues is a generally useful way of increasing protein stability. 2009 Wiley-Liss, Inc.

The optimal graph partitioning problem

DEFF Research Database (Denmark)

Sørensen, Michael Malmros; Holm, Søren

1993-01-01

. This problem can be formulated as a MILP, which turns out to be completely symmetrical with respect to the p classes, and the gap between the relaxed LP solution and the optimal solution is the largest one possible. These two properties make it very difficult to solve even smaller problems. In this paper...

Adherence to two methods of education and metabolic control in ...

African Journals Online (AJOL)

BACKGROUND: Education in diabetes optimizes metabolic control, prevents acute and chronic complications, and improves quality of life. Our main objective was to evaluate if a better metabolic control is achieved in diabetic patients undergoing a program of intensive interactive care than in those with traditional care and ...

Sample size calculation in metabolic phenotyping studies.

Science.gov (United States)

Billoir, Elise; Navratil, Vincent; Blaise, Benjamin J

2015-09-01

The number of samples needed to identify significant effects is a key question in biomedical studies, with consequences on experimental designs, costs and potential discoveries. In metabolic phenotyping studies, sample size determination remains a complex step. This is due particularly to the multiple hypothesis-testing framework and the top-down hypothesis-free approach, with no a priori known metabolic target. Until now, there was no standard procedure available to address this purpose. In this review, we discuss sample size estimation procedures for metabolic phenotyping studies. We release an automated implementation of the Data-driven Sample size Determination (DSD) algorithm for MATLAB and GNU Octave. Original research concerning DSD was published elsewhere. DSD allows the determination of an optimized sample size in metabolic phenotyping studies. The procedure uses analytical data only from a small pilot cohort to generate an expanded data set. The statistical recoupling of variables procedure is used to identify metabolic variables, and their intensity distributions are estimated by Kernel smoothing or log-normal density fitting. Statistically significant metabolic variations are evaluated using the Benjamini-Yekutieli correction and processed for data sets of various sizes. Optimal sample size determination is achieved in a context of biomarker discovery (at least one statistically significant variation) or metabolic exploration (a maximum of statistically significant variations). DSD toolbox is encoded in MATLAB R2008A (Mathworks, Natick, MA) for Kernel and log-normal estimates, and in GNU Octave for log-normal estimates (Kernel density estimates are not robust enough in GNU octave). It is available at http://www.prabi.fr/redmine/projects/dsd/repository, with a tutorial at http://www.prabi.fr/redmine/projects/dsd/wiki. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Partitioning the metabolic scope: the importance of anaerobic metabolism and implications for the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis

DEFF Research Database (Denmark)

Ejbye-Ernst, Rasmus; Michaelsen, Thomas Y.; Tirsgaard, B.

2016-01-01

. aurata. In contrast, both species revealed significant negative correlations between aerobic and anaerobic components of the MS, indicating a trade-off where both components of the MS cannot be optimized simultaneously. Importantly, the fraction of the MS influenced by anaerobic metabolism was on average...... 24.3 and 26.1% in S. aurata and P. reticulata, respectively. These data highlight the importance of taking anaerobic metabolism into account when assessing effects of environmental variation on the MS, because the fraction where anaerobic metabolism occurs is a poor indicator of sustainable aerobic...

Anticipation in turn-taking: mechanisms and information sources.

Science.gov (United States)

Riest, Carina; Jorschick, Annett B; de Ruiter, Jan P

2015-01-01

During conversations participants alternate smoothly between speaker and hearer roles with only brief pauses and overlaps. There are two competing types of accounts about how conversationalists accomplish this: (a) the signaling approach and (b) the anticipatory ('projection') approach. We wanted to investigate, first, the relative merits of these two accounts, and second, the relative contribution of semantic and syntactic information to the timing of next turn initiation. We performed three button-press experiments using turn fragments taken from natural conversations to address the following questions: (a) Is turn-taking predominantly based on anticipation or on reaction, and (b) what is the relative contribution of semantic and syntactic information to accurate turn-taking. In our first experiment we gradually manipulated the information available for anticipation of the turn end (providing information about the turn end in advance to completely removing linguistic information). The results of our first experiment show that the distribution of the participants' estimation of turn-endings for natural turns is very similar to the distribution for pure anticipation. We conclude that listeners are indeed able to anticipate a turn-end and that this strategy is predominantly used in turn-taking. In Experiment 2 we collected purely reacted responses. We used the distributions from Experiments 1 and 2 together to estimate a new dependent variable called Reaction Anticipation Proportion. We used this variable in our third experiment where we manipulated the presence vs. absence of semantic and syntactic information by low-pass filtering open-class and closed class words in the turn. The results suggest that for turn-end anticipation, both semantic and syntactic information are needed, but that the semantic information is a more important anticipation cue than syntactic information.

Top Ten Secrets to Success with Optimization

OpenAIRE

Brown, Gerald G.

2004-01-01

This appears in PHALANX, Vol. 37, No. 4, pp. 12 ff, and is reprinted with permission of Military Operations Society, 2004. The Department of Defense coordinates the activities of millions of people using assets worth trillions of dollars. This is important, complex work. Computer-based decision support is universal, and this has enabled optimization to continue to enhance legacy manual planning methods. The success of real-world applications of optimization turns out to...

Radiation protection optimization in the CAETITE industrial complex

International Nuclear Information System (INIS)

Azevedo Py Junior, D.; Figueiredo, N.; Dos Santos Dias, P.L.; Mantovani Lima, H.

2002-01-01

This paper presents, briefly, the radiation protection aspects of process, project and operation of the Caetite Industrial Complex, CIC. Planing priorities were to minimize Environmental Radiological Impact and Occupational Radiological Risk - Based on previous experiences, the process and the project were optimized, in order to minimize environmental impact and allow simultaneous natural environment restoration and operation. Technical, practical and economical advantages became evident during all project fazes, from the initial project development to the conclusion of all decommissioning steps. Planing, conducts. adequate working methods and workers training, together, turned out to be the most efficient way for occupational radiological risk reduction. This efficiency was proved during operational tests and initial operation of the Complex. Radiation Protection optimization is achieved by worker's responsibility, turning safety corrections interference less frequents, rising consequently, minimizing environmental impact. (author)

Metabolic engineering of E. coli top 10 for production of vanillin through FA catabolic pathway and bioprocess optimization using RSM.

Science.gov (United States)

Chakraborty, Debkumar; Gupta, Gaganjot; Kaur, Baljinder

2016-12-01

Metabolic engineering and construction of recombinant Escherichia coli strains carrying feruloyl-CoA synthetase and enoyl-CoA hydratase genes for the bioconversion of ferulic acid to vanillin offers an alternative way to produce vanillin. Isolation and designing of fcs and ech genes was carried out using computer assisted protocol and the designed vanillin biosynthetic gene cassette was cloned in pCCIBAC expression vector for introduction in E. coli top 10. Recombinant strain was implemented for the statistical optimization of process parameters influencing F A to vanillin biotransformation. CCD matrix constituted of process variables like FA concentration, time, temperature and biomass with intracellular, extracellular and total vanillin productions as responses. Production was scaled up and 68 mg/L of vanillin was recovered from 10 mg/L of FA using cell extracts from 1 mg biomass within 30 min. Kinetic activity of enzymes were characterized. From LCMS-ESI analysis a metabolic pathway of FA degradation and vanillin production was predicted. Copyright © 2016 Elsevier Inc. All rights reserved.

On the (non-)optimality of Michell structures

DEFF Research Database (Denmark)

Sigmund, Ole; Aage, Niels; Andreassen, Erik

2016-01-01

Optimal analytical Michell frame structures have been extensively used as benchmark examples in topology optimization, including truss, frame, homogenization, density and level-set based approaches. However, as we will point out, partly the interpretation of Michell’s structural continua...... as discrete frame structures is not accurate and partly, it turns out that limiting structural topology to frame-like structures is a rather severe design restriction and results in structures that are quite far from being stiffness optimal. The paper discusses the interpretation of Michell’s theory...... in the context of numerical topology optimization and compares various topology optimization results obtained with the frame restriction to cases with no design restrictions. For all examples considered, the true stiffness optimal structures are composed of sheets (2D) or closed-walled shell structures (3D...

Breaking New Ground with High Resolution Turn-By-Turn BPMs at the ESRF

CERN Document Server

Farvacque, L; Scheidt, K

2001-01-01

This High-Resolution, Turn-by-Turn BPM system is a low-cost extension to the existing BPM system, based on the RF-multiplexing concept, used for slow Closed-Orbit measurements. With this extension Beam Position measurements in both planes, at all (224) BPMs in the 844 m ESRF Storage Ring, for up to 2048 Orbit Turns with 1 μm resolution are performed. The data acquisition is synchronised to a single, flat 1 μs, transverse deflection kick to the 1μs beamfill in the 2.8μs revolution period. The high quality of this synchronisation, together with the good reproducibility of the deflection kick and the overall stability of the Closed Orbit beam allows to repeat the kick and acquisition in many cycles. The subsequent averaging of the data obtained in these cycles yields the 1um resolution. The latter allows lattice measurements with high precision such as the localisation of very small focussing errors and modulation in Beta values and phase advances. It also finds an unique ...

Laterality of the lower limbs and carving turns

Directory of Open Access Journals (Sweden)

F Vaverka

2010-06-01

Full Text Available The aim of this study is to discover whether the lateral preference of the lower limbs influences the execution of successive carving turns or not. Six skilled skiers (men, right lower limb preference, age 26.5±1.61 years old, height 1.80±0.04 m, body weight 78.83±5.46 kg executed 30 (18 left, 12 right symmetrical carving turns. Kinetic analysis of the final vertical component of reaction force FZ(t measured dynamometrically provided the information about the time of initiation and steering phases of the turn and the maximum force, average force and force impulse. Differences between right and left turns are not statistically significant. Factual analyses of the magnitude of measured variables confirmed that left turns were found to have a longer duration, a shorter initiation and longer steering phase, and higher level of produced force and force impulse in comparison with right turns. Based on the results it can be concluded that the turns where the outer leg is the preferred limb are preferentially used to regulate the speed of the ride. The study of laterality in symmetrical carving turns has proven that lateral preference of lower extremities influences the execution of the turn also by expert skiers.

Nanostructural Evolution of Hard Turning Layers in Carburized Steel

Science.gov (United States)

Bedekar, Vikram

The mechanisms of failure for components subjected to contact fatigue are sensitive to the structure and properties of the material surface. Although, the bulk material properties are determined by the steel making, forming and the heat treatment; the near surface material properties are altered during final material removal processes such as hard turning or grinding. Therefore, the ability to optimize, modulate and predict the near surface properties during final metal removal operations would be extremely useful in the enhancement of service life of a component. Hard machining is known to induce severely deformed layers causing dramatic microstructural transformations. These transformations occur via grain refinement or thermal phenomena depending upon cutting conditions. The aim of this work is to engineer the near surface nanoscale structure and properties during hard turning by altering strain, strain rate, temperature and incoming microstructure. The near surface material transformations due to hard turning were studied on carburized SAE 8620 bearing steel. Variations in parent material microstructures were introduced by altering the retained austenite content. The strain, strain rate and temperature achieved during final metal cutting were altered by varying insert geometry, insert wear and cutting speed. The subsurface evolution was quantified by a series of advanced characterization techniques such as transmission electron microscopy (TEM), glancing angle X-ray diffraction (GAXRD), X-ray stress evaluation and nanoindentation which were coupled with numerical modeling. Results showed that the grain size of the nanocrystalline near surface microstructure can be effectively controlled by altering the insert geometry, insert wear, cutting speed and the incoming microstructure. It was also evident that the near surface retained austenite decreased at lower cutting speed indicating transformation due to plastic deformation, while it increased at higher cutting

A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis

Science.gov (United States)

Pedrolli, Danielle Biscaro; Kühm, Christian; Sévin, Daniel C.; Vockenhuber, Michael P.; Sauer, Uwe; Suess, Beatrix; Mack, Matthias

2015-01-01

Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient (“high levels”), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism. PMID:26494285

Wittgenstein and the linguistic turn in social theory

DEFF Research Database (Denmark)

Hermansen, Jens Christian

of Winch in social theory, the wider and more recent influence of Wittgenstein in areas such as technology and science studies, social theory, feminist and gender studies and conversation and discourse analysis is also considered. Historically, the readings of Wittgenstein in the social sciences have taken...... of the linguistic turn in social theory, the linguistic turn is a double-edged sword of both profound insights and limits; the claim is that the limits of the linguistic turn are the strengths of functionalist, structuralist and materialist approaches to the social sciences. The approach of the critical turn...... is to develop a more comprehensive social theory that is sensitive to these strengths and thus supersedes the limits of the linguistic turn. This paper suggests a different approach. Against the critical turn, the paper argues that the limits of the linguistic turn are identical with the very assumptions...

Characterization of beta-turn and Asx-turns mimicry in a model peptide: stabilization via C--H . . . O interaction.

Science.gov (United States)

Thakur, A K; Kishore, R

2006-04-15

The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the existence of a distinct conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees conformations, respectively, in conjunction with a gauche- disposition of the obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the newly described beta-turn- and Asx-turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essentially similar to the one perceived for a classical beta-turn and the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone torsion angles and the orientation of the central peptide bond, the overall mimicked topology resembles the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in high-resolution X-ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconventional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in peptides and proteins. Copyright 2006 Wiley Periodicals, Inc.

METHODICAL MODEL FOR TEACHING BASIC SKI TURN

Directory of Open Access Journals (Sweden)

Danijela Kuna

2013-07-01

Full Text Available With the aim of forming an expert model of the most important operators for basic ski turn teaching in ski schools, an experiment was conducted on a sample of 20 ski experts from different countries (Croatia, Bosnia and Herzegovina and Slovenia. From the group of the most commonly used operators for teaching basic ski turn the experts picked the 6 most important: uphill turn and jumping into snowplough, basic turn with hand sideways, basic turn with clapping, ski poles in front, ski poles on neck, uphill turn with active ski guiding. Afterwards, ranking and selection of the most efficient operators was carried out. Due to the set aim of research, a Chi square test was used, as well as the differences between frequencies of chosen operators, differences between values of the most important operators and differences between experts due to their nationality. Statistically significant differences were noticed between frequencies of chosen operators (c2= 24.61; p=0.01, while differences between values of the most important operators were not obvious (c2= 1.94; p=0.91. Meanwhile, the differences between experts concerning thier nationality were only noticeable in the expert evaluation of ski poles on neck operator (c2=7.83; p=0.02. Results of current research are reflected in obtaining useful information about methodological priciples of learning basic ski turn organization in ski schools.

Energetics of glucose metabolism: a phenomenological approach to metabolic network modeling.

Science.gov (United States)

Diederichs, Frank

2010-08-12

A new formalism to describe metabolic fluxes as well as membrane transport processes was developed. The new flux equations are comparable to other phenomenological laws. Michaelis-Menten like expressions, as well as flux equations of nonequilibrium thermodynamics, can be regarded as special cases of these new equations. For metabolic network modeling, variable conductances and driving forces are required to enable pathway control and to allow a rapid response to perturbations. When applied to oxidative phosphorylation, results of simulations show that whole oxidative phosphorylation cannot be described as a two-flux-system according to nonequilibrium thermodynamics, although all coupled reactions per se fulfill the equations of this theory. Simulations show that activation of ATP-coupled load reactions plus glucose oxidation is brought about by an increase of only two different conductances: a [Ca(2+)] dependent increase of cytosolic load conductances, and an increase of phosphofructokinase conductance by [AMP], which in turn becomes increased through [ADP] generation by those load reactions. In ventricular myocytes, this feedback mechanism is sufficient to increase cellular power output and O(2) consumption several fold, without any appreciable impairment of energetic parameters. Glucose oxidation proceeds near maximal power output, since transformed input and output conductances are nearly equal, yielding an efficiency of about 0.5. This conductance matching is fulfilled also by glucose oxidation of β-cells. But, as a price for the metabolic mechanism of glucose recognition, β-cells have only a limited capability to increase their power output.

Metabolic Modulators in Heart Disease: Past, Present, and Future.

Science.gov (United States)

Lopaschuk, Gary D

2017-07-01

Ischemic heart disease and heart failure are leading causes of mortality and morbidity worldwide. They continue to be major burden on health care systems throughout the world, despite major advances made over the past 40 years in developing new therapeutic approaches to treat these debilitating diseases. A potential therapeutic approach that has been underutilized in treating ischemic heart disease and heart failure is "metabolic modulation." Major alterations in myocardial energy substrate metabolism occur in ischemic heart disease and heart failure, and are associated with an energy deficit in the heart. A metabolic shift from mitochondrial oxidative metabolism to glycolysis, as well as an uncoupling between glycolysis and glucose oxidation, plays a crucial role in the development of cardiac inefficiency (oxygen consumed per work performed) and functional impairment in ischemic heart disease as well as in heart failure. This has led to the concept that optimizing energy substrate use with metabolic modulators can be a potentially promising approach to decrease the severity of ischemic heart disease and heart failure, primarily by improving cardiac efficiency. Two approaches for metabolic modulator therapy are to stimulate myocardial glucose oxidation and/or inhibit fatty acid oxidation. In this review, the past, present, and future of metabolic modulators as an approach to optimizing myocardial energy substrate metabolism and treating ischemic heart disease and heart failure are discussed. This includes a discussion of pharmacological interventions that target enzymes involved in fatty acid uptake, fatty acid oxidation, and glucose oxidation in the heart, as well as enzymes involved in ketone and branched chain amino acid catabolism in the heart. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Seafood-Processing Sludge Composting: Changes to Microbial Communities and Physico-Chemical Parameters of Static Treatment versus for Turning during the Maturation Stage

Science.gov (United States)

Alves, David; Mato, Salustiano

2016-01-01

In general, in composting facilities the active, or intensive, stage of the process is done separately from the maturation stage, using a specific technology and time. The pre-composted material to be matured can contain enough biodegradable substrates to cause microbial proliferation, which in turn can cause temperatures to increase. Therefore, not controlling the maturation period during waste management at an industrial level can result in undesired outcomes. The main hypothesis of this study is that controlling the maturation stage through turning provides one with an optimized process when compared to the static approach. The waste used was sludge from a seafood-processing plant, mixed with shredded wood (1:2, v/v). The composting system consists of an intensive stage in a 600L static reactor, followed by maturation in triplicate in 200L boxes for 112 days. Two tests were carried out with the same process in reactor and different treatments in boxes: static maturation and turning during maturation when the temperature went above 55°C. PLFAs, organic matter, pH, electrical conductivity, forms of nitrogen and carbon, hydrolytic enzymes and respiratory activity were periodically measured. Turning significantly increased the duration of the thermophilic phase and consequently increased the organic-matter degradation. PCA differentiated significantly the two treatments in function of tracking parameters, especially pH, total carbon, forms of nitrogen and C/N ratio. So, stability and maturity optimum values for compost were achieved in less time with turnings. Whereas turning resulted in microbial-group stabilization and a low mono/sat ratio, static treatment produced greater variability in microbial groups and a high mono/sat ratio, the presence of more degradable substrates causes changes in microbial communities and their study during maturation gives an approach of the state of organic-matter degradation. Obtaining quality compost and optimizing the composting

Pathway Design, Engineering, and Optimization.

Science.gov (United States)

Garcia-Ruiz, Eva; HamediRad, Mohammad; Zhao, Huimin

The microbial metabolic versatility found in nature has inspired scientists to create microorganisms capable of producing value-added compounds. Many endeavors have been made to transfer and/or combine pathways, existing or even engineered enzymes with new function to tractable microorganisms to generate new metabolic routes for drug, biofuel, and specialty chemical production. However, the success of these pathways can be impeded by different complications from an inherent failure of the pathway to cell perturbations. Pursuing ways to overcome these shortcomings, a wide variety of strategies have been developed. This chapter will review the computational algorithms and experimental tools used to design efficient metabolic routes, and construct and optimize biochemical pathways to produce chemicals of high interest.

Generalized Lions-Peetre interpolation construction and optimal embedding theorems for Sobolev spaces

International Nuclear Information System (INIS)

Ovchinnikov, V I

2014-01-01

In the paper, a new description of the generalized Lions-Peetre method of means is found, which enables one to evaluate the interpolation orbits of spaces constructed by this method. The list of these spaces includes all Lorentz spaces with functional parameters, Orlicz spaces, and spaces close to them. This leads in turn to new optimal embedding theorems for Sobolev spaces produced using the Lions-Peetre construction in rearrangement invariant spaces. It turns out that the optimal space of the embedding is also a generalized Lions-Peetre space whose parameters are explicitly evaluated. Bibliography: 18 titles

Experience sharing, emotional reciprocity, and turn-taking

Directory of Open Access Journals (Sweden)

Melisa eStevanovic

2015-04-01

Full Text Available In this perspective article, we consider the relationship between experience sharing and turn-taking. There is much evidence suggesting that human social interaction is permeated by two temporal organizations: (1 the sequential framework of turn-taking and (2 the concurrent framework of emotional reciprocity. From this perspective, we introduce two alternative hypotheses about how the relationship between experience sharing and turn-taking could be viewed. According to the first hypothesis, the home environment of experience sharing is in the concurrent framework of emotional reciprocity, while the motivation to share experiences is in tension with the sequential framework of turn-taking. According to the second hypothesis, then again, people’s inclination to coordinate their actions in terms of turn-taking is motivated precisely by their propensity to share experiences. We consider theoretical and empirical ideas in favor of both of these hypotheses and discuss their implications for future research.

Circadian physiology of metabolism.

Science.gov (United States)

Panda, Satchidananda

2016-11-25

A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

Robotic lower limb prosthesis design through simultaneous computer optimizations of human and prosthesis costs

Science.gov (United States)

Handford, Matthew L.; Srinivasan, Manoj

2016-02-01

Robotic lower limb prostheses can improve the quality of life for amputees. Development of such devices, currently dominated by long prototyping periods, could be sped up by predictive simulations. In contrast to some amputee simulations which track experimentally determined non-amputee walking kinematics, here, we explicitly model the human-prosthesis interaction to produce a prediction of the user’s walking kinematics. We obtain simulations of an amputee using an ankle-foot prosthesis by simultaneously optimizing human movements and prosthesis actuation, minimizing a weighted sum of human metabolic and prosthesis costs. The resulting Pareto optimal solutions predict that increasing prosthesis energy cost, decreasing prosthesis mass, and allowing asymmetric gaits all decrease human metabolic rate for a given speed and alter human kinematics. The metabolic rates increase monotonically with speed. Remarkably, by performing an analogous optimization for a non-amputee human, we predict that an amputee walking with an appropriately optimized robotic prosthesis can have a lower metabolic cost - even lower than assuming that the non-amputee’s ankle torques are cost-free.

Optimal PMU Placement with Uncertainty Using Pareto Method

Directory of Open Access Journals (Sweden)

A. Ketabi

2012-01-01

Full Text Available This paper proposes a method for optimal placement of Phasor Measurement Units (PMUs in state estimation considering uncertainty. State estimation has first been turned into an optimization exercise in which the objective function is selected to be the number of unobservable buses which is determined based on Singular Value Decomposition (SVD. For the normal condition, Differential Evolution (DE algorithm is used to find the optimal placement of PMUs. By considering uncertainty, a multiobjective optimization exercise is hence formulated. To achieve this, DE algorithm based on Pareto optimum method has been proposed here. The suggested strategy is applied on the IEEE 30-bus test system in several case studies to evaluate the optimal PMUs placement.

Exploring interaction between a non-speaking boy using aided AAC and his everyday communication partners: features of turn organizing and turn design

DEFF Research Database (Denmark)

Pilesjö, Maja Sigurd; Rasmussen, Gitte

2011-01-01

-at-action is suggested. The analyses demonstrate that the boy’s turn-at-actions are oriented to as a co-constructed and thus interactionally achieved unit: the boy points at a bliss symbol which is given voice by the speaking co-participant. In and through the relevant made voicing of the turn-at-action, a turn...... AAC, bliss symbolics. The analysis indicates that the participants can collaborately create and orient to units in interaction equivalent to turns in interaction although they differ dramatically from ordinary turns-at-talk. In order to capture the nature of the described units, the category turn...

An improved chaotic fruit fly optimization based on a mutation strategy for simultaneous feature selection and parameter optimization for SVM and its applications.

Science.gov (United States)

Ye, Fei; Lou, Xin Yuan; Sun, Lin Fu

2017-01-01

This paper proposes a new support vector machine (SVM) optimization scheme based on an improved chaotic fly optimization algorithm (FOA) with a mutation strategy to simultaneously perform parameter setting turning for the SVM and feature selection. In the improved FOA, the chaotic particle initializes the fruit fly swarm location and replaces the expression of distance for the fruit fly to find the food source. However, the proposed mutation strategy uses two distinct generative mechanisms for new food sources at the osphresis phase, allowing the algorithm procedure to search for the optimal solution in both the whole solution space and within the local solution space containing the fruit fly swarm location. In an evaluation based on a group of ten benchmark problems, the proposed algorithm's performance is compared with that of other well-known algorithms, and the results support the superiority of the proposed algorithm. Moreover, this algorithm is successfully applied in a SVM to perform both parameter setting turning for the SVM and feature selection to solve real-world classification problems. This method is called chaotic fruit fly optimization algorithm (CIFOA)-SVM and has been shown to be a more robust and effective optimization method than other well-known methods, particularly in terms of solving the medical diagnosis problem and the credit card problem.

Primordial spectra from sudden turning trajectory

Science.gov (United States)

Noumi, Toshifumi; Yamaguchi, Masahide

2013-12-01

Effects of heavy fields on primordial spectra of curvature perturbations are discussed in inflationary models with a sudden turning trajectory. When heavy fields are excited after the sudden turn and oscillate around the bottom of the potential, the following two effects are generically induced: deformation of the inflationary background spacetime and conversion interactions between adiabatic and isocurvature perturbations, both of which can affect the primordial density perturbations. In this paper, we calculate primordial spectra in inflationary models with sudden turning potentials taking into account both of the two effects appropriately. We find that there are some non-trivial correlations between the two effects in the power spectrum and, as a consequence, the primordial scalar power spectrum has a peak around the scale exiting the horizon at the turn. Though both effects can induce parametric resonance amplifications, they are shown to be canceled out for the case with the canonical kinetic terms. The peak feature and the scale dependence of bispectra are also discussed.

Copper metabolism: a multicompartmental model of copper kinetics in the rat

International Nuclear Information System (INIS)

Dunn, M.A.

1985-01-01

A qualitative multicompartmental model was developed that describes the whole-body kinetics of copper metabolism in the adult rat. The model was developed from radiocopper percent dose vs. time data measured over a three day period in plasma, liver, skin, skeletal muscle, bile and feces after the intravenous injection of 10 μg copper labeled with 64 Cu. Plasma radiocopper was separated into ceruloplasmin (Cp) and nonceruloplasmin (NCp) fractions. Liver cytosolic radiocopper was fractionated into void volume superoxide dismutase (SOD) containing and metallothionein fractions by gel filtration. Liver particulate fractions were isolated by differential centrifugation. The SAAM and CONSAM modeling programs were used to develop the model. The sizes of compartments, fractional rate constants and mass transfer rates between compartments were evaluated. The intracellular metabolism of copper was similar in hepatic and extrahepatic tissues being comprised of a faster turning over compartment (FTC) exchanging copper with NCp and a slower turning over compartment (STC) with input from Cp. Output from the STC was into the FTC. In the liver the STC was postulated to represent SOD copper which unlike the extrahepatic tissues received much of its input from the FTC. A small amount of biliary copper (9%) was postulated to return to plasma NCp by enterohepatic recycling. The model developed was contrasted and compared with two previous models of copper metabolism

Identification of parallel and divergent optimization solutions for homologous metabolic enzymes

Directory of Open Access Journals (Sweden)

Robert F. Standaert

2018-06-01

Full Text Available Metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB, a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI, from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA, the oxidation product of 4-HB. Neither enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA, duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI, growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity. Keywords: Lignin, Protocatechuate, Experimental evolution

Identification of parallel and divergent optimization solutions for homologous metabolic enzymes.

Science.gov (United States)

Standaert, Robert F; Giannone, Richard J; Michener, Joshua K

2018-06-01

Metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI , from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neither enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA , duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI , growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.

Estradiol to testosterone ratio in metabolic syndrome men aged started 40 years above

Science.gov (United States)

Kusuma, R.; Siregar, Y.; Mardianto

2018-03-01

Disruption of adipose tissue, an endocrine organ, could turn out into the so-called metabolic syndrome. Aging men with lowering testosterone were related to metabolic syndrome and excessive aromatase activity in adipose tissue would increase estradiol level. This study hypothesized that estradiol to testosterone ratio is increasedin aging, metabolic syndrome men. A total of 52 men were randomly recruited for this study. A blood samplewas drawn before 11.00 AM after 10 hoursof overnight fasting, then aliquot serum kept in -20°C pending the research. Subjects were divided evenly into the metabolic syndrome and nonmetabolicsyndrome group. The hormonal assaywas measured on the day of research. Then examined with student t-test. Estradiol level in metabolic syndrome group was increased, but insignificant differ to the other group. Testosterone level decreased and significantly different between groups. In conclusion, estradiol to testosterone ratio was increased in themetabolic syndrome group but insignificant.

Multi-objective optimization model of CNC machining to minimize processing time and environmental impact

Science.gov (United States)

Hamada, Aulia; Rosyidi, Cucuk Nur; Jauhari, Wakhid Ahmad

2017-11-01

Minimizing processing time in a production system can increase the efficiency of a manufacturing company. Processing time are influenced by application of modern technology and machining parameter. Application of modern technology can be apply by use of CNC machining, one of the machining process can be done with a CNC machining is turning. However, the machining parameters not only affect the processing time but also affect the environmental impact. Hence, optimization model is needed to optimize the machining parameters to minimize the processing time and environmental impact. This research developed a multi-objective optimization to minimize the processing time and environmental impact in CNC turning process which will result in optimal decision variables of cutting speed and feed rate. Environmental impact is converted from environmental burden through the use of eco-indicator 99. The model were solved by using OptQuest optimization software from Oracle Crystal Ball.

Prolonged platelet preservation by transient metabolic suppression

NARCIS (Netherlands)

Badlou, Bahram Alamdary

2006-01-01

Introduction: Different clinical studies have shown that transfusion of stored platelets results in better haemostasis in patients with thrombocytopenia with and without a platelet function defect. Objectives: Current preservation procedures aim to optimally preserve the metabolic status of

Artificial Intelligence Based Selection of Optimal Cutting Tool and Process Parameters for Effective Turning and Milling Operations

Science.gov (United States)

Saranya, Kunaparaju; John Rozario Jegaraj, J.; Ramesh Kumar, Katta; Venkateshwara Rao, Ghanta

2016-06-01

With the increased trend in automation of modern manufacturing industry, the human intervention in routine, repetitive and data specific activities of manufacturing is greatly reduced. In this paper, an attempt has been made to reduce the human intervention in selection of optimal cutting tool and process parameters for metal cutting applications, using Artificial Intelligence techniques. Generally, the selection of appropriate cutting tool and parameters in metal cutting is carried out by experienced technician/cutting tool expert based on his knowledge base or extensive search from huge cutting tool database. The present proposed approach replaces the existing practice of physical search for tools from the databooks/tool catalogues with intelligent knowledge-based selection system. This system employs artificial intelligence based techniques such as artificial neural networks, fuzzy logic and genetic algorithm for decision making and optimization. This intelligence based optimal tool selection strategy is developed using Mathworks Matlab Version 7.11.0 and implemented. The cutting tool database was obtained from the tool catalogues of different tool manufacturers. This paper discusses in detail, the methodology and strategies employed for selection of appropriate cutting tool and optimization of process parameters based on multi-objective optimization criteria considering material removal rate, tool life and tool cost.

Metabolic changes after prior treatment with ethanol. Evidence against in involvement of the Na+ + K+-activated ATPase in the increase in ethanol metabolism.

Science.gov (United States)

Yuki, T; Thurman, R G; Schwabe, U; Scholz, R

1980-01-01

In perfused rat liver, the inhibition of ethanol uptake by ouabain does not follow the rapid inhibition of the Na+ K+- activated ATPase as assessed by changes in perfusate [K+] (half-time, t 1/2 = 2--3 min), but correlated rather with the slow inhibition of oxygen uptake (maximal inhibition = 40% in 20 min). The data indicate that ouabain exerts its effect on ethanol metabolism via the following sequence of events; inhibition of the sodium pump is followed gradually by a perturbation of the intracellular cation milieu; this leads to an inhibition of the mitochondrial respiratory chain, resulting in diminished rate of NADH oxidation, which in turn causes in inhibition of ethanol metabolism. PMID:6249265

Kantian Turning Point in Gadamer's Philosophical Hermeneutics

Directory of Open Access Journals (Sweden)

Kristína Bosáková

2016-11-01

Full Text Available The paper is treating the theme of a Kantian turning-point in the philosophical hermeneutics of H.- G. Gadamer based on of the harmonic relationship between metaphysics and science in Kantian philosophy from the point of view of the philosophical hermeneutics of Gadamer. The philosophical work of Kant had such an influence on Gadamer that without exaggerating we can talk about the Kantian turning-point in Gadamerian hermeneutics. Grondin, a former student of Gadamer, is talking about Kantian turning-point on the field of aesthetics, but in reality Kantian turning-point means much more than a mere change in the reception of the concept of judgement. It is a discovery of harmonical relationship between the beauty and the moral, between the reason and the sensitivity, between the modern sciences and the metaphysical tradition in the Kantian philosophy, made by Gadamer. This is what we call the Kantian turning-point in Gadamerian hermeneutics.

Mini-review: In vitro Metabolic Engineering for Biomanufacturing of High-value Products

Directory of Open Access Journals (Sweden)

Weihua Guo

Full Text Available With the breakthroughs in biomolecular engineering and synthetic biology, many valuable biologically active compound and commodity chemicals have been successfully manufactured using cell-based approaches in the past decade. However, because of the high complexity of cell metabolism, the identification and optimization of rate-limiting metabolic pathways for improving the product yield is often difficult, which represents a significant and unavoidable barrier of traditional in vivo metabolic engineering. Recently, some in vitro engineering approaches were proposed as alternative strategies to solve this problem. In brief, by reconstituting a biosynthetic pathway in a cell-free environment with the supplement of cofactors and substrates, the performance of each biosynthetic pathway could be evaluated and optimized systematically. Several value-added products, including chemicals, nutraceuticals, and drug precursors, have been biosynthesized as proof-of-concept demonstrations of in vitro metabolic engineering. This mini-review summarizes the recent progresses on the emerging topic of in vitro metabolic engineering and comments on the potential application of cell-free technology to speed up the “design-build-test” cycles of biomanufacturing. Keywords: Cell-free, Biosynthesis, Metabolic pathways, Design-build-test cycle

Some Studies on Reduction of Ovality in Turned Component-Case study

Directory of Open Access Journals (Sweden)

Nilesh Dhirajlal Ghetiya

2014-08-01

Full Text Available In the competitive market and globalization phase, industries are required to manufacture good quality machine tools with optimized performance at the moderate cost. Moreover, the industries are facing competition internationally due to worldwide globalization of business. This work aims to reduce the error called ovality in the turned work piece. This work piece is a clutch component used for the clutch assembly. For the clutch to work perfectly, it is required for its component to be precise and error free. The machining parameters like cutting speed, feed rate and depth of cut are taken as input parameters and the ovality as output response. Response surface methodology is used for the optimization of process parameters. The most significant process parameter causing the ovality has been found. The other attempts like balancing of the work piece and radiography of the work piece is done to solve the problem which is causing the ovality. The centrifugal force analysis of the component is carried out using finite element analysis.

Searching for Criteria in Evaluating the Monofin Swimming Turn from the Perspective of Coaching and Improving Technique

Science.gov (United States)

Rejman, Marek; Borowska, Grażyna

2008-01-01

This study aims to analysise the selected kinematic parameters of the monofin swimming turn. The high complexity of performing turns is hindered by the large surface of the monofin, which disturbs control and sense of the body in water. A lack of objective data available on monofin swimming turns has resulted in field research connected with the specification of parameters needed for the evaluation of the technique. Therefore, turns observed in elite swimmers contain underlying conclusions for objective criteria, ensuring the highest level of coaching and the improving of turns in young swimmers. Six, high level, male swimmers participated in the study. The subject of the analysis was the fastest turn, from one out of three trial turns made after swimming a distance of 25 m. Images of the turns were collected from two cameras located under water in accordance with the procedures of the previous analyses of freestyle turns. The images were digitized and analysed by the SIMI®- Movement Analysis System. The interdependency of the total turn time and the remaining recorded parameters, constituted the basis for analysis of the kinematic parameters of five turn phases. The interdependency was measured using r- Pearson’s correlation coefficients. The novel character of the subject covered in this study, forced interpretation of the results on the basis of turn analyses in freestyle swimming. The results allow for the creation of a diagram outlinig area of search for an effective and efficient monofin swimming turn mechanism. The activities performed from the moment of wall contact until the commencement of stroking seem to be crucial for turn improvement. A strong belief has resulted that, the correct monofin swimming turn, is more than just a simple consequence of the fastest performance of all its components. The most important criteria in evaluating the quality of the monofin swimming turn are: striving for the optimal extension of wall contact time, push-off time

Exposure of clinical MRSA heterogeneous strains to β-lactams redirects metabolism to optimize energy production through the TCA cycle.

Science.gov (United States)

Keaton, Mignon A; Rosato, Roberto R; Plata, Konrad B; Singh, Christopher R; Rosato, Adriana E

2013-01-01

R-MRSA clinical strains undergo when exposed to β-lactam pressure, indicating that the energy production is redirected to supply the cell wall synthesis/metabolism, which in turn contributes to the survival response in the presence of β-lactam antibiotics.

Exposure of clinical MRSA heterogeneous strains to β-lactams redirects metabolism to optimize energy production through the TCA cycle.

Directory of Open Access Journals (Sweden)

Mignon A Keaton

adaptation that HeR-MRSA clinical strains undergo when exposed to β-lactam pressure, indicating that the energy production is redirected to supply the cell wall synthesis/metabolism, which in turn contributes to the survival response in the presence of β-lactam antibiotics.

Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy.

Science.gov (United States)

Amoedo, N D; Obre, E; Rossignol, R

2017-08-01

The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro. Such contradictory findings raised several questions concerning the optimization of drug discovery strategies in the field of cancer metabolism. For instance, the cell culture models in 2D or 3D might already show strong limitations to mimic the tumor micro- and macro-environment. The microenvironment of tumors is composed of cancer cells of variegated metabolic profiles, supporting local metabolic exchanges and symbiosis, but also of immune cells and stroma that further interact with and reshape cancer cell metabolism. The macroenvironment includes the different tissues of the organism, capable of exchanging signals and fueling the tumor 'a distance'. Moreover, most metabolic targets were identified from their increased expression in tumor transcriptomic studies, or from targeted analyses looking at the metabolic impact of particular oncogenes or tumor suppressors on selected metabolic pathways. Still, very few targets were identified from in vivo analyses of tumor metabolism in patients because such studies are difficult and adequate imaging methods are only currently being developed for that purpose. For instance, perfusion of patients with [ 13 C]-glucose allows deciphering the metabolomics of tumors and opens a new area in the search for effective targets. Metabolic imaging with positron emission tomography and other techniques that do not involve [ 13 C] can also be used to evaluate tumor

Metabolic engineering in methanotrophic bacteria

Energy Technology Data Exchange (ETDEWEB)

Kalyuzhnaya, MG; Puri, AW; Lidstrom, ME

2015-05-01

Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Metabolic syndrome and benign prostatic hyperplasia: An update

Directory of Open Access Journals (Sweden)

Ho-Yin Ngai

2017-07-01

Full Text Available Metabolic syndrome (MetS is a cluster of metabolic abnormalities related to central adiposity and insulin resistance. Its importance is increasingly recognized as it associates with increased risks of metabolic and cardiovascular diseases. These metabolic aberrations of MetS may lead to development of benign prostatic hyperplasia (BPH and lower urinary tract symptoms (LUTS in men. A 26.5%–55.6% prevalence of MetS in men with LUTS was reported in worldwide studies. Although the exact biological pathway is not clear yet, insulin resistance, increased visceral adiposity, sex hormone alterations and cellular inflammatory reactions played significant roles in the related pathophysiological processes. Clinician should recognize the cardiovascular and metabolic impacts of MetS in men with LUTS, early risk factors optimization and use of appropriate medical therapy may possibly alter or slower the progression of LUTS/BPH, and potentially avoid unnecessary morbidities and mortalities from cardiovascular and metabolic diseases for those men.

The venom optimization hypothesis revisited.

Science.gov (United States)

Morgenstern, David; King, Glenn F

2013-03-01

Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the "venom optimization hypothesis" (Wigger et al. (2002) Toxicon 40, 749-752), also known as "venom metering", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. Copyright © 2012 Elsevier Ltd. All rights reserved.

The risk of metabolic syndrome and nutrition

Directory of Open Access Journals (Sweden)

Aleksandr Konstantinovich Kuntsevich

2015-02-01

Full Text Available In the present literature review modern epidemiological studies the role of nutrition in the prevalence of the metabolic syndrome. Were analyzed mainly work on the association of certain types of dietary intake of the population to the risk of metabolic syndrome in several Western and Asian countries. The purpose of these studies was to determine deemed "good" type and the "bad" type of food, risk assessment and exchange of metabolic disorders to determine the optimal dietary recommendations.  Application of factor and cluster analysis allowed in a number of studies to identify groups of products associated with a decrease in the prevalence of metabolic syndrome and to estimate the odds ratios of metabolic syndrome when compared with the "bad" diet.  A number of papers were obtained confirm the effectiveness of the Mediterranean diet in the prevention of metabolic disorders. Commitment to the traditional Western diet is associated with deterioration in health, compared with the recommended "healthy" diet.  Data from epidemiological studies nutrition and metabolic disorders associated with a number of diseases, may be useful in determining how the recommendations on the best type of feeding the population, so to identify ways to further research.

Metabolic modelling of polyhydroxyalkanoate copolymers production by mixed microbial cultures

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Reis Maria AM

2008-07-01

Full Text Available Abstract Background This paper presents a metabolic model describing the production of polyhydroxyalkanoate (PHA copolymers in mixed microbial cultures, using mixtures of acetic and propionic acid as carbon source material. Material and energetic balances were established on the basis of previously elucidated metabolic pathways. Equations were derived for the theoretical yields for cell growth and PHA production on mixtures of acetic and propionic acid as functions of the oxidative phosphorylation efficiency, P/O ratio. The oxidative phosphorylation efficiency was estimated from rate measurements, which in turn allowed the estimation of the theoretical yield coefficients. Results The model was validated with experimental data collected in a sequencing batch reactor (SBR operated under varying feeding conditions: feeding of acetic and propionic acid separately (control experiments, and the feeding of acetic and propionic acid simultaneously. Two different feast and famine culture enrichment strategies were studied: (i either with acetate or (ii with propionate as carbon source material. Metabolic flux analysis (MFA was performed for the different feeding conditions and culture enrichment strategies. Flux balance analysis (FBA was used to calculate optimal feeding scenarios for high quality PHA polymers production, where it was found that a suitable polymer would be obtained when acetate is fed in excess and the feeding rate of propionate is limited to ~0.17 C-mol/(C-mol.h. The results were compared with published pure culture metabolic studies. Conclusion Acetate was more conducive toward the enrichment of a microbial culture with higher PHA storage fluxes and yields as compared to propionate. The P/O ratio was not only influenced by the selected microbial culture, but also by the carbon substrate fed to each culture, where higher P/O ratio values were consistently observed for acetate than propionate. MFA studies suggest that when mixtures of

Bifurcations of optimal vector fields: an overview

NARCIS (Netherlands)

Kiseleva, T.; Wagener, F.; Rodellar, J.; Reithmeier, E.

2009-01-01

We develop a bifurcation theory for the solution structure of infinite horizon optimal control problems with one state variable. It turns out that qualitative changes of this structure are connected to local and global bifurcations in the state-costate system. We apply the theory to investigate an

Optimal siting of capacitors in radial distribution network using Whale Optimization Algorithm

Directory of Open Access Journals (Sweden)

D.B. Prakash

2017-12-01

Full Text Available In present days, continuous effort is being made in bringing down the line losses of the electrical distribution networks. Therefore proper allocation of capacitors is of utmost importance because, it will help in reducing the line losses and maintaining the bus voltage. This in turn results in improving the stability and reliability of the system. In this paper Whale Optimization Algorithm (WOA is used to find optimal sizing and placement of capacitors for a typical radial distribution system. Multi objectives such as operating cost reduction and power loss minimization with inequality constraints on voltage limits are considered and the proposed algorithm is validated by applying it on standard radial systems: IEEE-34 bus and IEEE-85 bus radial distribution test systems. The results obtained are compared with those of existing algorithms. The results show that the proposed algorithm is more effective in bringing down the operating costs and in maintaining better voltage profile. Keywords: Whale Optimization Algorithm (WOA, Optimal allocation and sizing of capacitors, Power loss reduction and voltage stability improvement, Radial distribution system, Operating cost minimization

Review Essay: Turn, Turn, Turn Around—Till Categories Blur

Directory of Open Access Journals (Sweden)

Lars Allolio-Näcke

2008-01-01

Full Text Available I begin this review by introducing the book and discussing its manifest content chapter by chapter (see 2.1, focusing particularly on the author's argumentation concerning the development of new orientations in cultural studies and on how, in relation to the turns discussed, the names of the researchers and central categories involved are collected. In a second step, I give a close reading of the book's latent content, which I consider to be more important (see 2.2. In this context I discuss several questions of scientific politics—especially the issue of hegemonic claims. Thirdly, I read the book from the critical standpoint of a psychologist, a sociologist and a theologian and show the shortcomings of BACHMANN-MEDICK's outsider perspective on these disciplines. In this regard I read the book again and provide a critique of the quality of the author's scientific performance (see 3. Finally, I state the reasons I do not recommend reading this book (see 4. URN: urn:nbn:de:0114-fqs0801266

[Study of beta-turns in globular proteins].

Science.gov (United States)

Amirova, S R; Milchevskiĭ, Iu V; Filatov, I V; Esipova, N G; Tumanian, V G

2005-01-01

The formation of beta-turns in globular proteins has been studied by the method of molecular mechanics. Statistical method of discriminant analysis was applied to calculate energy components and sequences of oligopeptide segments, and after this prediction of I type beta-turns has been drawn. The accuracy of true positive prediction is 65%. Components of conformational energy considerably affecting beta-turn formation were delineated. There are torsional energy, energy of hydrogen bonds, and van der Waals energy.

Abdominal obesity and metabolic syndrome: exercise as medicine?

Science.gov (United States)

Paley, Carole A; Johnson, Mark I

2018-01-01

Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

What is the role of metabolic hormones in taste buds of the tongue.

Science.gov (United States)

Cai, Huan; Maudsley, Stuart; Martin, Bronwen

2014-01-01

Gustation is one of the important chemical senses that guides the organism to identify nutrition while avoiding toxic chemicals. An increasing number of metabolic hormones and/or hormone receptors have been identified in the taste buds of the tongue and are involved in modulating taste perception. The gustatory system constitutes an additional endocrine regulatory locus that affects food intake, and in turn whole-body energy homeostasis. Here we provide an overview of the main metabolic hormones known to be present in the taste buds of the tongue; discuss their potential functional roles in taste perception and energy homeostasis and how their functional integrity is altered in the metabolic imbalance status (obesity and diabetes) and aging process. Better understanding of the functional roles of metabolic hormones in flavor perception as well as the link between taste perception and peripheral metabolism may be vital for developing strategies to promote healthier eating and prevent obesity or lifestyle-related disorders. © 2014 S. Karger AG, Basel.

Divertor design through shape optimization

International Nuclear Information System (INIS)

Dekeyser, W.; Baelmans, M.; Reiter, D.

2012-01-01

Due to the conflicting requirements, complex physical processes and large number of design variables, divertor design for next step fusion reactors is a challenging problem, often relying on large numbers of computationally expensive numerical simulations. In this paper, we attempt to partially automate the design process by solving an appropriate shape optimization problem. Design requirements are incorporated in a cost functional which measures the performance of a certain design. By means of changes in the divertor shape, which in turn lead to changes in the plasma state, this cost functional can be minimized. Using advanced adjoint methods, optimal solutions are computed very efficiently. The approach is illustrated by designing divertor targets for optimal power load spreading, using a simplified edge plasma model (copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Oxidative Stress and the Homeodynamics of Iron Metabolism

Science.gov (United States)

Bresgen, Nikolaus; Eckl, Peter M.

2015-01-01

Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stress—i.e., enhanced formation of reactive oxygen species (ROS)—however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress. PMID:25970586

Multiscale modeling and topology optimization of poroelastic actuators

DEFF Research Database (Denmark)

Andreasen, Casper Schousboe; Sigmund, Ole

2012-01-01

This paper presents a method for design of optimized poroelastic materials which under internal pressurization turn into actuators for application in, for example, linear motors. The actuators are modeled in a two-scale fluid–structure interaction approach. The fluid saturated material microstruc...

Tomographic reconstruction of transverse phase space from turn-by-turn profile data

CERN Document Server

Hancock, S; Lindroos, M

1999-01-01

Tomographic methods have the potential for useful application in beam diagnostics. The tomographic reconstruction of transverse phase space density from turn-by-turn profile data has been studied with particular attention to the effects of dispersion and chromaticity. It is shown that the modified Algebraic Reconstruction Technique (ART) that deals successfully with the problem of non-linear motion in the longitudinal plane cannot, in general, be extended to cover the transverse case. Instead, an approach is proposed in which the effect of dispersion is deconvoluted from the measured profiles before the phase space picture is reconstructed using either the modified ART algorithm or the inverse Radon Transform. This requires an accurate knowledge of the momentum distribution of the beam and the modified ART reconstruction of longitudinal phase space density yields just such information. The method has been tested extensively with simulated data.

Cancer treatment induced metabolic syndrome: Improving outcome with lifestyle.

Science.gov (United States)

Westerink, N L; Nuver, J; Lefrandt, J D; Vrieling, A H; Gietema, J A; Walenkamp, A M E

2016-12-01

Increasing numbers of long-term cancer survivors face important treatment related adverse effects. Cancer treatment induced metabolic syndrome (CTIMetS) is an especially prevalent and harmful condition. The aetiology of CTIMetS likely differs from metabolic syndrome in the general population, but effective treatment and prevention methods are probably similar. In this review, we summarize the potential mechanisms leading to the development of CTIMetS after various types of cancer treatment. Furthermore, we propose a safe and accessible method to treat or prevent CTIMetS through lifestyle change. In particular, we suggest that a lifestyle intervention and optimization of energy balance can prevent or mitigate the development of CTIMetS, which may contribute to optimal survivorship care. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A review of parameters and heuristics for guiding metabolic pathfinding.

Science.gov (United States)

Kim, Sarah M; Peña, Matthew I; Moll, Mark; Bennett, George N; Kavraki, Lydia E

2017-09-15

Recent developments in metabolic engineering have led to the successful biosynthesis of valuable products, such as the precursor of the antimalarial compound, artemisinin, and opioid precursor, thebaine. Synthesizing these traditionally plant-derived compounds in genetically modified yeast cells introduces the possibility of significantly reducing the total time and resources required for their production, and in turn, allows these valuable compounds to become cheaper and more readily available. Most biosynthesis pathways used in metabolic engineering applications have been discovered manually, requiring a tedious search of existing literature and metabolic databases. However, the recent rapid development of available metabolic information has enabled the development of automated approaches for identifying novel pathways. Computer-assisted pathfinding has the potential to save biochemists time in the initial discovery steps of metabolic engineering. In this paper, we review the parameters and heuristics used to guide the search in recent pathfinding algorithms. These parameters and heuristics capture information on the metabolic network structure, compound structures, reaction features, and organism-specificity of pathways. No one metabolic pathfinding algorithm or search parameter stands out as the best to use broadly for solving the pathfinding problem, as each method and parameter has its own strengths and shortcomings. As assisted pathfinding approaches continue to become more sophisticated, the development of better methods for visualizing pathway results and integrating these results into existing metabolic engineering practices is also important for encouraging wider use of these pathfinding methods.

Metabolic engineering of Yarrowia lipolytica for industrial applications.

Science.gov (United States)

Zhu, Quinn; Jackson, Ethel N

2015-12-01

Yarrowia lipolytica is a safe and robust yeast that has a history of industrial applications. Its physiological, metabolic and genomic characteristics have made it a superior host for metabolic engineering. The results of optimizing internal pathways and introducing new pathways have demonstrated that Y. lipolytica can be a platform cell factory for cost-effective production of chemicals and fuels derived from fatty acids, lipids and acetyl-CoA. Two products have been commercialized from metabolically engineered Y. lipolytica strains producing high amounts of omega-3 eicosapentaenoic acid, and more products are on the way to be produced at industrial scale. Here we review recent progress in metabolic engineering of Y. lipolytica for production of biodiesel fuel, functional fatty acids and carotenoids. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Turning to Ontology in STS? Turning to STS through ‘Ontology’

NARCIS (Netherlands)

van Heur, B.; Leydesdorff, L.; Wyatt, S.

2012-01-01

We examine the evidence for the claim of an ‘ontological turn’ in science and technology studies (STS). Despite an increase in references to ‘ontology’ in STS since 1989, we show that there has not so much been an ontological turn as multiple discussions deploying the language of ontology,

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

KAUST Repository

Hefzi, Hooman

2016-11-23

Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production. The models accurately predict growth phenotypes and known auxotrophies in CHO cells. With the models, we quantify the protein synthesis capacity of CHO cells and demonstrate that common bioprocess treatments, such as histone deacetylase inhibitors, inefficiently increase product yield. However, our simulations show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway. This model will further accelerate CHO cell engineering and help optimize bioprocesses.

Evaluation of Frameworks for HSCT Design Optimization

Science.gov (United States)

Krishnan, Ramki

1998-01-01

This report is an evaluation of engineering frameworks that could be used to augment, supplement, or replace the existing FIDO 3.5 (Framework for Interdisciplinary Design and Optimization Version 3.5) framework. The report begins with the motivation for this effort, followed by a description of an "ideal" multidisciplinary design and optimization (MDO) framework. The discussion then turns to how each candidate framework stacks up against this ideal. This report ends with recommendations as to the "best" frameworks that should be down-selected for detailed review.

Network synchronization: optimal and pessimal scale-free topologies

International Nuclear Information System (INIS)

Donetti, Luca; Hurtado, Pablo I; Munoz, Miguel A

2008-01-01

By employing a recently introduced optimization algorithm we construct optimally synchronizable (unweighted) networks for any given scale-free degree distribution. We explore how the optimization process affects degree-degree correlations and observe a generic tendency toward disassortativity. Still, we show that there is not a one-to-one correspondence between synchronizability and disassortativity. On the other hand, we study the nature of optimally un-synchronizable networks, that is, networks whose topology minimizes the range of stability of the synchronous state. The resulting 'pessimal networks' turn out to have a highly assortative string-like structure. We also derive a rigorous lower bound for the Laplacian eigenvalue ratio controlling synchronizability, which helps understanding the impact of degree correlations on network synchronizability

“ Metabolic Ride” - One Concept Evaluation Tool For Metabolic Biochemistry Teaching For Graduate Students In Biological Sciences And Related Areas.

Directory of Open Access Journals (Sweden)

H. H. Gaeta et al.

2017-07-01

Full Text Available Biochemistry subject in general has a high degree of difficulty and complexity. Therefore, application of playful and creative games as teaching methodology has spread in various disciplines of life sciences. "METABOLIC RIDE" board game is a conceptual and perceptual evaluation tool for metabolic biochemistry teaching, aiming to review concepts transmitted in classroom, promoting a competitive challenge to students without denying tools that are at their disposal, stimulating their skills. OBJECTIVES. Correlate metabolic routes importance and their interconnections to establish that metabolic pathways are interconnected, such as a railway map. MATERIAL AND METHODS. This game was developed based on a board game Ticket to Ride. Players purchase enzyme cards, which must be used to claim metabolic routes. The goal is to complete the route previously drawn to earn points and the player who builds the longest continuous route will also earn bonus points. In each turn, players can: buy more card, claim a route or pick up additional destination tickets. The game should be played in groups of 5 to 6 students in 6 to 8 groups. Previously there will be theoretical classes. The activity was designed to last 4 hours. Use of didatic books and internet by players are encouraged. RESULTS. This game proved to be an excellent tool for student’s complementary evaluation, which stimulated teamwork and competitiveness within classroom, which allowed to analyze student’s perception regarding metabolic subjects. On the other hand, for teacher and students participating in compulsory traineeship program this game demonstrated to students new ways to approach complex subjects in biochemistry using creativity. CONCLUSION: Overall, students had a good impression of “Metabolic Ride” game since it helped to secure and administer metabolism subject in a competitive and team work way.

An improved chaotic fruit fly optimization based on a mutation strategy for simultaneous feature selection and parameter optimization for SVM and its applications

Science.gov (United States)

Lou, Xin Yuan; Sun, Lin Fu

2017-01-01

This paper proposes a new support vector machine (SVM) optimization scheme based on an improved chaotic fly optimization algorithm (FOA) with a mutation strategy to simultaneously perform parameter setting turning for the SVM and feature selection. In the improved FOA, the chaotic particle initializes the fruit fly swarm location and replaces the expression of distance for the fruit fly to find the food source. However, the proposed mutation strategy uses two distinct generative mechanisms for new food sources at the osphresis phase, allowing the algorithm procedure to search for the optimal solution in both the whole solution space and within the local solution space containing the fruit fly swarm location. In an evaluation based on a group of ten benchmark problems, the proposed algorithm’s performance is compared with that of other well-known algorithms, and the results support the superiority of the proposed algorithm. Moreover, this algorithm is successfully applied in a SVM to perform both parameter setting turning for the SVM and feature selection to solve real-world classification problems. This method is called chaotic fruit fly optimization algorithm (CIFOA)-SVM and has been shown to be a more robust and effective optimization method than other well-known methods, particularly in terms of solving the medical diagnosis problem and the credit card problem. PMID:28369096

Toward Optimal Transport Networks

Science.gov (United States)

Alexandrov, Natalia; Kincaid, Rex K.; Vargo, Erik P.

2008-01-01

Strictly evolutionary approaches to improving the air transport system a highly complex network of interacting systems no longer suffice in the face of demand that is projected to double or triple in the near future. Thus evolutionary approaches should be augmented with active design methods. The ability to actively design, optimize and control a system presupposes the existence of predictive modeling and reasonably well-defined functional dependences between the controllable variables of the system and objective and constraint functions for optimization. Following recent advances in the studies of the effects of network topology structure on dynamics, we investigate the performance of dynamic processes on transport networks as a function of the first nontrivial eigenvalue of the network's Laplacian, which, in turn, is a function of the network s connectivity and modularity. The last two characteristics can be controlled and tuned via optimization. We consider design optimization problem formulations. We have developed a flexible simulation of network topology coupled with flows on the network for use as a platform for computational experiments.

Protein design in systems metabolic engineering for industrial strain development.

Science.gov (United States)

Chen, Zhen; Zeng, An-Ping

2013-05-01

Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intermittent metabolic switching, neuroplasticity and brain health

Science.gov (United States)

Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

2018-01-01

During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

The Optimal Portfolio Selection Model under g-Expectation

Directory of Open Access Journals (Sweden)

Li Li

2014-01-01

complicated and sophisticated, the optimal solution turns out to be surprisingly simple, the payoff of a portfolio of two binary claims. Also I give the economic meaning of my model and the comparison with that one in the work of Jin and Zhou, 2008.

Fatty Acids and NLRP3 Inflammasome-Mediated Inflammation in Metabolic Tissues.

Science.gov (United States)

Ralston, Jessica C; Lyons, Claire L; Kennedy, Elaine B; Kirwan, Anna M; Roche, Helen M

2017-08-21

Worldwide obesity rates have reached epidemic proportions and significantly contribute to the growing prevalence of metabolic diseases. Chronic low-grade inflammation, a hallmark of obesity, involves immune cell infiltration into expanding adipose tissue. In turn, obesity-associated inflammation can lead to complications in other metabolic tissues (e.g., liver, skeletal muscle, pancreas) through lipotoxicity and inflammatory signaling networks. Importantly, although numerous signaling pathways are known to integrate metabolic and inflammatory processes, the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is now noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome can be influenced by various metabolites, including fatty acids. Specifically, although saturated fatty acids may promote NLRP3 inflammasome activation, monounsaturated fatty acids and polyunsaturated fatty acids have recently been shown to impede NLRP3 activity. Therefore, the NLRP3 inflammasome and associated metabolic inflammation have key roles in the relationships among fatty acids, metabolites, and metabolic disease. This review focuses on the ability of fatty acids to influence inflammation and the NLRP3 inflammasome across numerous metabolic tissues in the body. In addition, we explore some perspectives for the future, wherein recent work in the immunology field clearly demonstrates that metabolic reprogramming defines immune cell functionality. Although there is a paucity of information about how diet and fatty acids modulate this process, it is possible that this will open up a new avenue of research relating to nutrient-sensitive metabolic inflammation.

Experimental study of the chip morphology in turning hardened AISI D2 steel

Energy Technology Data Exchange (ETDEWEB)

Mhamdi, Mohamed Baccar; Bayraktar, Emin [Supmeca, Paris (France); Salem, Sahbi Ben; Boujelbene, Mohamed [National Engineering School of Tunis, Tunis (Turkey)

2013-11-15

The study of local mechanisms of material removal is essential in all problems of shaping by machining. Indeed, the mastery of surfaces generated by cutting requires an understanding of cutting mechanisms. The turning of steels with high mechanical properties using the cutting tool, often called 'hard turning,' is a new technique for the mechanical industry, and hence the need to understand the cutting mechanisms. The steel type EN X160CrMoV12 treated to 62 HRC (cold work tool steel: AISI D2 with a martensite matrix and distribution of primary and secondary carbides) is the subject of this study. Hard turning tests were carried out for this steel at different cutting conditions, with the aim to understand the mechanism of chip formation in order to be able to obtain the optimal cutting conditions. The chips obtained were examined under a microscope. The observation showed that the chip formation is influenced by cutting conditions. The chips contained a white layer, and this layer was examined under scanning electronic microscope (SEM) to study its variation depending on cutting parameters. The study shown, that cutting forces decrease with the increase of cutting speed. However, ANOVA method was used to establish the effect of the cutting conditions on experimental obtained results. Analysis of plastic deformation of the chip and the shear angle was made according to cutting conditions. Finally, a microhardness test was carried out to relate the mechanical properties and the microstructures of white layers.

Turning to alcohol?

International Nuclear Information System (INIS)

Reiboro, S.K.

1998-01-01

Brazil is examining whether turning to alcohol could solve its problems. The fuel alcohol producers are lobbying hard for the government to increase the use of alcohol to fuel the country's cars. Not only does using alcohol reduce CO 2 , runs the argument, but the Kyoto agreement might just attract international financing for the project. (author)

First turn simulations in the cooler synchrotron COSY

International Nuclear Information System (INIS)

Dinev, D.

1991-07-01

This paper is devoted to the first turn correction and related problems in particle accelerators of synchrotron type. The paper consists of two parts. The first part is a survey of the existing methods for first turn steering. The second part is entirely devoted to the first turn in the cooler synchrotron COSY which is under assembling in KFA-Julich, Germany. (orig.)

First turn around strategy for RHIC

International Nuclear Information System (INIS)

Milutinovic, J.; Ruggiero, A.G.

1991-01-01

The authors present a strategy for achieving the so-called first turn around in RHIC. The strategy is based on the same method proposed to correct a distorted closed orbit in RHIC, i.e. on a generalization of the local three-bump method. They found out that the method is very effective in passing the beam through a non-ideal, insufficiently known, machine. The perturbed lattice was generated by the code PATRIS, which was also adapted to control the newly developed software. In ten distributions of errors the software was capable of passing the beam through in 2-3 injection attempts, at full sextupole strength. It was also determined that once the beam makes the first turn around and all the correctors are energized, it stays in the machine for at least several hundred turns

Modeling and multi-objective optimization of surface roughness and productivity in dry turning of AISI 52100 steel using (TiCN-TiN coating cermet tools

Directory of Open Access Journals (Sweden)

Ouahid Keblouti

2017-01-01

Full Text Available The present work concerns an experimental study of turning with coated cermet tools with TiCN-TiN coating layer of AISI 52100 bearing steel. The main objectives are firstly focused on the effect of cutting parameters and coating material on the performances of cutting tools. Secondly, to perform a Multi-objective optimization for minimizing surface roughness (Ra and maximizing material removal rate by desirability approach. A mathematical model was developed based on the Response Surface Methodology (RSM. ANOVA method was used to quantify the cutting parameters effects on the machining surface quality and the material removal rate. The results analysis shows that the feed rate has the most effect on the surface quality. The effect of coating layers on the surface quality is also studied. It is observed that a lower surface roughness is obtained when using PVD (TiCN-TiN coated insert when compared with uncoated tool. The values of root mean square deviation and coefficient of correlation between the theoretical and experimental data are also given in this work where the maximum calculated error is 2.65 %.

Synthetic biology and metabolic engineering.

Science.gov (United States)

Stephanopoulos, Gregory

2012-11-16

Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

Performance evaluation of Titanium nitride coated tool in turning of mild steel

Science.gov (United States)

Srinivas, B.; Pramod Kumar, G.; Cheepu, Muralimohan; Jagadeesh, N.; kumar, K. Ravi; Haribabu, S.

2018-03-01

The growth in demand for bio-gradable materials is opened as a venue for using vegetable oils, coconut oils etc., as alternate to the conventional coolants for machining operations. At present in manufacturing industries the demand for surface quality is increasing rapidly along with dimensional accuracy and geometric tolerances. The present study is influence of cutting parameters on the surface roughness during the turning of mild steel with TiN coated carbide tool using groundnut oil and soluble oil as coolants. The results showed vegetable gave closer surface finish compares with soluble oil. Cutting parameters has been optimized with Taguchi technique. In this paper, the main objective is to optimize the cutting parameters and reduce surface roughness analogous to increase the tool life by apply the coating on the carbide inserts. The cost of the coating is more, but economically efficient than changing the tools frequently. The plots were generated and analysed to find the relationship between them which are confirmed by performing a comparison study between the predicted results and theoretical results.

The Protein Cost of Metabolic Fluxes: Prediction from Enzymatic Rate Laws and Cost Minimization.

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Elad Noor

2016-11-01

Full Text Available Bacterial growth depends crucially on metabolic fluxes, which are limited by the cell's capacity to maintain metabolic enzymes. The necessary enzyme amount per unit flux is a major determinant of metabolic strategies both in evolution and bioengineering. It depends on enzyme parameters (such as kcat and KM constants, but also on metabolite concentrations. Moreover, similar amounts of different enzymes might incur different costs for the cell, depending on enzyme-specific properties such as protein size and half-life. Here, we developed enzyme cost minimization (ECM, a scalable method for computing enzyme amounts that support a given metabolic flux at a minimal protein cost. The complex interplay of enzyme and metabolite concentrations, e.g. through thermodynamic driving forces and enzyme saturation, would make it hard to solve this optimization problem directly. By treating enzyme cost as a function of metabolite levels, we formulated ECM as a numerically tractable, convex optimization problem. Its tiered approach allows for building models at different levels of detail, depending on the amount of available data. Validating our method with measured metabolite and protein levels in E. coli central metabolism, we found typical prediction fold errors of 4.1 and 2.6, respectively, for the two kinds of data. This result from the cost-optimized metabolic state is significantly better than randomly sampled metabolite profiles, supporting the hypothesis that enzyme cost is important for the fitness of E. coli. ECM can be used to predict enzyme levels and protein cost in natural and engineered pathways, and could be a valuable computational tool to assist metabolic engineering projects. Furthermore, it establishes a direct connection between protein cost and thermodynamics, and provides a physically plausible and computationally tractable way to include enzyme kinetics into constraint-based metabolic models, where kinetics have usually been ignored or

Mn2+-ZnSe/ZnS@SiO2 Nanoparticles for Turn-on Luminescence Thiol Detection

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Mohammad S. Yazdanparast

2017-08-01

Full Text Available Biological thiols are antioxidants essential for the prevention of disease. For example, low levels of the tripeptide glutathione are associated with heart disease, cancer, and dementia. Mn2+-doped wide bandgap semiconductor nanocrystals exhibit luminescence and magnetic properties that make them attractive for bimodal imaging. We found that these nanocrystals and silica-encapsulated nanoparticle derivatives exhibit enhanced luminescence in the presence of thiols in both organic solvent and aqueous solution. The key to using these nanocrystals as sensors is control over their surfaces. The addition of a ZnS barrier layer or shell produces more stable nanocrystals that are isolated from their surroundings, and luminescence enhancement is only observed with thinner, intermediate shells. Tunability is demonstrated with dodecanethiol and sensitivities decrease with thin, medium, and thick shells. Turn-on nanoprobe luminescence is also generated by several biological thiols, including glutathione, N-acetylcysteine, cysteine, and dithiothreitol. Nanoparticles prepared with different ZnS shell thicknesses demonstrated varying sensitivity to glutathione, which allows for the tuning of particle sensitivity without optimization. The small photoluminescence response to control amino acids and salts indicates selectivity for thiols. Preliminary magnetic measurements highlight the challenge of optimizing sensors for different imaging modalities. In this work, we assess the prospects of using these nanoparticles as luminescent turn-on thiol sensors and for MRI.

Optimal Design of Pension Funds : A Mission Impossible

NARCIS (Netherlands)

Suijs, J.P.M.; De Waegenaere, A.M.B.; Borm, P.E.M.

1998-01-01

Nowadays many employers offer their employees the possibility of an insurance against too large losses in income when retiring or becoming disabled. This paper models the optimization problem of the employer when setting up such a so-called pension fund. not surprisingly, it turns out that the

Synthesis of conformationally restricted beta-turn mimics

NARCIS (Netherlands)

IJsselstijn, M.

2006-01-01

This thesis aims at developing methods for introducing conformational restriction in Beta-turns, the turn elements present in Beta-sheets. A conformationally restricted peptide might either be formed via incorporation of a bridging diamino acids in a growing peptide chain, or via covalent bond

Turn key contracts

International Nuclear Information System (INIS)

Feretic, D.

1975-01-01

The aim of this summary is to point out some specific areas which have to be covered in a turn-key contract and which are of primarily interest to the buyer of a nuclear plant. It will be assumed that the buyer is utility company in a developing country and a plant supplier a company in an industrial country. (orig./FW) [de

Metabolic network modeling of microbial interactions in natural and engineered environmental systems

Directory of Open Access Journals (Sweden)

Octavio ePerez-Garcia

2016-05-01

Full Text Available We review approaches to characterize metabolic interactions within microbial communities using Stoichiometric Metabolic Network (SMN models for applications in environmental and industrial biotechnology. SMN models are computational tools used to evaluate the metabolic engineering potential of various organisms. They have successfully been applied to design and optimize the microbial production of antibiotics, alcohols and amino acids by single strains. To date however, such models have been rarely applied to analyze and control the metabolism of more complex microbial communities. This is largely attributed to the diversity of microbial community functions, metabolisms and interactions. Here, we firstly review different types of microbial interaction and describe their relevance for natural and engineered environmental processes. Next, we provide a general description of the essential methods of the SMN modeling workflow including the steps of network reconstruction, simulation through Flux Balance Analysis (FBA, experimental data gathering, and model calibration. Then we broadly describe and compare four approaches to model microbial interactions using metabolic networks, i.e. i lumped networks, ii compartment per guild networks, iii bi-level optimization simulations and iv dynamic-SMN methods. These approaches can be used to integrate and analyze diverse microbial physiology, ecology and molecular community data. All of them (except the lumped approach are suitable for incorporating species abundance data but so far they have been used only to model simple communities of two to eight different species. Interactions based on substrate exchange and competition can be directly modeled using the above approaches. However, interactions based on metabolic feedbacks, such as product inhibition and synthropy require extensions to current models, incorporating gene regulation and compounding accumulation mechanisms. SMN models of microbial

[Construction of high-yield strain by optimizing lycopene cyclase for β-carotene production].

Science.gov (United States)

Jin, Yingfu; Han, Li; Zhang, Shasha; Li, Shizhong; Liu, Weifeng; Tao, Yong

2017-11-25

To optimize key enzymes, such as to explore the gene resources and to modify the expression level, can maximize metabolic pathways of target products. β-carotene is a terpenoid compound with important application value. Lycopene cyclase (CrtY) is the key enzyme in β-carotene biosynthesis pathway, catalyzing flavin adenine dinucleotide (FAD)-dependent cyclization reaction and β-carotene synthesis from lycopene precursor. We optimized lycopene cyclase (CrtY) to improve the synthesis of β-carotene and determined the effect of CrtY expression on metabolic pathways. Frist, we developed a β-carotene synthesis module by coexpressing the lycopene β-cyclase gene crtY with crtEBI module in Escherichia coli. Then we simultaneously optimized the ribosome-binding site (RBS) intensity and the species of crtY using oligo-linker mediated DNA assembly method (OLMA). Five strains with high β-carotene production capacity were screened out from the OLMA library. The β-carotene yields of these strains were up to 15.79-18.90 mg/g DCW (Dry cell weight), 65% higher than that of the original strain at shake flask level. The optimal strain CP12 was further identified and evaluated for β-carotene production at 5 L fermentation level. After process optimization, the final β-carotene yield could reach to 1.9 g/L. The results of RBS strength and metabolic intermediate analysis indicated that an appropriate expression level of CrtY could be beneficial for the function of the β-carotene synthesis module. The results of this study provide important insight into the optimization of β-carotene synthesis pathway in metabolic engineering.

The role of metabolic engineering in the production of secondary metabolites

DEFF Research Database (Denmark)

Nielsen, Jens Bredal

1998-01-01

In the production of secondary metabolites yield and productivity are the most important design parameters. The focus is therefore to direct the carbon fluxes towards the product of interest, and this can be obtained through metabolic engineering whereby directed genetic changes are introduced...... into the production strain. In this process it is, however, important to analyze the metabolic network through measurement of the intracellular metabolites and the flux distributions. Besides playing an important role in the optimization of existing processes, metabolic engineering also offers the possibility...

Stepping in Place While Voluntarily Turning Around Produces a Long-Lasting Posteffect Consisting in Inadvertent Turning While Stepping Eyes Closed

Directory of Open Access Journals (Sweden)

Stefania Sozzi

2016-01-01

Full Text Available Training subjects to step in place on a rotating platform while maintaining a fixed body orientation in space produces a posteffect consisting in inadvertent turning around while stepping in place eyes closed (podokinetic after-rotation, PKAR. We tested the hypothesis that voluntary turning around while stepping in place also produces a posteffect similar to PKAR. Sixteen subjects performed 12 min of voluntary turning while stepping around their vertical axis eyes closed and 12 min of stepping in place eyes open on the center of a platform rotating at 60°/s (pretests. Then, subjects continued stepping in place eyes closed for at least 10 min (posteffect. We recorded the positions of markers fixed to head, shoulder, and feet. The posteffect of voluntary turning shared all features of PKAR. Time decay of angular velocity, stepping cadence, head acceleration, and ratio of angular velocity after to angular velocity before were similar between both protocols. Both postrotations took place inadvertently. The posteffects are possibly dependent on the repeated voluntary contraction of leg and foot intrarotating pelvic muscles that rotate the trunk over the stance foot, a synergy common to both protocols. We propose that stepping in place and voluntary turning can be a scheme ancillary to the rotating platform for training body segment coordination in patients with impairment of turning synergies of various origin.

Network synchronization: optimal and pessimal scale-free topologies

Energy Technology Data Exchange (ETDEWEB)

Donetti, Luca [Departamento de Electronica y Tecnologia de Computadores and Instituto de Fisica Teorica y Computacional Carlos I, Facultad de Ciencias, Universidad de Granada, 18071 Granada (Spain); Hurtado, Pablo I; Munoz, Miguel A [Departamento de Electromagnetismo y Fisica de la Materia and Instituto Carlos I de Fisica Teorica y Computacional Facultad de Ciencias, Universidad de Granada, 18071 Granada (Spain)], E-mail: mamunoz@onsager.ugr.es

2008-06-06

By employing a recently introduced optimization algorithm we construct optimally synchronizable (unweighted) networks for any given scale-free degree distribution. We explore how the optimization process affects degree-degree correlations and observe a generic tendency toward disassortativity. Still, we show that there is not a one-to-one correspondence between synchronizability and disassortativity. On the other hand, we study the nature of optimally un-synchronizable networks, that is, networks whose topology minimizes the range of stability of the synchronous state. The resulting 'pessimal networks' turn out to have a highly assortative string-like structure. We also derive a rigorous lower bound for the Laplacian eigenvalue ratio controlling synchronizability, which helps understanding the impact of degree correlations on network synchronizability.

Train turn restrictions and line plan performance

DEFF Research Database (Denmark)

Burggraeve, Sofie; Bull, Simon Henry; Lusby, Richard Martin

In this paper we study the impact of the `turn conditions' in end stations on the performance of a line plan. If trains have to turn on their platform in an end station, the yoccupy the platform for several minutes. A more preferred option, from a timetabling point of view, would be that a train...... in a exible and large enough shunt. Starting from a given line plan, we compare two timetables, one where trains have to turn on their platform and one where trains can turn in a shunt. We evaluate the impact on the performance of the line plan by its feasibility for timetabling,the minimum overall buffer...... disappears from the platform in its end station after dwelling and only appears again when departing for a subsequent trip. In this case, the train will not interfere with other trains that dwell on the platform during the time between these events. However, this option is only possible if the train can stay...

Derrida’s Turn to Franciscan Philosophy

Directory of Open Access Journals (Sweden)

Marko Zlomislic

2008-12-01

Full Text Available Contemporary French philosophers such as Levinas, Bataille, and Derrida, along with the existentialists Kierkegaard and Nietzsche have all made use of Franciscan insights in order to safeguard the ipseity that cannot be reduced or totalized. In keeping with the taste that concerns me, this paper will examine Derrida’s turn to the poetry of Gerard Manley Hopkins and how such a turn may place Derrida within a catholic and Franciscan tradition.

Multidisciplinary Design and Optimization Framework for Aircraft Box Structures

NARCIS (Netherlands)

Van Dijk, R.E.C.; Zhao, X.; Wang, H.; Van Dalen, F.

2012-01-01

Competitive aircraft box structures are a perfect compromise between weight and price. The conceptual design process of these structures is a typical Multidisciplinary Design and Optimization effort, normally conducted by human engineers. The iterative nature of MDO turns development into a long and

Adaptive Evolution of Phosphorus Metabolism in Prochlorococcus

DEFF Research Database (Denmark)

Casey, John R; Mardinoglu, Adil; Nielsen, Jens

2016-01-01

Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high-light-adapted ecotype HLI of the marine picocyanobacterium Prochlorococcus marinus thrives. Physiological and regulatory control of phosphorus acquisition and partitioning has been observed in HLI both in culture...... and in the field; however, the optimization of phosphorus metabolism and associated gains for its phosphorus-limited-growth (PLG) phenotype have not been studied. Here, we reconstructed a genome-scale metabolic network of the HLI axenic strain MED4 (iJC568), consisting of 568 metabolic genes in relation to 794...... through drastic depletion of phosphorus-containing biomass components but also through network-wide reductions in phosphate-reaction participation and the loss of a key enzyme, succinate dehydrogenase. These alterations occur despite the stringency of having relatively few pathway redundancies...

Self-adaptive multimethod optimization applied to a tailored heating forging process

Science.gov (United States)

Baldan, M.; Steinberg, T.; Baake, E.

2018-05-01

The presented paper describes an innovative self-adaptive multi-objective optimization code. Investigation goals concern proving the superiority of this code compared to NGSA-II and applying it to an inductor’s design case study addressed to a “tailored” heating forging application. The choice of the frequency and the heating time are followed by the determination of the turns number and their positions. Finally, a straightforward optimization is performed in order to minimize energy consumption using “optimal control”.

performance characteristics of a cam turning attachment

African Journals Online (AJOL)

Dr Obe

ABSTRACT. A modification of a cylindrical turning unit has been done to give a non- cylindrical turning attachment for production of irregular shapes, like cams on the lathe machine. To assess the performance of the attachment, cutting forces have been measured using a 'Sigma' Cutting Tool. Dynamometer. Furthermore ...

A global evolutionary and metabolic analysis of human obesity gene risk variants.

Science.gov (United States)

Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

2017-09-05

It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

A theoretical case study of type I and type II beta-turns.

Science.gov (United States)

Czinki, Eszter; Császár, Attila G; Perczel, András

2003-03-03

NMR chemical shielding anisotropy tensors have been computed by employing a medium size basis set and the GIAO-DFT(B3LYP) formalism of electronic structure theory for all of the atoms of type I and type II beta-turn models. The models contain all possible combinations of the amino acid residues Gly, Ala, Val, and Ser, with all possible side-chain orientations where applicable in a dipeptide. The several hundred structures investigated contain either constrained or optimized phi, psi, and chi dihedral angles. A statistical analysis of the resulting large database was performed and multidimensional (2D and 3D) chemical-shift/chemical-shift plots were generated. The (1)H(alpha-13)C(alpha), (13)C(alpha-1)H(alpha-13)C(beta), and (13)C(alpha-1)H(alpha-13)C' 2D and 3D plots have the notable feature that the conformers clearly cluster in distinct regions. This allows straightforward identification of the backbone and side-chain conformations of the residues forming beta-turns. Chemical shift calculations on larger For-(L-Ala)(n)-NH(2) (n=4, 6, 8) models, containing a single type I or type II beta-turn, prove that the simple models employed are adequate. A limited number of chemical shift calculations performed at the highly correlated CCSD(T) level prove the adequacy of the computational method chosen. For all nuclei, statistically averaged theoretical and experimental shifts taken from the BioMagnetic Resonance Bank (BMRB) exhibit good correlation. These results confirm and extend our previous findings that chemical shift information from selected multiple-pulse NMR experiments could be employed directly to extract folding information for polypeptides and proteins.

Accessing Autonomic Function Can Early Screen Metabolic Syndrome

Science.gov (United States)

Dai, Meng; Li, Mian; Yang, Zhi; Xu, Min; Xu, Yu; Lu, Jieli; Chen, Yuhong; Liu, Jianmin; Ning, Guang; Bi, Yufang

2012-01-01

Background Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. Methodology and Principal Findings The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend metabolic syndrome components (p for trend metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61–0.64) for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. Conclusions and Significance In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome. PMID:22916265

Systematic optimization of fed-batch simultaneous saccharification and fermentation at high-solid loading based on enzymatic hydrolysis and dynamic metabolic modeling of Saccharomyces cerevisiae.

Science.gov (United States)

Unrean, Pornkamol; Khajeeram, Sutamat; Laoteng, Kobkul

2016-03-01

An integrative simultaneous saccharification and fermentation (SSF) modeling is a useful guiding tool for rapid process optimization to meet the techno-economic requirement of industrial-scale lignocellulosic ethanol production. In this work, we have developed the SSF model composing of a metabolic network of a Saccharomyces cerevisiae cell associated with fermentation kinetics and enzyme hydrolysis model to quantitatively capture dynamic responses of yeast cell growth and fermentation during SSF. By using model-based design of feeding profiles for substrate and yeast cell in the fed-batch SSF process, an efficient ethanol production with high titer of up to 65 g/L and high yield of 85 % of theoretical yield was accomplished. The ethanol titer and productivity was increased by 47 and 41 %, correspondingly, in optimized fed-batch SSF as compared to batch process. The developed integrative SSF model is, therefore, considered as a promising approach for systematic design of economical and sustainable SSF bioprocessing of lignocellulose.

Hatchability of chicken eggs as influenced by turning frequency in ...

African Journals Online (AJOL)

An experiment was conducted to determine the influence of turning frequency of chicken eggs on hatchability in hurricane lantern incubator. There were four treatments in which eggs were not turned in treatment one (control), those in treatment two were turned once daily (morning), treatment three turned twice daily ...

Particle swarm optimization of a neural network model in a ...

Indian Academy of Sciences (India)

. Since tool life is critically affected by the tool wear, accurate prediction of this wear ... In their work, they established an improvement in the quality ... objective optimization of hard turning using neural network modelling and swarm intelligence ...

Optimization and evaluation of probabilistic-logic sequence models

DEFF Research Database (Denmark)

Christiansen, Henning; Lassen, Ole Torp

to, in principle, Turing complete languages. In general, such models are computationally far to complex for direct use, so optimization by pruning and approximation are needed. % The first steps are made towards a methodology for optimizing such models by approximations using auxiliary models......Analysis of biological sequence data demands more and more sophisticated and fine-grained models, but these in turn introduce hard computational problems. A class of probabilistic-logic models is considered, which increases the expressibility from HMM's and SCFG's regular and context-free languages...

Study of surface roughness and flank wear in hard turning of AISI 4140 steel with coated ceramic inserts

Energy Technology Data Exchange (ETDEWEB)

Das, Sudhansu Ranjan; Kuma, Amaresh [National Institute of Technology, Jamshedpur (India); Dhupal, Debabrata [Veer Surendra Sai University of Technology, Burla (India)

2015-10-15

This experimental investigation deals with dry hard turning of AISI 4140 steel using PVD-TiN coated Al{sub 2}O{sub 3}+TiCN mixed ceramic inserts. The combined effect of cutting parameters (cutting speed, feed and depth of cut) on performance characteristics such as surface roughness and flank wear is explored by Full factorial design (FFD) and analysis of variance (ANOVA). The results show that feed is the principal cutting parameter influencing surface roughness, followed by cutting speed. However, flank wear is affected by the cutting speed and interaction of feed-depth of cut, although depth of cut has not been found statistically significant, but flank wear is an increasing function of depth of cut. Observations are made on the machined surface, and worn tool by Scanning electron microscope (SEM) to establish the process. Abrasion was the major wear mechanism found during hard turning within the studied range. The effect of tool wear on surface roughness was also studied. The experimental data were analyzed to predict the optimal range of surface roughness and flank wear. Based on Response surface methodology (RSM), mathematical models were developed for surface roughness (Ra) and flank wear (VB) with 95% confidence level. Finally, under optimum cutting conditions (obtained by response optimization technique), tool life was evaluated to perform cost analysis for justifying the economic viability of coated ceramic inserts in hard turning. The estimated machining cost per part for TiN coated ceramic was found to be lower (Rs. 12.31) because of higher tool life (51 min), which results in the reduction of downtime and increase in savings.

Study of surface roughness and flank wear in hard turning of AISI 4140 steel with coated ceramic inserts

International Nuclear Information System (INIS)

Das, Sudhansu Ranjan; Kuma, Amaresh; Dhupal, Debabrata

2015-01-01

This experimental investigation deals with dry hard turning of AISI 4140 steel using PVD-TiN coated Al_2O_3+TiCN mixed ceramic inserts. The combined effect of cutting parameters (cutting speed, feed and depth of cut) on performance characteristics such as surface roughness and flank wear is explored by Full factorial design (FFD) and analysis of variance (ANOVA). The results show that feed is the principal cutting parameter influencing surface roughness, followed by cutting speed. However, flank wear is affected by the cutting speed and interaction of feed-depth of cut, although depth of cut has not been found statistically significant, but flank wear is an increasing function of depth of cut. Observations are made on the machined surface, and worn tool by Scanning electron microscope (SEM) to establish the process. Abrasion was the major wear mechanism found during hard turning within the studied range. The effect of tool wear on surface roughness was also studied. The experimental data were analyzed to predict the optimal range of surface roughness and flank wear. Based on Response surface methodology (RSM), mathematical models were developed for surface roughness (Ra) and flank wear (VB) with 95% confidence level. Finally, under optimum cutting conditions (obtained by response optimization technique), tool life was evaluated to perform cost analysis for justifying the economic viability of coated ceramic inserts in hard turning. The estimated machining cost per part for TiN coated ceramic was found to be lower (Rs. 12.31) because of higher tool life (51 min), which results in the reduction of downtime and increase in savings.

Precision lens assembly with alignment turning system

Science.gov (United States)

Ho, Cheng-Fang; Huang, Chien-Yao; Lin, Yi-Hao; Kuo, Hui-Jean; Kuo, Ching-Hsiang; Hsu, Wei-Yao; Chen, Fong-Zhi

2017-10-01

The poker chip assembly with high precision lens barrels is widely applied to ultra-high performance optical system. ITRC applies the poker chip assembly technology to the high numerical aperture objective lenses and lithography projection lenses because of its high efficiency assembly process. In order to achieve high precision lens cell for poker chip assembly, an alignment turning system (ATS) is developed. The ATS includes measurement, alignment and turning modules. The measurement module is equipped with a non-contact displacement sensor (NCDS) and an autocollimator (ACM). The NCDS and ACM are used to measure centration errors of the top and the bottom surface of a lens respectively; then the amount of adjustment of displacement and tilt with respect to the rotational axis of the turning machine for the alignment module can be determined. After measurement, alignment and turning processes on the ATS, the centration error of a lens cell with 200 mm in diameter can be controlled within 10 arcsec. Furthermore, a poker chip assembly lens cell with three sub-cells is demonstrated, each sub-cells are measured and accomplished with alignment and turning processes. The lens assembly test for five times by each three technicians; the average transmission centration error of assembly lens is 12.45 arcsec. The results show that ATS can achieve high assembly efficiency for precision optical systems.

A novel ultrasensitive carboxymethyl chitosan-quantum dot-based fluorescence "turn on-off" nanosensor for lysozyme detection.

Science.gov (United States)

Song, Yu; Li, Yang; Liu, Ziping; Liu, Linlin; Wang, Xinyan; Su, Xingguang; Ma, Qiang

2014-11-15

In this work, we developed an ultrasensitive "turn on-off" fluorescence nanosensor for lysozyme (Lyz) detection. The novel nanosensor was constructed with the carboxymethyl chitosan modified CdTe quantum dots (CMCS-QDs). Firstly, the CMCS-QDs were fabricated via the electrostatic interaction between amino groups in CMCS polymeric chains and carboxyl groups on the surface of QDs. In the fluorescence "turn-on" step, the strong binding ability between Zn(2+) and CMCS on the surface of QDs can enhance the photoluminescence intensity (PL) of QDs. In the following fluorescence "turn-off" step, the N-acetyl-glucosamine (NAG) section along the CMCS chains was hydrolyzed by Lyz. As a result, Zn(2+) was released from the surface of QDs, and the Lyz-QDs complexes were formed to quench the QDs PL. Under the optimal conditions, there was a good linear relationship between the PL of QDs and the Lyz concentration (0.1-1.2 ng/mL) with the detection limit of 0.031 ng/mL. The developed method was ultrasensitive, highly selective and fast. It has been successfully employed in the detection of Lyz in the serum with satisfactory results. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison Performance of Genetic Algorithm and Ant Colony Optimization in Course Scheduling Optimizing

Directory of Open Access Journals (Sweden)

Imam Ahmad Ashari

2016-11-01

Full Text Available Scheduling problems at the university is a complex type of scheduling problems. The scheduling process should be carried out at every turn of the semester's. The core of the problem of scheduling courses at the university is that the number of components that need to be considered in making the schedule, some of the components was made up of students, lecturers, time and a room with due regard to the limits and certain conditions so that no collision in the schedule such as mashed room, mashed lecturer and others. To resolve a scheduling problem most appropriate technique used is the technique of optimization. Optimization techniques can give the best results desired. Metaheuristic algorithm is an algorithm that has a lot of ways to solve the problems to the very limit the optimal solution. In this paper, we use a genetic algorithm and ant colony optimization algorithm is an algorithm metaheuristic to solve the problem of course scheduling. The two algorithm will be tested and compared to get performance is the best. The algorithm was tested using data schedule courses of the university in Semarang. From the experimental results we conclude that the genetic algorithm has better performance than the ant colony optimization  algorithm in solving the case of course scheduling.

Optimal Deterministic Investment Strategies for Insurers

Directory of Open Access Journals (Sweden)

Ulrich Rieder

2013-11-01

Full Text Available We consider an insurance company whose risk reserve is given by a Brownian motion with drift and which is able to invest the money into a Black–Scholes financial market. As optimization criteria, we treat mean-variance problems, problems with other risk measures, exponential utility and the probability of ruin. Following recent research, we assume that investment strategies have to be deterministic. This leads to deterministic control problems, which are quite easy to solve. Moreover, it turns out that there are some interesting links between the optimal investment strategies of these problems. Finally, we also show that this approach works in the Lévy process framework.

Metabolic assessments during extra-vehicular activity

Science.gov (United States)

Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

Effects of Different Exercise Modes on the Urinary Metabolic Fingerprint of Men with and without Metabolic Syndrome.

Science.gov (United States)

Siopi, Aikaterina; Deda, Olga; Manou, Vasiliki; Kellis, Spyros; Kosmidis, Ioannis; Komninou, Despina; Raikos, Nikolaos; Christoulas, Kosmas; Theodoridis, Georgios A; Mougios, Vassilis

2017-01-26

Exercise is important in the prevention and treatment of the metabolic syndrome (MetS), a cluster of risk factors that raises morbidity. Metabolomics can facilitate the optimization of exercise prescription. This study aimed to investigate whether the response of the human urinary metabolic fingerprint to exercise depends on the presence of MetS or exercise mode. Twenty-three sedentary men (MetS, n = 9, and Healthy, n = 14) completed four trials: resting, high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE). Urine samples were collected pre-exercise and at 2, 4, and 24 h for targeted analysis by liquid chromatography-mass spectrometry. Time exerted the strongest differentiating effect, followed by exercise mode and health status. The greatest changes were observed in the first post-exercise samples, with a gradual return to baseline at 24 h. RE caused the greatest responses overall, followed by HIIE, while CME had minimal effect. The metabolic fingerprints of the two groups were separated at 2 h, after HIIE and RE; and at 4 h, after HIIE, with evidence of blunted response to exercise in MetS. Our findings show diverse responses of the urinary metabolic fingerprint to different exercise modes in men with and without metabolic syndrome.

Effects of Different Exercise Modes on the Urinary Metabolic Fingerprint of Men with and without Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Aikaterina Siopi

2017-01-01

Full Text Available Exercise is important in the prevention and treatment of the metabolic syndrome (MetS, a cluster of risk factors that raises morbidity. Metabolomics can facilitate the optimization of exercise prescription. This study aimed to investigate whether the response of the human urinary metabolic fingerprint to exercise depends on the presence of MetS or exercise mode. Twenty-three sedentary men (MetS, n = 9, and Healthy, n = 14 completed four trials: resting, high-intensity interval exercise (HIIE, continuous moderate-intensity exercise (CME, and resistance exercise (RE. Urine samples were collected pre-exercise and at 2, 4, and 24 h for targeted analysis by liquid chromatography-mass spectrometry. Time exerted the strongest differentiating effect, followed by exercise mode and health status. The greatest changes were observed in the first post-exercise samples, with a gradual return to baseline at 24 h. RE caused the greatest responses overall, followed by HIIE, while CME had minimal effect. The metabolic fingerprints of the two groups were separated at 2 h, after HIIE and RE; and at 4 h, after HIIE, with evidence of blunted response to exercise in MetS. Our findings show diverse responses of the urinary metabolic fingerprint to different exercise modes in men with and without metabolic syndrome.

Optimal Strategy and Business Models

DEFF Research Database (Denmark)

Johnson, Peter; Foss, Nicolai Juul

2016-01-01

This study picks up on earlier suggestions that control theory may further the study of strategy. Strategy can be formally interpreted as an idealized path optimizing heterogeneous resource deployment to produce maximum financial gain. Using standard matrix methods to describe the firm Hamiltonia...... variable of firm path, suggesting in turn that the firm's business model is the codification of the application of investment resources used to control the strategic path of value realization....

Structural and sequence features of two residue turns in beta-hairpins.

Science.gov (United States)

Madan, Bharat; Seo, Sung Yong; Lee, Sun-Gu

2014-09-01

Beta-turns in beta-hairpins have been implicated as important sites in protein folding. In particular, two residue β-turns, the most abundant connecting elements in beta-hairpins, have been a major target for engineering protein stability and folding. In this study, we attempted to investigate and update the structural and sequence properties of two residue turns in beta-hairpins with a large data set. For this, 3977 beta-turns were extracted from 2394 nonhomologous protein chains and analyzed. First, the distribution, dihedral angles and twists of two residue turn types were determined, and compared with previous data. The trend of turn type occurrence and most structural features of the turn types were similar to previous results, but for the first time Type II turns in beta-hairpins were identified. Second, sequence motifs for the turn types were devised based on amino acid positional potentials of two-residue turns, and their distributions were examined. From this study, we could identify code-like sequence motifs for the two residue beta-turn types. Finally, structural and sequence properties of beta-strands in the beta-hairpins were analyzed, which revealed that the beta-strands showed no specific sequence and structural patterns for turn types. The analytical results in this study are expected to be a reference in the engineering or design of beta-hairpin turn structures and sequences. © 2014 Wiley Periodicals, Inc.

Use of genome-scale microbial models for metabolic engineering

DEFF Research Database (Denmark)

Patil, Kiran Raosaheb; Åkesson, M.; Nielsen, Jens

2004-01-01

Metabolic engineering serves as an integrated approach to design new cell factories by providing rational design procedures and valuable mathematical and experimental tools. Mathematical models have an important role for phenotypic analysis, but can also be used for the design of optimal metaboli...... network structures. The major challenge for metabolic engineering in the post-genomic era is to broaden its design methodologies to incorporate genome-scale biological data. Genome-scale stoichiometric models of microorganisms represent a first step in this direction....

Diamond turning machine controller implementation

Energy Technology Data Exchange (ETDEWEB)

Garrard, K.P.; Taylor, L.W.; Knight, B.F.; Fornaro, R.J.

1988-12-01

The standard controller for a Pnuemo ASG 2500 Diamond Turning Machine, an Allen Bradley 8200, has been replaced with a custom high-performance design. This controller consists of four major components. Axis position feedback information is provided by a Zygo Axiom 2/20 laser interferometer with 0.1 micro-inch resolution. Hardware interface logic couples the computers digital and analog I/O channels to the diamond turning machine`s analog motor controllers, the laser interferometer, and other machine status and control information. It also provides front panel switches for operator override of the computer controller and implement the emergency stop sequence. The remaining two components, the control computer hardware and software, are discussed in detail below.

"Healing is a Done Deal": Temporality and Metabolic Healing Among Evangelical Christians in Samoa.

Science.gov (United States)

Hardin, Jessica

2016-01-01

Drawing on fieldwork in independent Samoa, in this article, I analyze the temporal dimensions of evangelical Christian healing of metabolic disorders. I explore how those suffering with metabolic disorders draw from multiple time-based notions of healing, drawing attention to the limits of biomedicine in contrast with the effectiveness of Divine healing. By simultaneously engaging evangelical and biomedical temporalities, I argue that evangelical Christians create wellness despite sickness and, in turn, re-signify chronic suffering as a long-term process of Christian healing. Positioning biomedical temporality and evangelical temporality as parallel yet distinctive ways of practicing healing, therefore, influences health care choices.

Hatchability of chicken eggs as influenced by turning frequency in ...

African Journals Online (AJOL)

STORAGESEVER

2008-12-03

Dec 3, 2008 ... Brake (2004) confirmed that absence of turning resulted in presentation of the head in the small end of the egg. Egg turning facilitated the transfer of yolk nutrients to the embryo via the sub-embryonic fluid (Deeming, 1989a). With modern incubators, automatic turning devices allow the eggs to be turned on ...

The Effect of a Textured Insole on Symmetry of Turning

Directory of Open Access Journals (Sweden)

Etem Curuk

2018-01-01

Full Text Available Turning while walking is a common daily activity. Individuals with unilateral impairment frequently perform turns asymmetrically. The purpose of the study was to investigate the effect of a discomfort-inducing textured insole on symmetry of turning. Nine healthy individuals performed turns to the right while walking with no insole, immediately after the insole was inserted in the right shoe, and after walking for six minutes with the insole. The duration of turning, displacements of pelvic markers, and perceived level of discomfort were evaluated. Utilizing the insole was associated with the increased level of perceived discomfort (p<0.05. Moreover, using the insole was linked to changes in the displacement of two pelvic markers and larger asymmetry index while turning immediately after the insole was inserted in the right shoe as compared to no insole condition (p<0.05. The duration of right turning increased immediately after the insole was inserted (p<0.05 and after walking with the insole for six minutes. The results indicate that the textured insole creates asymmetry of turning in healthy individuals. The outcome provides a background for future studies focused on using a textured insole to minimize the asymmetry of turning commonly seen in individuals with unilateral impairment.

Reducing the metabolic cost of walking with an ankle exoskeleton: interaction between actuation timing and power.

Science.gov (United States)

Galle, Samuel; Malcolm, Philippe; Collins, Steven Hartley; De Clercq, Dirk

2017-04-27

Powered ankle-foot exoskeletons can reduce the metabolic cost of human walking to below normal levels, but optimal assistance properties remain unclear. The purpose of this study was to test the effects of different assistance timing and power characteristics in an experiment with a tethered ankle-foot exoskeleton. Ten healthy female subjects walked on a treadmill with bilateral ankle-foot exoskeletons in 10 different assistance conditions. Artificial pneumatic muscles assisted plantarflexion during ankle push-off using one of four actuation onset timings (36, 42, 48 and 54% of the stride) and three power levels (average positive exoskeleton power over a stride, summed for both legs, of 0.2, 0.4 and 0.5 W∙kg -1 ). We compared metabolic rate, kinematics and electromyography (EMG) between conditions. Optimal assistance was achieved with an onset of 42% stride and average power of 0.4 W∙kg -1 , leading to 21% reduction in metabolic cost compared to walking with the exoskeleton deactivated and 12% reduction compared to normal walking without the exoskeleton. With suboptimal timing or power, the exoskeleton still reduced metabolic cost, but substantially less so. The relationship between timing, power and metabolic rate was well-characterized by a two-dimensional quadratic function. The assistive mechanisms leading to these improvements included reducing muscular activity in the ankle plantarflexors and assisting leg swing initiation. These results emphasize the importance of optimizing exoskeleton actuation properties when assisting or augmenting human locomotion. Our optimal assistance onset timing and average power levels could be used for other exoskeletons to improve assistance and resulting benefits.

Noise-dependent optimal strategies for quantum metrology

Science.gov (United States)

Huang, Zixin; Macchiavello, Chiara; Maccone, Lorenzo

2018-03-01

For phase estimation using qubits, we show that for some noise channels, the optimal entanglement-assisted strategy depends on the noise level. We note that there is a nontrivial crossover between the parallel-entangled strategy and the ancilla-assisted strategy: in the former the probes are all entangled; in the latter the probes are entangled with a noiseless ancilla but not among themselves. The transition can be explained by the fact that separable states are more robust against noise and therefore are optimal in the high-noise limit, but they are in turn outperformed by ancilla-assisted ones.

Characteristics of turn signal use at intersections in baseline naturalistic driving.

Science.gov (United States)

Sullivan, John M; Bao, Shan; Goudy, Roy; Konet, Heather

2015-01-01

The purpose of this study was to determine whether a driver's use of turn signals is sufficiently reliable to forecast a vehicle's future path around an intersection, when detailed information about the intersection is unavailable. Naturalistic observations of turn signal use among 108 drivers on surface streets were extracted from the baseline portion of a field operational test of a safety system. Left and right turns that resulted in heading changes of between 70 and 110° and turn radii between 18 and 90 m were selected from the dataset. The odds that a driver would signal a turn were modeled as a function of road type, turn direction, presence of a forward vehicle, whether the vehicle stopped before the turn, and driver age and gender. Overall, 25 percent of left turns and 29 percent of right turns were not signaled. Road type, turn direction, and presence of a forward vehicle were found to influence the odds that a turn is signaled, while gender and age of the driver did not. The results suggest that situational factors like road type and turn direction are more powerful predictors of whether a turn will be signaled than either age or gender. Signaling on major and minor surface roads was about 5 times more likely than on local roads and 1.5 times more likely when a forward vehicle was present, suggesting a possible effect of traffic volume. It was concluded that turn signal activation alone may be insufficiently reliable to forecast a driver's path. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of a representative reinsurer in optimal reinsurance

NARCIS (Netherlands)

Boonen, T.J.; Tan, K.S.; Zhuang, S.C.

2016-01-01

In this paper, we consider a one-period optimal reinsurance design model with nn reinsurers and an insurer. For very general preferences of the insurer and that all reinsurers use a distortion premium principle, we establish the existence of a representative reinsurer and this in turn facilitates

Application of a novel design paradigm to generate general nonpeptide combinatorial templates mimicking beta-turns: synthesis of ligands for melanocortin receptors.

Science.gov (United States)

Webb, Thomas R; Jiang, Luyong; Sviridov, Sergey; Venegas, Ruben E; Vlaskina, Anna V; McGrath, Douglas; Tucker, John; Wang, Jian; Deschenes, Alain; Li, Rongshi

2007-01-01

We report the further application of a novel approach to template and ligand design by the synthesis of agonists of the melanocortin receptor. This design method uses the conserved structural data from the three-dimensional conformations of beta-turn peptides to design rigid nonpeptide templates that mimic the orientation of the main chain C-alpha atoms in a peptide beta-turn. We report details on a new synthesis of derivatives of template 1 that are useful for the synthesis of exploratory libraries. The utility of this technique is further exemplified by several iterative rounds of high-throughput synthesis and screening, which result in new partially optimized nonpeptide agonists for several melanocortin receptors.

Diamond turning of Si and Ge single crystals

Energy Technology Data Exchange (ETDEWEB)

Blake, P.; Scattergood, R.O.

1988-12-01

Single-point diamond turning studies have been completed on Si and Ge crystals. A new process model was developed for diamond turning which is based on a critical depth of cut for plastic flow-to-brittle fracture transitions. This concept, when combined with the actual machining geometry for single-point turning, predicts that {open_quotes}ductile{close_quotes} machining is a combined action of plasticity and fracture. Interrupted cutting experiments also provide a meant to directly measure the critical depth parameter for given machining conditions.

A man in the loop trajectory optimization program (MILTOP)

Science.gov (United States)

Reinfields, J.

1974-01-01

An interactive trajectory optimization program is developed for use in initial fixing of launch configurations. The program is called MILTOP for Man-In-the-Loop-Trajectory Optimization-Program. The program is designed to facilitate quick look studies using man-machine decision combinations to reduce the time required to solve a given problem. MILTOP integrates the equations of motion of a point-mass in 3-Dimensions with drag as the only aerodynamic force present. Any point in time at which an integration step terminates, may be used as a decision-break-point, with complete user control over all variables and routines at this point. Automatic phases are provided for different modes of control: vertical rise, pitch-over, gravity turn, chi-freeze and control turn. Stage parameters are initialized from a separate routine so the user may fly as many stages as his problem demands. The MILTOP system uses both interactively on storage scope consoles, or in batch mode with numerical output on the live printer.

Lifestyle changes and prevention of metabolic syndrome in the Heart of New Ulm Project

Directory of Open Access Journals (Sweden)

Jeffrey J. VanWormer

2017-06-01

Full Text Available Prior research has shown that unhealthy lifestyles increase the risk for developing a number of chronic diseases, but there are few studies examining how lifestyle changes impact metabolic syndrome. This study analyzed the association between two-year changes in key lifestyle risk metrics and incident metabolic syndrome in adults. A retrospective cohort study was conducted using data from metabolic syndrome free adults in the Heart of New Ulm Project (New Ulm, MN. The outcome was incident metabolic syndrome observed two years after baseline in 2009. The primary predictor was change in optimal lifestyle score based on four behavioral risk factors, including smoking, alcohol use, fruit/vegetable consumption, and physical activity. In the analytical sample of 1059 adults, 12% developed metabolic syndrome by 2011. Multivariable regression models (adjusted for baseline lifestyle score, age, sex, education, cardiovascular disease, and diabetes revealed that a two-year decrease in optimal lifestyle score was associated with significantly greater odds of incident metabolic syndrome (OR = 2.92; 95% CI: 1.69, 5.04; p < 0.001. This association was primarily driven by changes in obesity, fruit/vegetable consumption, and alcohol intake. As compared to improving poor lifestyle habits, maintaining a healthy lifestyle seemed to be most helpful in avoiding metabolic syndrome over the two-year study timeframe.

Metabolic engineering of Pediococcus acidilactici BD16 for production of vanillin through ferulic acid catabolic pathway and process optimization using response surface methodology.

Science.gov (United States)

Kaur, Baljinder; Chakraborty, Debkumar; Kumar, Balvir

2014-10-01

Occurrence of feruloyl-CoA synthetase (fcs) and enoyl-CoA hydratase (ech) genes responsible for the bioconversion of ferulic acid to vanillin have been reported and characterized from Amycolatopsis sp., Streptomyces sp., and Pseudomonas sp. Attempts have been made to express these genes in Escherichia coli DH5α, E. coli JM109, and Pseudomonas fluorescens. However, none of the lactic acid bacteria strain having GRAS status was previously proposed for heterologous expression of fcs and ech genes for production of vanillin through biotechnological process. Present study reports heterologous expression of vanillin synthetic gene cassette bearing fcs and ech genes in a dairy isolate Pediococcus acidilactici BD16. After metabolic engineering, statistical optimization of process parameters that influence ferulic acid to vanillin biotransformation in the recombinant strain was carried out using central composite design of response surface methodology. After scale-up of the process, 3.14 mM vanillin was recovered from 1.08 mM ferulic acid per milligram of recombinant cell biomass within 20 min of biotransformation. From LCMS-ESI spectral analysis, a metabolic pathway of phenolic biotransformations was predicted in the recombinant P. acidilactici BD16 (fcs (+)/ech (+)).

TIGER: Toolbox for integrating genome-scale metabolic models, expression data, and transcriptional regulatory networks

Directory of Open Access Journals (Sweden)

Jensen Paul A

2011-09-01

Full Text Available Abstract Background Several methods have been developed for analyzing genome-scale models of metabolism and transcriptional regulation. Many of these methods, such as Flux Balance Analysis, use constrained optimization to predict relationships between metabolic flux and the genes that encode and regulate enzyme activity. Recently, mixed integer programming has been used to encode these gene-protein-reaction (GPR relationships into a single optimization problem, but these techniques are often of limited generality and lack a tool for automating the conversion of rules to a coupled regulatory/metabolic model. Results We present TIGER, a Toolbox for Integrating Genome-scale Metabolism, Expression, and Regulation. TIGER converts a series of generalized, Boolean or multilevel rules into a set of mixed integer inequalities. The package also includes implementations of existing algorithms to integrate high-throughput expression data with genome-scale models of metabolism and transcriptional regulation. We demonstrate how TIGER automates the coupling of a genome-scale metabolic model with GPR logic and models of transcriptional regulation, thereby serving as a platform for algorithm development and large-scale metabolic analysis. Additionally, we demonstrate how TIGER's algorithms can be used to identify inconsistencies and improve existing models of transcriptional regulation with examples from the reconstructed transcriptional regulatory network of Saccharomyces cerevisiae. Conclusion The TIGER package provides a consistent platform for algorithm development and extending existing genome-scale metabolic models with regulatory networks and high-throughput data.

Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

Energy Technology Data Exchange (ETDEWEB)

Çakır, Tunahan, E-mail: tcakir@gyte.edu.tr [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Khatibipour, Mohammad Jafar [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Department of Chemical Engineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey)

2014-12-03

The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

International Nuclear Information System (INIS)

Çakır, Tunahan; Khatibipour, Mohammad Jafar

2014-01-01

The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

Science.gov (United States)

Dolcos, Sanda; Hu, Yifan; Iordan, Alexandru D; Moore, Matthew; Dolcos, Florin

2016-02-01

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction.

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Dhar, Jesmita; Chakrabarti, Pinak; Saini, Harpreet; Raghava, Gajendra Pal Singh; Kishore, Raghuvansh

2015-02-01

Mimicry of structural motifs is a common feature in proteins. The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. Because of its shape this β-turn mimic is designated as ω-turn, which is found to occur ∼ three times per 100 residues. Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). Based on these angles there are two types of ω-turns, each of which can be further divided into two groups. C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. It is a stable scaffold and may be used in protein engineering and peptide design. © 2014 Wiley Periodicals, Inc.

Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders.

Science.gov (United States)

Yoo, Ji Youn; Kim, Sung Soo

2016-03-18

Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual's quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.

Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders

Directory of Open Access Journals (Sweden)

Ji Youn Yoo

2016-03-01

Full Text Available Metabolic disorders, including type 2 diabetes (T2DM and cardiovascular disease (CVD, present an increasing public health concern and can significantly undermine an individual’s quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity. The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.

Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders

Science.gov (United States)

Yoo, Ji Youn; Kim, Sung Soo

2016-01-01

Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual’s quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area. PMID:26999199

Tool geometry and damage mechanisms influencing CNC turning efficiency of Ti6Al4V

Science.gov (United States)

Suresh, Sangeeth; Hamid, Darulihsan Abdul; Yazid, M. Z. A.; Nasuha, Nurdiyanah; Ain, Siti Nurul

2017-12-01

Ti6Al4V or Grade 5 titanium alloy is widely used in the aerospace, medical, automotive and fabrication industries, due to its distinctive combination of mechanical and physical properties. Ti6Al4V has always been perverse during its machining, strangely due to the same mix of properties mentioned earlier. Ti6Al4V machining has resulted in shorter cutting tool life which has led to objectionable surface integrity and rapid failure of the parts machined. However, the proven functional relevance of this material has prompted extensive research in the optimization of machine parameters and cutting tool characteristics. Cutting tool geometry plays a vital role in ensuring dimensional and geometric accuracy in machined parts. In this study, an experimental investigation is actualized to optimize the nose radius and relief angles of the cutting tools and their interaction to different levels of machining parameters. Low elastic modulus and thermal conductivity of Ti6Al4V contribute to the rapid tool damage. The impact of these properties over the tool tips damage is studied. An experimental design approach is utilized in the CNC turning process of Ti6Al4V to statistically analyze and propose optimum levels of input parameters to lengthen the tool life and enhance surface characteristics of the machined parts. A greater tool nose radius with a straight flank, combined with low feed rates have resulted in a desirable surface integrity. The presence of relief angle has proven to aggravate tool damage and also dimensional instability in the CNC turning of Ti6Al4V.

Fatty acids from diet and microbiota regulate energy metabolism [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Joe Alcock

2015-09-01

Full Text Available A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.

Optimal cutoff points for HOMA-IR and QUICKI in the diagnosis of metabolic syndrome and non-alcoholic fatty liver disease: A population based study.

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Motamed, Nima; Miresmail, Seyed Javad Haji; Rabiee, Behnam; Keyvani, Hossein; Farahani, Behzad; Maadi, Mansooreh; Zamani, Farhad

2016-03-01

The present study was carried out to determine the optimal cutoff points for homeostatic model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) in the diagnosis of metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). The baseline data of 5511 subjects aged ≥18years of a cohort study in northern Iran were utilized to analyze. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory capability of HOMA-IR and QUICKI in the diagnosis of MetS and NAFLD. Youden index was utilized to determine the optimal cutoff points of HOMA-IR and QUICKI in the diagnosis of MetS and NAFLD. The optimal cutoff points for HOMA-IR in the diagnosis of MetS and NAFLD were 2.0 [sensitivity=64.4%, specificity=66.8%] and 1.79 [sensitivity=66.2%, specificity=62.2%] in men and were 2.5 [sensitivity=57.6%, specificity=67.9%] and 1.95 [sensitivity=65.1%, specificity=54.7%] in women respectively. Furthermore, the optimal cutoff points for QUICKI in the diagnosis of MetS and NAFLD were 0.343 [sensitivity=63.7%, specificity=67.8%] and 0.347 [sensitivity=62.9%, specificity=65.0%] in men and were 0.331 [sensitivity=55.7%, specificity=70.7%] and 0.333 [sensitivity=53.2%, specificity=67.7%] in women respectively. Not only the optimal cutoff points of HOMA-IR and QUICKI were different for MetS and NAFLD, but also different cutoff points were obtained for men and women for each of these two conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Beam polarization during a Siberian snake turn-on

International Nuclear Information System (INIS)

Anferov, Vladimir A.

1999-01-01

Installing Siberian snakes in a circular proton accelerator allows one to overcome all spin depolarizing resonances even at very high energies. However, Siberian snake application at low energies is technically rather difficult. Turning snake on at some energy during acceleration would allow using Siberian snakes even in rings with low injection energies. It is shown that the beam polarization would be preserved during the snake ramp, provided that the snake is turned on in more than ten turns, and the energy is set near a half-integer Gγ

Finite-size effect on optimal efficiency of heat engines.

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Tajima, Hiroyasu; Hayashi, Masahito

2017-07-01

The optimal efficiency of quantum (or classical) heat engines whose heat baths are n-particle systems is given by the strong large deviation. We give the optimal work extraction process as a concrete energy-preserving unitary time evolution among the heat baths and the work storage. We show that our optimal work extraction turns the disordered energy of the heat baths to the ordered energy of the work storage, by evaluating the ratio of the entropy difference to the energy difference in the heat baths and the work storage, respectively. By comparing the statistical mechanical optimal efficiency with the macroscopic thermodynamic bound, we evaluate the accuracy of the macroscopic thermodynamics with finite-size heat baths from the statistical mechanical viewpoint. We also evaluate the quantum coherence effect on the optimal efficiency of the cycle processes without restricting their cycle time by comparing the classical and quantum optimal efficiencies.

Emerging health problems among women: Inactivity, obesity, and metabolic syndrome

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Yi-Ju Tsai

2014-02-01

Full Text Available The increase in obesity and metabolic syndrome has been documented worldwide. However, few studies have investigated the risk of inactivity, obesity, and metabolic syndrome specifically in women. Hormone balance plays a crucial role in regulating metabolism and helps to maintain optimal health. It is likely that the sex difference in obesity may be due to the variation in hormone concentration throughout a woman's life, which predisposes them to weight gain. This paper reviews previous literature and discusses factors that influence the risk of adiposity-related health consequences among women for three critical biological transitions throughout a woman's life: puberty, menopause, and pregnancy. To improve quality of life and metabolic health for women, interventions are needed to target women at different transition stages and provide tailored health education programs. Interventions should raise awareness of physical inactivity, obesity, and metabolic syndrome, and promote healthy behavioral change in women.

First turn around strategy for RHIC

International Nuclear Information System (INIS)

Milutinovic, J.; Ruggiero, A.G.

1991-06-01

We present a strategy for achieving the so-called first turn around in RHIC. The strategy is based on the same method we had proposed to correct a distorted closed orbit in RHIC, i.e., on a generalization of the local three-bump method. We found out that the method is very effective in passing the beam through a non-ideal, insufficiently known, machine. We tested that software on ten different Gaussian distributions of dominant orbit distorting lattice imperfections. The perturbed lattice was generated by the code PATRIS, which was also adapted to control the newly developed software. In all of the ten distributions the software was capable of passing the beam through in 2--3 injection attempts, at full sextupole strength. It was also determined that once the beam makes the first turn around and all the correctors are energized, it stays in the machine for at least several hundred turns that we had checked. The quality of the orbit, that was established in this way, was also found to be very good, i.e., the residual distortions at the places of large beta function were much less than one millimeter. With one or two monitors/correctors broken, the software established a first turn around without any extra difficulties. The quality of such orbit was, of course, somewhat degraded, especially around the broken devices. It was also observed that, in the process of actual closing, the beam develops free betatron oscillations in the amplitude range of 1--5 mm, which can be reduced either by changing the injection conditions to better match the actual closed orbit or by an appropriate damping device. The hardware proposed for RHIC is more than sufficient to meet the demands of the first turn controlling software. The maximum kick angle to be applied to the beam would require less than 2/3 of the corrector's top strength even at the top magnetic rigidity Bρ = 850 T·m, which means that the correctors will be performing an easy task at injection

Capturing the essence of a metabolic network: a flux balance analysis approach.

Science.gov (United States)

Murabito, Ettore; Simeonidis, Evangelos; Smallbone, Kieran; Swinton, Jonathan

2009-10-07

As genome-scale metabolic reconstructions emerge, tools to manage their size and complexity will be increasingly important. Flux balance analysis (FBA) is a constraint-based approach widely used to study the metabolic capabilities of cellular or subcellular systems. FBA problems are highly underdetermined and many different phenotypes can satisfy any set of constraints through which the metabolic system is represented. Two of the main concerns in FBA are exploring the space of solutions for a given metabolic network and finding a specific phenotype which is representative for a given task such as maximal growth rate. Here, we introduce a recursive algorithm suitable for overcoming both of these concerns. The method proposed is able to find the alternate optimal patterns of active reactions of an FBA problem and identify the minimal subnetwork able to perform a specific task as optimally as the whole. Our method represents an alternative to and an extension of other approaches conceived for exploring the space of solutions of an FBA problem. It may also be particularly helpful in defining a scaffold of reactions upon which to build up a dynamic model, when the important pathways of the system have not yet been well-defined.

Cogeneration system simulation/optimization

International Nuclear Information System (INIS)

Puppa, B.A.; Chandrashekar, M.

1992-01-01

Companies are increasingly turning to computer software programs to improve and streamline the analysis o cogeneration systems. This paper introduces a computer program which originated with research at the University of Waterloo. The program can simulate and optimize any type of layout of cogeneration plant. An application of the program to a cogeneration feasibility study for a university campus is described. The Steam and Power Plant Optimization System (SAPPOS) is a PC software package which allows users to model any type of steam/power plant on a component-by-component basis. Individual energy/steam balances can be done quickly to model any scenario. A typical days per month cogeneration simulation can also be carried out to provide a detailed monthly cash flow and energy forecast. This paper reports that SAPPOS can be used for scoping, feasibility, and preliminary design work, along with financial studies, gas contract studies, and optimizing the operation of completed plants. In the feasibility study presented, SAPPOS is used to evaluate both diesel engine and gas turbine combined cycle options

Molecular Imaging Of Metabolic Reprogramming In Mutant IDH Cells

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Pavithra eViswanath

2016-03-01

Full Text Available Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70-90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutarate (α-KG. Mutations in the enzyme lead to loss of wild-type enzymatic activity and a neomorphic activity that converts α-KG to 2-hydroxyglutarate (2-HG. In turn, 2-HG, which has been termed an oncometabolite, inhibits key α-KG- dependent enzymes, resulting in alterations of the cellular epigenetic profile and, subsequently, inhibition of differentiation and initiation of tumorigenesis. In addition, it is now clear that the IDH mutation also induces a broad metabolic reprogramming that extends beyond 2-HG production, and this reprogramming often differs from what has been previously reported in other cancer types. In this review we will discuss in detail what is known to date about the metabolic reprogramming of mutant IDH cells and how this reprogramming has been investigated using molecular metabolic imaging. We will describe how metabolic imaging has helped shed light on the basic biology of mutant IDH cells and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor mutant IDH tumors in vivo.

Medium dependent dual turn on/turn off fluorescence sensing for Cu2 + ions using AMI/SDS assemblies

Science.gov (United States)

Gujar, Varsha B.; Ottoor, Divya

2017-02-01

Behavior of Amiloride (AMI) as a metal ion sensor in anionic surfactant assemblies of varying concentrations at different pH is depicted in this work. From a non-sensor fluorophore, AMI has been transformed in to a tunable fluorosensor for Cu2 + ions in various SDS concentrations. At premicellar concentration of SDS, ion-pair complex is expected to be formed between AMI and SDS due to electrostatic interactions between them. However at CMC concentrations of SDS, fluorescence intensity of AMI is greatly enhanced with red shift in emission, due to the incorporation of AMI molecule in the hydrophobic micellar interface. The behavior of metal sensing by AMI-SDS assemblies gives rise to several interesting observations. Micellation of SDS has been greatly enhanced by increasing copper ion concentrations, as these counter ions screens the charge on monomers of SDS which lead to the aggregation at premicellar concentrations only. Concentrations and pH dependent discrete trends of interactions between SDS-AMI and SDS-Cu2 + ions, have given tunable fluorescence responses (fluorescence turn on/turn off) of AMI for added Cu2 + ions. The electrostatic interaction between the metal cations and the anionic surfactants is the driving force for bringing the metal ions near to the vicinity of micelle where AMI resides. Thus, a comprehensive understanding of the mechanism related to the 'turn on-turn off' fluorescence response of AMI with respect to pH and SDS concentration for effective Cu2 + ion sensing is illustrated in this work.

Nutrition and the science of disease prevention: a systems approach to support metabolic health

Science.gov (United States)

Bennett, Brian J.; Hall, Kevin D.; Hu, Frank B.; McCartney, Anne L.; Roberto, Christina

2017-01-01

Progress in nutritional science, genetics, computer science, and behavioral economics can be leveraged to address the challenge of noncommunicable disease. This report highlights the connection between nutrition and the complex science of preventing disease and discusses the promotion of optimal metabolic health, building on input from several complementary disciplines. The discussion focuses on (1) the basic science of optimal metabolic health, including data from gene–diet interactions, microbiome, and epidemiological research in nutrition, with the goal of defining better targets and interventions, and (2) how nutrition, from pharma to lifestyle, can build on systems science to address complex issues. PMID:26415028

Reconceptualizing Autonomy: A Relational Turn in Bioethics.

Science.gov (United States)

Jennings, Bruce

2016-05-01

History's judgment on the success of bioethics will not depend solely on the conceptual creativity and innovation in the field at the level of ethical and political theory, but this intellectual work is not insignificant. One important new development is what I shall refer to as the relational turn in bioethics. This development represents a renewed emphasis on the ideographic approach, which interprets the meaning of right and wrong in human actions as they are inscribed in social and cultural practices and in structures of lived meaning and interdependence; in an ideographic approach, the task of bioethics is to bring practice into theory, not the other way around. The relational turn in bioethics may profoundly affect the critical questions that the field asks and the ethical guidance it offers society, politics, and policy. The relational turn provides a way of correcting the excessive atomism of many individualistic perspectives that have been, and continue to be, influential in bioethics. Nonetheless, I would argue that most of the work reflecting the relational turn remains distinctively liberal in its respect for the ethical significance of the human individual. It moves away from individualism, but not from the value of individuality.In this review essay, I shall focus on how the relational turn has manifested itself in work on core concepts in bioethics, especially liberty and autonomy. Following a general review, I conclude with a brief consideration of two important recent books in this area: Jennifer Nedelsky's Law's Relations and Rachel Haliburton's Autonomy and the Situated Self. © 2016 The Hastings Center.

Optimally frugal foraging

Science.gov (United States)

Bénichou, O.; Bhat, U.; Krapivsky, P. L.; Redner, S.

2018-02-01

We introduce the frugal foraging model in which a forager performs a discrete-time random walk on a lattice in which each site initially contains S food units. The forager metabolizes one unit of food at each step and starves to death when it last ate S steps in the past. Whenever the forager eats, it consumes all food at its current site and this site remains empty forever (no food replenishment). The crucial property of the forager is that it is frugal and eats only when encountering food within at most k steps of starvation. We compute the average lifetime analytically as a function of the frugality threshold and show that there exists an optimal strategy, namely, an optimal frugality threshold k* that maximizes the forager lifetime.

Simulation of turn-by-turn passage of protons through the H-minus stripping foil in booster

Energy Technology Data Exchange (ETDEWEB)

Gardner, C. [Brookhaven National Lab. (BNL), Upton, NY (United States)

2017-07-06

Equations for transverse emittance growth due to multiple passes of circulating proton beam through the H-minus stripping foil in Booster were developed in [1]. These were based on simple principles of statistics and simple assumptions about the initial distribution of particles incident on the foil. It was assumed there that the foil dimensions and position of the incoming beam are such that all particles hit the foil on every turn around the machine. In the present note we assume only that all incoming H-minus ions from Linac hit the foil and are stripped of their electrons. The resulting protons circulate indefinitely around the machine. Setups in which the foil width is reduced so that not all protons hit the foil on every turn are studied here by simulation. The aim is to determine the effectiveness of such setups in reducing the emittance growth of circulating proton beam during the injection of H-minus beam. The simulations also serve as a check of the equations developed in [1], and vice versa. The particulars of the simulation setup are given in Sections 1 through 11. Figures 1 through 12 show simulation results for the case in which all particles hit the foil on every turn. The results are in good agreement with those obtained from the equations of reference [1]. Figures 13 through 19 show simulation results for various setups in which the foil width is reduced. These results are summarized in Section 12. In all gures the horizontal axis gives the turn number. The unit of the vertical axis is micrometers ( m) in all plots of emittance.

Multi-turn multi-gap transmission line resonators - Concept, design and first implementation at 4.7T and 7T.

Science.gov (United States)

Frass-Kriegl, Roberta; Laistler, Elmar; Hosseinnezhadian, Sajad; Schmid, Albrecht Ingo; Moser, Ewald; Poirier-Quinot, Marie; Darrasse, Luc; Ginefri, Jean-Christophe

2016-12-01

A novel design scheme for monolithic transmission line resonators (TLRs) is presented - the multi-turn multi-gap TLR (MTMG-TLR) design. The MTMG-TLR design enables the construction of TLRs with multiple turns and multiple gaps. This presents an additional degree of freedom in tuning self-resonant TLRs, as their resonance frequency is fully determined by the coil geometry (e.g. diameter, number of turns, conductor width, etc.). The novel design is evaluated at 4.7T and 7T by simulations and experiments, where it is demonstrated that MTMG-TLRs can be used for MRI, and that the B 1 distribution of MTMG-TLRs strongly depends on the number and distribution of turns. A comparison to conventional loop coils revealed that the B 1 performance of MTMG-TLRs is comparable to a loop coil with the same mean diameter; however, lower 10g SAR values were found for MTMG-TLRs. The MTMG-TLR design is expected to bring most benefits at high static field, where it allows for independent size and frequency selection, which cannot be achieved with standard TLR design. However, it also enables more accurate geometric optimization at low static field. Thereby, the MTMG-TLR design preserves the intrinsic advantages of TLRs, i.e. mechanical flexibility, high SAR efficiency, mass production, and coil miniaturization. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The ontological turn meets the certainty of death.

Science.gov (United States)

McDonald, Maryon

2017-08-01

The 'ontological turn' involves some anthropological points of long standing but the approaches recently coordinated into this turn have been presented as a 'call to arms', as shaking up 'mono-realist singularities' and as inherently political. This fighting talk has no doubt made important contributions to anthropology and insights from the ontological turn can help in anthropological understandings of medical practices. However, this paper contends that this helpfulness is also limited and that a call to arms may be inappropriate. This point is made through an ethnographic understanding of medical concern about the diagnosis of death.

Effects of Metformin on the Cerebral Metabolic Changes in Type 2 Diabetic Patients

Directory of Open Access Journals (Sweden)

Yung-Cheng Huang

2014-01-01

Full Text Available Metformin, a widely used antidiabetic drug, has numerous effects on human metabolism. Based on emerging cellular, animal, and epidemiological studies, we hypothesized that metformin leads to cerebral metabolic changes in diabetic patients. To explore metabolism-influenced foci of brain, we used 2-deoxy-2-[18F]fluoro-D-glucose (FDG positron emission tomography for type 2 diabetic patients taking metformin (MET, n=18, withdrawing from metformin (wdMET, n=13, and not taking metformin (noMET, n=9. Compared with the noMET group, statistical parametric mapping showed that the MET group had clusters with significantly higher metabolism in right temporal, right frontal, and left occipital lobe white matter and lower metabolism in the left parahippocampal gyrus, left fusiform gyrus, and ventromedial prefrontal cortex. In volume of interest (VOI- based group comparisons, the normalized FDG uptake values of both hypermetabolic and hypometabolic clusters were significantly different between groups. The VOI-based correlation analysis across the MET and wdMET groups showed a significant negative correlation between normalized FDG uptake values of hypermetabolic clusters and metformin withdrawal durations and a positive but nonsignificant correlation in the turn of hypometabolic clusters. Conclusively, metformin affects cerebral metabolism in some white matter and semantic memory related sites in patients with type 2 diabetes.

Postural hemodynamic changes after turning to prone position

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Микола Віталійович Лизогуб

2015-03-01

Full Text Available Background of study. Prone position is one of the most complex positions for anesthesiologist as it is accompanied by several physiological changes that can lead to specific complications. Hemodynamic changes are most controversial.Aim of study was to establish hemodynamic changes in non-anaesthetized patients in prone position depending on body mass index.Material and methods. We examined central hemodynamics in 40 patients the day before surgery using thoracic rheography in supine position, in prone position 5 min after turning and in prone position 20 min after turning. Patients were divided into 2 groups according to body mass index (18-25 and 26-35.Results. Patients with normal body weight did not have any hemodynamic changes after turning to prone position. Patients with increased body weight had higher cardiac index. After turning to prone position obese patients’ cardiac output and cardiac index reduced 22% comparing with supine position. After 20 min in prone position these hemodynamic parameters were found to be reduced to the same level.Conclusion. Significant hemodynamic changes after turning from supine to prone position were revealed only in patients with increased body mass index. In these patients cardiac index in prone position was reduced by 22% comparing to supine position

Accessing autonomic function can early screen metabolic syndrome.

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Kan Sun

Full Text Available BACKGROUND: Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend <0.0001. Moreover, EZSCAN value was associated with an increase in the number of metabolic syndrome components (p for trend <0.0001. Compared with the no risk group (EZSCAN value 0-24, participants at the high risk group (EZSCAN value: 50-100 had a 2.35 fold increased risk of prevalent metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61-0.64 for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. CONCLUSIONS AND SIGNIFICANCE: In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome.

1.06 μm 150 psec laser damage study of diamond turned, diamond turned/polished and polished metal mirrors

International Nuclear Information System (INIS)

Saito, T.T.; Milam, D.; Baker, P.; Murphy, G.

1975-01-01

Using a well characterized 1.06 μm 150 ps glass laser pulse the damage characteristics for diamond turned, diamond turned/ polished, and polished copper and silver mirrors less than 5 cm diameter were studied. Although most samples were tested with a normal angle of incidence, some were tested at 45 0 with different linear polarization showing an increase in damage threshold for S polarization. Different damage mechanisms observed will be discussed. Laser damage is related to residual surface influences of the fabrication process. First attempts to polish diamond turned surfaces resulted in a significant decrease in laser damage threshold. The importance of including the heat of fusion in the one dimensional heat analysis of the theoretical damage threshold and how close the samples came to the theoretical damage threshold is discussed. (auth)

Turning around Newton's Second Law

Science.gov (United States)

Goff, John Eric

2004-01-01

Conceptual and quantitative difficulties surrounding Newton's second law often arise among introductory physics students. Simply turning around how one expresses Newton's second law may assist students in their understanding of a deceptively simple-looking equation.

OptFlux: an open-source software platform for in silico metabolic engineering.

Science.gov (United States)

Rocha, Isabel; Maia, Paulo; Evangelista, Pedro; Vilaça, Paulo; Soares, Simão; Pinto, José P; Nielsen, Jens; Patil, Kiran R; Ferreira, Eugénio C; Rocha, Miguel

2010-04-19

Over the last few years a number of methods have been proposed for the phenotype simulation of microorganisms under different environmental and genetic conditions. These have been used as the basis to support the discovery of successful genetic modifications of the microbial metabolism to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications. OptFlux is an open-source and modular software aimed at being the reference computational application in the field. It is the first tool to incorporate strain optimization tasks, i.e., the identification of Metabolic Engineering targets, using Evolutionary Algorithms/Simulated Annealing metaheuristics or the previously proposed OptKnock algorithm. It also allows the use of stoichiometric metabolic models for (i) phenotype simulation of both wild-type and mutant organisms, using the methods of Flux Balance Analysis, Minimization of Metabolic Adjustment or Regulatory on/off Minimization of Metabolic flux changes, (ii) Metabolic Flux Analysis, computing the admissible flux space given a set of measured fluxes, and (iii) pathway analysis through the calculation of Elementary Flux Modes. OptFlux also contemplates several methods for model simplification and other pre-processing operations aimed at reducing the search space for optimization algorithms. The software supports importing/exporting to several flat file formats and it is compatible with the SBML standard. OptFlux has a visualization module that allows the analysis of the model structure that is compatible with the layout information of Cell Designer, allowing the superimposition of simulation results with the model graph. The OptFlux software is freely available, together with documentation and other resources, thus bridging the gap from research in strain optimization

Alternative Fuels Data Center: Central Ohio Turns Trash Into Natural Gas

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Central Ohio Turns Trash Into Natural Gas to someone by E-mail Share Alternative Fuels Data Center : Central Ohio Turns Trash Into Natural Gas on Facebook Tweet about Alternative Fuels Data Center: Central Ohio Turns Trash Into Natural Gas on Twitter Bookmark Alternative Fuels Data Center: Central Ohio Turns

Multi-objective experimental design for (13)C-based metabolic flux analysis.

Science.gov (United States)

Bouvin, Jeroen; Cajot, Simon; D'Huys, Pieter-Jan; Ampofo-Asiama, Jerry; Anné, Jozef; Van Impe, Jan; Geeraerd, Annemie; Bernaerts, Kristel

2015-10-01

(13)C-based metabolic flux analysis is an excellent technique to resolve fluxes in the central carbon metabolism but costs can be significant when using specialized tracers. This work presents a framework for cost-effective design of (13)C-tracer experiments, illustrated on two different networks. Linear and non-linear optimal input mixtures are computed for networks for Streptomyces lividans and a carcinoma cell line. If only glucose tracers are considered as labeled substrate for a carcinoma cell line or S. lividans, the best parameter estimation accuracy is obtained by mixtures containing high amounts of 1,2-(13)C2 glucose combined with uniformly labeled glucose. Experimental designs are evaluated based on a linear (D-criterion) and non-linear approach (S-criterion). Both approaches generate almost the same input mixture, however, the linear approach is favored due to its low computational effort. The high amount of 1,2-(13)C2 glucose in the optimal designs coincides with a high experimental cost, which is further enhanced when labeling is introduced in glutamine and aspartate tracers. Multi-objective optimization gives the possibility to assess experimental quality and cost at the same time and can reveal excellent compromise experiments. For example, the combination of 100% 1,2-(13)C2 glucose with 100% position one labeled glutamine and the combination of 100% 1,2-(13)C2 glucose with 100% uniformly labeled glutamine perform equally well for the carcinoma cell line, but the first mixture offers a decrease in cost of $ 120 per ml-scale cell culture experiment. We demonstrated the validity of a multi-objective linear approach to perform optimal experimental designs for the non-linear problem of (13)C-metabolic flux analysis. Tools and a workflow are provided to perform multi-objective design. The effortless calculation of the D-criterion can be exploited to perform high-throughput screening of possible (13)C-tracers, while the illustrated benefit of multi

INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division

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Graeme J. Gowans

2018-01-01

Full Text Available Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC. Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC1-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin to restrict proliferation to metabolically optimal states.

Role of innate lymphoid cells in obesity and metabolic disease

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Saetang, Jirakrit; Sangkhathat, Surasak

2018-01-01

The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853

Systems genetics of metabolism: the use of the BXD murine reference panel for multiscalar integration of traits

NARCIS (Netherlands)

Andreux, Pénélope A.; Williams, Evan G.; Koutnikova, Hana; Houtkooper, Riekelt H.; Champy, Marie-France; Henry, Hugues; Schoonjans, Kristina; Williams, Robert W.; Auwerx, Johan

2012-01-01

Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the

Optimization of catalytic glycerol steam reforming to light olefins using Cu/ZSM-5 catalyst

International Nuclear Information System (INIS)

Zakaria, Z.Y.; Amin, N.A.S.; Linnekoski, J.

2014-01-01

Highlights: • Glycerol steam reforming to light olefin using Cu/ZSM-5 process was optimized. • Response surface methodology and multi-objective genetic algorithm were employed. • Second order polynomial model produced adequately fitted experimental data. • Thermodynamic study inferred high temperature requirement for ethylene formation. • Turn-over-frequency at optimized responses is higher than the non-optimized process. - Abstract: Response surface methodology (RSM) and multi-objective genetic algorithm was employed to optimize the process parameters for catalytic conversion of glycerol, a byproduct from biodiesel production, to light olefins using Cu/ZSM-5 catalyst. The effects of operating temperature, weight hourly space velocity (WHSV) and glycerol concentration on light olefins selectivity and yield were observed. Experimental results revealed the data adequately fitted into a second-order polynomial model. The linear temperature and quadratic WHSV terms gave significant effect on both responses. Optimization of both the responses indicated that temperature favouring high light olefin formation lied beyond the experimental design range. The trend in the temperature profile concurred commensurately with the thermodynamic analysis. Multi-objective genetic algorithm was performed to attain a single set of processing parameters that could produce both the highest light olefin selectivity and yield. The turn-over-frequency (TOF) of the optimized responses demonstrated a slightly higher value than the one which was not optimized. Combination of RSM, multi-objective response and thermodynamic is useful to determine the process optimal operating conditions for industrial applications

Engineering tolerance to industrially relevant stress factors in yeast cell factories.

Science.gov (United States)

Deparis, Quinten; Claes, Arne; Foulquié-Moreno, Maria R; Thevelein, Johan M

2017-06-01

The main focus in development of yeast cell factories has generally been on establishing optimal activity of heterologous pathways and further metabolic engineering of the host strain to maximize product yield and titer. Adequate stress tolerance of the host strain has turned out to be another major challenge for obtaining economically viable performance in industrial production. Although general robustness is a universal requirement for industrial microorganisms, production of novel compounds using artificial metabolic pathways presents additional challenges. Many of the bio-based compounds desirable for production by cell factories are highly toxic to the host cells in the titers required for economic viability. Artificial metabolic pathways also turn out to be much more sensitive to stress factors than endogenous pathways, likely because regulation of the latter has been optimized in evolution in myriads of environmental conditions. We discuss different environmental and metabolic stress factors with high relevance for industrial utilization of yeast cell factories and the experimental approaches used to engineer higher stress tolerance. Improving stress tolerance in a predictable manner in yeast cell factories should facilitate their widespread utilization in the bio-based economy and extend the range of products successfully produced in large scale in a sustainable and economically profitable way. © FEMS 2017.

Engineering tolerance to industrially relevant stress factors in yeast cell factories

Science.gov (United States)

Deparis, Quinten; Claes, Arne; Foulquié-Moreno, Maria R.

2017-01-01

Abstract The main focus in development of yeast cell factories has generally been on establishing optimal activity of heterologous pathways and further metabolic engineering of the host strain to maximize product yield and titer. Adequate stress tolerance of the host strain has turned out to be another major challenge for obtaining economically viable performance in industrial production. Although general robustness is a universal requirement for industrial microorganisms, production of novel compounds using artificial metabolic pathways presents additional challenges. Many of the bio-based compounds desirable for production by cell factories are highly toxic to the host cells in the titers required for economic viability. Artificial metabolic pathways also turn out to be much more sensitive to stress factors than endogenous pathways, likely because regulation of the latter has been optimized in evolution in myriads of environmental conditions. We discuss different environmental and metabolic stress factors with high relevance for industrial utilization of yeast cell factories and the experimental approaches used to engineer higher stress tolerance. Improving stress tolerance in a predictable manner in yeast cell factories should facilitate their widespread utilization in the bio-based economy and extend the range of products successfully produced in large scale in a sustainable and economically profitable way. PMID:28586408

1H NMR spectroscopy-based interventional metabolic phenotyping

DEFF Research Database (Denmark)

Lauridsen, Michael B; Bliddal, Henning; Christensen, Robin

2010-01-01

1H NMR spectroscopy-based metabolic phenotyping was used to identify biomarkers in the plasma of patients with rheumatoid arthritis (RA). Forty-seven patients with RA (23 with active disease at baseline and 24 in remission) and 51 healthy subjects were evaluated during a one-year follow-up with a......1H NMR spectroscopy-based metabolic phenotyping was used to identify biomarkers in the plasma of patients with rheumatoid arthritis (RA). Forty-seven patients with RA (23 with active disease at baseline and 24 in remission) and 51 healthy subjects were evaluated during a one-year follow......-up with assessments of disease activity (DAS-28) and 1H NMR spectroscopy of plasma samples. Discriminant analysis provided evidence that the metabolic profiles predicted disease severity. Cholesterol, lactate, acetylated glycoprotein, and lipid signatures were found to be candidate biomarkers for disease severity.......0007). However, after 31 days of optimized therapy, the two patient groups were not significantly different (P=0.91). The metabolic profiles of both groups of RA patients were different from the healthy subjects. 1H NMR-based metabolic phenotyping of plasma samples in patients with RA is well suited...

Dietary carbohydrates and triacylglycerol metabolism.

Science.gov (United States)

Roche, H M

1999-02-01

There is a growing body of scientific evidence which demonstrates that plasma triacylglycerol (TAG) concentration, especially in the postprandial state, is an important risk factor in relation to the development of CHD. Postprandial hypertriacylglycerolaemia is associated with a number of adverse metabolic risk factors, including the preponderance of small dense LDL, low HDL-cholesterol concentrations and elevated factor VII activity. Traditionally, a low-fat high-carbohydrate diet was used to prevent CHD because it effectively reduces plasma cholesterol concentrations, but this dietary regimen increases plasma TAG concentrations and reduces HDL-cholesterol concentrations. There is substantial epidemiological evidence which demonstrates that high plasma TAG and low plasma HDL concentrations are associated with an increased risk of CHD. Thus, there is reason for concern that the adverse effects of low-fat high-carbohydrate diets on TAG and HDL may counteract or negate the beneficial effect of reducing LDL-cholesterol concentrations. Although there have been no prospective studies to investigate whether reduced fat intake has an adverse effect on CHD, there is strong epidemiological evidence that reducing total fat intake is not protective against CHD. On the other hand, high-fat diets predispose to obesity, and central obesity adversely affects TAG metabolism. There is substantial evidence that in free-living situations low-fat high-carbohydrate diets lead to weight loss, which in turn will correct insulin resistance and plasma TAG metabolism. Clearly there is a need for prospective studies to resolve the issue as to whether low-fat high-carbohydrate diets play an adverse or beneficial role in relation to the development of CHD.

A Metabolic Race

Directory of Open Access Journals (Sweden)

A.M.S. Costa et al.

2017-07-01

Full Text Available Metabolic Syndrome describes a set of metabolic risk factors that manifest in an individual and some aspects contribute to its appearance: genetic, overweight and the absence of physical activity. So, a board game was created to simulate the environment and routine experienced by UFF students that could contribute  to the development of Metabolic Syndrome. Players move along a simplified map of Niterói city, where places as Antônio Pedro Hospital (HUAP are pointed out. OBJECTIVES: This project aimed to develop an educational game to consolidate Metabolic Syndrome biochemical events. MATERIAL E METHODS: Each group receives a board, pins, dice, question, challenge and diagnostics cards. One student performs the family doctor function, responsable for delivering cards, reading activities and providing diagnosis to players when game is over.The scoring system is based on 3 criteria for Metabolic Syndrome diagnosis: glycemia, abdominal obesity and HDL cholesterol. At the end of game, it is possible to calculate the rates of each player and provide proportional diagnosis. The winner is the healthiest that first arrives at HUAP. RESULTS AND DISCUSSION: The game was applied to 50 students and only 10% classified the subject-matter as difficult. This finding highlight the need to establish new methods to enhance the teaching and learning process and decrease the students’ dificulties. Students evaluated the game as an important educational support and 85% of them agreed it complements  and consolidate the content discussed in classroom. Finally, the game was very highly rated by students according to their perception about their own performance while playing.  In addition, 95 % students pointed they would play again and 98% said they think games are able to optimize learning. CONCLUSIONS: It was possible not only to approximate biochemical phenomena to the students’ daily life, but also to solidify the theoretical concepts in a dynamic and fun

History of Education in Canada: Historiographic "Turns" and Widening Horizons

Science.gov (United States)

Bruno-Jofré, Rosa

2014-01-01

This paper explores major historiographic "turns" in history of education with a focus, although not exclusively, on English-speaking Canada. It addresses the transformative intellectual impact of the turn toward social history on the history of education, the impact of cultural history and the linguistic turn, the reception of Michel…

Turn-taking cue delays in human-robot communication

NARCIS (Netherlands)

Cuijpers, R. H.; Van Den Goor, V. J.P.

2017-01-01

Fluent communication between a human and a robot relies on the use of effective turn-taking cues. In human speech staying silent after a sequence of utterances is usually accompanied by an explicit turnyielding cue to signal the end of a turn. Here we study the effect of the timing of four

Human Rights Education and the Post Secular Turn

Science.gov (United States)

Bowie, Bob

2012-01-01

This article questions whether human rights education (HRE) scholarship is responding adequately to the post secular turn in thinking about the place and nature of religion in society. Here the post secular turn is used to describe the discrediting of secularisation theory, the recognition of religion as an enduring and pervasive global cultural…

Model-independent analysis of the Fermilab Tevatron turn-by-turn beam position monitor measurements

Science.gov (United States)

Petrenko, A. V.; Valishev, A. A.; Lebedev, V. A.

2011-09-01

Coherent transverse beam oscillations in the Tevatron were analyzed with the model-independent analysis (MIA) technique. This allowed one to obtain the model-independent values of coupled betatron amplitudes, phase advances, and dispersion function around the ring from a single dipole kick measurement. In order to solve the MIA mode mixing problem which limits the accuracy of determination of the optical functions, we have developed a new technique of rotational MIA mode untangling. The basic idea is to treat each beam position monitor (BPM) as two BPMs separated in a ring by exactly one turn. This leads to a simple criterion of MIA mode separation: the betatron phase advance between any BPM and its counterpart shifted by one turn should be equal to the betatron tune and therefore should not depend on the BPM position in the ring. Furthermore, we describe a MIA-based technique to locate vibrating magnets in a storage ring.

Model-independent analysis of the Fermilab Tevatron turn-by-turn beam position monitor measurements

Directory of Open Access Journals (Sweden)

A. V. Petrenko

2011-09-01

Full Text Available Coherent transverse beam oscillations in the Tevatron were analyzed with the model-independent analysis (MIA technique. This allowed one to obtain the model-independent values of coupled betatron amplitudes, phase advances, and dispersion function around the ring from a single dipole kick measurement. In order to solve the MIA mode mixing problem which limits the accuracy of determination of the optical functions, we have developed a new technique of rotational MIA mode untangling. The basic idea is to treat each beam position monitor (BPM as two BPMs separated in a ring by exactly one turn. This leads to a simple criterion of MIA mode separation: the betatron phase advance between any BPM and its counterpart shifted by one turn should be equal to the betatron tune and therefore should not depend on the BPM position in the ring. Furthermore, we describe a MIA-based technique to locate vibrating magnets in a storage ring.

Metabolic engineering of Ustilago trichophora TZ1 for improved malic acid production

Directory of Open Access Journals (Sweden)

Thiemo Zambanini

2017-06-01

These results open up a wide range of possibilities for further optimization, especially combinatorial metabolic engineering to increase the flux from pyruvate to malic acid and to reduce by-product formation.

Compensations for increased rotational inertia during human cutting turns.

Science.gov (United States)

Qiao, Mu; Brown, Brian; Jindrich, Devin L

2014-02-01

Locomotion in a complex environment is often not steady state, but unsteady locomotion (stability and maneuverability) is not well understood. We investigated the strategies used by humans to perform sidestep cutting turns when running. Previous studies have argued that because humans have small yaw rotational moments of inertia relative to body mass, deceleratory forces in the initial velocity direction that occur during the turning step, or 'braking' forces, could function to prevent body over-rotation during turns. We tested this hypothesis by increasing body rotational inertia and testing whether braking forces during stance decreased. We recorded ground reaction force and body kinematics from seven participants performing 45 deg sidestep cutting turns and straight running at five levels of body rotational inertia, with increases up to fourfold. Contrary to our prediction, braking forces remained consistent at different rotational inertias, facilitated by anticipatory changes to body rotational speed. Increasing inertia revealed that the opposing effects of several turning parameters, including rotation due to symmetrical anterior-posterior forces, result in a system that can compensate for fourfold changes in rotational inertia with less than 50% changes to rotational velocity. These results suggest that in submaximal effort turning, legged systems may be robust to changes in morphological parameters, and that compensations can involve relatively minor adjustments between steps to change initial stance conditions.

[Optimal energy supply in different age groups of critically ill children on mechanical ventilation].

Science.gov (United States)

Li, X H; Ji, J; Qian, S Y

2018-01-02

Objective: To analyze the resting energy expenditure and optimal energy supply in different age groups of critically ill children on mechanical ventilation in pediatric intensive care unit (PICU). Methods: Patients on mechanical ventilation hospitalized in PICU of Beijing Children's Hospital from March 2015 to March 2016 were enrolled prospectively. Resting energy expenditure of patients was calculated by US Med Graphic company critical care management (CCM) energy metabolism test system after mechanical ventilation. Patients were divided into three groups:10 years. The relationship between the measured and predictive resting energy expenditure was analyzed with correlation analysis; while the metabolism status and the optimal energy supply in different age groups were analyzed with chi square test and variance analysis. Results: A total of 102 patients were enrolled, the measured resting energy expenditure all correlated with predictive resting energy expenditure in different age groups (10 years ( r= 0.5, P= 0.0) ) . A total of 40 cases in group, including: 14 cases of low metabolism (35%), 14 cases of normal metabolism (35%), and 12 cases of high metabolism (30%); 45 cases in 3-10 years group, including: 22 cases of low metabolism (49%), 19 cases of normal metabolism (42%), 4 cases of high metabolism (9%); 17 cases in > 10 years group, including: 12 cases of low metabolism (71%), 4 cases of normal metabolism (23%), 1 case of high metabolism (6%). Metabolism status showed significant differences between different age groups ( χ (2)=11.30, P age groups ( F= 46.57, Pgroup, (184±53) kJ/ (kg⋅d) in 3-10 years group, and (120±30) kJ/ (kg⋅d) in > 10 years group. Conclusion: The resting energy metabolism of the critically ill children on mechanical ventilation is negatively related to the age. The actual energy requirement should be calculated according to different ages.

ANN-PSO Integrated Optimization Methodology for Intelligent Control of MMC Machining

Science.gov (United States)

Chandrasekaran, Muthumari; Tamang, Santosh

2017-08-01

Metal Matrix Composites (MMC) show improved properties in comparison with non-reinforced alloys and have found increased application in automotive and aerospace industries. The selection of optimum machining parameters to produce components of desired surface roughness is of great concern considering the quality and economy of manufacturing process. In this study, a surface roughness prediction model for turning Al-SiCp MMC is developed using Artificial Neural Network (ANN). Three turning parameters viz., spindle speed ( N), feed rate ( f) and depth of cut ( d) were considered as input neurons and surface roughness was an output neuron. ANN architecture having 3 -5 -1 is found to be optimum and the model predicts with an average percentage error of 7.72 %. Particle Swarm Optimization (PSO) technique is used for optimizing parameters to minimize machining time. The innovative aspect of this work is the development of an integrated ANN-PSO optimization method for intelligent control of MMC machining process applicable to manufacturing industries. The robustness of the method shows its superiority for obtaining optimum cutting parameters satisfying desired surface roughness. The method has better convergent capability with minimum number of iterations.

Characterization of jellyfish turning using 3D-PTV

Science.gov (United States)

Xu, Nicole; Dabiri, John

2017-11-01

Aurelia aurita are oblate, radially symmetric jellyfish that consist of a gelatinous bell and subumbrellar muscle ring, which contracts to provide motive force. Swimming is typically modeled as a purely vertical motion; however, asymmetric activations of swim pacemakers (sensory organs that innervate the muscle at eight locations around the bell margin) result in turning and more complicated swim behaviors. More recent studies have examined flow fields around turning jellyfish, but the input/output relationship between locomotive controls and swim trajectories is unclear. To address this, bell kinematics for both straight swimming and turning are obtained using 3D particle tracking velocimetry (3D-PTV) by injecting biocompatible elastomer tags into the bell, illuminating the tank with ultraviolet light, and tracking the resulting fluorescent particles in a multi-camera setup. By understanding these kinematics in both natural and externally controlled free-swimming animals, we can connect neuromuscular control mechanisms to existing flow measurements of jellyfish turning for applications in designing more energy efficient biohybrid robots and underwater vehicles. NSF GRFP.

Zigzag turning preference of freely crawling cells.

Directory of Open Access Journals (Sweden)

Taeseok Daniel Yang

Full Text Available The coordinated motion of a cell is fundamental to many important biological processes such as development, wound healing, and phagocytosis. For eukaryotic cells, such as amoebae or animal cells, the cell motility is based on crawling and involves a complex set of internal biochemical events. A recent study reported very interesting crawling behavior of single cell amoeba: in the absence of an external cue, free amoebae move randomly with a noisy, yet, discernible sequence of 'run-and-turns' analogous to the 'run-and-tumbles' of swimming bacteria. Interestingly, amoeboid trajectories favor zigzag turns. In other words, the cells bias their crawling by making a turn in the opposite direction to a previous turn. This property enhances the long range directional persistence of the moving trajectories. This study proposes that such a zigzag crawling behavior can be a general property of any crawling cells by demonstrating that 1 microglia, which are the immune cells of the brain, and 2 a simple rule-based model cell, which incorporates the actual biochemistry and mechanics behind cell crawling, both exhibit similar type of crawling behavior. Almost all legged animals walk by alternating their feet. Similarly, all crawling cells appear to move forward by alternating the direction of their movement, even though the regularity and degree of zigzag preference vary from one type to the other.

Effects of turning and through lane sharing on traffic performance at intersections

Science.gov (United States)

Li, Xiang; Sun, Jian-Qiao

2016-02-01

Turning vehicles strongly influence traffic flows at intersections. Effective regulation of turning vehicles is important to achieve better traffic performance. This paper studies the impact of lane sharing and turning signals on traffic performance at intersections by using cellular automata. Both right-turn and left-turn lane sharing are studied. Interactions between vehicles and pedestrians are considered. The transportation efficiency, road safety and energy economy are the traffic performance metrics. Extensive simulations are carried out to study the traffic performance indices. It is observed that shared turning lanes and permissive left-turn signal improve the transportation efficiency and reduce the fuel consumption in most cases, but the safety is usually sacrificed. It is not always beneficial for the through vehicles when they are allowed to be in the turning lanes.

Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.

Science.gov (United States)

Thai, Minh; Graham, Nicholas A; Braas, Daniel; Nehil, Michael; Komisopoulou, Evangelia; Kurdistani, Siavash K; McCormick, Frank; Graeber, Thomas G; Christofk, Heather R

2014-04-01

Virus infections trigger metabolic changes in host cells that support the bioenergetic and biosynthetic demands of viral replication. Although recent studies have characterized virus-induced changes in host cell metabolism (Munger et al., 2008; Terry et al., 2012), the molecular mechanisms by which viruses reprogram cellular metabolism have remained elusive. Here, we show that the gene product of adenovirus E4ORF1 is necessary for adenovirus-induced upregulation of host cell glucose metabolism and sufficient to promote enhanced glycolysis in cultured epithelial cells by activation of MYC. E4ORF1 localizes to the nucleus, binds to MYC, and enhances MYC binding to glycolytic target genes, resulting in elevated expression of specific glycolytic enzymes. E4ORF1 activation of MYC promotes increased nucleotide biosynthesis from glucose intermediates and enables optimal adenovirus replication in primary lung epithelial cells. Our findings show how a viral protein exploits host cell machinery to reprogram cellular metabolism and promote optimal progeny virion generation. Copyright © 2014 Elsevier Inc. All rights reserved.

In silico optimization of critical currents in superconductors

Energy Technology Data Exchange (ETDEWEB)

Kimmel, Gregory; Sadovskyy, Ivan A.; Glatz, Andreas

2017-07-01

For many technological applications of superconductors the performance of a material is determined by the highest current it can carry losslessly-the critical current. In turn, the critical current can be controlled by adding nonsuperconducting defects in the superconductor matrix. Here we report on systematic comparison of different local and global optimization strategies to predict optimal structures of pinning centers leading to the highest possible critical currents. We demonstrate performance of these methods for a superconductor with randomly placed spherical, elliptical, and columnar defects.

HPC CLOUD APPLIED TO LATTICE OPTIMIZATION

Energy Technology Data Exchange (ETDEWEB)

Sun, Changchun; Nishimura, Hiroshi; James, Susan; Song, Kai; Muriki, Krishna; Qin, Yong

2011-03-18

As Cloud services gain in popularity for enterprise use, vendors are now turning their focus towards providing cloud services suitable for scientific computing. Recently, Amazon Elastic Compute Cloud (EC2) introduced the new Cluster Compute Instances (CCI), a new instance type specifically designed for High Performance Computing (HPC) applications. At Berkeley Lab, the physicists at the Advanced Light Source (ALS) have been running Lattice Optimization on a local cluster, but the queue wait time and the flexibility to request compute resources when needed are not ideal for rapid development work. To explore alternatives, for the first time we investigate running the Lattice Optimization application on Amazon's new CCI to demonstrate the feasibility and trade-offs of using public cloud services for science.

HPC Cloud Applied To Lattice Optimization

International Nuclear Information System (INIS)

Sun, Changchun; Nishimura, Hiroshi; James, Susan; Song, Kai; Muriki, Krishna; Qin, Yong

2011-01-01

As Cloud services gain in popularity for enterprise use, vendors are now turning their focus towards providing cloud services suitable for scientific computing. Recently, Amazon Elastic Compute Cloud (EC2) introduced the new Cluster Compute Instances (CCI), a new instance type specifically designed for High Performance Computing (HPC) applications. At Berkeley Lab, the physicists at the Advanced Light Source (ALS) have been running Lattice Optimization on a local cluster, but the queue wait time and the flexibility to request compute resources when needed are not ideal for rapid development work. To explore alternatives, for the first time we investigate running the Lattice Optimization application on Amazon's new CCI to demonstrate the feasibility and trade-offs of using public cloud services for science.

Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils

Science.gov (United States)

Álvarez-Yela, Astrid Catalina; Gómez-Cano, Fabio; Zambrano, María Mercedes; Husserl, Johana; Danies, Giovanna; Restrepo, Silvia; González-Barrios, Andrés Fernando

2017-01-01

Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA) were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community. PMID:28767679

Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils.

Directory of Open Access Journals (Sweden)

María Camila Alvarez-Silva

Full Text Available Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community.

Association of carbohydrate and fat intake with metabolic syndrome.

Science.gov (United States)

Kwon, Yu-Jin; Lee, Hye-Sun; Lee, Ji-Won

2018-04-01

In Asia, dietary pattern has been changed with increased intake of refined carbohydrates, sugar, and saturated fat, while the prevalence of metabolic syndrome (MetS) is on the rise. However, it remains unclear whether a high-carbohydrate or a high-fat diet is more metabolically harmful, and the optimal amount of carbohydrates and fat has not been determined. The aim of our study was to examine the role of carbohydrate and fat intake in MetS in a Korean population. Data were obtained from a large, population-based, cross-sectional study (6737 males and 8845 females). The subjects were divided into nine groups based on carbohydrate and fat proportion, and multiple logistic regression analysis was performed after adjusting for confounding variables. Regardless of fat intake, the risk of MetS significantly increased in males with higher carbohydrate proportions (of total energy intake). In females, the risk of MetS was significantly elevated only in those with both the highest carbohydrate proportion and lowest fat proportion. A high carbohydrate proportion was associated with a higher prevalence of MetS in males, and a high carbohydrate proportion combined with a low fat proportion was associated with MetS in females. Our results indicate that reduction of excessive carbohydrate intake paired with an adequate fat intake, taking into consideration optimal types of fat, is useful for MetS prevention. Longitudinal studies are needed to clarify the optimal types and amounts of carbohydrate and fat proportions as well as the mechanism underlying these relationships. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Phenomenology and the Empirical Turn

NARCIS (Netherlands)

Zwier, Jochem; Blok, Vincent; Lemmens, Pieter

2016-01-01

This paper provides a phenomenological analysis of postphenomenological philosophy of technology. While acknowledging that the results of its analyses are to be recognized as original, insightful, and valuable, we will argue that in its execution of the empirical turn, postphenomenology forfeits

CLUSTER ENERGY OPTIMIZATION: A THEORETICAL APPROACH

OpenAIRE

Vikram Yadav; G. Sahoo

2013-01-01

The optimization of energy consumption in the cloud computing environment is the question how to use various energy conservation strategies to efficiently allocate resources. The need of differentresources in cloud environment is unpredictable. It is observed that load management in cloud is utmost needed in order to provide QOS. The jobs at over-loaded physical machine are shifted to under-loadedphysical machine and turning the idle machine off in order to provide green cloud. For energy opt...

An adaptive dual-optimal path-planning technique for unmanned air vehicles

Directory of Open Access Journals (Sweden)

Whitfield Clifford A.

2016-01-01

Full Text Available A multi-objective technique for unmanned air vehicle path-planning generation through task allocation has been developed. The dual-optimal path-planning technique generates real-time adaptive flight paths based on available flight windows and environmental influenced objectives. The environmentally-influenced flight condition determines the aircraft optimal orientation within a downstream virtual window of possible vehicle destinations that is based on the vehicle’s kinematics. The intermittent results are then pursued by a dynamic optimization technique to determine the flight path. This path-planning technique is a multi-objective optimization procedure consisting of two goals that do not require additional information to combine the conflicting objectives into a single-objective. The technique was applied to solar-regenerative high altitude long endurance flight which can benefit significantly from an adaptive real-time path-planning technique. The objectives were to determine the minimum power required flight paths while maintaining maximum solar power for continual surveillance over an area of interest (AOI. The simulated path generation technique prolonged the flight duration over a sustained turn loiter flight path by approximately 2 months for a year of flight. The potential for prolonged solar powered flight was consistent for all latitude locations, including 2 months of available flight at 60° latitude, where sustained turn flight was no longer capable.

Turning points in the history of mathematics

CERN Document Server

Grant, Hardy

2015-01-01

This book explores some of the major turning points in the history of mathematics, ranging from ancient Greece to the present, demonstrating the drama that has often been a part of its evolution. Studying these breakthroughs, transitions, and revolutions, their stumbling-blocks and their triumphs, can help illuminate the importance of the history of mathematics for its teaching, learning, and appreciation. Some of the turning points considered are the rise of the axiomatic method (most famously in Euclid), and the subsequent major changes in it (for example, by David Hilbert); the “wedding,” via analytic geometry, of algebra and geometry; the “taming” of the infinitely small and the infinitely large; the passages from algebra to algebras, from geometry to geometries, and from arithmetic to arithmetics; and the revolutions in the late nineteenth and early twentieth centuries that resulted from Georg Cantor’s creation of transfinite set theory. The origin of each turning point is discussed, along with...

High-throughput metabolic state analysis: The missing link in integrated functional genomics of yeasts

DEFF Research Database (Denmark)

Villas-Bôas, Silas Granato; Moxley, Joel. F; Åkesson, Mats Fredrik

2005-01-01

that achieve comparable throughput, effort and cost compared with DNA arrays. Our sample workup method enables simultaneous metabolite measurements throughout central carbon metabolism and amino acid biosynthesis, using a standard GC-MS platform that was optimized for this Purpose. As an implementation proof......-of-concept, we assayed metabolite levels in two yeast strains and two different environmental conditions in the context of metabolic pathway reconstruction. We demonstrate that these differential metabolite level data distinguish among sample types, such as typical metabolic fingerprinting or footprinting. More...

Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Amanda L. Peterson

2016-09-01

Full Text Available Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect—an increase in glycolytic activity at the expense of oxidative phosphorylation—and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions.

Slave nodes and the controllability of metabolic networks

International Nuclear Information System (INIS)

Kim, Dong-Hee; Motter, Adilson E

2009-01-01

Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell behavior of a large metabolic network be controlled by constraining the flux of one or more reactions in the network? This touches upon the issue of the number of degrees of freedom contained by one such network. Using the metabolic network of Escherichia coli as a model system, here we address this question theoretically by exploring not only reaction deletions, but also a continuum of all possible reaction expression levels. We show that the behavior of the metabolic network can be largely manipulated by the pinned expression of a single reaction. In particular, a relevant fraction of the metabolic reactions exhibits canalizing interactions, in that the specification of one reaction flux determines cellular growth as well as the fluxes of most other reactions in optimal steady states. The activity of individual reactions can thus be used as surrogates to monitor and possibly control cellular growth and other whole-cell behaviors. In addition to its implications for the study of control processes, our methodology provides a new approach to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts.

Differential Bees Flux Balance Analysis with OptKnock for in silico microbial strains optimization.

Directory of Open Access Journals (Sweden)

Yee Wen Choon

Full Text Available Microbial strains optimization for the overproduction of desired phenotype has been a popular topic in recent years. The strains can be optimized through several techniques in the field of genetic engineering. Gene knockout is a genetic engineering technique that can engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, the complexities of the metabolic networks have made the process to identify the effects of genetic modification on the desirable phenotypes challenging. Furthermore, a vast number of reactions in cellular metabolism often lead to the combinatorial problem in obtaining optimal gene deletion strategy. Basically, the size of a genome-scale metabolic model is usually large. As the size of the problem increases, the computation time increases exponentially. In this paper, we propose Differential Bees Flux Balance Analysis (DBFBA with OptKnock to identify optimal gene knockout strategies for maximizing the production yield of desired phenotypes while sustaining the growth rate. This proposed method functions by improving the performance of a hybrid of Bees Algorithm and Flux Balance Analysis (BAFBA by hybridizing Differential Evolution (DE algorithm into neighborhood searching strategy of BAFBA. In addition, DBFBA is integrated with OptKnock to validate the results for improving the reliability the work. Through several experiments conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as the model organisms, DBFBA has shown a better performance in terms of computational time, stability, growth rate, and production yield of desired phenotypes compared to the methods used in previous works.

Modulation of sulfur metabolism enables efficient glucosinolate engineering

Directory of Open Access Journals (Sweden)

Geu-Flores Fernando

2011-01-01

Full Text Available Abstract Background Metabolic engineering in heterologous organisms is an attractive approach to achieve efficient production of valuable natural products. Glucosinolates represent a good example of such compounds as they are thought to be the cancer-preventive agents in cruciferous plants. We have recently demonstrated that it is feasible to engineer benzylglucosinolate (BGLS in the non-cruciferous plant Nicotiana benthamiana by transient expression of five genes from Arabidopsis thaliana. In the same study, we showed that co-expression of a sixth Arabidopsis gene, γ-glutamyl peptidase 1 (GGP1, resolved a metabolic bottleneck, thereby increasing BGLS accumulation. However, the accumulation did not reach the expected levels, leaving room for further optimization. Results To optimize heterologous glucosinolate production, we have in this study performed a comparative metabolite analysis of BGLS-producing N. benthamiana leaves in the presence or absence of GGP1. The analysis revealed that the increased BGLS levels in the presence of GGP1 were accompanied by a high accumulation of the last intermediate, desulfoBGLS, and a derivative thereof. This evidenced a bottleneck in the last step of the pathway, the transfer of sulfate from 3'-phosphoadenosine-5'-phosphosulfate (PAPS to desulfoBGLS by the sulfotransferase AtSOT16. While substitution of AtSOT16 with alternative sulfotransferases did not alleviate the bottleneck, experiments with the three genes involved in the formation and recycling of PAPS showed that co-expression of adenosine 5'-phosphosulfate kinase 2 (APK2 alone reduced the accumulation of desulfoBGLS and its derivative by more than 98% and increased BGLS accumulation 16-fold. Conclusion Adjusting sulfur metabolism by directing sulfur from primary to secondary metabolism leads to a remarkable improvement in BGLS accumulation and thereby represents an important step towards a clean and efficient production of glucosinolates in

Transmission tariffs based on optimal power flow

International Nuclear Information System (INIS)

Wangensteen, Ivar; Gjelsvik, Anders

1998-01-01

This report discusses transmission pricing as a means of obtaining optimal scheduling and dispatch in a power system. This optimality includes consumption as well as generation. The report concentrates on how prices can be used as signals towards operational decisions of market participants (generators, consumers). The main focus is on deregulated systems with open access to the network. The optimal power flow theory, with demand side modelling included, is briefly reviewed. It turns out that the marginal costs obtained from the optimal power flow gives the optimal transmission tariff for the particular load flow in case. There is also a correspondence between losses and optimal prices. Emphasis is on simple examples that demonstrate the connection between optimal power flow results and tariffs. Various cases, such as open access and single owner are discussed. A key result is that the location of the ''marketplace'' in the open access case does not influence the net economical result for any of the parties involved (generators, network owner, consumer). The optimal power flow is instantaneous, and in its standard form cannot deal with energy constrained systems that are coupled in time, such as hydropower systems with reservoirs. A simplified example of how the theory can be extended to such a system is discussed. An example of the influence of security constraints on prices is also given. 4 refs., 24 figs., 7 tabs

Understanding Regulation of Metabolism through Feasibility Analysis

Science.gov (United States)

Nikerel, Emrah; Berkhout, Jan; Hu, Fengyuan; Teusink, Bas; Reinders, Marcel J. T.; de Ridder, Dick

2012-01-01

Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but through non-obvious combinations of hierarchical (gene and enzyme levels) and metabolic regulation (mass action and allosteric interaction). Quantitative analyses relating changes in metabolic fluxes to changes in transcript or protein levels have revealed a remarkable lack of understanding of the regulation of these networks. We study metabolic regulation via feasibility analysis (FA). Inspired by the constraint-based approach of Flux Balance Analysis, FA incorporates a model describing kinetic interactions between molecules. We enlarge the portfolio of objectives for the cell by defining three main physiologically relevant objectives for the cell: function, robustness and temporal responsiveness. We postulate that the cell assumes one or a combination of these objectives and search for enzyme levels necessary to achieve this. We call the subspace of feasible enzyme levels the feasible enzyme space. Once this space is constructed, we can study how different objectives may (if possible) be combined, or evaluate the conditions at which the cells are faced with a trade-off among those. We apply FA to the experimental scenario of long-term carbon limited chemostat cultivation of yeast cells, studying how metabolism evolves optimally. Cells employ a mixed strategy composed of increasing enzyme levels for glucose uptake and hexokinase and decreasing levels of the remaining enzymes. This trade-off renders the cells specialized in this low-carbon flux state to compete for the available glucose and get rid of over-overcapacity. Overall, we show that FA is a powerful tool for systems biologists to study regulation of metabolism, interpret experimental data and evaluate hypotheses. PMID

Density of Plutonium Turnings Generated from Machining Activities

Energy Technology Data Exchange (ETDEWEB)

Gonzales, John Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Vigil, Duane M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Jachimowski, Thomas A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Archuleta, Alonso [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Arellano, Gerald Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Melton, Vince Lee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-10-20

The purpose of this project was to determine the density of plutonium (Pu) turnings generated from the range of machining activities, using both surrogate material and machined Pu turnings. Verify that 500 grams (g) of plutonium will fit in a one quart container using a surrogate equivalent volume and that 100 grams of Pu will fit in a one quart Savy container.

Robust output LQ optimal control via integral sliding modes

CERN Document Server

Fridman, Leonid; Bejarano, Francisco Javier

2014-01-01

Featuring original research from well-known experts in the field of sliding mode control, this monograph presents new design schemes for implementing LQ control solutions in situations where the output system is the only information provided about the state of the plant. This new design works under the restrictions of matched disturbances without losing its desirable features. On the cutting-edge of optimal control research, Robust Output LQ Optimal Control via Integral Sliding Modes is an excellent resource for both graduate students and professionals involved in linear systems, optimal control, observation of systems with unknown inputs, and automatization. In the theory of optimal control, the linear quadratic (LQ) optimal problem plays an important role due to its physical meaning, and its solution is easily given by an algebraic Riccati equation. This solution turns out to be restrictive, however, because of two assumptions: the system must be free from disturbances and the entire state vector must be kn...

The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

Science.gov (United States)

Ganguli, Suman; Hunt, C Anthony

2004-01-01

Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

Prediction and analysis of beta-turns in proteins by support vector machine.

Science.gov (United States)

Pham, Tho Hoan; Satou, Kenji; Ho, Tu Bao

2003-01-01

Tight turn has long been recognized as one of the three important features of proteins after the alpha-helix and beta-sheet. Tight turns play an important role in globular proteins from both the structural and functional points of view. More than 90% tight turns are beta-turns. Analysis and prediction of beta-turns in particular and tight turns in general are very useful for the design of new molecules such as drugs, pesticides, and antigens. In this paper, we introduce a support vector machine (SVM) approach to prediction and analysis of beta-turns. We have investigated two aspects of applying SVM to the prediction and analysis of beta-turns. First, we developed a new SVM method, called BTSVM, which predicts beta-turns of a protein from its sequence. The prediction results on the dataset of 426 non-homologous protein chains by sevenfold cross-validation technique showed that our method is superior to the other previous methods. Second, we analyzed how amino acid positions support (or prevent) the formation of beta-turns based on the "multivariable" classification model of a linear SVM. This model is more general than the other ones of previous statistical methods. Our analysis results are more comprehensive and easier to use than previously published analysis results.

Model-based design of bistable cell factories for metabolic engineering.

Science.gov (United States)

Srinivasan, Shyam; Cluett, William R; Mahadevan, Radhakrishnan

2018-04-15

Metabolism can exhibit dynamic phenomena like bistability due to the presence of regulatory motifs like the positive feedback loop. As cell factories, microorganisms with bistable metabolism can have a high and a low product flux at the two stable steady states, respectively. The exclusion of metabolic regulation and network dynamics limits the ability of pseudo-steady state stoichiometric models to detect the presence of bistability, and reliably assess the outcomes of design perturbations to metabolic networks. Using kinetic models of metabolism, we assess the change in the bistable characteristics of the network, and suggest designs based on perturbations to the positive feedback loop to enable the network to produce at its theoretical maximum rate. We show that the most optimal production design in parameter space, for a small bistable metabolic network, may exist at the boundary of the bistable region separating it from the monostable region of low product fluxes. The results of our analysis can be broadly applied to other bistable metabolic networks with similar positive feedback network topologies. This can complement existing model-based design strategies by providing a smaller number of feasible designs that need to be tested in vivo. http://lmse.biozone.utoronto.ca/downloads/. krishna.mahadevan@utoronto.ca. Supplementary data are available at Bioinformatics online.

Effects of dual task on turning ability in stroke survivors and older adults.

Science.gov (United States)

Hollands, K L; Agnihotri, D; Tyson, S F

2014-09-01

Turning is an integral component of independent mobility in which stroke survivors frequently fall. This study sought to measure the effects of competing cognitive demands on the stepping patterns of stroke survivors, compared to healthy age-match adults, during turning as a putative mechanism for falls. Walking and turning (90°) was assessed under single (walking and turning alone) and dual task (subtracting serial 3s while walking and turning) conditions using an electronic, pressure-sensitive walkway. Dependent measures were time to turn, variability in time to turn, step length, step width and single support time during three steps of the turn. Turning ability in single and dual task conditions was compared between stroke survivors (n=17, mean ± SD: 59 ± 113 months post-stroke, 64 ± 10 years of age) and age-matched healthy counterparts (n=15). Both groups took longer, were more variable, tended to widen the second step and, crucially, increased single support time on the inside leg of the turn while turning and distracted. Increased single support time during turning may represent biomechanical mechanism, within stepping patterns of turning under distraction, for increased risk of falls for both stroke survivors and older adults. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Experimental investigation on hard turning using mixed ceramic insert under accelerated cooling environment

Directory of Open Access Journals (Sweden)

Ramanuj Kumar

2018-05-01

Full Text Available The present study reports on the application of accelerated cooling environment (ACE in hard turning of AISI D2 steel (55 ± 1HRC using mixed ceramic insert (Al2O3 + TiCN which is rarely being investigated and to address the major problems of brittle fracture of tool tip that arises through cutting forces and friction at tool-work and chip-tool interface. In spraying process, some portion of spraying coolant vaporize due to heat when it reaches to cutting zone where as remaining portion of coolant easily penetrate in cutting zone through capillary action and reduces friction as well as heat in cutting zone. Abrasion and chipping are noticed to be dominant wear mechanism. Cutting speed and depth of cut are significant for flank wear as well as cutting temperature whereas feed is significant for average surface roughness. Serrated chips have been identified at higher cutting speed and higher feeds. Optimal parametric combination is found to be d1-f1-v2 (0.1mm-0.04 m/min-108 m/min and tool life and machining cost per part are 70 minutes and Rs 76.76 respectively. Investigation shows the worthy of application of ACE in hard turning in industrial sectors ecologically and economically. Empirical models reveal statistically significance due to higher coefficient of correlations.

Hydrodynamics of Turning Flocks

OpenAIRE

Yang, Xingbo; Marchetti, M. Cristina

2014-01-01

We present a hydrodynamic model of flocking that generalizes the familiar Toner-Tu equations to incorporate turning inertia of well-polarized flocks. The continuum equations controlled by only two dimensionless parameters, orientational inertia and alignment strength, are derived by coarse graining the inertial spin model recently proposed by Cavagna et al. The interplay between orientational inertia and bend elasticity of the flock yields anisotropic spin waves that mediate the propagation o...

OpenTURNS, an open source uncertainty engineering software

International Nuclear Information System (INIS)

Popelin, A.L.; Dufoy, A.

2013-01-01

The needs to assess robust performances for complex systems have lead to the emergence of a new industrial simulation challenge: to take into account uncertainties when dealing with complex numerical simulation frameworks. EDF has taken part in the development of an Open Source software platform dedicated to uncertainty propagation by probabilistic methods, named OpenTURNS for Open source Treatment of Uncertainty, Risk and Statistics. OpenTURNS includes a large variety of qualified algorithms in order to manage uncertainties in industrial studies, from the uncertainty quantification step (with possibilities to model stochastic dependence thanks to the copula theory and stochastic processes), to the uncertainty propagation step (with some innovative simulation algorithms as the ziggurat method for normal variables) and the sensitivity analysis one (with some sensitivity index based on the evaluation of means conditioned to the realization of a particular event). It also enables to build some response surfaces that can include the stochastic modeling (with the chaos polynomial method for example). Generic wrappers to link OpenTURNS to the modeling software are proposed. At last, OpenTURNS is largely documented to provide rules to help use and contribution

A prospective observational study of ICU patient position and frequency of turning.

Science.gov (United States)

Goldhill, D R; Badacsonyi, A; Goldhill, A A; Waldmann, C

2008-05-01

Positioning and turning critically ill patients may be beneficial but there are little data on current practice. We prospectively recorded patient position every hour over two separate days in 40 British intensive care units and analysed 393 sets of observation. Five patients were prone at any time and 3.8% (day 1) and 5% (day 2) were on rotating beds. Patients were on their back for 46.1% of observations, turned left for 28.4% and right for 25.5%, and head up for 97.4%. A turn was defined as a change between on back, turned left or turned right. The average time (SD) between turns was 4.85 (3.3) h. There was no significant association between the average time between turns and age, weight, height, gender, respiratory diagnosis, intubated and ventilated, sedation score, day of week or nurse:patient ratio. There was a significant difference between hospitals in the frequency with which patients were turned.

Experimental Research and Mathematical Modeling of Parameters Effecting on Cutting Force and SurfaceRoughness in CNC Turning Process

Science.gov (United States)

Zeqiri, F.; Alkan, M.; Kaya, B.; Toros, S.

2018-01-01

In this paper, the effects of cutting parameters on cutting forces and surface roughness based on Taguchi experimental design method are determined. Taguchi L9 orthogonal array is used to investigate the effects of machining parameters. Optimal cutting conditions are determined using the signal/noise (S/N) ratio which is calculated by average surface roughness and cutting force. Using results of analysis, effects of parameters on both average surface roughness and cutting forces are calculated on Minitab 17 using ANOVA method. The material that was investigated is Inconel 625 steel for two cases with heat treatment and without heat treatment. The predicted and calculated values with measurement are very close to each other. Confirmation test of results showed that the Taguchi method was very successful in the optimization of machining parameters for maximum surface roughness and cutting forces in the CNC turning process.

Using support vector machine to predict beta- and gamma-turns in proteins.

Science.gov (United States)

Hu, Xiuzhen; Li, Qianzhong

2008-09-01

By using the composite vector with increment of diversity, position conservation scoring function, and predictive secondary structures to express the information of sequence, a support vector machine (SVM) algorithm for predicting beta- and gamma-turns in the proteins is proposed. The 426 and 320 nonhomologous protein chains described by Guruprasad and Rajkumar (Guruprasad and Rajkumar J. Biosci 2000, 25,143) are used for training and testing the predictive model of the beta- and gamma-turns, respectively. The overall prediction accuracy and the Matthews correlation coefficient in 7-fold cross-validation are 79.8% and 0.47, respectively, for the beta-turns. The overall prediction accuracy in 5-fold cross-validation is 61.0% for the gamma-turns. These results are significantly higher than the other algorithms in the prediction of beta- and gamma-turns using the same datasets. In addition, the 547 and 823 nonhomologous protein chains described by Fuchs and Alix (Fuchs and Alix Proteins: Struct Funct Bioinform 2005, 59, 828) are used for training and testing the predictive model of the beta- and gamma-turns, and better results are obtained. This algorithm may be helpful to improve the performance of protein turns' prediction. To ensure the ability of the SVM method to correctly classify beta-turn and non-beta-turn (gamma-turn and non-gamma-turn), the receiver operating characteristic threshold independent measure curves are provided. (c) 2008 Wiley Periodicals, Inc.

Roles of renal ammonia metabolism other than in acid-base homeostasis.

Science.gov (United States)

Weiner, I David

2017-06-01

The importance of renal ammonia metabolism in acid-base homeostasis is well known. However, the effects of renal ammonia metabolism other than in acid-base homeostasis are not as widely recognized. First, ammonia differs from almost all other solutes in the urine in that it does not result from arterial delivery. Instead, ammonia is produced by the kidney, and only a portion of the ammonia produced is excreted in the urine, with the remainder returned to the systemic circulation through the renal veins. In normal individuals, systemic ammonia addition is metabolized efficiently by the liver, but in patients with either acute or chronic liver disease, conditions that increase the addition of ammonia of renal origin to the systemic circulation can result in precipitation and/or worsening of hyperammonemia. Second, ammonia appears to serve as an intrarenal paracrine signaling molecule. Hypokalemia increases proximal tubule ammonia production and secretion as well as reabsorption in the thick ascending limb of the loop of Henle, thereby increasing delivery to the renal interstitium and the collecting duct. In the collecting duct, ammonia decreases potassium secretion and stimulates potassium reabsorption, thereby decreasing urinary potassium excretion and enabling feedback correction of the initiating hypokalemia. Finally, the stimulation of renal ammonia metabolism by hypokalemia may contribute to the development of metabolic alkalosis, which in turn can stimulate NaCl reabsorption and contribute to the intravascular volume expansion, increased blood pressure and diuretic resistance that can develop with hypokalemia. The evidence supporting these novel non-acid-base roles of renal ammonia metabolism is discussed in this review.

Mechanisms of triglyceride metabolism in patients with bile acid diarrhea.

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Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

2016-08-14

Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment.

SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

Energy Technology Data Exchange (ETDEWEB)

Epstein, T; Xu, L; Gillies, R; Gatenby, R [Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

2014-06-01

Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

International Nuclear Information System (INIS)

Epstein, T; Xu, L; Gillies, R; Gatenby, R

2014-01-01

Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

Energy Optimal Trajectories in Human Arm Motion Aiming for Assistive Robots

Directory of Open Access Journals (Sweden)

Lelai Zhou

2017-01-01

Full Text Available The energy expenditure in human arm has been of great interests for seeking optimal human arm trajectories. This paper presents a new way for calculating metabolic energy consumption of human arm motions. The purpose is to reveal the relationship between the energy consumption and the trajectory of arm motion, and further, the acceleration and arm orientation contributions. Human arm motion in horizontal plane is investigated by virtue of Qualisys motion capture system. The motion data is post-processed by a biomechanical model to obtain the metabolic expenditure. Results on the arm motion kinematics, dynamics and metabolic energy consumption, are included.

The metabolic regulator CodY links L. monocytogenes metabolism to virulence by directly activating the virulence regulatory gene, prfA

Science.gov (United States)

Lobel, Lior; Sigal, Nadejda; Borovok, Ilya; Belitsky, Boris R.; Sonenshein, Abraham L.; Herskovits, Anat A.

2015-01-01

Summary Metabolic adaptations are critical to the ability of bacterial pathogens to grow within host cells and are normally preceded by sensing of host-specific metabolic signals, which in turn can influence the pathogen's virulence state. Previously, we reported that the intracellular bacterial pathogen Listeria monocytogenes responds to low availability of branched-chain amino acids (BCAA) within mammalian cells by up-regulating both BCAA biosynthesis and virulence genes. The induction of virulence genes required the BCAA-responsive transcription regulator, CodY, but the molecular mechanism governing this mode of regulation was unclear. In this report, we demonstrate that CodY directly binds the coding sequence of the L. monocytogenes master virulence activator gene, prfA, 15 nt downstream of its start codon, and that this binding results in up-regulation of prfA transcription specifically under low concentrations of BCAA. Mutating this site abolished CodY binding and reduced prfA transcription in macrophages, and attenuated bacterial virulence in mice. Notably, the mutated binding site did not alter prfA transcription or PrfA activity under other conditions that are known to activate PrfA, such as during growth in the presence of glucose-1-phosphate. This study highlights the tight crosstalk between L. monocytogenes metabolism and virulence' while revealing novel features of CodY-mediated regulation. PMID:25430920

pi-Turns: types, systematics and the context of their occurrence in protein structures.

Science.gov (United States)

Dasgupta, Bhaskar; Chakrabarti, Pinak

2008-09-22

For a proper understanding of protein structure and folding it is important to know if a polypeptide segment adopts a conformation inherent in the sequence or it depends on the context of its flanking secondary structures. Turns of various lengths have been studied and characterized starting from three-residue gamma-turn to six-residue pi-turn. The Schellman motif occurring at the C-terminal end of alpha-helices is a classical example of hydrogen bonded pi-turn involving residues at (i) and (i+5) positions. Hydrogen bonded and non-hydrogen bonded beta- and alpha-turns have been identified previously; likewise, a systematic characterization of pi-turns would provide valuable insight into turn structures. An analysis of protein structures indicates that at least 20% of pi-turns occur independent of the Schellman motif. The two categories of pi-turns, designated as pi-HB and SCH, have been further classified on the basis of backbone conformation and both have AAAa as the major class. They differ in the residue usage at position (i+1), the former having a large preference for Pro that is absent in the latter. As in the case of shorter length beta- and alpha-turns, pi-turns have also been identified not only on the basis of the existence of hydrogen bond, but also using the distance between terminal C alpha-atoms, and this resulted in a comparable number of non-hydrogen-bonded pi-turns (pi-NHB). The presence of shorter beta- and alpha-turns within all categories of pi-turns, the subtle variations in backbone torsion angles along the turn residues, the location of the turns in the context of tertiary structures have been studied. pi-turns have been characterized, first using hydrogen bond and the distance between C alpha atoms of the terminal residues, and then using backbone torsion angles. While the Schellman motif has a structural role in helix termination, many of the pi-HB turns, being located on surface cavities, have functional role and there is also sequence

Membrane lipid alterations in the metabolic syndrome and the role of dietary oils.

Science.gov (United States)

Perona, Javier S

2017-09-01

The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue. Diet intervention has been proposed as a powerful tool to prevent the development of the metabolic syndrome, since healthy diets have been shown to have a protective role against the components of the metabolic syndrome. Particularly, dietary fatty acids are capable of modulating the deleterious effects of these conditions, among other mechanisms, by modifications of the lipid composition of the membranes in insulin-sensitive tissues. However, there is still scarce data based of high-level evidence on the effects of dietary oils on the effects of the metabolic syndrome and its components. This review summarizes the current knowledge on the effects of dietary oils on improving alterations of the components of the metabolic syndrome. It also examines their influence in the modulation of plasma membrane lipid composition and in the functionality of membrane proteins involved in insulin activity, like the insulin receptor, GLUT-4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty acids and cholesterol, and, in turn, the key features of the metabolic syndrome. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

Topological side-chain classification of beta-turns: ideal motifs for peptidomimetic development.

Science.gov (United States)

Tran, Tran Trung; McKie, Jim; Meutermans, Wim D F; Bourne, Gregory T; Andrews, Peter R; Smythe, Mark L

2005-08-01

Beta-turns are important topological motifs for biological recognition of proteins and peptides. Organic molecules that sample the side chain positions of beta-turns have shown broad binding capacity to multiple different receptors, for example benzodiazepines. Beta-turns have traditionally been classified into various types based on the backbone dihedral angles (phi2, psi2, phi3 and psi3). Indeed, 57-68% of beta-turns are currently classified into 8 different backbone families (Type I, Type II, Type I', Type II', Type VIII, Type VIa1, Type VIa2 and Type VIb and Type IV which represents unclassified beta-turns). Although this classification of beta-turns has been useful, the resulting beta-turn types are not ideal for the design of beta-turn mimetics as they do not reflect topological features of the recognition elements, the side chains. To overcome this, we have extracted beta-turns from a data set of non-homologous and high-resolution protein crystal structures. The side chain positions, as defined by C(alpha)-C(beta) vectors, of these turns have been clustered using the kth nearest neighbor clustering and filtered nearest centroid sorting algorithms. Nine clusters were obtained that cluster 90% of the data, and the average intra-cluster RMSD of the four C(alpha)-C(beta) vectors is 0.36. The nine clusters therefore represent the topology of the side chain scaffold architecture of the vast majority of beta-turns. The mean structures of the nine clusters are useful for the development of beta-turn mimetics and as biological descriptors for focusing combinatorial chemistry towards biologically relevant topological space.

An optimized histochemical method to assess skeletal muscle glycogen and lipid stores reveals two metabolically distinct populations of type I muscle fibers

DEFF Research Database (Denmark)

Prats Gavalda, Clara; Gomez-Cabello, Alba; Nordby, Pernille

2013-01-01

Skeletal muscle energy metabolism has been a research focus of physiologists for more than a century. Yet, how the use of intramuscular carbohydrate and lipid energy stores are coordinated during different types of exercise remains a subject of debate. Controversy arises from contradicting data...... preservation of muscle energy stores, air drying cryosections or cycles of freezing-thawing need to be avoided. Furthermore, optimization of the imaging settings in order to specifically image intracellular lipid droplets stained with oil red O or Bodipy-493/503 is shown. When co-staining lipid droplets...... distinct myosin heavy chain I expressing fibers: I-1 fibers have a smaller crossectional area, a higher density of lipid droplets, and a tendency to lower glycogen content compared to I-2 fibers. Type I-2 fibers have similar lipid content than IIA. Exhaustive exercise lead to glycogen depletion in type IIA...

Optimal Time-Abstract Schedulers for CTMDPs and Markov Games

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Markus Rabe

2010-06-01

Full Text Available We study time-bounded reachability in continuous-time Markov decision processes for time-abstract scheduler classes. Such reachability problems play a paramount role in dependability analysis and the modelling of manufacturing and queueing systems. Consequently, their analysis has been studied intensively, and techniques for the approximation of optimal control are well understood. From a mathematical point of view, however, the question of approximation is secondary compared to the fundamental question whether or not optimal control exists. We demonstrate the existence of optimal schedulers for the time-abstract scheduler classes for all CTMDPs. Our proof is constructive: We show how to compute optimal time-abstract strategies with finite memory. It turns out that these optimal schedulers have an amazingly simple structure---they converge to an easy-to-compute memoryless scheduling policy after a finite number of steps. Finally, we show that our argument can easily be lifted to Markov games: We show that both players have a likewise simple optimal strategy in these more general structures.