Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data

PubMed Central

Aorigele; Zeng, Weiming; Hong, Xiaomin

2016-01-01

Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes (high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm (ICA) which performs global search and tabu search (TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes. PMID:27579323

Optimal fractional order PID design via Tabu Search based algorithm.

PubMed

Ateş, Abdullah; Yeroglu, Celaleddin

2016-01-01

This paper presents an optimization method based on the Tabu Search Algorithm (TSA) to design a Fractional-Order Proportional-Integral-Derivative (FOPID) controller. All parameter computations of the FOPID employ random initial conditions, using the proposed optimization method. Illustrative examples demonstrate the performance of the proposed FOPID controller design method. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

An Elitist Multiobjective Tabu Search for Optimal Design of Groundwater Remediation Systems.

PubMed

Yang, Yun; Wu, Jianfeng; Wang, Jinguo; Zhou, Zhifang

2017-11-01

This study presents a new multiobjective evolutionary algorithm (MOEA), the elitist multiobjective tabu search (EMOTS), and incorporates it with MODFLOW/MT3DMS to develop a groundwater simulation-optimization (SO) framework based on modular design for optimal design of groundwater remediation systems using pump-and-treat (PAT) technique. The most notable improvement of EMOTS over the original multiple objective tabu search (MOTS) lies in the elitist strategy, selection strategy, and neighborhood move rule. The elitist strategy is to maintain all nondominated solutions within later search process for better converging to the true Pareto front. The elitism-based selection operator is modified to choose two most remote solutions from current candidate list as seed solutions to increase the diversity of searching space. Moreover, neighborhood solutions are uniformly generated using the Latin hypercube sampling (LHS) in the bounded neighborhood space around each seed solution. To demonstrate the performance of the EMOTS, we consider a synthetic groundwater remediation example. Problem formulations consist of two objective functions with continuous decision variables of pumping rates while meeting water quality requirements. Especially, sensitivity analysis is evaluated through the synthetic case for determination of optimal combination of the heuristic parameters. Furthermore, the EMOTS is successfully applied to evaluate remediation options at the field site of the Massachusetts Military Reservation (MMR) in Cape Cod, Massachusetts. With both the hypothetical and the large-scale field remediation sites, the EMOTS-based SO framework is demonstrated to outperform the original MOTS in achieving the performance metrics of optimality and diversity of nondominated frontiers with desirable stability and robustness. © 2017, National Ground Water Association.

A Tabu-Search Heuristic for Deterministic Two-Mode Blockmodeling of Binary Network Matrices.

PubMed

Brusco, Michael; Steinley, Douglas

2011-10-01

Two-mode binary data matrices arise in a variety of social network contexts, such as the attendance or non-attendance of individuals at events, the participation or lack of participation of groups in projects, and the votes of judges on cases. A popular method for analyzing such data is two-mode blockmodeling based on structural equivalence, where the goal is to identify partitions for the row and column objects such that the clusters of the row and column objects form blocks that are either complete (all 1s) or null (all 0s) to the greatest extent possible. Multiple restarts of an object relocation heuristic that seeks to minimize the number of inconsistencies (i.e., 1s in null blocks and 0s in complete blocks) with ideal block structure is the predominant approach for tackling this problem. As an alternative, we propose a fast and effective implementation of tabu search. Computational comparisons across a set of 48 large network matrices revealed that the new tabu-search heuristic always provided objective function values that were better than those of the relocation heuristic when the two methods were constrained to the same amount of computation time.

Network reliability maximization for stochastic-flow network subject to correlated failures using genetic algorithm and tabu\\xA0search

NASA Astrophysics Data System (ADS)

Yeh, Cheng-Ta; Lin, Yi-Kuei; Yang, Jo-Yun

2018-07-01

Network reliability is an important performance index for many real-life systems, such as electric power systems, computer systems and transportation systems. These systems can be modelled as stochastic-flow networks (SFNs) composed of arcs and nodes. Most system supervisors respect the network reliability maximization by finding the optimal multi-state resource assignment, which is one resource to each arc. However, a disaster may cause correlated failures for the assigned resources, affecting the network reliability. This article focuses on determining the optimal resource assignment with maximal network reliability for SFNs. To solve the problem, this study proposes a hybrid algorithm integrating the genetic algorithm and tabu search to determine the optimal assignment, called the hybrid GA-TS algorithm (HGTA), and integrates minimal paths, recursive sum of disjoint products and the correlated binomial distribution to calculate network reliability. Several practical numerical experiments are adopted to demonstrate that HGTA has better computational quality than several popular soft computing algorithms.

Tabu Search enhances network robustness under targeted attacks

NASA Astrophysics Data System (ADS)

Sun, Shi-wen; Ma, Yi-lin; Li, Rui-qi; Wang, Li; Xia, Cheng-yi

2016-03-01

We focus on the optimization of network robustness with respect to intentional attacks on high-degree nodes. Given an existing network, this problem can be considered as a typical single-objective combinatorial optimization problem. Based on the heuristic Tabu Search optimization algorithm, a link-rewiring method is applied to reconstruct the network while keeping the degree of every node unchanged. Through numerical simulations, BA scale-free network and two real-world networks are investigated to verify the effectiveness of the proposed optimization method. Meanwhile, we analyze how the optimization affects other topological properties of the networks, including natural connectivity, clustering coefficient and degree-degree correlation. The current results can help to improve the robustness of existing complex real-world systems, as well as to provide some insights into the design of robust networks.

The benefits of adaptive parametrization in multi-objective Tabu Search optimization

NASA Astrophysics Data System (ADS)

Ghisu, Tiziano; Parks, Geoffrey T.; Jaeggi, Daniel M.; Jarrett, Jerome P.; Clarkson, P. John

2010-10-01

In real-world optimization problems, large design spaces and conflicting objectives are often combined with a large number of constraints, resulting in a highly multi-modal, challenging, fragmented landscape. The local search at the heart of Tabu Search, while being one of its strengths in highly constrained optimization problems, requires a large number of evaluations per optimization step. In this work, a modification of the pattern search algorithm is proposed: this modification, based on a Principal Components' Analysis of the approximation set, allows both a re-alignment of the search directions, thereby creating a more effective parametrization, and also an informed reduction of the size of the design space itself. These changes make the optimization process more computationally efficient and more effective - higher quality solutions are identified in fewer iterations. These advantages are demonstrated on a number of standard analytical test functions (from the ZDT and DTLZ families) and on a real-world problem (the optimization of an axial compressor preliminary design).

Tabu search algorithm for the distance-constrained vehicle routing problem with split deliveries by order.

PubMed

Xia, Yangkun; Fu, Zhuo; Pan, Lijun; Duan, Fenghua

2018-01-01

The vehicle routing problem (VRP) has a wide range of applications in the field of logistics distribution. In order to reduce the cost of logistics distribution, the distance-constrained and capacitated VRP with split deliveries by order (DCVRPSDO) was studied. We show that the customer demand, which can't be split in the classical VRP model, can only be discrete split deliveries by order. A model of double objective programming is constructed by taking the minimum number of vehicles used and minimum vehicle traveling cost as the first and the second objective, respectively. This approach contains a series of constraints, such as single depot, single vehicle type, distance-constrained and load capacity limit, split delivery by order, etc. DCVRPSDO is a new type of VRP. A new tabu search algorithm is designed to solve the problem and the examples testing show the efficiency of the proposed algorithm. This paper focuses on constructing a double objective mathematical programming model for DCVRPSDO and designing an adaptive tabu search algorithm (ATSA) with good performance to solving the problem. The performance of the ATSA is improved by adding some strategies into the search process, including: (a) a strategy of discrete split deliveries by order is used to split the customer demand; (b) a multi-neighborhood structure is designed to enhance the ability of global optimization; (c) two levels of evaluation objectives are set to select the current solution and the best solution; (d) a discriminating strategy of that the best solution must be feasible and the current solution can accept some infeasible solution, helps to balance the performance of the solution and the diversity of the neighborhood solution; (e) an adaptive penalty mechanism will help the candidate solution be closer to the neighborhood of feasible solution; (f) a strategy of tabu releasing is used to transfer the current solution into a new neighborhood of the better solution.

Tabu search algorithm for the distance-constrained vehicle routing problem with split deliveries by order

PubMed Central

Xia, Yangkun; Pan, Lijun; Duan, Fenghua

2018-01-01

The vehicle routing problem (VRP) has a wide range of applications in the field of logistics distribution. In order to reduce the cost of logistics distribution, the distance-constrained and capacitated VRP with split deliveries by order (DCVRPSDO) was studied. We show that the customer demand, which can’t be split in the classical VRP model, can only be discrete split deliveries by order. A model of double objective programming is constructed by taking the minimum number of vehicles used and minimum vehicle traveling cost as the first and the second objective, respectively. This approach contains a series of constraints, such as single depot, single vehicle type, distance-constrained and load capacity limit, split delivery by order, etc. DCVRPSDO is a new type of VRP. A new tabu search algorithm is designed to solve the problem and the examples testing show the efficiency of the proposed algorithm. This paper focuses on constructing a double objective mathematical programming model for DCVRPSDO and designing an adaptive tabu search algorithm (ATSA) with good performance to solving the problem. The performance of the ATSA is improved by adding some strategies into the search process, including: (a) a strategy of discrete split deliveries by order is used to split the customer demand; (b) a multi-neighborhood structure is designed to enhance the ability of global optimization; (c) two levels of evaluation objectives are set to select the current solution and the best solution; (d) a discriminating strategy of that the best solution must be feasible and the current solution can accept some infeasible solution, helps to balance the performance of the solution and the diversity of the neighborhood solution; (e) an adaptive penalty mechanism will help the candidate solution be closer to the neighborhood of feasible solution; (f) a strategy of tabu releasing is used to transfer the current solution into a new neighborhood of the better solution. PMID:29763419

A Runtime Performance Predictor for Selecting Tabu Tenures

NASA Technical Reports Server (NTRS)

Allen, John A.; Minton, Steven N.

1997-01-01

One of the drawbacks of parameter based systems, such as tabu search, is the difficulty of finding the correct parameter for a particular problem. Often, rule-of-thumb advice is given which may have little or no applicability to the domain or problem instance at hand. This paper describes the application of a general technique, Runtime Performance Predictors (RPP) which can be used to determine, in an efficient manner, the correct tabu tenure for a particular problem instance. The details of the approach and a demonstration using a variant of GSAT are presented.

A stochastic tabu search algorithm to align physician schedule with patient flow.

PubMed

Niroumandrad, Nazgol; Lahrichi, Nadia

2018-06-01

In this study, we consider the pretreatment phase for cancer patients. This is defined as the period between the referral to a cancer center and the confirmation of the treatment plan. Physicians have been identified as bottlenecks in this process, and the goal is to determine a weekly cyclic schedule that improves the patient flow and shortens the pretreatment duration. High uncertainty is associated with the arrival day, profile and type of cancer of each patient. We also include physician satisfaction in the objective function. We present a MIP model for the problem and develop a tabu search algorithm, considering both deterministic and stochastic cases. Experiments show that our method compares very well to CPLEX under deterministic conditions. We describe the stochastic approach in detail and present a real application.

Manipulating Tabu List to Handle Machine Breakdowns in Job Shop Scheduling Problems

NASA Astrophysics Data System (ADS)

Nababan, Erna Budhiarti; SalimSitompul, Opim

2011-06-01

Machine breakdowns in a production schedule may occur on a random basis that make the well-known hard combinatorial problem of Job Shop Scheduling Problems (JSSP) becomes more complex. One of popular techniques used to solve the combinatorial problems is Tabu Search. In this technique, moves that will be not allowed to be revisited are retained in a tabu list in order to avoid in gaining solutions that have been obtained previously. In this paper, we propose an algorithm to employ a second tabu list to keep broken machines, in addition to the tabu list that keeps the moves. The period of how long the broken machines will be kept on the list is categorized using fuzzy membership function. Our technique are tested to the benchmark data of JSSP available on the OR library. From the experiment, we found that our algorithm is promising to help a decision maker to face the event of machine breakdowns.

Protein structure prediction with local adjust tabu search algorithm

PubMed Central

2014-01-01

Background Protein folding structure prediction is one of the most challenging problems in the bioinformatics domain. Because of the complexity of the realistic protein structure, the simplified structure model and the computational method should be adopted in the research. The AB off-lattice model is one of the simplification models, which only considers two classes of amino acids, hydrophobic (A) residues and hydrophilic (B) residues. Results The main work of this paper is to discuss how to optimize the lowest energy configurations in 2D off-lattice model and 3D off-lattice model by using Fibonacci sequences and real protein sequences. In order to avoid falling into local minimum and faster convergence to the global minimum, we introduce a novel method (SATS) to the protein structure problem, which combines simulated annealing algorithm and tabu search algorithm. Various strategies, such as the new encoding strategy, the adaptive neighborhood generation strategy and the local adjustment strategy, are adopted successfully for high-speed searching the optimal conformation corresponds to the lowest energy of the protein sequences. Experimental results show that some of the results obtained by the improved SATS are better than those reported in previous literatures, and we can sure that the lowest energy folding state for short Fibonacci sequences have been found. Conclusions Although the off-lattice models is not very realistic, they can reflect some important characteristics of the realistic protein. It can be found that 3D off-lattice model is more like native folding structure of the realistic protein than 2D off-lattice model. In addition, compared with some previous researches, the proposed hybrid algorithm can more effectively and more quickly search the spatial folding structure of a protein chain. PMID:25474708

77 FR 43817 - Notice of Submission for OMB Review; Office of Postsecondary Education; Talent Search (TS) Annual...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-26

...; Talent Search (TS) Annual Performance Report SUMMARY: The Talent Search program provides Federal... Records Management Services, Office of Management, publishes this notice containing proposed information... records. Title of Collection: Talent Search (TS) Annual Performance Report. OMB Control Number: Pending...

75 FR 67705 - Office of Postsecondary Education; Overview Information; Talent Search (TS) Program; Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-03

... DEPARTMENT OF EDUCATION Office of Postsecondary Education; Overview Information; Talent Search (TS... currently being served by a Talent Search project, especially schools that the State has identified as the... reliable third-party sources when providing information on the implementation of their Talent Search...

A Biogeography-Based Optimization Algorithm Hybridized with Tabu Search for the Quadratic Assignment Problem

PubMed Central

Lim, Wee Loon; Wibowo, Antoni; Desa, Mohammad Ishak; Haron, Habibollah

2016-01-01

The quadratic assignment problem (QAP) is an NP-hard combinatorial optimization problem with a wide variety of applications. Biogeography-based optimization (BBO), a relatively new optimization technique based on the biogeography concept, uses the idea of migration strategy of species to derive algorithm for solving optimization problems. It has been shown that BBO provides performance on a par with other optimization methods. A classical BBO algorithm employs the mutation operator as its diversification strategy. However, this process will often ruin the quality of solutions in QAP. In this paper, we propose a hybrid technique to overcome the weakness of classical BBO algorithm to solve QAP, by replacing the mutation operator with a tabu search procedure. Our experiments using the benchmark instances from QAPLIB show that the proposed hybrid method is able to find good solutions for them within reasonable computational times. Out of 61 benchmark instances tested, the proposed method is able to obtain the best known solutions for 57 of them. PMID:26819585

A Biogeography-Based Optimization Algorithm Hybridized with Tabu Search for the Quadratic Assignment Problem.

PubMed

Lim, Wee Loon; Wibowo, Antoni; Desa, Mohammad Ishak; Haron, Habibollah

2016-01-01

The quadratic assignment problem (QAP) is an NP-hard combinatorial optimization problem with a wide variety of applications. Biogeography-based optimization (BBO), a relatively new optimization technique based on the biogeography concept, uses the idea of migration strategy of species to derive algorithm for solving optimization problems. It has been shown that BBO provides performance on a par with other optimization methods. A classical BBO algorithm employs the mutation operator as its diversification strategy. However, this process will often ruin the quality of solutions in QAP. In this paper, we propose a hybrid technique to overcome the weakness of classical BBO algorithm to solve QAP, by replacing the mutation operator with a tabu search procedure. Our experiments using the benchmark instances from QAPLIB show that the proposed hybrid method is able to find good solutions for them within reasonable computational times. Out of 61 benchmark instances tested, the proposed method is able to obtain the best known solutions for 57 of them.

Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions.

PubMed

Rusu, Mirabela; Birmanns, Stefan

2010-04-01

A structural characterization of multi-component cellular assemblies is essential to explain the mechanisms governing biological function. Macromolecular architectures may be revealed by integrating information collected from various biophysical sources - for instance, by interpreting low-resolution electron cryomicroscopy reconstructions in relation to the crystal structures of the constituent fragments. A simultaneous registration of multiple components is beneficial when building atomic models as it introduces additional spatial constraints to facilitate the native placement inside the map. The high-dimensional nature of such a search problem prevents the exhaustive exploration of all possible solutions. Here we introduce a novel method based on genetic algorithms, for the efficient exploration of the multi-body registration search space. The classic scheme of a genetic algorithm was enhanced with new genetic operations, tabu search and parallel computing strategies and validated on a benchmark of synthetic and experimental cryo-EM datasets. Even at a low level of detail, for example 35-40 A, the technique successfully registered multiple component biomolecules, measuring accuracies within one order of magnitude of the nominal resolutions of the maps. The algorithm was implemented using the Sculptor molecular modeling framework, which also provides a user-friendly graphical interface and enables an instantaneous, visual exploration of intermediate solutions. (c) 2009 Elsevier Inc. All rights reserved.

A Hybrid Tabu Search Heuristic for a Bilevel Competitive Facility Location Model

NASA Astrophysics Data System (ADS)

Küçükaydın, Hande; Aras, Necati; Altınel, I. Kuban

We consider a problem in which a firm or franchise enters a market by locating new facilities where there are existing facilities belonging to a competitor. The firm aims at finding the location and attractiveness of each facility to be opened so as to maximize its profit. The competitor, on the other hand, can react by adjusting the attractiveness of its existing facilities, opening new facilities and/or closing existing ones with the objective of maximizing its own profit. The demand is assumed to be aggregated at certain points in the plane and the facilities of the firm can be located at prespecified candidate sites. We employ Huff's gravity-based rule in modeling the behavior of the customers where the fraction of customers at a demand point that visit a certain facility is proportional to the facility attractiveness and inversely proportional to the distance between the facility site and demand point. We formulate a bilevel mixed-integer nonlinear programming model where the firm entering the market is the leader and the competitor is the follower. In order to find a feasible solution of this model, we develop a hybrid tabu search heuristic which makes use of two exact methods as subroutines: a gradient ascent method and a branch-and-bound algorithm with nonlinear programming relaxation.

Crystal structures of nematode (parasitic T. spiralis and free living C. elegans), compared to mammalian, thymidylate synthases (TS). Molecular docking and molecular dynamics simulations in search for nematode-specific inhibitors of TS.

PubMed

Jarmuła, Adam; Wilk, Piotr; Maj, Piotr; Ludwiczak, Jan; Dowierciał, Anna; Banaszak, Katarzyna; Rypniewski, Wojciech; Cieśla, Joanna; Dąbrowska, Magdalena; Frączyk, Tomasz; Bronowska, Agnieszka K; Jakowiecki, Jakub; Filipek, Sławomir; Rode, Wojciech

2017-10-01

Three crystal structures are presented of nematode thymidylate synthases (TS), including Caenorhabditis elegans (Ce) enzyme without ligands and its ternary complex with dUMP and Raltitrexed, and binary complex of Trichinella spiralis (Ts) enzyme with dUMP. In search of differences potentially relevant for the development of species-specific inhibitors of the nematode enzyme, a comparison was made of the present Ce and Ts enzyme structures, as well as binary complex of Ce enzyme with dUMP, with the corresponding mammalian (human, mouse and rat) enzyme crystal structures. To complement the comparison, tCONCOORD computations were performed to evaluate dynamic behaviors of mammalian and nematode TS structures. Finally, comparative molecular docking combined with molecular dynamics and free energy of binding calculations were carried out to search for ligands showing selective affinity to T. spiralis TS. Despite an overall strong similarity in structure and dynamics of nematode vs mammalian TSs, a pool of ligands demonstrating predictively a strong and selective binding to TsTS has been delimited. These compounds, the E63 family, locate in the dimerization interface of TsTS where they exert species-specific interactions with certain non-conserved residues, including hydrogen bonds with Thr174 and hydrophobic contacts with Phe192, Cys191 and Tyr152. The E63 family of ligands opens the possibility of future development of selective inhibitors of TsTS and effective agents against trichinellosis. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Framework for Medical Web Information Foraging Using Hybrid ACO and Tabu Search.

PubMed

Drias, Yassine; Kechid, Samir; Pasi, Gabriella

2016-01-01

We present in this paper a novel approach based on multi-agent technology for Web information foraging. We proposed for this purpose an architecture in which we distinguish two important phases. The first one is a learning process for localizing the most relevant pages that might interest the user. This is performed on a fixed instance of the Web. The second takes into account the openness and dynamicity of the Web. It consists on an incremental learning starting from the result of the first phase and reshaping the outcomes taking into account the changes that undergoes the Web. The system was implemented using a colony of artificial ants hybridized with tabu search in order to achieve more effectiveness and efficiency. To validate our proposal, experiments were conducted on MedlinePlus, a real website dedicated for research in the domain of Health in contrast to other previous works where experiments were performed on web logs datasets. The main results are promising either for those related to strong Web regularities and for the response time, which is very short and hence complies the real time constraint.

A New TS Algorithm for Solving Low-Carbon Logistics Vehicle Routing Problem with Split Deliveries by Backpack-From a Green Operation Perspective.

PubMed

Xia, Yangkun; Fu, Zhuo; Tsai, Sang-Bing; Wang, Jiangtao

2018-05-10

In order to promote the development of low-carbon logistics and economize logistics distribution costs, the vehicle routing problem with split deliveries by backpack is studied. With the help of the model of classical capacitated vehicle routing problem, in this study, a form of discrete split deliveries was designed in which the customer demand can be split only by backpack. A double-objective mathematical model and the corresponding adaptive tabu search (TS) algorithm were constructed for solving this problem. By embedding the adaptive penalty mechanism, and adopting the random neighborhood selection strategy and reinitialization principle, the global optimization ability of the new algorithm was enhanced. Comparisons with the results in the literature show the effectiveness of the proposed algorithm. The proposed method can save the costs of low-carbon logistics and reduce carbon emissions, which is conducive to the sustainable development of low-carbon logistics.

A New TS Algorithm for Solving Low-Carbon Logistics Vehicle Routing Problem with Split Deliveries by Backpack—From a Green Operation Perspective

PubMed Central

Fu, Zhuo; Wang, Jiangtao

2018-01-01

In order to promote the development of low-carbon logistics and economize logistics distribution costs, the vehicle routing problem with split deliveries by backpack is studied. With the help of the model of classical capacitated vehicle routing problem, in this study, a form of discrete split deliveries was designed in which the customer demand can be split only by backpack. A double-objective mathematical model and the corresponding adaptive tabu search (TS) algorithm were constructed for solving this problem. By embedding the adaptive penalty mechanism, and adopting the random neighborhood selection strategy and reinitialization principle, the global optimization ability of the new algorithm was enhanced. Comparisons with the results in the literature show the effectiveness of the proposed algorithm. The proposed method can save the costs of low-carbon logistics and reduce carbon emissions, which is conducive to the sustainable development of low-carbon logistics. PMID:29747469

Minimization of municipal solid waste transportation route in West Jakarta using Tabu Search method

NASA Astrophysics Data System (ADS)

Chaerul, M.; Mulananda, A. M.

2018-04-01

Indonesia still adopts the concept of collect-haul-dispose for municipal solid waste handling and it leads to the queue of the waste trucks at final disposal site (TPA). The study aims to minimize the total distance of waste transportation system by applying a Transshipment model. In this case, analogous of transshipment point is a compaction facility (SPA). Small capacity of trucks collects the waste from waste temporary collection points (TPS) to the compaction facility which located near the waste generator. After compacted, the waste is transported using big capacity of trucks to the final disposal site which is located far away from city. Problem related with the waste transportation can be solved using Vehicle Routing Problem (VRP). In this study, the shortest distance of route from truck pool to TPS, TPS to SPA, and SPA to TPA was determined by using meta-heuristic methods, namely Tabu Search 2 Phases. TPS studied is the container type with total 43 units throughout the West Jakarta City with 38 units of Armroll truck with capacity of 10 m3 each. The result determines the assignment of each truck from the pool to the selected TPS, SPA and TPA with the total minimum distance of 2,675.3 KM. The minimum distance causing the total cost for waste transportation to be spent by the government also becomes minimal.

Solving the competitive facility location problem considering the reactions of competitor with a hybrid algorithm including Tabu Search and exact method

NASA Astrophysics Data System (ADS)

Bagherinejad, Jafar; Niknam, Azar

2018-03-01

In this paper, a leader-follower competitive facility location problem considering the reactions of the competitors is studied. A model for locating new facilities and determining levels of quality for the facilities of the leader firm is proposed. Moreover, changes in the location and quality of existing facilities in a competitive market where a competitor offers the same goods or services are taken into account. The competitor could react by opening new facilities, closing existing ones, and adjusting the quality levels of its existing facilities. The market share, captured by each facility, depends on its distance to customer and its quality that is calculated based on the probabilistic Huff's model. Each firm aims to maximize its profit subject to constraints on quality levels and budget of setting up new facilities. This problem is formulated as a bi-level mixed integer non-linear model. The model is solved using a combination of Tabu Search with an exact method. The performance of the proposed algorithm is compared with an upper bound that is achieved by applying Karush-Kuhn-Tucker conditions. Computational results show that our algorithm finds near the upper bound solutions in a reasonable time.

Multimodal Logistics Network Design over Planning Horizon through a Hybrid Meta-Heuristic Approach

NASA Astrophysics Data System (ADS)

Shimizu, Yoshiaki; Yamazaki, Yoshihiro; Wada, Takeshi

Logistics has been acknowledged increasingly as a key issue of supply chain management to improve business efficiency under global competition and diversified customer demands. This study aims at improving a quality of strategic decision making associated with dynamic natures in logistics network optimization. Especially, noticing an importance to concern with a multimodal logistics under multiterms, we have extended a previous approach termed hybrid tabu search (HybTS). The attempt intends to deploy a strategic planning more concretely so that the strategic plan can link to an operational decision making. The idea refers to a smart extension of the HybTS to solve a dynamic mixed integer programming problem. It is a two-level iterative method composed of a sophisticated tabu search for the location problem at the upper level and a graph algorithm for the route selection at the lower level. To keep efficiency while coping with the resulting extremely large-scale problem, we invented a systematic procedure to transform the original linear program at the lower-level into a minimum cost flow problem solvable by the graph algorithm. Through numerical experiments, we verified the proposed method outperformed the commercial software. The results indicate the proposed approach can make the conventional strategic decision much more practical and is promising for real world applications.

A Multi-Start Evolutionary Local Search for the Two-Echelon Location Routing Problem

NASA Astrophysics Data System (ADS)

Nguyen, Viet-Phuong; Prins, Christian; Prodhon, Caroline

This paper presents a new hybrid metaheuristic between a greedy randomized adaptive search procedure (GRASP) and an evolutionary/iterated local search (ELS/ILS), using Tabu list to solve the two-echelon location routing problem (LRP-2E). The GRASP uses in turn three constructive heuristics followed by local search to generate the initial solutions. From a solution of GRASP, an intensification strategy is carried out by a dynamic alternation between ELS and ILS. In this phase, each child is obtained by mutation and evaluated through a splitting procedure of giant tour followed by a local search. The tabu list, defined by two characteristics of solution (total cost and number of trips), is used to avoid searching a space already explored. The results show that our metaheuristic clearly outperforms all previously published methods on LRP-2E benchmark instances. Furthermore, it is competitive with the best meta-heuristic published for the single-echelon LRP.

A computational model of visual marking using an inter-connected network of spiking neurons: the spiking search over time & space model (sSoTS).

PubMed

Mavritsaki, Eirini; Heinke, Dietmar; Humphreys, Glyn W; Deco, Gustavo

2006-01-01

In the real world, visual information is selected over time as well as space, when we prioritise new stimuli for attention. Watson and Humphreys [Watson, D., Humphreys, G.W., 1997. Visual marking: prioritizing selection for new objects by top-down attentional inhibition of old objects. Psychological Review 104, 90-122] presented evidence that new information in search tasks is prioritised by (amongst other processes) active ignoring of old items - a process they termed visual marking. In this paper we present, for the first time, an explicit computational model of visual marking using biologically plausible activation functions. The "spiking search over time and space" model (sSoTS) incorporates different synaptic components (NMDA, AMPA, GABA) and a frequency adaptation mechanism based on [Ca(2+)] sensitive K(+) current. This frequency adaptation current can act as a mechanism that suppresses the previously attended items. We show that, when coupled with a process of active inhibition applied to old items, frequency adaptation leads to old items being de-prioritised (and new items prioritised) across time in search. Furthermore, the time course of these processes mimics the time course of the preview effect in human search. The results indicate that the sSoTS model can provide a biologically plausible account of human search over time as well as space.

Available Transfer Capability Determination Using Hybrid Evolutionary Algorithm

NASA Astrophysics Data System (ADS)

Jirapong, Peeraool; Ongsakul, Weerakorn

2008-10-01

This paper proposes a new hybrid evolutionary algorithm (HEA) based on evolutionary programming (EP), tabu search (TS), and simulated annealing (SA) to determine the available transfer capability (ATC) of power transactions between different control areas in deregulated power systems. The optimal power flow (OPF)-based ATC determination is used to evaluate the feasible maximum ATC value within real and reactive power generation limits, line thermal limits, voltage limits, and voltage and angle stability limits. The HEA approach simultaneously searches for real power generations except slack bus in a source area, real power loads in a sink area, and generation bus voltages to solve the OPF-based ATC problem. Test results on the modified IEEE 24-bus reliability test system (RTS) indicate that ATC determination by the HEA could enhance ATC far more than those from EP, TS, hybrid TS/SA, and improved EP (IEP) algorithms, leading to an efficient utilization of the existing transmission system.

Capacity improvement using simulation optimization approaches: A case study in the thermotechnology industry

NASA Astrophysics Data System (ADS)

Yelkenci Köse, Simge; Demir, Leyla; Tunalı, Semra; Türsel Eliiyi, Deniz

2015-02-01

In manufacturing systems, optimal buffer allocation has a considerable impact on capacity improvement. This study presents a simulation optimization procedure to solve the buffer allocation problem in a heat exchanger production plant so as to improve the capacity of the system. For optimization, three metaheuristic-based search algorithms, i.e. a binary-genetic algorithm (B-GA), a binary-simulated annealing algorithm (B-SA) and a binary-tabu search algorithm (B-TS), are proposed. These algorithms are integrated with the simulation model of the production line. The simulation model, which captures the stochastic and dynamic nature of the production line, is used as an evaluation function for the proposed metaheuristics. The experimental study with benchmark problem instances from the literature and the real-life problem show that the proposed B-TS algorithm outperforms B-GA and B-SA in terms of solution quality.

Landscape Analysis and Algorithm Development for Plateau Plagued Search Spaces

DTIC Science & Technology

2011-02-28

Final Report for AFOSR #FA9550-08-1-0422 Landscape Analysis and Algorithm Development for Plateau Plagued Search Spaces August 1, 2008 to November 30...focused on developing high level general purpose algorithms , such as Tabu Search and Genetic Algorithms . However, understanding of when and why these... algorithms perform well still lags. Our project extended the theory of certain combi- natorial optimization problems to develop analytical

Non-adaptive and adaptive hybrid approaches for enhancing water quality management

NASA Astrophysics Data System (ADS)

Kalwij, Ineke M.; Peralta, Richard C.

2008-09-01

SummaryUsing optimization to help solve groundwater management problems cost-effectively is becoming increasingly important. Hybrid optimization approaches, that combine two or more optimization algorithms, will become valuable and common tools for addressing complex nonlinear hydrologic problems. Hybrid heuristic optimizers have capabilities far beyond those of a simple genetic algorithm (SGA), and are continuously improving. SGAs having only parent selection, crossover, and mutation are inefficient and rarely used for optimizing contaminant transport management. Even an advanced genetic algorithm (AGA) that includes elitism (to emphasize using the best strategies as parents) and healing (to help assure optimal strategy feasibility) is undesirably inefficient. Much more efficient than an AGA is the presented hybrid (AGCT), which adds comprehensive tabu search (TS) features to an AGA. TS mechanisms (TS probability, tabu list size, search coarseness and solution space size, and a TS threshold value) force the optimizer to search portions of the solution space that yield superior pumping strategies, and to avoid reproducing similar or inferior strategies. An AGCT characteristic is that TS control parameters are unchanging during optimization. However, TS parameter values that are ideal for optimization commencement can be undesirable when nearing assumed global optimality. The second presented hybrid, termed global converger (GC), is significantly better than the AGCT. GC includes AGCT plus feedback-driven auto-adaptive control that dynamically changes TS parameters during run-time. Before comparing AGCT and GC, we empirically derived scaled dimensionless TS control parameter guidelines by evaluating 50 sets of parameter values for a hypothetical optimization problem. For the hypothetical area, AGCT optimized both well locations and pumping rates. The parameters are useful starting values because using trial-and-error to identify an ideal combination of control

ChemTS: an efficient python library for de novo molecular generation.

PubMed

Yang, Xiufeng; Zhang, Jinzhe; Yoshizoe, Kazuki; Terayama, Kei; Tsuda, Koji

2017-01-01

Automatic design of organic materials requires black-box optimization in a vast chemical space. In conventional molecular design algorithms, a molecule is built as a combination of predetermined fragments. Recently, deep neural network models such as variational autoencoders and recurrent neural networks (RNNs) are shown to be effective in de novo design of molecules without any predetermined fragments. This paper presents a novel Python library ChemTS that explores the chemical space by combining Monte Carlo tree search and an RNN. In a benchmarking problem of optimizing the octanol-water partition coefficient and synthesizability, our algorithm showed superior efficiency in finding high-scoring molecules. ChemTS is available at https://github.com/tsudalab/ChemTS.

ChemTS: an efficient python library for de novo molecular generation

PubMed Central

Yang, Xiufeng; Zhang, Jinzhe; Yoshizoe, Kazuki; Terayama, Kei; Tsuda, Koji

2017-01-01

Abstract Automatic design of organic materials requires black-box optimization in a vast chemical space. In conventional molecular design algorithms, a molecule is built as a combination of predetermined fragments. Recently, deep neural network models such as variational autoencoders and recurrent neural networks (RNNs) are shown to be effective in de novo design of molecules without any predetermined fragments. This paper presents a novel Python library ChemTS that explores the chemical space by combining Monte Carlo tree search and an RNN. In a benchmarking problem of optimizing the octanol-water partition coefficient and synthesizability, our algorithm showed superior efficiency in finding high-scoring molecules. ChemTS is available at https://github.com/tsudalab/ChemTS. PMID:29435094

ChemTS: an efficient python library for de novo molecular generation

NASA Astrophysics Data System (ADS)

Yang, Xiufeng; Zhang, Jinzhe; Yoshizoe, Kazuki; Terayama, Kei; Tsuda, Koji

2017-12-01

Automatic design of organic materials requires black-box optimization in a vast chemical space. In conventional molecular design algorithms, a molecule is built as a combination of predetermined fragments. Recently, deep neural network models such as variational autoencoders and recurrent neural networks (RNNs) are shown to be effective in de novo design of molecules without any predetermined fragments. This paper presents a novel Python library ChemTS that explores the chemical space by combining Monte Carlo tree search and an RNN. In a benchmarking problem of optimizing the octanol-water partition coefficient and synthesizability, our algorithm showed superior efficiency in finding high-scoring molecules. ChemTS is available at https://github.com/tsudalab/ChemTS.

A Group Theoretic Approach to Metaheuristic Local Search for Partitioning Problems

DTIC Science & Technology

2005-05-01

Tabu Search. Mathematical and Computer Modeling 39: 599-616. 107 Daskin , M.S., E. Stern. 1981. A Hierarchical Objective Set Covering Model for EMS... A Group Theoretic Approach to Metaheuristic Local Search for Partitioning Problems by Gary W. Kinney Jr., B.G.S., M.S. Dissertation Presented to the...DISTRIBUTION STATEMENT A Approved for Public Release Distribution Unlimited The University of Texas at Austin May, 2005 20050504 002 REPORT

An impatient evolutionary algorithm with probabilistic tabu search for unified solution of some NP-hard problems in graph and set theory via clique finding.

PubMed

Guturu, Parthasarathy; Dantu, Ram

2008-06-01

Many graph- and set-theoretic problems, because of their tremendous application potential and theoretical appeal, have been well investigated by the researchers in complexity theory and were found to be NP-hard. Since the combinatorial complexity of these problems does not permit exhaustive searches for optimal solutions, only near-optimal solutions can be explored using either various problem-specific heuristic strategies or metaheuristic global-optimization methods, such as simulated annealing, genetic algorithms, etc. In this paper, we propose a unified evolutionary algorithm (EA) to the problems of maximum clique finding, maximum independent set, minimum vertex cover, subgraph and double subgraph isomorphism, set packing, set partitioning, and set cover. In the proposed approach, we first map these problems onto the maximum clique-finding problem (MCP), which is later solved using an evolutionary strategy. The proposed impatient EA with probabilistic tabu search (IEA-PTS) for the MCP integrates the best features of earlier successful approaches with a number of new heuristics that we developed to yield a performance that advances the state of the art in EAs for the exploration of the maximum cliques in a graph. Results of experimentation with the 37 DIMACS benchmark graphs and comparative analyses with six state-of-the-art algorithms, including two from the smaller EA community and four from the larger metaheuristics community, indicate that the IEA-PTS outperforms the EAs with respect to a Pareto-lexicographic ranking criterion and offers competitive performance on some graph instances when individually compared to the other heuristic algorithms. It has also successfully set a new benchmark on one graph instance. On another benchmark suite called Benchmarks with Hidden Optimal Solutions, IEA-PTS ranks second, after a very recent algorithm called COVER, among its peers that have experimented with this suite.

Reliable Transition State Searches Integrated with the Growing String Method.

PubMed

Zimmerman, Paul

2013-07-09

The growing string method (GSM) is highly useful for locating reaction paths connecting two molecular intermediates. GSM has often been used in a two-step procedure to locate exact transition states (TS), where GSM creates a quality initial structure for a local TS search. This procedure and others like it, however, do not always converge to the desired transition state because the local search is sensitive to the quality of the initial guess. This article describes an integrated technique for simultaneous reaction path and exact transition state search. This is achieved by implementing an eigenvector following optimization algorithm in internal coordinates with Hessian update techniques. After partial convergence of the string, an exact saddle point search begins under the constraint that the maximized eigenmode of the TS node Hessian has significant overlap with the string tangent near the TS. Subsequent optimization maintains connectivity of the string to the TS as well as locks in the TS direction, all but eliminating the possibility that the local search leads to the wrong TS. To verify the robustness of this approach, reaction paths and TSs are found for a benchmark set of more than 100 elementary reactions.

A new memetic algorithm for mitigating tandem automated guided vehicle system partitioning problem

NASA Astrophysics Data System (ADS)

Pourrahimian, Parinaz

2017-11-01

Automated Guided Vehicle System (AGVS) provides the flexibility and automation demanded by Flexible Manufacturing System (FMS). However, with the growing concern on responsible management of resource use, it is crucial to manage these vehicles in an efficient way in order reduces travel time and controls conflicts and congestions. This paper presents the development process of a new Memetic Algorithm (MA) for optimizing partitioning problem of tandem AGVS. MAs employ a Genetic Algorithm (GA), as a global search, and apply a local search to bring the solutions to a local optimum point. A new Tabu Search (TS) has been developed and combined with a GA to refine the newly generated individuals by GA. The aim of the proposed algorithm is to minimize the maximum workload of the system. After all, the performance of the proposed algorithm is evaluated using Matlab. This study also compared the objective function of the proposed MA with GA. The results showed that the TS, as a local search, significantly improves the objective function of the GA for different system sizes with large and small numbers of zone by 1.26 in average.

Improved hybrid optimization algorithm for 3D protein structure prediction.

PubMed

Zhou, Changjun; Hou, Caixia; Wei, Xiaopeng; Zhang, Qiang

2014-07-01

A new improved hybrid optimization algorithm - PGATS algorithm, which is based on toy off-lattice model, is presented for dealing with three-dimensional protein structure prediction problems. The algorithm combines the particle swarm optimization (PSO), genetic algorithm (GA), and tabu search (TS) algorithms. Otherwise, we also take some different improved strategies. The factor of stochastic disturbance is joined in the particle swarm optimization to improve the search ability; the operations of crossover and mutation that are in the genetic algorithm are changed to a kind of random liner method; at last tabu search algorithm is improved by appending a mutation operator. Through the combination of a variety of strategies and algorithms, the protein structure prediction (PSP) in a 3D off-lattice model is achieved. The PSP problem is an NP-hard problem, but the problem can be attributed to a global optimization problem of multi-extremum and multi-parameters. This is the theoretical principle of the hybrid optimization algorithm that is proposed in this paper. The algorithm combines local search and global search, which overcomes the shortcoming of a single algorithm, giving full play to the advantage of each algorithm. In the current universal standard sequences, Fibonacci sequences and real protein sequences are certified. Experiments show that the proposed new method outperforms single algorithms on the accuracy of calculating the protein sequence energy value, which is proved to be an effective way to predict the structure of proteins.

A tabu search evalutionary algorithm for multiobjective optimization: Application to a bi-criterion aircraft structural reliability problem

NASA Astrophysics Data System (ADS)

Long, Kim Chenming

Real-world engineering optimization problems often require the consideration of multiple conflicting and noncommensurate objectives, subject to nonconvex constraint regions in a high-dimensional decision space. Further challenges occur for combinatorial multiobjective problems in which the decision variables are not continuous. Traditional multiobjective optimization methods of operations research, such as weighting and epsilon constraint methods, are ill-suited to solving these complex, multiobjective problems. This has given rise to the application of a wide range of metaheuristic optimization algorithms, such as evolutionary, particle swarm, simulated annealing, and ant colony methods, to multiobjective optimization. Several multiobjective evolutionary algorithms have been developed, including the strength Pareto evolutionary algorithm (SPEA) and the non-dominated sorting genetic algorithm (NSGA), for determining the Pareto-optimal set of non-dominated solutions. Although numerous researchers have developed a wide range of multiobjective optimization algorithms, there is a continuing need to construct computationally efficient algorithms with an improved ability to converge to globally non-dominated solutions along the Pareto-optimal front for complex, large-scale, multiobjective engineering optimization problems. This is particularly important when the multiple objective functions and constraints of the real-world system cannot be expressed in explicit mathematical representations. This research presents a novel metaheuristic evolutionary algorithm for complex multiobjective optimization problems, which combines the metaheuristic tabu search algorithm with the evolutionary algorithm (TSEA), as embodied in genetic algorithms. TSEA is successfully applied to bicriteria (i.e., structural reliability and retrofit cost) optimization of the aircraft tail structure fatigue life, which increases its reliability by prolonging fatigue life. A comparison for this

Bi-criteria travelling salesman subtour problem with time threshold

NASA Astrophysics Data System (ADS)

Kumar Thenepalle, Jayanth; Singamsetty, Purusotham

2018-03-01

This paper deals with the bi-criteria travelling salesman subtour problem with time threshold (BTSSP-T), which comes from the family of the travelling salesman problem (TSP) and is NP-hard in the strong sense. The problem arises in several application domains, mainly in routing and scheduling contexts. Here, the model focuses on two criteria: total travel distance and gains attained. The BTSSP-T aims to determine a subtour that starts and ends at the same city and visits a subset of cities at a minimum travel distance with maximum gains, such that the time spent on the tour does not exceed the predefined time threshold. A zero-one integer-programming problem is adopted to formulate this model with all practical constraints, and it includes a finite set of feasible solutions (one for each tour). Two algorithms, namely, the Lexi-Search Algorithm (LSA) and the Tabu Search (TS) algorithm have been developed to solve the BTSSP-T problem. The proposed LSA implicitly enumerates the feasible patterns and provides an efficient solution with backtracking, whereas the TS, which is metaheuristic, will give the better approximate solution. A numerical example is demonstrated in order to understand the search mechanism of the LSA. Numerical experiments are carried out in the MATLAB environment, on the different benchmark instances available in the TSPLIB domain as well as on randomly generated test instances. The experimental results show that the proposed LSA works better than the TS algorithm in terms of solution quality and, computationally, both LSA and TS are competitive.

A capacitated vehicle routing problem with order available time in e-commerce industry

NASA Astrophysics Data System (ADS)

Liu, Ling; Li, Kunpeng; Liu, Zhixue

2017-03-01

In this article, a variant of the well-known capacitated vehicle routing problem (CVRP) called the capacitated vehicle routing problem with order available time (CVRPOAT) is considered, which is observed in the operations of the current e-commerce industry. In this problem, the orders are not available for delivery at the beginning of the planning period. CVRPOAT takes all the assumptions of CVRP, except the order available time, which is determined by the precedent order picking and packing stage in the warehouse of the online grocer. The objective is to minimize the sum of vehicle completion times. An efficient tabu search algorithm is presented to tackle the problem. Moreover, a Lagrangian relaxation algorithm is developed to obtain the lower bounds of reasonably sized problems. Based on the test instances derived from benchmark data, the proposed tabu search algorithm is compared with a published related genetic algorithm, as well as the derived lower bounds. Also, the tabu search algorithm is compared with the current operation strategy of the online grocer. Computational results indicate that the gap between the lower bounds and the results of the tabu search algorithm is small and the tabu search algorithm is superior to the genetic algorithm. Moreover, the CVRPOAT formulation together with the tabu search algorithm performs much better than the current operation strategy of the online grocer.

Solving large scale traveling salesman problems by chaotic neurodynamics.

PubMed

Hasegawa, Mikio; Ikeguch, Tohru; Aihara, Kazuyuki

2002-03-01

We propose a novel approach for solving large scale traveling salesman problems (TSPs) by chaotic dynamics. First, we realize the tabu search on a neural network, by utilizing the refractory effects as the tabu effects. Then, we extend it to a chaotic neural network version. We propose two types of chaotic searching methods, which are based on two different tabu searches. While the first one requires neurons of the order of n2 for an n-city TSP, the second one requires only n neurons. Moreover, an automatic parameter tuning method of our chaotic neural network is presented for easy application to various problems. Last, we show that our method with n neurons is applicable to large TSPs such as an 85,900-city problem and exhibits better performance than the conventional stochastic searches and the tabu searches.

Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.

PubMed

Nakagawa, Tateo; Shimada, Mitsuo; Kurita, Nobuhiro; Iwata, Takashi; Nishioka, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Utsunomiya, Tohru

2012-06-01

The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.

Gradient gravitational search: An efficient metaheuristic algorithm for global optimization.

PubMed

Dash, Tirtharaj; Sahu, Prabhat K

2015-05-30

The adaptation of novel techniques developed in the field of computational chemistry to solve the concerned problems for large and flexible molecules is taking the center stage with regard to efficient algorithm, computational cost and accuracy. In this article, the gradient-based gravitational search (GGS) algorithm, using analytical gradients for a fast minimization to the next local minimum has been reported. Its efficiency as metaheuristic approach has also been compared with Gradient Tabu Search and others like: Gravitational Search, Cuckoo Search, and Back Tracking Search algorithms for global optimization. Moreover, the GGS approach has also been applied to computational chemistry problems for finding the minimal value potential energy of two-dimensional and three-dimensional off-lattice protein models. The simulation results reveal the relative stability and physical accuracy of protein models with efficient computational cost. © 2015 Wiley Periodicals, Inc.

A Comparison of Tropical Storm (TS) and Non-TS Gust Factors for Assessing Peak Wind Probabilities at the Eastern Range

NASA Technical Reports Server (NTRS)

Merceret, Francis J.; Crawford, Winifred C.

2010-01-01

Peak wind speed is an important forecast element to ensure the safety of personnel and flight hardware at Kennedy Space Center (KSC) and the Cape Canaveral Air Force Station (CCAFS) in East-Central Florida. The 45th Weather Squadron (45 WS), the organization that issues forecasts for the KSC/CCAFS area, finds that peak winds are more difficult to forecast than mean winds. This difficulty motivated the 45 WS to request two independent studies. The first (Merceret 2009) was the development of a reliable model for gust factors (GF) relating the peak to the mean wind speed in tropical storms (TS). The second (Lambert et al. 2008) was a climatological study of non-TS cool season (October-April) mean and peak wind speeds by the Applied Meteorology Unit (AMU; Bauman et al. 2004) without the use of GF. Both studies presented their statistics as functions of mean wind speed and height. Most of the few comparisons of TS and non-TS GF in the literature suggest that non-TS GF at a given height and mean wind speed are smaller than the corresponding TS GF. The investigation reported here converted the non-TS peak wind statistics calculated by the AMU to the equivalent GF statistics and compared them with the previous TS GF results. The advantage of this effort over all previously reported studies of its kind is that the TS and non-TS data were taken from the same towers in the same locations. This eliminates differing surface attributes, including roughness length and thermal properties, as a major source of variance in the comparison. The goal of this study is two-fold: to determine the relationship between the non-TS and TS GF and their standard deviations (GFSD) and to determine if models similar to those developed for TS data in Merceret (2009) could be developed for the non-TS environment. The results are consistent with the literature, but include much more detailed, quantitative information on the nature of the relationship between TS and non-TS GF and GFSD as a function

Trail-Based Search for Efficient Event Report to Mobile Actors in Wireless Sensor and Actor Networks.

PubMed

Xu, Zhezhuang; Liu, Guanglun; Yan, Haotian; Cheng, Bin; Lin, Feilong

2017-10-27

In wireless sensor and actor networks, when an event is detected, the sensor node needs to transmit an event report to inform the actor. Since the actor moves in the network to execute missions, its location is always unavailable to the sensor nodes. A popular solution is the search strategy that can forward the data to a node without its location information. However, most existing works have not considered the mobility of the node, and thus generate significant energy consumption or transmission delay. In this paper, we propose the trail-based search (TS) strategy that takes advantage of actor's mobility to improve the search efficiency. The main idea of TS is that, when the actor moves in the network, it can leave its trail composed of continuous footprints. The search packet with the event report is transmitted in the network to search the actor or its footprints. Once an effective footprint is discovered, the packet will be forwarded along the trail until it is received by the actor. Moreover, we derive the condition to guarantee the trail connectivity, and propose the redundancy reduction scheme based on TS (TS-R) to reduce nontrivial transmission redundancy that is generated by the trail. The theoretical and numerical analysis is provided to prove the efficiency of TS. Compared with the well-known expanding ring search (ERS), TS significantly reduces the energy consumption and search delay.

Neuropsychological functioning in children with Tourette syndrome (TS).

PubMed

Rasmussen, Carmen; Soleimani, Maryam; Carroll, Alan; Hodlevskyy, Oleksander

2009-11-01

We examined whether children with Tourette syndrome (TS) displayed a unique pattern of neuropsychological deficits on the CANTAB relative to control children. We also looked at whether children with TS and other comorbidities had more neuropsychological impairments than those with uncomplicated TS and how age was related to the profile of neuropsychological deficits in TS. Participants included 38 children with TS (aged 7 to 13 years) and 38 control children (aged 6 to 12 years). All children were administered 8 subtests from the CANTAB and parents and teachers completed the BRIEF rating scale on children in the TS group. Children with TS displayed deficits relative to control children on measures of visual memory, executive functioning, and attention from the CANTAB. Among the TS group, age was negatively correlated with performance on measures of executive functioning, speed of response and working memory. Identifying the pattern of neuropsychological deficits in children with TS on the CANTAB is important for highlighting areas of deficit that can be targeted for intervention and teaching strategies. With further research, the CANTAB may prove to be a useful resource in the assessment and treatment of children with TS.

A Comparison of Tropical Storm (TS) and Non-TS Gust Factors for Assessing Peak Wind Probabilities at the Eastern Range

NASA Technical Reports Server (NTRS)

Merceret, Francis J.; Crawford, Winifred C.

2010-01-01

Knowledge of peak wind speeds is important to the safety of personnel and flight hardware at Kennedy Space Center (KSC) and the Cape Canaveral Air Force Station (CCAFS), but they are more difficult to forecast than mean wind speeds. Development of a reliable model for the gust factor (GF) relating the peak to the mean wind speed motivated a previous study of GF in tropical storms. The same motivation inspired a climatological study of non-TS peak wind speed statistics without the use of GF. Both studies presented their respective statistics as functions of mean wind speed and height. The few comparisons of IS and non-TS GF in the literature suggest that the non-TS GF at a given height and mean wind speed are smaller than the corresponding TS GF. The investigation reported here converted the non-TS peak wind statistics mentioned above to the equivalent GF statistics and compared the results with the previous TS GF results. The advantage of this effort over all previously reported studies of its kind is that the TS and non-TS data are taken from the same towers in the same locations. That eliminates differing surface attributes, including roughness length and thermal properties, as a major source of variance in the comparison. The results are consistent with the literature, but include much more detailed, quantitative information on the nature of the relationship between TS and non-TS GF as a function of height and mean wind speed. In addition, the data suggest the possibility of providing an operational model for non-TS GF as a function of height and wind speed in a manner similar to the one previously developed for TS GF.

Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms dependent on lipid mediators and cytokine production.

PubMed

Zoccal, Karina Furlani; Bitencourt, Claudia da Silva; Sorgi, Carlos Artério; Bordon, Karla de Castro Figueiredo; Sampaio, Suely Vilela; Arantes, Eliane Candiani; Faccioli, Lúcia Helena

2013-01-01

Inflammatory mediators are thought to be involved in the systemic and local immune response induced by the Tityus serrulatus scorpion envenomation. New functional aspects of lipid mediators have recently been described. Here, we examine the unreported role of lipid mediators in cell recruitment to the peritoneal cavity after an injection with Ts2 or Ts6 toxins isolated from the T. serrulatus scorpion venom. In this report, we demonstrate that following a single intraperitoneal (i.p.) injection of Ts2 or Ts6 (250 μg/kg) in mice, there was an induction of leukocytosis with a predominance of neutrophils observed at 4, 24, 48 and 96 h. Moreover, total protein, leukotriene (LT)B(4), prostaglandin (PG)E(2) and pro-inflammatory cytokine levels were increased. We also observed an increase of regulatory cytokines, including interleukin (IL)-10, after the Ts2 injection. Finally, we observed that Ts2 or Ts6 injection in 5-lipoxygenase (LO) deficient mice and in wild type (WT) 129sv mice pre-treated with LTs and PGs inhibitors (MK-886 and celecoxib, respectively) a reduction the influx of leukocytes occurs in comparison to WT. The recruitment of these cells demonstrated a phenotype characteristic of neutrophils, macrophages, CD4 and CD8 lymphocytes expressing GR1+, F4/80+, CD3+/CD4+ and CD3+/CD8+, respectively. In conclusion, our data demonstrate that Ts2 and Ts6 induce inflammation by mechanisms dependent on lipid mediators and cytokine production. Ts2 may play a regulatory role whereas Ts6 exhibits pro-inflammatory activity exclusively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Intelligent ensemble T-S fuzzy neural networks with RCDPSO_DM optimization for effective handling of complex clinical pathway variances.

PubMed

Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Yao, Yang

2013-07-01

Takagi-Sugeno (T-S) fuzzy neural networks (FNNs) can be used to handle complex, fuzzy, uncertain clinical pathway (CP) variances. However, there are many drawbacks, such as slow training rate, propensity to become trapped in a local minimum and poor ability to perform a global search. In order to improve overall performance of variance handling by T-S FNNs, a new CP variance handling method is proposed in this study. It is based on random cooperative decomposing particle swarm optimization with double mutation mechanism (RCDPSO_DM) for T-S FNNs. Moreover, the proposed integrated learning algorithm, combining the RCDPSO_DM algorithm with a Kalman filtering algorithm, is applied to optimize antecedent and consequent parameters of constructed T-S FNNs. Then, a multi-swarm cooperative immigrating particle swarm algorithm ensemble method is used for intelligent ensemble T-S FNNs with RCDPSO_DM optimization to further improve stability and accuracy of CP variance handling. Finally, two case studies on liver and kidney poisoning variances in osteosarcoma preoperative chemotherapy are used to validate the proposed method. The result demonstrates that intelligent ensemble T-S FNNs based on the RCDPSO_DM achieves superior performances, in terms of stability, efficiency, precision and generalizability, over PSO ensemble of all T-S FNNs with RCDPSO_DM optimization, single T-S FNNs with RCDPSO_DM optimization, standard T-S FNNs, standard Mamdani FNNs and T-S FNNs based on other algorithms (cooperative particle swarm optimization and particle swarm optimization) for CP variance handling. Therefore, it makes CP variance handling more effective. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trail-Based Search for Efficient Event Report to Mobile Actors in Wireless Sensor and Actor Networks †

PubMed Central

Xu, Zhezhuang; Liu, Guanglun; Yan, Haotian; Cheng, Bin; Lin, Feilong

2017-01-01

In wireless sensor and actor networks, when an event is detected, the sensor node needs to transmit an event report to inform the actor. Since the actor moves in the network to execute missions, its location is always unavailable to the sensor nodes. A popular solution is the search strategy that can forward the data to a node without its location information. However, most existing works have not considered the mobility of the node, and thus generate significant energy consumption or transmission delay. In this paper, we propose the trail-based search (TS) strategy that takes advantage of actor’s mobility to improve the search efficiency. The main idea of TS is that, when the actor moves in the network, it can leave its trail composed of continuous footprints. The search packet with the event report is transmitted in the network to search the actor or its footprints. Once an effective footprint is discovered, the packet will be forwarded along the trail until it is received by the actor. Moreover, we derive the condition to guarantee the trail connectivity, and propose the redundancy reduction scheme based on TS (TS-R) to reduce nontrivial transmission redundancy that is generated by the trail. The theoretical and numerical analysis is provided to prove the efficiency of TS. Compared with the well-known expanding ring search (ERS), TS significantly reduces the energy consumption and search delay. PMID:29077017

Self-Adaptive Stepsize Search Applied to Optimal Structural Design

NASA Astrophysics Data System (ADS)

Nolle, L.; Bland, J. A.

Structural engineering often involves the design of space frames that are required to resist predefined external forces without exhibiting plastic deformation. The weight of the structure and hence the weight of its constituent members has to be as low as possible for economical reasons without violating any of the load constraints. Design spaces are usually vast and the computational costs for analyzing a single design are usually high. Therefore, not every possible design can be evaluated for real-world problems. In this work, a standard structural design problem, the 25-bar problem, has been solved using self-adaptive stepsize search (SASS), a relatively new search heuristic. This algorithm has only one control parameter and therefore overcomes the drawback of modern search heuristics, i.e. the need to first find a set of optimum control parameter settings for the problem at hand. In this work, SASS outperforms simulated-annealing, genetic algorithms, tabu search and ant colony optimization.

A Novel Adjustment Method for Shearer Traction Speed through Integration of T-S Cloud Inference Network and Improved PSO

PubMed Central

Si, Lei; Wang, Zhongbin; Yang, Yinwei

2014-01-01

In order to efficiently and accurately adjust the shearer traction speed, a novel approach based on Takagi-Sugeno (T-S) cloud inference network (CIN) and improved particle swarm optimization (IPSO) is proposed. The T-S CIN is built through the combination of cloud model and T-S fuzzy neural network. Moreover, the IPSO algorithm employs parameter automation adjustment strategy and velocity resetting to significantly improve the performance of basic PSO algorithm in global search and fine-tuning of the solutions, and the flowchart of proposed approach is designed. Furthermore, some simulation examples are carried out and comparison results indicate that the proposed method is feasible, efficient, and is outperforming others. Finally, an industrial application example of coal mining face is demonstrated to specify the effect of proposed system. PMID:25506358

Antifungal Activity against Filamentous Fungi of Ts1, a Multifunctional Toxin from Tityus serrulatus Scorpion Venom

PubMed Central

Santussi, Welligton M.; Bordon, Karla C. F.; Rodrigues Alves, Ana P. N.; Cologna, Camila T.; Said, Suraia; Arantes, Eliane C.

2017-01-01

Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A. nidulans, A. niger, A. terreus, Neurospora crassa, Penicillium corylophilum, P. ochrochloron, P. verrucosum, P. viridicatum, P. waksmanii, and Talaromyces flavus) was evaluated by quantitative microplate reader assay. Tsv (100 and 500 μg/well, which correspond to 1 and 5 mg/mL, respectively, of total soluble protein) was active in inhibiting growth of A. nidulans, A. terreus, P. corylophilum, and P. verrucosum, especially in the higher concentration used and at the first 30 h. After this period, fungi might have used Tsv components as alternative sources of nutrients, and therefore, increased their growth tax. Only fractions IX, X, XI, XIIA, XIIB (3 and 7.5 μg/well, which correspond to 30 and 75 μg/mL, respectively, of total soluble protein) and Ts1 (1.5, 3, and 6 μg/well, which correspond to 2.18, 4.36, and 8.72 μM, respectively) showed antifungal activity. Ts1 showed to be a non-morphogenic toxin with dose-dependent activity against A. nidulans, inhibiting 100% of fungal growth from 3 μg/well (4.36 μM). The inhibitory effect of Ts1 against A. nidulans growth was accompanied by fungistatic effects and was not amended by 1 mM CaCl2 or tetrodotoxin (46.98 and 93.96 μM). The structural differences between Ts1 and drosomycin, a potent cysteine-rich antifungal peptide, are discussed here. Our results highlight the antifungal potential of the first cysteine

The Don'ts and Don'ts of Teaching

ERIC Educational Resources Information Center

Rubinstein, Gary

2012-01-01

Gary Rubinstein doesn't buy the adage that rules--for students or for teachers--must be stated positively, without don'ts or nots. So he lists 10 rules for things teachers must not do in their first years. Tops on his list is "Don't try to teach too much in one day," which Rubinstein says is a common mis-step because teacher preparation programs,…

3'-UTR Polymorphisms of MTHFR and TS Associated with Osteoporotic Vertebral Compression Fracture Susceptibility in Postmenopausal Women.

PubMed

Ahn, Tae-Keun; Kim, Jung Oh; Kim, Hyun Woo; Park, Han Sung; Shim, Jeong Hyun; Ropper, Alexander E; Han, In Bo; Kim, Nam Keun

2018-03-12

Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase ( MTHFR ) and thymidylate synthase ( TS ) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.

Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

PubMed

Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O

2016-01-01

Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

The three Ts of giving.

PubMed

Yarborough, Craig S

2009-04-01

The profession of dentistry is recognized as one of the most trusted, honest, and ethical professions by many sources. But are we the most generous with the three Ts of philanthropic giving: time, talent, and treasure? We are fortunate to be able to do what we do and are rewarded accordingly. No matter what stage of dentistry our career is in, we should be able to give back to our profession, our communities, and society in one, if not all three, of the Ts of philanthropy.

Comparative genomic analysis reveals a novel mitochondrial isoform of human rTS protein and unusual phylogenetic distribution of the rTS gene

PubMed Central

Liang, Ping; Nair, Jayakumar R; Song, Lei; McGuire, John J; Dolnick, Bruce J

2005-01-01

Background The rTS gene (ENOSF1), first identified in Homo sapiens as a gene complementary to the thymidylate synthase (TYMS) mRNA, is known to encode two protein isoforms, rTSα and rTSβ. The rTSβ isoform appears to be an enzyme responsible for the synthesis of signaling molecules involved in the down-regulation of thymidylate synthase, but the exact cellular functions of rTS genes are largely unknown. Results Through comparative genomic sequence analysis, we predicted the existence of a novel protein isoform, rTS, which has a 27 residue longer N-terminus by virtue of utilizing an alternative start codon located upstream of the start codon in rTSβ. We observed that a similar extended N-terminus could be predicted in all rTS genes for which genomic sequences are available and the extended regions are conserved from bacteria to human. Therefore, we reasoned that the protein with the extended N-terminus might represent an ancestral form of the rTS protein. Sequence analysis strongly predicts a mitochondrial signal sequence in the extended N-terminal of human rTSγ, which is absent in rTSβ. We confirmed the existence of rTS in human mitochondria experimentally by demonstrating the presence of both rTSγ and rTSβ proteins in mitochondria isolated by subcellular fractionation. In addition, our comprehensive analysis of rTS orthologous sequences reveals an unusual phylogenetic distribution of this gene, which suggests the occurrence of one or more horizontal gene transfer events. Conclusion The presence of two rTS isoforms in mitochondria suggests that the rTS signaling pathway may be active within mitochondria. Our report also presents an example of identifying novel protein isoforms and for improving gene annotation through comparative genomic analysis. PMID:16162288

Relationship between polysomnographic sleep architecture and behavior in medication-free children with TS, ADHD, TS and ADHD, and controls.

PubMed

Stephens, Robyn J; Chung, Sharon A; Jovanovic, Dragana; Guerra, Randy; Stephens, Brandon; Sandor, Paul; Shapiro, Colin M

2013-01-01

To describe the relationship between sleep architecture and behavioral measures in unmedicated children and adolescents with Tourette syndrome (TS), attention-deficit hyperactivity disorder (ADHD), TS and comorbid ADHD (TS + ADHD), and healthy controls. The study also set out to examine differences in sleep architecture with each diagnosis. A cross-sectional, 2-night consecutive polysomnographic sleep study was conducted in 90 children. All participants were matched for age, gender, and level of intelligence. Scores on the Child Behavior Checklist delinquency measure were modestly but significantly correlated with the number of movements during REM sleep (r = .36, p = .003). Significant correlations were also noted among the number of total arousals and arousals from slow wave sleep (SWS), and scores on the measures of conduct disorder, hyperactivity/immaturity, and restless/disorganized behaviors. There were a few significant differences in sleep architecture among the diagnostic groups. The ADHD-only group exhibited a significantly higher number of total arousals (p < .01) and arousals from SWS (p < .01) compared with the other three study groups. Our findings indicate that children with TS and/or ADHD and who have more arousals from sleep are significantly more likely to have issues with conduct disorder, hyperactivity/immaturity, and restless/disorganized behavior. It was also noted that having ADHD, alone or comorbid with TS, is associated with a significantly greater number of movements during both non-REM and REM sleep. This study underscores the compelling need for the diagnosis and treatment of any sleep disorders in children with TS and/or ADHD so as to facilitate better management of problem behaviors.

Fundamental study on micro calcification detection using twinkling sign (TS): the effect of stiffness of surrounding tissue on the appearance of TS.

PubMed

Liu, Lei; Funamoto, Kenichi; Tanabe, Masayuki; Hayase, Toshiyuki

2013-01-01

The twinkling sign (TS) observed in ultrasound imaging (e.g., color flow mode and pulse Doppler mode) has been reported in previous researches as a potential phenomenon to detect micro calcification in soft tissue. However, the mechanism of the twinkling sign has not been clearly understood yet. The authors investigated the effect of stiffness of surrounding tissue on the appearance of TS using the soft tissue-mimicking phantoms and a medical ultrasound device. The author used Poly (vinyl alcohol) hydro (PVA-H) gel as the material of phantom and developed three phantoms with different PVA concentration; 8 %wt, 10 %wt and 15 %wt those correspond to Young's modulus (E) as 50 kPa, 100 kPa and 230 kPa, respectively. Micro glass and CaCO3 particles were embedded in the phantoms as pseudo micro calcification. The authors observed TS in each phantom and analyzed the temporal average of TS. The temporal average of TS was largest in the 8 %wt (E = 50 kPa) PVA-H gel phantom, and decreased with increasing the phantom stiffness. The result indicated that the micro oscillation of the particles had a close relationship with the occurrence of TS.

An analysis of iterated local search for job-shop scheduling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitley, L. Darrell; Howe, Adele E.; Watson, Jean-Paul

2003-08-01

Iterated local search, or ILS, is among the most straightforward meta-heuristics for local search. ILS employs both small-step and large-step move operators. Search proceeds via iterative modifications to a single solution, in distinct alternating phases. In the first phase, local neighborhood search (typically greedy descent) is used in conjunction with the small-step operator to transform solutions into local optima. In the second phase, the large-step operator is applied to generate perturbations to the local optima obtained in the first phase. Ideally, when local neighborhood search is applied to the resulting solution, search will terminate at a different local optimum, i.e.,more » the large-step perturbations should be sufficiently large to enable escape from the attractor basins of local optima. ILS has proven capable of delivering excellent performance on numerous N P-Hard optimization problems. [LMS03]. However, despite its implicity, very little is known about why ILS can be so effective, and under what conditions. The goal of this paper is to advance the state-of-the-art in the analysis of meta-heuristics, by providing answers to this research question. They focus on characterizing both the relationship between the structure of the underlying search space and ILS performance, and the dynamic behavior of ILS. The analysis proceeds in the context of the job-shop scheduling problem (JSP) [Tai94]. They begin by demonstrating that the attractor basins of local optima in the JSP are surprisingly weak, and can be escaped with high probaiblity by accepting a short random sequence of less-fit neighbors. this result is used to develop a new ILS algorithms for the JSP, I-JAR, whose performance is competitive with tabu search on difficult benchmark instances. They conclude by developing a very accurate behavioral model of I-JAR, which yields significant insights into the dynamics of search. The analysis is based on a set of 100 random 10 x 10 problem instances, in

A Particle Swarm Optimization-Based Approach with Local Search for Predicting Protein Folding.

PubMed

Yang, Cheng-Hong; Lin, Yu-Shiun; Chuang, Li-Yeh; Chang, Hsueh-Wei

2017-10-01

The hydrophobic-polar (HP) model is commonly used for predicting protein folding structures and hydrophobic interactions. This study developed a particle swarm optimization (PSO)-based algorithm combined with local search algorithms; specifically, the high exploration PSO (HEPSO) algorithm (which can execute global search processes) was combined with three local search algorithms (hill-climbing algorithm, greedy algorithm, and Tabu table), yielding the proposed HE-L-PSO algorithm. By using 20 known protein structures, we evaluated the performance of the HE-L-PSO algorithm in predicting protein folding in the HP model. The proposed HE-L-PSO algorithm exhibited favorable performance in predicting both short and long amino acid sequences with high reproducibility and stability, compared with seven reported algorithms. The HE-L-PSO algorithm yielded optimal solutions for all predicted protein folding structures. All HE-L-PSO-predicted protein folding structures possessed a hydrophobic core that is similar to normal protein folding.

Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.

PubMed

De Savi, Chris; Pape, Andrew; Sawyer, Yvonne; Milne, David; Davies, Chris; Cumming, John G; Ting, Attilla; Lamont, Scott; Smith, Peter D; Tart, Jonathon; Page, Ken; Moore, Peter

2011-06-01

A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics. Copyright © 2011 Elsevier Ltd. All rights reserved.

Differentiation of Mycoplasma gallisepticum vaccine strains ts-11 and 6/85 from commonly used Mycoplasma gallisepticum challenge strains by PCR.

PubMed

Evans, J D; Leigh, S A

2008-09-01

Mycoplasma gallisepticum (MG) is an important avian pathogen causing significant economic losses within the poultry industry. In an effort to develop tools to aid in MG research and diagnostics, we have compared sequences of the attenuated MG vaccine strain ts-11 to those of commonly used pathogenic challenge strains in search of a simple means of differentiation. Via gapA sequence alignments and comparisons, we have identified and designed primers facilitating strain differentiation. When applied to conventional polymerase chain reaction (PCR) assay at low annealing temperature, the primer sets allow for the differentiation of MG attenuated vaccine strains ts-11 as well as the attenuated MG vaccine strain 6/85 from the commonly utilized MG challenge strains R(low), R, and S6. Conventional PCR differentiation is based on the visualization of sole products with the attenuated MG strains ts-11 and 6/85 and the lack of the corresponding products from MG strains R(low), R, and S6. When applied to MG strain F, product visualization varies with the applied primer set. The differentiation of MG strains ts-11 and 6/85 from the pathogenic challenge strains was also accomplished via real-time analyses, however, the primer sets were not able to differentiate MG strains ts-11 and 6/85 from selected MG field isolates.

Variable (Tg, Ts) Measurements of Alkane Dissociative Sticking Coefficients

NASA Astrophysics Data System (ADS)

Valadez, Leticia; Dewitt, Kristy; Abbott, Heather; Kolasinski, Kurt; Harrision, Ian

2006-03-01

Dissociative sticking coefficients S(Tg, Ts) for CH4 and C2H6 on Pt(111) have been measured as a function of gas temperature (Tg) and surface temperature (Ts) using an effusive molecular beam. Microcanonical unimolecular rate theory (MURT) was employed to extract transition state characteristics [e.g., E0(CH4) = 52.5±3.5 kJ/mol-1 and E0(C2H6) = 26.5±3 kJ/mol-1]. MURT allows our S(Tg, Ts) values to be directly compared to other supersonic molecular beam and thermal equilibrium sticking measurements. The S(Tg, Ts) depend strongly on Ts, however, only for CH4 is a strong Tg dependence observed. The fairly weak Tg dependence for C2H6 suggests that vibrational mode specific behavior and/or molecular rotations play stronger roles in the dissociative chemisorption of C2H6 than they do for CH4. Interestingly, thermal S(Tg=Ts) predictions based on MURT modeling of our CH4/Pt(111) data are three orders of magnitude higher than recent thermal equilibrium measurements on supported Pt nanocrystallite catalysts [J. M. Wei, E. Iglesia, J. Phys. Chem. B 108, 4094 (2004)].

GapA+ Mycoplasma gallisepticum ts-11 has improved vaccine characteristics.

PubMed

Shil, Pollob K; Kanci, Anna; Browning, Glenn F; Marenda, Marc S; Noormohammadi, Amir H; Markham, Philip F

2011-06-01

Mycoplasma gallisepticum (MG) is an important poultry pathogen that causes respiratory disease and loss of production worldwide, and is currently controlled with live attenuated vaccines. These vaccines have limitations as they vary in their pathogenicity, the protection afforded and their transmissibility, but have been shown to effectively reduce losses associated with challenge in the field. A live attenuated vaccine, ts-11, has been used for the control of M. gallisepticum in several countries. This vaccine is highly dose-dependent and the flock antibody response is weak. GapA is the primary cytadherence molecule in M. gallisepticum, and the absence of GapA expression has been observed in the vast majority of cells in the ts-11 vaccine strain. In this study the immunogenicity of a GapA(+) M. gallisepticum ts-11 vaccine was investigated in specific-pathogen-free chickens. Birds vaccinated with GapA(+) M. gallisepticum ts-11 were protected against clinical signs of disease following challenge with virulent M. gallisepticum, and GapA(+) M. gallisepticum ts-11 was shown to be non-pathogenic and more immunogenic at a lower dose than the currently available M. gallisepticum ts-11 vaccine. Thus, GapA(+) M. gallisepticum ts-11 appears to have improved potential as a vaccine candidate.

TS expression predicts postoperative recurrence in adenocarcinoma of the lung.

PubMed

Shimokawa, Hidehiko; Uramoto, Hidetaka; Onitsuka, Takamitsu; Iwata, Teruo; Nakagawa, Makoto; Ono, Kenji; Hanagiri, Takeshi

2011-06-01

Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers for either selecting appropriate candidates or for predicting clinical recurrence exist. Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our department. We analyzed the thymidylate synthase (TS) and dihydrofolate reductase (DHFR) expressions in the primary lung adenocarcinoma by immunohistochemisty. The strong expression of TS and DHFR was identified in 39 (21.3%) and 120 (65.6%) patients, respectively. The strong TS expression was identified in 11 (39.3%) of 28 patients and 28 (18.1%) of 155 patients in patients with and without recurrence, respectively (p=0.012). The strong DHFR expression was also identified in 23 (82.1%) and 97 (62.6%) of the patients with and without recurrence, respectively (p=0.045). Logistic regression models indicated the strong TS expression to be an independent factor for tumor recurrence. The strong TS and DHFR expression was associated with a poorer disease-free survival (DFS) according to the survival analysis. A multivariate analysis demonstrated the strong TS expression to be independently associated with an increased risk for poor DFS. The strong TS expression may be a useful marker for predicting postoperative recurrence in patients with lung adenocarcinoma following surgery. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

On metaheuristic "failure modes": a case study in Tabu search for job-shop scheduling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watson, Jean-Paul

2005-06-01

In this paper, we analyze the relationship between pool maintenance schemes, long-term memory mechanisms, and search space structure, with the goal of placing metaheuristic design on a more concrete foundation.

Electrostatic channeling in P. falciparum DHFR-TS: Brownian dynamics and Smoluchowski modeling.

PubMed

Metzger, Vincent T; Eun, Changsun; Kekenes-Huskey, Peter M; Huber, Gary; McCammon, J Andrew

2014-11-18

We perform Brownian dynamics simulations and Smoluchowski continuum modeling of the bifunctional Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the objective of understanding the electrostatic channeling of dihydrofolate generated at the TS active site to the DHFR active site. The results of Brownian dynamics simulations and Smoluchowski continuum modeling suggest that compared to Leishmania major DHFR-TS, P. falciparum DHFR-TS has a lower but significant electrostatic-mediated channeling efficiency (?15-25%) at physiological pH (7.0) and ionic strength (150 mM). We also find that removing the electric charges from key basic residues located between the DHFR and TS active sites significantly reduces the channeling efficiency of P. falciparum DHFR-TS. Although several protozoan DHFR-TS enzymes are known to have similar tertiary and quaternary structure, subtle differences in structure, active-site geometry, and charge distribution appear to influence both electrostatic-mediated and proximity-based substrate channeling.

Cell cycle phase dependent emergence of thymidylate synthase studied by monoclonal antibody (M-TS-4).

PubMed

Shibui, S; Hoshino, T; Iwasaki, K; Nomura, K; Jastreboff, M M

1989-05-01

A method of identifying thymidylate synthase (TS) at the cellular level was developed using anti-TS monoclonal antibody (M-TS-4), a monoclonal antibody created against purified TS from a HeLa cell line. In HeLa cells and four human glioma cell lines (U-251, U-87, 343-MGA, and SF-188), TS was identified primarily in the cytoplasm. Autoradiographic and flow cytometric studies showed that TS appeared mainly in the G1 phase and subsided early in the S phase; thus, the G1 phase can be divided into TS-positive and -negative fractions. Nuclear TS was not demonstrated unequivocally with M-TS-4, and the relationship between nuclear TS and DNA synthesis could not be determined. Although the percentage of TS-positive cells was larger than the S-phase fraction measured by autoradiography after a pulse of tritiated thymidine or by the immunoperoxidase method using BUdR, the ratios were within a similar range (1.2-1.4) in all cell lines studied. Therefore, the S-phase fraction can be estimated indirectly from the percentage of TS-positive cells measured by M-TS-4. Because the emergence of TS detected by our method is cell cycle dependent, M-TS-4 may be useful for biochemical studies of TS and for cytokinetic analysis.

Using multilevel growth curve modeling to examine emotional modulation of temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR).

PubMed

Rhudy, Jamie L; Martin, Satin L; Terry, Ellen L; Delventura, Jennifer L; Kerr, Kara L; Palit, Shreela

2012-11-01

Emotion can modulate pain and spinal nociception, and correlational data suggest that cognitive-emotional processes can facilitate wind-up-like phenomena (ie, temporal summation of pain). However, there have been no experimental studies that manipulated emotion to determine whether within-subject changes in emotion influence temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception). The present study presented a series of emotionally charged pictures (mutilation, neutral, erotic) during which electric stimuli at 2 Hz were delivered to the sural nerve to evoke TS-pain and TS-NFR. Participants (n=46 healthy; 32 female) were asked to rate their emotional reactions to pictures as a manipulation check. Pain outcomes were analyzed using statistically powerful multilevel growth curve models. Results indicated that emotional state was effectively manipulated. Further, emotion modulated the overall level of pain and NFR; pain and NFR were highest during mutilation and lowest during erotic pictures. Although pain and NFR both summated in response to the 2-Hz stimulation series, the magnitude of pain summation (TS-pain) and NFR summation (TS-NFR) was not modulated by picture-viewing. These results imply that, at least in healthy humans, within-subject changes in emotions do not promote central sensitization via amplification of temporal summation. However, future studies are needed to determine whether these findings generalize to clinical populations (eg, chronic pain). Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

TS Gene Polymorphisms Correlate with Susceptibility to Acute Lymphocytic Leukemia in Children.

PubMed

Zou, Runyin; He, Xiangling; Wu, Yanpeng; Tian, Xin; You, Yalan; Zheng, Mincui; Li, Wanli; Zou, Hui; Liu, Hua; Zhu, Xiujuan; Zhu, Chengguang

2017-06-24

BACKGROUND Acute lymphocytic leukemia (ALL) in children is a clonal disease of bone marrow hematopoietic stem cells. This study aimed to explore the associations between MTHFR or TS genetic polymorphisms and susceptibility to acute lymphocytic leukemia (ALL) in children. MATERIAL AND METHODS This case-control study included 79 ALL patients (case group) and 102 non-ALL patients (control group). Post-PCR genomic DNA sequencing revealed MTHFR C677T and MTHFR A1298C genotypes and TS polymorphisms. The χ² test was used to compare differences in MTHFR and TS polymorphisms (including genotypic and allelic distributions) between groups. Logistic regression analysis was used to determine genetic polymorphisms and ALL risk associations. RESULTS The results indicated that TS 3R allele frequency was significantly higher in the case group than in the control group (χ²=7.45, P<0.05). The MTHFR C677T and MTHFR A1298C polymorphisms were not associated with ALL risk. Compared to the TS 2R/2R genotype, subjects carrying TS 2R/3R were twice as likely to develop ALL, and the TS 3R/3R+3R/4R genotype carried a 4-fold higher risk of developing ALL (OR=1.96, CI: 1.14-3.36). CONCLUSIONS The TS genetic polymorphisms increase the ALL risk. The TS 3R allele was a risk factor for ALL. There were no associations between MTHFR C677T or MTHFR A1298C polymorphisms and ALL susceptibility.

Analysis of 320 gastroenteropancreatic neuroendocrine tumors identifies TS expression as independent biomarker for survival.

PubMed

Lee, Hye Seung; Chen, Min; Kim, Ji Hun; Kim, Woo Ho; Ahn, Soyeon; Maeng, Kyungah; Allegra, Carmen J; Kaye, Frederic J; Hochwald, Steven N; Zajac-Kaye, Maria

2014-07-01

Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair, is both a potential tumor prognostic biomarker as well as a tumorigenic oncogene in animal models. We have now studied the clinical implications of TS expression in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these results to other cell cycle biomarker genes. Protein tissue arrays were used to study TS, Ki-67, Rb, pRb, E2F1, p18, p21, p27 and menin expression in 320 human GEP-NETs samples. Immunohistochemical expression was correlated with univariate and multivariate predictors of survival utilizing Kaplan Meier and Cox proportional hazards models. Real time RT-PCR was used to validate these findings. We found that 78 of 320 GEP-NETs (24.4%) expressed TS. NETs arising in the colon, stomach and pancreas showed the highest expression of TS (47.4%, 42.6% and 37.3%, respectively), whereas NETs of the appendix, rectum and duodenum displayed low TS expression (3.3%, 12.9% and 15.4%, respectively). TS expression in GEP-NETs was associated with poorly differentiated endocrine carcinoma, angiolymphatic invasion, lymph node metastasis and distant metastasis (p < 0.05). Patients with TS-positive NETs had markedly worse outcomes than TS-negative NETs as shown by univariate (p < 0.001) and multivariate (p = 0.01) survival analyses. Expression of p18 predicted survival in TS-positive patients that received chemotherapy (p = 0.015). In conclusion, TS protein expression was an independent prognostic biomarker for GEP-NETs. The strong association of increased TS expression with aggressive disease and early death supports the role of TS as a cancer promoting agent in these tumors. © 2013 UICC.

Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS.

PubMed

Pestronk, Alan; Schmidt, Robert E; Choksi, Rati M; Sommerville, R Brian; Al-Lozi, Muhammad T

2012-06-01

In this investigation we studied clinical and laboratory features of polyneuropathies in patients with serum IgM binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS). We retrospectively compared 58 patients with selective IgM binding to TS-HDS to 41 consecutive patients with polyneuropathies without TS-HDS binding. Patients with IgM vs. TS-HDS commonly had distal, sensory, axonal neuropathies. Weakness was associated with IgM M-proteins. Hand pain and serum IgM M-proteins were more common than in control neuropathy patients. TS-HDS antibody binding was often selectively κ class. Biopsies showed capillary pathology with thickened basal lamina and C5b9 complement deposition. IgM in sera with TS-HDS antibodies often bound to capillaries. Serum IgM binding to TS-HDS is associated with painful, sensory > motor, polyneuropathies with an increased frequency of persistent hand discomfort, serum IgM M-proteins, and capillary pathology. Serum IgM binding to TS-HDS suggests a possible immune etiology underlying some otherwise idiopathic sensory polyneuropathies. Copyright © 2011 Wiley Periodicals, Inc.

Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome

PubMed Central

Best, Tyler K.; Cramer, Nathan P.; Chakrabarti, Lina; Haydar, Tarik F.; Galdzicki, Zygmunt

2013-01-01

GABAergic dysfunction is implicated in hippocampal deficits of the Ts65Dn mouse model of Down syndrome (DS). Since Ts65Dn mice overexpress G-protein coupled inward-rectifying potassium (GIRK2) containing channels, we sought to evaluate whether increased GABAergic function disrupts the functioning of hippocampal circuitry. After confirming that GABAB/GIRK current density is significantly elevated in Ts65Dn CA1 pyramidal neurons, we compared monosynaptic inhibitory inputs in CA1 pyramidal neurons in response to proximal (stratum radiatum; SR) and distal (stratum lacunosum moleculare; SLM) stimulation of diploid and Ts65Dn acute hippocampal slices. Synaptic GABAB and GABAA mediated currents evoked by SR stimulation were generally unaffected in Ts65Dn CA1 neurons. However, the GABAB/GABAA ratios evoked by stimulation within the SLM of Ts65Dn hippocampus were significantly larger in magnitude, consistent with increased GABAB/GIRK currents after SLM stimulation. These results indicate that GIRK overexpression in Ts65Dn has functional consequences which affect the balance between GABAB and GABAA inhibition of CA1 pyramidal neurons, most likely in a pathway specific manner, and may contribute to cognitive deficits reported in these mice. PMID:22178330

LIDAR TS for ITER core plasma. Part II: simultaneous two wavelength LIDAR TS

NASA Astrophysics Data System (ADS)

Gowers, C.; Nielsen, P.; Salzmann, H.

2017-12-01

We have shown recently, and in more detail at this conference (Salzmann et al) that the LIDAR approach to ITER core TS measurements requires only two mirrors in the inaccessible port plug area of the machine. This leads to simplified and robust alignment, lower risk of mirror damage by plasma contamination and much simpler calibration, compared with the awkward and vulnerable optical geometry of the conventional imaging TS approach, currently under development by ITER. In the present work we have extended the simulation code used previously to include the case of launching two laser pulses, of different wavelengths, simultaneously in LIDAR geometry. The aim of this approach is to broaden the choice of lasers available for the diagnostic. In the simulation code it is assumed that two short duration (300 ps) laser pulses of different wavelengths, from an Nd:YAG laser are launched through the plasma simultaneously. The temperature and density profiles are deduced in the usual way but from the resulting combined scattered signals in the different spectral channels of the single spectrometer. The spectral response and quantum efficiencies of the detectors used in the simulation are taken from catalogue data for commercially available Hamamatsu MCP-PMTs. The response times, gateability and tolerance to stray light levels of this type of photomultiplier have already been demonstrated in the JET LIDAR system and give sufficient spatial resolution to meet the ITER specification. Here we present the new simulation results from the code. They demonstrate that when the detectors are combined with this two laser, LIDAR approach, the full range of the specified ITER core plasma Te and ne can be measured with sufficient accuracy. So, with commercially available detectors and a simple modification of a Nd:YAG laser similar to that currently being used in the design of the conventional ITER core TS design mentioned above, the ITER requirements can be met.

TS mRNA levels can predict pemetrexed and raltitrexed sensitivity in colorectal cancer.

PubMed

Zhang, Qun; Shen, Jie; Wang, Hao; Hu, Jing; Yu, Lixia; Xie, Li; Wei, Jia; Liu, Baorui; Guan, Wenxian; Qian, Xiaoping

2014-02-01

The purpose of the study is to analyze the relationship between tumor thymidylate synthase (TS) mRNA expression levels and raltitrexed/pemetrexed/5-FU sensitivity. We collected freshly removed colorectal tumor specimens from 50 patients. Chemosensitivities to anticancer drugs were evaluated by histoculture drug response assay. We adopted quantitative reverse transcription polymerase chain reaction for TS mRNA detection and immunohistochemical staining for assessing TS expression in tumor tissues. There is a significant relationship between TS mRNA expression levels and in vitro chemosensitivity of freshly removed colorectal tumor specimens to pemetrexed (P < 0.001)/raltitrexed (P = 0.004)/5-FU (P = 0.007). TS mRNA expression levels can predict pemetrexed and raltitrexed sensitivity in colorectal cancer.

Thymidylate synthase (TS) gene expression in primary lung cancer patients: a large-scale study in Japanese population.

PubMed

Tanaka, F; Wada, H; Fukui, Y; Fukushima, M

2011-08-01

Previous small-sized studies showed lower thymidylate synthase (TS) expression in adenocarcinoma of the lung, which may explain higher antitumor activity of TS-inhibiting agents such as pemetrexed. To quantitatively measure TS gene expression in a large-scale Japanese population (n = 2621) with primary lung cancer, laser-captured microdissected sections were cut from primary tumors, surrounding normal lung tissues and involved nodes. TS gene expression level in primary tumor was significantly higher than that in normal lung tissue (mean TS/β-actin, 3.4 and 1.0, respectively; P < 0.01), and TS gene expression level was further higher in involved node (mean TS/β-actin, 7.7; P < 0.01). Analyses of TS gene expression levels in primary tumor according to histologic cell type revealed that small-cell carcinoma showed highest TS expression (mean TS/β-actin, 13.8) and that squamous cell carcinoma showed higher TS expression as compared with adenocarcinoma (mean TS/β-actin, 4.3 and 2.3, respectively; P < 0.01); TS gene expression was significantly increased along with a decrease in the grade of tumor cell differentiation. There was no significant difference in TS gene expression according to any other patient characteristics including tumor progression. Lower TS expression in adenocarcinoma of the lung was confirmed in a large-scale study.

Evaluation of the egg transmission and pathogenicity of Mycoplasma gallisepticum isolates genotyped as ts-11.

PubMed

Armour, Natalie K; Ferguson-Noel, Naola

2015-01-01

Live Mycoplasma gallisepticum vaccines are used for the control of respiratory disease, egg production losses and egg transmission associated with M. gallisepticum infection in long-lived poultry. The first field case of apparent increased virulence and vertical transmission of ts-11, a live M. gallisepticum vaccine, has been reported. In that study a M. gallisepticum isolate from the broiler progeny of ts-11-vaccinated breeders was genotyped as ts-11 by sequence analysis of four different genetic targets and Random Amplified Polymorphic DNA and found to be significantly more virulent than ts-11 vaccine. The objective of the current study was to evaluate the rate of egg transmission and pathogenicity of ts-11 vaccine and isolates recovered from ts-11-vaccinated breeders (K6222B) and their broiler progeny (K6216D) which had been genotyped as ts-11. Groups of 28-week-old specific pathogen-free chickens at 87% average weekly egg production were inoculated with sterile broth media (negative controls), ts-11 vaccine, K6222B, K6216D or R strain (positive controls) by eye-drop and aerosol. K6216D transmitted via the egg at an average rate of 4.0% in the third and fourth weeks post-infection, while egg transmission of K6222B and ts-11 vaccine was not detected. M. gallisepticum was isolated from the air sacs, ovaries and oviducts of hens infected with K6216D and K6222B, but not from those infected with ts-11 vaccine. K6216D and K6222B both induced respiratory signs and significantly more tracheal colonization and more severe tracheal and air sac lesions than ts-11 vaccine (P ≤ 0.05). There were no substantial differences in the egg production of ts-11, K6216D and K6222B infected groups. These results provide the first conclusive evidence of transovarian transmission of an isolate genotyped as ts-11 and indicate that isolates genotyed as ts-11 vary in their virulence and ability to transmit via the egg.

Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

PubMed

Shimizu, A; Kaira, K; Okubo, Y; Utsumi, D; Bolag, A; Yasuda, M; Takahashi, K; Ishikawa, O

2017-01-01

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

Replacing Ag(TS)SCH(2)-R with Ag(TS)O(2)C-R in EGaIn-based tunneling junctions does not significantly change rates of charge transport.

PubMed

Liao, Kung-Ching; Yoon, Hyo Jae; Bowers, Carleen M; Simeone, Felice C; Whitesides, George M

2014-04-07

This paper compares rates of charge transport by tunneling across junctions with the structures Ag(TS) X(CH2 )2n CH3  //Ga2 O3  /EGaIn (n=1-8 and X= SCH2  and O2 C); here Ag(TS) is template-stripped silver, and EGaIn is the eutectic alloy of gallium and indium. Its objective was to compare the tunneling decay coefficient (β, Å(-1) ) and the injection current (J0 , A cm(-2) ) of the junctions comprising SAMs of n-alkanethiolates and n-alkanoates. Replacing Ag(TS) SCH2 -R with Ag(TS) O2 C-R (R=alkyl chains) had no significant influence on J0 (ca. 3×10(3)  A cm(-2) ) or β (0.75-0.79 Å(-1) )-an indication that such changes (both structural and electronic) in the Ag(TS) XR interface do not influence the rate of charge transport. A comparison of junctions comprising oligo(phenylene)carboxylates and n-alkanoates showed, as expected, that β for aliphatic (0.79 Å(-1) ) and aromatic (0.60 Å(-1) ) SAMs differed significantly. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precursor effect on the property and catalytic behavior of Fe-TS-1 in butadiene epoxidation

NASA Astrophysics Data System (ADS)

Wu, Mei; Zhao, Huahua; Yang, Jian; Zhao, Jun; Song, Huanling; Chou, Lingjun

2017-11-01

The effect of iron precursor on the property and catalytic behavior of iron modified titanium silicalite molecular sieve (Fe-TS-1) catalysts in butadiene selective epoxidation has been studied. Three Fe-TS-1 catalysts were prepared, using iron nitrate, iron chloride and iron sulfate as precursors, which played an important role in adjusting the textural properties and chemical states of TS-1. Of the prepared Fe-TS-1 catalysts, those modified by iron nitrate (FN-TS-1) exhibited a significant enhanced performance in butadiene selective epoxidation compared to those derived from iron sulfate (FS-TS-1) or iron chloride (FC-TS-1) precursors. To obtain a deep understanding of their structure-performance relationship, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Temperature programmed desorption of NH3 (NH3-TPD), Diffuse reflectance UV-Vis spectra (DR UV-Vis), Fourier transformed infrared spectra (FT-IR) and thermal gravimetric analysis (TGA) were conducted to characterize Fe-TS-1 catalysts. Experimental results indicated that textural structures and acid sites of modified catalysts as well as the type of Fe species influenced by the precursors were all responsible for the activity and product distribution.

Identifying antimalarial compounds targeting dihydrofolate reductase-thymidylate synthase (DHFR-TS) by chemogenomic profiling.

PubMed

Aroonsri, Aiyada; Akinola, Olugbenga; Posayapisit, Navaporn; Songsungthong, Warangkhana; Uthaipibull, Chairat; Kamchonwongpaisan, Sumalee; Gbotosho, Grace O; Yuthavong, Yongyuth; Shaw, Philip J

2016-07-01

The mode of action of many antimalarial drugs is unknown. Chemogenomic profiling is a powerful method to address this issue. This experimental approach entails disruption of gene function and phenotypic screening for changes in sensitivity to bioactive compounds. Here, we describe the application of reverse genetics for chemogenomic profiling in Plasmodium. Plasmodium falciparum parasites harbouring a transgenic insertion of the glmS ribozyme downstream of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene were used for chemogenomic profiling of antimalarial compounds to identify those which target DHFR-TS. DHFR-TS expression can be attenuated by exposing parasites to glucosamine. Parasites with attenuated DHFR-TS expression were significantly more sensitive to antifolate drugs known to target DHFR-TS. In contrast, no change in sensitivity to other antimalarial drugs with different modes of action was observed. Chemogenomic profiling was performed using the Medicines for Malaria Venture (Switzerland) Malaria Box compound library, and two compounds were identified as novel DHFR-TS inhibitors. We also tested the glmS ribozyme in Plasmodium berghei, a rodent malaria parasite. The expression of reporter genes with downstream glmS ribozyme could be attenuated in transgenic parasites comparable with that obtained in P. falciparum. The chemogenomic profiling method was applied in a P. berghei line expressing a pyrimethamine-resistant Toxoplasma gondii DHFR-TS reporter gene under glmS ribozyme control. Parasites with attenuated expression of this gene were significantly sensitised to antifolates targeting DHFR-TS, but not other drugs with different modes of action. In conclusion, these data show that the glmS ribozyme reverse genetic tool can be applied for identifying primary targets of antimalarial compounds in human and rodent malaria parasites. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Water-soluble phenol TS-13 combats acute but not chronic inflammation.

PubMed

Menshchikova, Elena; Tkachev, Victor; Lemza, Anna; Sharkova, Tatyana; Kandalintseva, Natalya; Vavilin, Valentin; Safronova, Olga; Zenkov, Nikolay

2014-09-01

This study was conducted to evaluate the effect of the synthetic water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling system, in experimental models of acute and chronic inflammation. Acute local inflammation was induced by intraplantar carrageenan injection into rat hind paws, and acute systemic inflammation was modeled by intravenous zymosan injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic inflammation was investigated in rat models of air pouch and collagen-induced arthritis. The effects of TS-13 treatment were estimated by changes in the intensity of inflammation (paw edema, liver infiltration, animal survival, exudation, and clinical score of arthritis) and by the effects on reactive oxygen species (ROS) generation by leukocytes from peripheral blood and inflammatory exudates. We found the significant increase in expression of mRNA, content of protein and activity of a well-characterized Nrf2 target enzyme glutathione S-transferase P1, as well as nuclear extract protein binding to the ARE consensus sequence in liver of mice fed with diet containing TS-13. TS-13 markedly attenuated carrageenan-induced paw edema, reduced blood granulocyte number and volume density of liver infiltrates in the systemic zymosan-induced inflammation model, and increased mice survival after lipopolysaccharide-induced septic shock. However, TS-13 administration did not influence cell and protein exudation into air pouches and suppressed clinical manifestation of collagen-induced polyarthritis only at early stages. Nevertheless, TS-13 inhibited the generation of ROS by leukocytes in all inflammation models. The data suggest that the anti-inflammatory effects of Keap1/Nrf2/ARE system are more prominent against acute innate-mediated inflammation than chronic immune inflammation. This narrows the potential therapeutic efficacy of ARE inducers in inflammation treatment.

VISIT-TS: A multimedia tool for population studies on tic disorders.

PubMed

Vachon, M Jonathan; Striley, Catherine W; Gordon, Mollie R; Schroeder, Miriam L; Bihun, Emily C; Koller, Jonathan M; Black, Kevin J

2016-01-01

Population-based assessment of Tourette syndrome (TS) and other tic disorders produces a paradox. On one hand, ideally diagnosis of tic disorders requires expert observation. In fact, diagnostic criteria for TS explicitly require expert assessment of tics for a definite diagnosis. On the other hand, large-scale population surveys with expert assessment of every subject are impracticable. True, several published studies have successfully used expert assessment to find tic prevalence in a representative population (e.g. all students in a school district). However, extending these studies to larger populations is daunting. We created a multimedia tool to demonstrate tics to a lay audience, discuss their defining and common attributes, and address features that differentiate tics from other movements and vocalizations. A first version was modified to improve clarity and to include a more diverse group in terms of age and ethnicity. The result is a tool intended for epidemiological research. It may also provide additional benefits, such as more representative minority recruitment for other TS studies and increased community awareness of TS.

Optimising mobile phase composition, its flow-rate and column temperature in HPLC using taboo search.

PubMed

Guillaume, Y C; Peyrin, E

2000-03-06

A chemometric methodology is proposed to study the separation of seven p-hydroxybenzoic esters in reversed phase liquid chromatography (RPLC). Fifteen experiments were found to be necessary to find a mathematical model which linked a novel chromatographic response function (CRF) with the column temperature, the water fraction in the mobile phase and its flow rate. The CRF optimum was determined using a new algorithm based on Glover's taboo search (TS). A flow-rate of 0.9 ml min(-1) with a water fraction of 0.64 in the ACN-water mixture and a column temperature of 10 degrees C gave the most efficient separation conditions. The usefulness of TS was compared with the pure random search (PRS) and simplex search (SS). As demonstrated by calculations, the algorithm avoids entrapment in local minima and continues the search to give a near-optimal final solution. Unlike other methods of global optimisation, this procedure is generally applicable, easy to implement, derivative free, conceptually simple and could be used in the future for much more complex optimisation problems.

Deep-HiTS: Rotation Invariant Convolutional Neural Network for Transient Detection

NASA Astrophysics Data System (ADS)

Cabrera-Vives, Guillermo; Reyes, Ignacio; Förster, Francisco; Estévez, Pablo A.; Maureira, Juan-Carlos

2017-02-01

We introduce Deep-HiTS, a rotation-invariant convolutional neural network (CNN) model for classifying images of transient candidates into artifacts or real sources for the High cadence Transient Survey (HiTS). CNNs have the advantage of learning the features automatically from the data while achieving high performance. We compare our CNN model against a feature engineering approach using random forests (RFs). We show that our CNN significantly outperforms the RF model, reducing the error by almost half. Furthermore, for a fixed number of approximately 2000 allowed false transient candidates per night, we are able to reduce the misclassified real transients by approximately one-fifth. To the best of our knowledge, this is the first time CNNs have been used to detect astronomical transient events. Our approach will be very useful when processing images from next generation instruments such as the Large Synoptic Survey Telescope. We have made all our code and data available to the community for the sake of allowing further developments and comparisons at https://github.com/guille-c/Deep-HiTS. Deep-HiTS is licensed under the terms of the GNU General Public License v3.0.

Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer.

PubMed

van der Zee, J A; van Eijck, C H J; Hop, W C J; van Dekken, H; Dicheva, B M; Seynhaeve, A L B; Koning, G A; Eggermont, A M M; Ten Hagen, T L M

2012-11-01

Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer. TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors. High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10). TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tumorigenic Evaluation of Jet Fuels JP-TS and JP-7.

DTIC Science & Technology

1991-04-01

DTIC AL-TR-1991 0020 3 ELECTE0 AD-A252 012 JUN 2 6 1992• • TUMORIGENIC EVALUATION OF JET FUELS JP-TS AND JP-7 E. R. Kinkead C. L. Gaworski C. D...Evaluation of Jet Fuels JP-TS and JP-7. The research described in this report began in March 1981 and was completed in February 1991 under U.S. Air Force...of jet engines in military and commercial aircraft has led to the development of a number of petroleum distillate fuels with special properties. These

Evaluation of Mycoplasma gallisepticum (MG) ts-304 vaccine as a live attenuated vaccine in turkeys.

PubMed

Kanci, Anna; Wijesurendra, Dinidu S; Wawegama, Nadeeka K; Underwood, Gregory J; Noormohammadi, Amir H; Markham, Philip F; Browning, Glenn F

2018-04-25

Mycoplasma gallisepticum (MG) is an important pathogen of poultry worldwide that causes chronic respiratory disease (CRD) in chickens and infectious sinusitis in turkeys. Vaxsafe MG (strain ts-11) is a live attenuated temperature sensitive vaccine that has been proven to be effective in controlling CRD in chickens, but it is not efficacious in turkeys. The gapA gene, which encodes a mature cytadhesin protein with a molecular weight of approximately 105 kDa, is not expressed in strain ts-11 because a 20 base pair reiterated sequence introduces a frame shift and causes premature truncation of the translated peptide. A GapA positive clone, MG ts-304, isolated from strain ts-11 has been shown to have enhanced efficacy in chickens. Here we describe studies we conducted to assess the safety and efficacy of the MG ts-304 vaccine candidate in turkeys. We found that MG ts-304 was able to colonise the trachea of 3-week-old turkeys and was safe, even at a tenfold overdose, inducing no adverse clinical signs of respiratory disease or significant gross lesions in the respiratory tract (air sacs or trachea), and was poorly transmissible to in-contact birds. We also showed that it was efficacious when administered to 3-week-old turkeys, inducing protective immunity against challenge with the M.gallisepticum wild-type strain Ap3AS. MG ts-304 is therefore a promising live attenuated vaccine candidate for use in turkeys. Copyright © 2018. Published by Elsevier Ltd.

Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function

PubMed Central

2015-01-01

The nucleus tractus solitarii (nTS) is the initial central termination site for visceral afferents and is important for modulation and integration of multiple reflexes including cardiorespiratory reflexes. Glutamate is the primary excitatory neurotransmitter in the nTS and is removed from the extracellular milieu by excitatory amino acid transporters (EAATs). The goal of this study was to elucidate the role of EAATs in the nTS on basal synaptic and neuronal function and cardiorespiratory regulation. The majority of glutamate clearance in the central nervous system is believed to be mediated by astrocytic EAAT 1 and 2. We confirmed the presence of EAAT 1 and 2 within the nTS and their colocalization with astrocytic markers. EAAT blockade with dl-threo-β-benzyloxyaspartic acid (TBOA) produced a concentration-related depolarization, increased spontaneous excitatory postsynaptic current (EPSC) frequency, and enhanced action potential discharge in nTS neurons. Solitary tract-evoked EPSCs were significantly reduced by EAAT blockade. Microinjection of TBOA into the nTS of anesthetized rats induced apneic, sympathoinhibitory, depressor, and bradycardic responses. These effects mimicked the response to microinjection of exogenous glutamate, and glutamate responses were enhanced by EAAT blockade. Together these data indicate that EAATs tonically restrain nTS excitability to modulate cardiorespiratory function. PMID:26719090

Effects of Tityus serrulatus scorpion venom and its toxin TsTX-V on neurotransmitter uptake in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cecchini, Alessandra L.; Vollum Institute, Oregon Health Sciences University, Portland, Oregon 9701; Vasconcelos, Flavio

2006-12-01

Scorpion neurotoxins targeting the Na{sub v} channel can be classified into two classes: {alpha}- and {beta}-neurotoxins and are reported as highly active in mammalian brain. In this work, we evaluate the effects of Tityus serrulatus venom (Ts venom) and its {alpha}-neurotoxin TsTX-V on {gamma}-aminobutyric acid (GABA), dopamine (DA) and glutamate (Glu) uptake in isolated rat brain synaptosomes. TsTX-V was isolated from Ts venom by ion exchange chromatography followed by reverse-phase (C18) high-performance liquid chromatography. Neither Ts venom nor TsTX-V was able to affect {sup 3}H-Glu uptake. On the other hand, Ts venom (0.13 {mu}g/mg) significantly inhibited both {sup 3}H-GABA andmore » {sup 3}H-DA uptake ({approx} 50%). TsTX-V showed IC{sub 5} values of 9.37 {mu}M and 22.2 {mu}M for the inhibition of {sup 3}H-GABA and {sup 3}H-DA uptake, respectively. These effects were abolished by pre-treatment with tetrodotoxin (TTX, 1 {mu}M), indicating the involvement of voltage-gated Na{sup +} channels in this process. In the absence of Ca{sup 2+}, and at low Ts venom concentrations, the reduction of {sup 3}H-GABA uptake was not as marked as in the presence of Ca{sup 2+}. TsTX-V did not reduce {sup 3}H-GABA uptake in COS-7 cells expressing the GABA transporters GAT-1 and GAT-3, suggesting that this toxin indirectly reduces the transport. The reduced {sup 3}H-GABA uptake by synaptosomes might be due to rapid cell depolarization as revealed by confocal microscopy of C6 glioma cells. Thus, TsTX-V causes a reduction of {sup 3}H-GABA and {sup 3}H-DA uptake in a Ca{sup 2+}-dependent manner, not directly affecting GABA transporters, but, in consequence of depolarization, involving voltage-gated Na{sup +} channels.« less

Cloning and characterization of EF-Tu and EF-Ts from Pseudomonas aeruginosa.

PubMed

Palmer, Stephanie O; Rangel, Edna Y; Montalvo, Alberto E; Tran, Alexis T; Ferguson, Kate C; Bullard, James M

2013-01-01

We have cloned genes encoding elongation factors EF-Tu and EF-Ts from Pseudomonas aeruginosa and expressed and purified the proteins to greater than 95% homogeneity. Sequence analysis indicated that P. aeruginosa EF-Tu and EF-Ts are 84% and 55% identical to E. coli counterparts, respectively. P. aeruginosa EF-Tu was active when assayed in GDP exchange assays. Kinetic parameters for the interaction of EF-Tu with GDP in the absence of EF-Ts were observed to be K M = 33 μM, k cat (obs) = 0.003 s(-1), and the specificity constant k cat (obs)/K M was 0.1 × 10(-3) s(-1) μM(-1). In the presence of EF-Ts, these values were shifted to K M = 2 μM, k cat (obs) = 0.005 s(-1), and the specificity constant k(cat)(obs)/K M was 2.5 × 10(-3) s(-1) μM(-1). The equilibrium dissociation constants governing the binding of EF-Tu to GDP (K GDP) were 30-75 nM and to GTP (K GTP) were 125-200 nM. EF-Ts stimulated the exchange of GDP by EF-Tu 10-fold. P. aeruginosa EF-Tu was active in forming a ternary complex with GTP and aminoacylated tRNA and was functional in poly(U)-dependent binding of Phe-tRNA(Phe) at the A-site of P. aeruginosa ribosomes. P. aeruginosa EF-Tu was active in poly(U)-programmed polyphenylalanine protein synthesis system composed of all P. aeruginosa components.

Assembly of Q{beta} viral RNA polymerase with host translational elongation factors EF-Tu and -Ts.

PubMed

Takeshita, Daijiro; Tomita, Kozo

2010-09-07

Replication and transcription of viral RNA genomes rely on host-donated proteins. Qbeta virus infects Escherichia coli and replicates and transcribes its own genomic RNA by Qbeta replicase. Qbeta replicase requires the virus-encoded RNA-dependent RNA polymerase (beta-subunit), and the host-donated translational elongation factors EF-Tu and -Ts, as active core subunits for its RNA polymerization activity. Here, we present the crystal structure of the core Qbeta replicase, comprising the beta-subunit, EF-Tu and -Ts. The beta-subunit has a right-handed structure, and the EF-Tu:Ts binary complex maintains the structure of the catalytic core crevasse of the beta-subunit through hydrophobic interactions, between the finger and thumb domains of the beta-subunit and domain-2 of EF-Tu and the coiled-coil motif of EF-Ts, respectively. These hydrophobic interactions are required for the expression and assembly of the Qbeta replicase complex. Thus, EF-Tu and -Ts have chaperone-like functions in the maintenance of the structure of the active Qbeta replicase. Modeling of the template RNA and the growing RNA in the catalytic site of the Qbeta replicase structure also suggests that structural changes of the RNAs and EF-Tu:Ts should accompany processive RNA polymerization and that EF-Tu:Ts in the Qbeta replicase could function to modulate the RNA folding and structure.

Lifespan analysis of brain development, gene expression and behavioral phenotypes in the Ts1Cje, Ts65Dn and Dp(16)1/Yey mouse models of Down syndrome.

PubMed

Aziz, Nadine M; Guedj, Faycal; Pennings, Jeroen L A; Olmos-Serrano, Jose Luis; Siegel, Ashley; Haydar, Tarik F; Bianchi, Diana W

2018-06-12

Down syndrome (DS) results from triplication of human chromosome 21. Neuropathological hallmarks of DS include atypical central nervous system development that manifests prenatally and extends throughout life. As a result, individuals with DS exhibit cognitive and motor deficits, and have delays in achieving developmental milestones. To determine whether different mouse models of DS recapitulate the human prenatal and postnatal phenotypes, here, we directly compared brain histogenesis, gene expression and behavior over the lifespan of three cytogenetically distinct mouse models of DS: Ts1Cje, Ts65Dn and Dp(16)1/Yey. Histological data indicated that Ts65Dn mice were the most consistently affected with respect to somatic growth, neurogenesis and brain morphogenesis. Embryonic and adult gene expression results showed that Ts1Cje and Ts65Dn brains had considerably more differentially expressed (DEX) genes compared with Dp(16)1/Yey mice, despite the larger number of triplicated genes in the latter model. In addition, DEX genes showed little overlap in identity and chromosomal distribution in the three models, leading to dissimilarities in affected functional pathways. Perinatal and adult behavioral testing also highlighted differences among the models in their abilities to achieve various developmental milestones and perform hippocampal- and motor-based tasks. Interestingly, Dp(16)1/Yey mice showed no abnormalities in prenatal brain phenotypes, yet they manifested behavioral deficits starting at postnatal day 15 that continued through adulthood. In contrast, Ts1Cje mice showed mildly abnormal embryonic brain phenotypes, but only select behavioral deficits as neonates and adults. Altogether, our data showed widespread and unexpected fundamental differences in behavioral, gene expression and brain development phenotypes between these three mouse models. Our findings illustrate unique limitations of each model when studying aspects of brain development and function in DS

Quantitative Assessment of RNA-Protein Interactions with High Throughput Sequencing - RNA Affinity Profiling (HiTS-RAP)

PubMed Central

Ozer, Abdullah; Tome, Jacob M.; Friedman, Robin C.; Gheba, Dan; Schroth, Gary P.; Lis, John T.

2016-01-01

Because RNA-protein interactions play a central role in a wide-array of biological processes, methods that enable a quantitative assessment of these interactions in a high-throughput manner are in great demand. Recently, we developed the High Throughput Sequencing-RNA Affinity Profiling (HiTS-RAP) assay, which couples sequencing on an Illumina GAIIx with the quantitative assessment of one or several proteins’ interactions with millions of different RNAs in a single experiment. We have successfully used HiTS-RAP to analyze interactions of EGFP and NELF-E proteins with their corresponding canonical and mutant RNA aptamers. Here, we provide a detailed protocol for HiTS-RAP, which can be completed in about a month (8 days hands-on time) including the preparation and testing of recombinant proteins and DNA templates, clustering DNA templates on a flowcell, high-throughput sequencing and protein binding with GAIIx, and finally data analysis. We also highlight aspects of HiTS-RAP that can be further improved and points of comparison between HiTS-RAP and two other recently developed methods, RNA-MaP and RBNS. A successful HiTS-RAP experiment provides the sequence and binding curves for approximately 200 million RNAs in a single experiment. PMID:26182240

[Correlation between thermostability of the xylanase EvXyn11(TS) and its N-terminal disulfide bridge].

PubMed

Min, Rou; Li, Jianfang; Gao, Shujuan; Zhang, Huimin; Wu, Jing; Wu, Minchen

2013-04-04

To reveal the correlation between thermostability of xylanase EvXyn11(TS) and its N-terminal disulfide bridge, an EvXyn11(TS)-encoding gene (Syxyn11) was synthesized and subjected to site-directed mutagenesis. Multiple homology alignment of protein primary structures between the EvXyn11(TS) and several GH family 11 xylanases displayed that, in their N-termini, only EvXyn11(TS) contained a disulfide bridge (Cys5-Cys32), whose effect on the xylanase thermostability was predicted by molecular dynamics simulation. We constructed a gene Syxyn11(M), encoding the mutated xylanase (EvXyn11(M)) without N-terminal disulfide bridge. Then, Syxyn11 and Syxyn11(M) were expressed in Pichia pastoris GS115, and temperature and pH properties of the expressed enzymes were analyzed. The analytical results displayed that the temperature optimum of EvXyn11(M) was 70 degrees C, which was 15 degrees C lower than that of EvXyn11(TS). The half-life (t1/2(90)) of EvXyn11(TS) at 90 degrees C was 32 min, while the t1/2(70) of EvXyn11(M) at 70 degrees C was only 8.0 min. The important role of the N-terminal disulfide bridge on the thermostability of EvXyn11(TS) was first predicted by molecular dynamics simulation, and confirmed by site-directed mutagenesis. This work provided a novel strategy to improve thermostabilities of the mesophilic family 11 xylanases with high specific activities.

A Geographical Heuristic Routing Protocol for VANETs.

PubMed

Urquiza-Aguiar, Luis; Tripp-Barba, Carolina; Aguilar Igartua, Mónica

2016-09-23

Vehicular ad hoc networks (VANETs) leverage the communication system of Intelligent Transportation Systems (ITS). Recently, Delay-Tolerant Network (DTN) routing protocols have increased their popularity among the research community for being used in non-safety VANET applications and services like traffic reporting. Vehicular DTN protocols use geographical and local information to make forwarding decisions. However, current proposals only consider the selection of the best candidate based on a local-search. In this paper, we propose a generic Geographical Heuristic Routing (GHR) protocol that can be applied to any DTN geographical routing protocol that makes forwarding decisions hop by hop. GHR includes in its operation adaptations simulated annealing and Tabu-search meta-heuristics, which have largely been used to improve local-search results in discrete optimization. We include a complete performance evaluation of GHR in a multi-hop VANET simulation scenario for a reporting service. Our study analyzes all of the meaningful configurations of GHR and offers a statistical analysis of our findings by means of MANOVA tests. Our results indicate that the use of a Tabu list contributes to improving the packet delivery ratio by around 5% to 10%. Moreover, if Tabu is used, then the simulated annealing routing strategy gets a better performance than the selection of the best node used with carry and forwarding (default operation).

A Geographical Heuristic Routing Protocol for VANETs

PubMed Central

Urquiza-Aguiar, Luis; Tripp-Barba, Carolina; Aguilar Igartua, Mónica

2016-01-01

Vehicular ad hoc networks (VANETs) leverage the communication system of Intelligent Transportation Systems (ITS). Recently, Delay-Tolerant Network (DTN) routing protocols have increased their popularity among the research community for being used in non-safety VANET applications and services like traffic reporting. Vehicular DTN protocols use geographical and local information to make forwarding decisions. However, current proposals only consider the selection of the best candidate based on a local-search. In this paper, we propose a generic Geographical Heuristic Routing (GHR) protocol that can be applied to any DTN geographical routing protocol that makes forwarding decisions hop by hop. GHR includes in its operation adaptations simulated annealing and Tabu-search meta-heuristics, which have largely been used to improve local-search results in discrete optimization. We include a complete performance evaluation of GHR in a multi-hop VANET simulation scenario for a reporting service. Our study analyzes all of the meaningful configurations of GHR and offers a statistical analysis of our findings by means of MANOVA tests. Our results indicate that the use of a Tabu list contributes to improving the packet delivery ratio by around 5% to 10%. Moreover, if Tabu is used, then the simulated annealing routing strategy gets a better performance than the selection of the best node used with carry and forwarding (default operation). PMID:27669254

Clinical outcomes of TS-1 chemotherapy for advanced and recurrent gastric cancer.

PubMed

Lee, Sung Ryol; Kim, Hyung Ook; Yoo, Chang Hak

2011-09-01

Titanium silicate (TS)-1 chemotherapy has been widely used against gastric cancer in Japan. The aim of the present study was to assess the efficacy and hematological safety of TS-1 as treatment for advanced and recurrent gastric cancer. From September 2006 to February 2011, 51 advanced or recurrent gastric cancers were treated with TS-1. One course of treatment consisted of 40, 50, or 60 mg/m(2) of TS-1 twice a day for 28 days, followed by withdrawal for two weeks. The primary end point was progression-free survival (PFS), and the secondary end point was overall survival (OS). The disease control rate was 39.2% (complete response, 0/51; partial response, 6/51; stable disease, 14/51; progressive disease, 23/51; not evaluable, 8/51). The median PFS was 4.0 months (95% confidence interval [CI], 2.2 to 5.7); the median PFS of the advanced group was 6.0 months (95% CI, 2.8 to 9.1), and the median PFS of the recurrent group was 3.0 months (95% CI, 1.8 to 4.1). The median OS was 11.0 months (95% CI, 6.3 to 15.6); the median OS of the advanced group was 10.0 months (95% CI, 4.9 to 15.0), and the median OS of the recurrent group was 14.0 months (95% CI, 4.1 to 23.8). Grade 3 or 4 hematological toxicity occurred in three patients (5.9%), anemia occurred in two patients (3.9%), and thrombocytopenia occurred in one patient (2%). TS-1 chemotherapy was safe and effective, with relatively long PFS and OS in patients with advanced and recurrent gastric cancers.

E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

PubMed

Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz

2016-07-01

The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

Digastric Muscle Phenotypes of the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Connor, Nadine P.

2016-01-01

Down syndrome is frequently associated with complex difficulties in oromotor development, feeding, and swallowing. However, the muscle phenotypes underlying these deficits are unclear. We tested the hypotheses that the Ts65Dn mouse model of DS has significantly altered myosin heavy chain (MyHC) isoform profiles of the muscles involved in feeding and swallowing, as well as reductions in the speed of these movements during behavioral assays. SDS-PAGE, immunofluorescence, and qRT-PCR were used to assess MyHC isoform expression in pertinent muscles, and functional feeding and swallowing performance were quantified through videofluoroscopy and mastication assays. We found that both the anterior digastric (ADG) and posterior digastric (PDG) muscles in 11-day old and 5–6 week old Ts65Dn groups showed significantly lower MyHC 2b protein levels than in age-matched euploid control groups. In videofluoroscopic and videotape assays used to quantify swallowing and mastication performance, 5–6 week old Ts65Dn and euploid controls showed similar swallow rates, inter-swallow intervals, and mastication rates. In analysis of adults, 10–11 week old Ts65Dn mice revealed significantly less MyHC 2b mRNA expression in the posterior digastric, but not the anterior digastric muscle as compared with euploid controls. Analysis of MyHC 2b protein levels across an adult age range (10–53 weeks of age) revealed lower levels of MyHC 2b protein in the PDG of Ts65Dn than in euploids, but similar levels of MyHC 2b in the ADG. Cumulatively, these results indicate biochemical differences in some, but not all, muscles involved in swallowing and jaw movement in Ts65Dn mice that manifest early in post-natal development, and persist into adulthood. These findings suggest potential utility of this model for future investigations of the mechanisms of oromotor difficulties associated with Down syndrome. PMID:27336944

Synthesis of mesoporous TS-1 using a hybrid SiO{sub 2}–TiO{sub 2} xerogel for catalytic oxidative desulfurization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Seung-Tae; Jeong, Kwang-Eun; Jeong, Soon-Yong

2012-12-15

Graphical abstract: Display Omitted Highlights: ► Meso-TS-1 catalyst was synthesized using a SiO{sub 2}–TiO{sub 2} xerogel with an organosilane precursor. ► Hierarchical pore structure was confirmed by characterization of the materials. ► Catalytic activity was tested using oxidative desulfurization of the model sulfur compounds. ► Meso-TS-1 demonstrated significantly improved catalytic activity than TS-1. -- Abstract: Mesoporous TS-1 (M-TS-1) was synthesized using a hybrid SiO{sub 2}–TiO{sub 2} xerogel combined with an organosilane precursor. Prepared samples were characterized by XRD, UV–vis spectroscopy, SEM, and N{sub 2} adsorption–desorption measurement. M-TS-1, prepared in 2 days, showed high crystallinity and the best textural properties amongmore » the samples. The N{sub 2} adsorption–desorption isotherms of M-TS-1 exhibited a hysteresis loop at pressure higher than P/P{sub 0} = 0.4, clearly indicating the existence of mesopores. M-TS-1 has significantly larger mesopore volume (0.48 cm{sup 3}/g) than that of conventional TS-1 (0.07 cm{sup 3}/g), and showed a narrow peak centered at ca. 6.3 nm. In the oxidative desulfurization reaction, M-TS-1 was more active than conventional TS-1 at the same Ti-loading; M-TS-1 produced a dibenzothiophene (DBT) conversion of 96%, whereas conventional TS-1 produced a final DBT conversion of 5.6% after a reaction time of 180 min. Oxidative desulfurization over TS-1 was influenced both by electron density and steric hindrance in the sulfur compounds tested.« less

Standardizing procedures to study sensitization of human spinal nociceptive processes: comparing parameters for temporal summation of the nociceptive flexion reflex (TS-NFR).

PubMed

Terry, Ellen L; France, Christopher R; Bartley, Emily J; Delventura, Jennifer L; Kerr, Kara L; Vincent, Ashley L; Rhudy, Jamie L

2011-09-01

Temporal summation of pain (TS-pain) is the progressive increase in pain ratings during a series of noxious stimulations. TS-pain has been used to make inferences about sensitization of spinal nociceptive processes; however, pain report can be biased thereby leading to problems with this inference. Temporal summation of the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception) can potentially overcome report bias, but there have been few attempts (generally with small Ns) to standardize TS-NFR procedures. In this study, 50 healthy participants received 25 series of noxious electric stimulations to evoke TS-NFR and TS-pain. Goals were to: 1) determine the stimulation frequency that best elicits TS-NFR and reduces electromyogram (EMG) contamination from muscle tension, 2) determine the minimum number of stimulations per series before NFR summation asymptotes, 3) compare NFR definition intervals (90-150ms vs. 70-150ms post-stimulation), and 4) compare TS-pain and TS-NFR when different stimulation frequencies are used. Results indicated TS-NFR should be elicited by a series of three stimuli delivered at 2.0Hz and TS-NFR should be defined from a 70-150ms post-stimulation scoring interval. Unfortunately, EMG contamination from muscle tension was greatest during 2.0Hz series. Discrepancies were noted between TS-NFR and TS-pain which raise concerns about using pain ratings to infer changes in spinal nociceptive processes. And finally, some individuals did not have reliable NFRs when the stimulation intensity was set at NFR threshold during TS-NFR testing; therefore, a higher intensity is needed. Implications of findings are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Characterization and evolution of tetrameric photosystem I from the thermophilic cyanobacterium Chroococcidiopsis sp TS-821.

PubMed

Li, Meng; Semchonok, Dmitry A; Boekema, Egbert J; Bruce, Barry D

2014-03-01

Photosystem I (PSI) is a reaction center associated with oxygenic photosynthesis. Unlike the monomeric reaction centers in green and purple bacteria, PSI forms trimeric complexes in most cyanobacteria with a 3-fold rotational symmetry that is primarily stabilized via adjacent PsaL subunits; however, in plants/algae, PSI is monomeric. In this study, we discovered a tetrameric form of PSI in the thermophilic cyanobacterium Chroococcidiopsis sp TS-821 (TS-821). In TS-821, PSI forms tetrameric and dimeric species. We investigated these species by Blue Native PAGE, Suc density gradient centrifugation, 77K fluorescence, circular dichroism, and single-particle analysis. Transmission electron microscopy analysis of native membranes confirms the presence of the tetrameric PSI structure prior to detergent solubilization. To investigate why TS-821 forms tetramers instead of trimers, we cloned and analyzed its psaL gene. Interestingly, this gene product contains a short insert between the second and third predicted transmembrane helices. Phylogenetic analysis based on PsaL protein sequences shows that TS-821 is closely related to heterocyst-forming cyanobacteria, some of which also have a tetrameric form of PSI. These results are discussed in light of chloroplast evolution, and we propose that PSI evolved stepwise from a trimeric form to tetrameric oligomer en route to becoming monomeric in plants/algae.

Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test in a randomized trial.

PubMed

Crowther, Mark; Cook, Deborah; Guyatt, Gordon; Zytaruk, Nicole; McDonald, Ellen; Williamson, David; Albert, Martin; Dodek, Peter; Finfer, Simon; Vallance, Shirley; Heels-Ansdell, Diane; McIntyre, Lauralyn; Mehta, Sangeeta; Lamontagne, Francois; Muscedere, John; Jacka, Michael; Lesur, Olivier; Kutsiogiannis, Jim; Friedrich, Jan; Klinger, James R; Qushmaq, Ismael; Burry, Lisa; Khwaja, Kosar; Sheppard, Jo-Ann; Warkentin, Theodore E

2014-06-01

Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting. To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143). Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50×10(9)/L, platelets decreased to 50% of ICU admission value (if admission value<100×10(9)/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores; the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA). Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts

The effects of EF-Ts and bismuth on EF-Tu in Helicobacter pylori: implications for an elegant timing for the introduction of EF-Ts in the elongation and EF-Tu as a potential drug target.

PubMed

Wang, Dongxian; Luo, Benping; Shan, Weiran; Hao, Mingcong; Sun, Xuesong; Ge, Ruiguang

2013-06-01

Helicobacter pylori is a common human pathogen responsible for various gastric diseases. Bismuth can effectively inhibit the growth of this bacterium and is commonly recommended for the treatment of the related diseases. Translation elongation factors EF-Tu and EF-Ts are two important components of the protein translation system. EF-Ts has inhibitory effects on the GTPase activity of EF-Tu and enhances GDP release, a hint that careful timing for the introduction of EF-Ts in the elongation should be accomplished to prevent the complete inhibition of the elongation process. Bismuth inhibits the chaperone activity of EF-Tu, and has opposite effects on the elongation activity: inhibitory effects on the intrinsic GTPase activity and stimulation of GDP release. The present work deepens our understanding of the bacterial elongation process as mediated by EF-Tu and EF-Ts and extends our knowledge about the inhibitory effects of bismuth-based drugs against Helicobacter pylori.

Assessment of the 4Ts pretest clinical scoring system as a predictor of heparin-induced thrombocytopenia.

PubMed

Strutt, Jaclyn K; Mackey, Jennifer E; Johnson, Stephen M; Sylvia, Lynne M

2011-02-01

To evaluate the utility of the 4Ts clinical scoring system as a pretest probability method for the detection of heparin-induced thrombocytopenia (HIT). Prospective observational study. Medical and surgical inpatients at a tertiary care medical center. Eighty consecutive patients with suspicion of HIT who had a polyspecific enzyme-linked immunosorbent assay (ELISA) performed between December 1, 2008, and April 1, 2009, for detection of platelet factor 4 (PF4)-heparin antibodies. The predictive value of the 4Ts scoring system as determined by using a standard laboratory marker of HIT--the ELISA--and the interrater reliability of the scoring system were assessed. Sixty-seven (84%) of the 80 patients had low clinical probability of HIT based on the calculated 4Ts score. The ELISA result was negative for PF4-heparin antibodies in 74 patients (93%). Based on the results of the ELISA, the negative predictive value of the 4Ts score was 91%. Each 4Ts score was calculated by two independent investigators and adjudicated by a third investigator when necessary. The interrater reliability of the scoring system was fair (Cohen κ coefficient 0.362, 95% confidence interval [CI] 0.222-0.502; weighted κ coefficient 0.554 (95% CI 0.441-0.667). Determination of the timing of HIT was associated with the largest number of discrepancies (16) between evaluators, followed by other causes of thrombocytopenia (15), degree of decline in platelet count (14), and the presence of thrombosis or other sequelae (2). A low 4Ts score supports a low probability of HIT based on the results of the polyspecific ELISA. Overall, the interrater reliability of the scoring system was fair. Components of the 4Ts scoring system need to be further clarified or modified in order to improve interrater reliability and thereby increase the clinical utility of this pretest probability model.

TS-Chemscore, a Target-Specific Scoring Function, Significantly Improves the Performance of Scoring in Virtual Screening.

PubMed

Wang, Wen-Jing; Huang, Qi; Zou, Jun; Li, Lin-Li; Yang, Sheng-Yong

2015-07-01

Most of the scoring functions currently used in structure-based drug design belong to 'universal' scoring functions, which often give a poor correlation between the calculated scores and experimental binding affinities. In this investigation, we proposed a simple strategy to construct target-specific scoring functions based on known 'universal' scoring functions. This strategy was applied to Chemscore, a widely used empirical scoring function, which led to a new scoring function, termed TS-Chemscore. TS-Chemscore was validated on 14 protein targets, which cover a wide range of biological target categories. The results showed that TS-Chemscore significantly improved the correlation between the calculated scores and experimental binding affinities compared with the original Chemscore. TS-Chemscore was then applied in virtual screening to retrieve novel JAK3 and YopH inhibitors. Top 30 compounds for each target were selected for experimental validation. Six active compounds for JAK3 and four for YopH were obtained. These compounds were out of the lists of top 30 compounds sorted by Chemscore. Collectively, TS-Chemscore established in this study showed a better performance in virtual screening than its counterpart Chemscore. © 2014 John Wiley & Sons A/S.

ENVIRONMENTAL TECHNOLOGY VERIFICATION: JOINT (NSF-EPA) VERIFICATION STATEMENT AND REPORT: TRITON SYSTEMS, LLC SOLID BOWL CENTRIFUGE, MODEL TS-5000

EPA Science Inventory

Verification testing of the Triton Systems, LLC Solid Bowl Centrifuge Model TS-5000 (TS-5000) was conducted at the Lake Wheeler Road Field Laboratory Swine Educational Unit in Raleigh, North Carolina. The TS-5000 was 48" in diameter and 30" deep, with a bowl capacity of 16 ft3. ...

Combining local and global limitations of visual search.

PubMed

Põder, Endel

2017-04-01

There are different opinions about the roles of local interactions and central processing capacity in visual search. This study attempts to clarify the problem using a new version of relevant set cueing. A central precue indicates two symmetrical segments (that may contain a target object) within a circular array of objects presented briefly around the fixation point. The number of objects in the relevant segments, and density of objects in the array were varied independently. Three types of search experiments were run: (a) search for a simple visual feature (color, size, and orientation); (b) conjunctions of simple features; and (c) spatial configuration of simple features (rotated Ts). For spatial configuration stimuli, the results were consistent with a fixed global processing capacity and standard crowding zones. For simple features and their conjunctions, the results were different, dependent on the features involved. While color search exhibits virtually no capacity limits or crowding, search for an orientation target was limited by both. Results for conjunctions of features can be partly explained by the results from the respective features. This study shows that visual search is limited by both local interference and global capacity, and the limitations are different for different visual features.

Structural outline of the detailed mechanism for elongation factor Ts-mediated guanine nucleotide exchange on elongation factor Tu.

PubMed

Thirup, Søren S; Van, Lan Bich; Nielsen, Tine K; Knudsen, Charlotte R

2015-07-01

Translation elongation factor EF-Tu belongs to the superfamily of guanine-nucleotide binding proteins, which play key cellular roles as regulatory switches. All G-proteins require activation via exchange of GDP for GTP to carry out their respective tasks. Often, guanine-nucleotide exchange factors are essential to this process. During translation, EF-Tu:GTP transports aminoacylated tRNA to the ribosome. GTP is hydrolyzed during this process, and subsequent reactivation of EF-Tu is catalyzed by EF-Ts. The reaction path of guanine-nucleotide exchange is structurally poorly defined for EF-Tu and EF-Ts. We have determined the crystal structures of the following reaction intermediates: two structures of EF-Tu:GDP:EF-Ts (2.2 and 1.8Å resolution), EF-Tu:PO4:EF-Ts (1.9Å resolution), EF-Tu:GDPNP:EF-Ts (2.2Å resolution) and EF-Tu:GDPNP:pulvomycin:Mg(2+):EF-Ts (3.5Å resolution). These structures provide snapshots throughout the entire exchange reaction and suggest a mechanism for the release of EF-Tu in its GTP conformation. An inferred sequence of events during the exchange reaction is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.

PubMed

De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim

2016-10-28

Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry.

PubMed

Yoshida, Kanako; Kuramitsu, Yasuhiro; Murakami, Kohei; Ryozawa, Shomei; Taba, Kumiko; Kaino, Seiji; Zhang, Xiulian; Sakaida, Isao; Nakamura, Kazuyuki

2011-06-01

TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.

Robust Stabilization of T-S Fuzzy Stochastic Descriptor Systems via Integral Sliding Modes.

PubMed

Li, Jinghao; Zhang, Qingling; Yan, Xing-Gang; Spurgeon, Sarah K

2017-09-19

This paper addresses the robust stabilization problem for T-S fuzzy stochastic descriptor systems using an integral sliding mode control paradigm. A classical integral sliding mode control scheme and a nonparallel distributed compensation (Non-PDC) integral sliding mode control scheme are presented. It is shown that two restrictive assumptions previously adopted developing sliding mode controllers for Takagi-Sugeno (T-S) fuzzy stochastic systems are not required with the proposed framework. A unified framework for sliding mode control of T-S fuzzy systems is formulated. The proposed Non-PDC integral sliding mode control scheme encompasses existing schemes when the previously imposed assumptions hold. Stability of the sliding motion is analyzed and the sliding mode controller is parameterized in terms of the solutions of a set of linear matrix inequalities which facilitates design. The methodology is applied to an inverted pendulum model to validate the effectiveness of the results presented.

Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models.

PubMed

Li, Wenlin; Schaeffer, R Dustin; Otwinowski, Zbyszek; Grishin, Nick V

2016-01-01

The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a community-wide blind test experiment to reveal the best accomplishments of structure modeling. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differences between close models is difficult because of the lack of uncertainty estimations for this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to estimate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic resonance are deposited as ensembles of alternative conformers that reflect the structural flexibility, whereas standard X-ray refinement produces the static structure averaged over time and space for the dynamic ensembles. To recapitulate the structural heterogeneous ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets to generate structural ensembles for our GDT_TS uncertainty analysis. Using those generated ensembles, our study demonstrates that the time-averaged refinements produced structure ensembles with better agreement with the experimental datasets than the averaged X-ray structures with B-factors. The uncertainty of the GDT_TS scores, quantified by their standard deviations (SDs), increases for scores lower than 50 and 70, with maximum SDs of 0.3 and 1.23 for X-ray and NMR structures, respectively. We also applied our procedure to the high accuracy version of GDT-based score and produced similar results with slightly higher SDs. To facilitate score comparisons by the community, we developed a user-friendly web server that produces structure ensembles for NMR and X-ray structures and is accessible at http://prodata.swmed.edu/SEnCS. Our work helps to identify the significance of GDT_TS score differences, as well as to provide structure ensembles for estimating SDs of any scores.

Development of an Operational TS Dataset Production System for the Data Assimilation System

NASA Astrophysics Data System (ADS)

Kim, Sung Dae; Park, Hyuk Min; Kim, Young Ho; Park, Kwang Soon

2017-04-01

An operational TS (Temperature and Salinity) dataset production system was developed to provide near real-time data to the data assimilation system periodically. It collects the latest 15 days' TS data of the north western pacific area (20°N - 55°N, 110°E - 150°E), applies QC tests to the archived data and supplies them to numerical prediction models of KIOST (Korea Institute of Ocean Science and Technology). The latest real-time TS data are collected from Argo GDAC and GTSPP data server every week. Argo data are downloaded from /latest_data directory of Argo GDAC. Because many duplicated data exist when all profile data are extracted from all Argo netCDF files, DB system is used to avoid duplication. All metadata (float ID, location, observation date and time, etc) of all Argo floats is stored into Database system and a Matlab program was developed to manipulate DB data, to check the duplication and to exclude duplicated data. GTSPP data are downloaded from /realtime directory of GTSPP data service. The latest data except ARGO data are extracted from the original data. Another Matlab program was coded to inspect all collected data using 10 QC tests and produce final dataset which can be used by the assimilation system. Three regional range tests to inspect annual, seasonal and monthly variations are included in the QC procedures. The C program was developed to provide regional ranges to data managers. It can calculate upper limit and lower limit of temperature and salinity at depth from 0 to 1550m. The final TS dataset contains the latest 15 days' TS data in netCDF format. It is updated every week and transmitted to numerical modeler of KIOST for operational use.

Analysis of telomerase activity based on a spired DNA tetrahedron TS primer.

PubMed

Li, Yan; Wen, Yanli; Wang, Lele; Liang, Wen; Xu, Li; Ren, Shuzhen; Zou, Ziying; Zuo, Xiaolei; Fan, Chunhai; Huang, Qing; Liu, Gang; Jia, Nengqin

2015-05-15

The development of sensitive telomerase biosensors is hindered by the restricted accessibility of telomere strand (TS) primer and the limited enzyme reaction space, which is mainly confined by the vertical distance. In this work, we designed an electrochemical telomerase biosensor based on a spired DNA tetrahedron TS primer (STTS). By adding a rigid dsDNA spire onto the top of the DNA tetrahedron, we successfully regulated the distance between the TS primer and the surface, and thus greatly facilitated the telomerase elongation on surface. The signal-to-noise ratio was 2 times higher than TSP without the spire structure. The limit of detection was calculated to be lower than 10 HeLa cells, which is at least 2 magnitudes lower than other surface extension-based electrochemical telomerase sensors without amplification. The practicability of STTS sensor was also demonstrated by analysing various other cell lines including cancer cells, stem cells of high telomerase activity and somatic cells of low telomerase activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Prognostic impact of blood biomarkers TS and DPD in neoadjuvant-treated esophageal cancer patients.

PubMed

Grimminger, Peter P; Maus, Martin K H; Bergenthal, Juliane; Wandhöfer, Christoph; Fetzner, Ullrich K; Herbold, Till; Bollschweiler, Elfriede; Hölscher, Arnulf H; Brabender, Jan

2015-03-01

The prognostic value of TS (thymidylate synthase) and DPD (dihydropyrimidine dehydrogenase) RNA expression in the blood of patients with esophageal cancer is not known. The aim of the present study was to evaluate the significance of these molecular alterations in the blood as a prognostic marker for patients with neoadjuvant-treated esophageal cancer. A total of 29 patients with locally advanced esophageal cancer (cT3-T4, Nx, M0) were enrolled in this prospective study. All patients received neoadjuvant chemoradiation followed by a transthoracic resection (curative transthoracic en bloc esophagectomy, RO). Peripheral blood samples were drawn before initiation of therapy. The analysis was performed using quantitative real-time-polymerase chain reaction (RT-PCR). The histomorphological regressions grading after neoadjuvant therapy was defined as follows: major response (MaR)=less than 10% vital tumor tissue, minor response (MiR)=more than 10% vital tumor tissue. Nineteen out of 29 patients (65.5%) had a MiR and 10 (34.5%) had a MaR. The median survival of patients was 2.08 years (range=0.15-4.53). Among the tested genes, the RNA expression of TS was significantly associated with prognosis of patients. Patients with TS expression above 0.78 had a median survival of 1.1 years (range=0.21-3.96) compared to 2.6 years (range=0.15 to 4.53) in patients with TS expression lower than 0.78 (p=0.031, log rank test). There was no association between clinical variables (e.g., tumor stage, gender, age, etc.) and the RNA expression of TS in the serum. The RNA expression of TS in the blood is a potential prognostic marker in patients with neoadjuvant-treated esophageal cancer. The significance of these molecular alterations as non-invasive prognostic marker for esophageal cancer should be evaluated in prospective studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Study of the Integration of the CNU-TS-1 Mobile Tunnel Monitoring System.

PubMed

Du, Liming; Zhong, Ruofei; Sun, Haili; Zhu, Qiang; Zhang, Zhen

2018-02-01

A rapid, precise and automated means for the regular inspection and maintenance of a large number of tunnels is needed. Based on the depth study of the tunnel monitoring method, the CNU-TS-1 mobile tunnel monitoring system (TS1) is developed and presented. It can efficiently obtain the cross-sections that are orthogonal to the tunnel in a dynamic way, and the control measurements that depend on design data are eliminated. By using odometers to locate the cross-sections and correcting the data based on longitudinal joints of tunnel segment lining, the cost of the system has been significantly reduced, and the interval between adjacent cross-sections can reach 1-2 cm when pushed to collect data at a normal walking speed. Meanwhile, the relative deformation of tunnel can be analyzed by selecting cross-sections from original data. Through the measurement of the actual tunnel, the applicability of the system for tunnel deformation detection is verified, and the system is shown to be 15 times more efficient than that of the total station. The simulation experiment of the tunnel deformation indicates that the measurement accuracy of TS1 for cross-sections is 1.1 mm. Compared with the traditional method, TS1 improves the efficiency as well as increases the density of the obtained points.

Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

PubMed Central

López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

2016-01-01

Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

75 FR 7044 - T&S Hardwoods, Inc., Sylva, NC; Notice of Negative Determination Regarding Application for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-16

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-70,783] T&S Hardwoods, Inc., Sylva, NC; Notice of Negative Determination Regarding Application for Reconsideration By application... production of hardwood lumber from the subject facility to a foreign country. T&S Hardwoods, Inc. did not...

Characterization and identification of a chlorine-resistant bacterium, Sphingomonas TS001, from a model drinking water distribution system.

PubMed

Sun, Wenjun; Liu, Wenjun; Cui, Lifeng; Zhang, Minglu; Wang, Bei

2013-08-01

This study describes the identification and characterization of a new chlorine resistant bacterium, Sphingomonas TS001, isolated from a model drinking water distribution system. The isolate was identified by 16s rRNA gene analysis and morphological and physiological characteristics. Phylogenetic analysis indicates that TS001 belongs to the genus Sphingomonas. The model distribution system HPC results showed that, when the chlorine residual was greater than 0.7 mg L(-1), 100% of detected heterotrophic bacteria (HPC) was TS001. The bench-scale inactivation efficiency testing showed that this strain was very resistant to chlorine, and 4 mg L(-1) of chlorine with 240 min retention time provided only approximately 5% viability reduction of TS001. In contrast, a 3-log inactivation (99.9%) was obtained for UV fluencies of 40 mJ cm(-2). A high chlorine-resistant and UV sensitive bacterium, Sphingomonas TS001, was documented for the first time. Copyright © 2013 Elsevier B.V. All rights reserved.

Total gastrectomy increases the incidence of grade III and IV toxicities in patients with gastric cancer receiving adjuvant TS-1 treatment.

PubMed

Chou, Wen-Chi; Chang, Chia-Lun; Liu, Keng-Hao; Hsu, Jun-Te; Cheng, Wei Hong; Hsu, Hung-Chih; Shen, Wen-Chi; Hung, Yu-Shin; Chen, Jen-Shi

2013-11-01

We aimed to evaluate the safety and efficacy of TS-1 adjuvant chemotherapy in Taiwanese patients with gastric cancer. We included in this study patients with locally advanced gastric cancer who received adjuvant TS-1 or 5-fluorouracil chemotherapy after curative surgery and extended lymph node dissection between 1 June 2008 and 31 December 2012 at Chang Gung Memorial Hospital. Patient characteristics, tumor features, safety profiles and compliance with TS-1 treatment were retrospectively analyzed from medical charts. Forty patients received adjuvant chemotherapy with TS-1 and 193 with 5-fluorouracil within the study period. The 1- and 2-year overall survival rates were 90.6% and 87% in the TS-1 group and 95.4% and 86.8% in the 5-fluorouracil group (P = 0.34). The 1- and 2-year disease-free survival rates were 90.6% and 74.7% in the TS-1 group and 88% and 75.7% in the 5-fluorouracil group (P = 0.66). In the TS-1 group, tumor recurrence was more frequent in those with >15 metastatic lymph nodes than ≤15. Overall, 78.9%, 74.3%, 62.1% and 56% of patients underwent TS-1 treatment for at least 3, 6, 9 and 12 months, respectively. The most common adverse events of TS-1 were skin hyperpigmentation (55%), diarrhea (27.5%), dizziness (27.5%) and leucopenia (20%). Severe adverse events (SAEs; grade III or IV toxicity) were diarrhea (7.5%), stomatitis (7.5%), leukopenia (5%), vomiting (2.5%), anorexia (2.5%) and dizziness (2.5%). Patients who underwent total gastrectomy had a significantly greater risk of TS-1-related SAEs than patients who underwent subtotal gastrectomy (40% versus 8%, P = 0.014). The incidence of SAEs during TS-1 therapy was more common in Taiwanese patients with gastric cancer who underwent total gastrectomy compared with those who underwent subtotal gastrectomy. Clinicians must be aware of and able to manage these SAEs to maximize patient compliance with adjuvant TS-1.

[Phenolic antioxidant TS-13 regulating ARE-dependent genes induces tumor cell death by mitochondria-dependent pathway].

PubMed

Martinovich, G G; Martinovich, I V; Zenkov, N K; Men'shikova, E B; Kandalintseva, N V; Cherenkevich, S N

2015-01-01

Effects of water-soluble phenolic antioxidant sodium 3-(3'-tret-butyl-4'-hydroxyphenyl)-propyl thiosulfonate (TS-13), potassium 3,5-dimethyl-4-hydroxybenzyl thioetanoate (BEP-11-K) and potassium 3-(3',5'-ditretbutyl-4'-hydroxyphenyl)-propionate (potassium phenosan) on tumor cells proliferative activity and the role of redox-dependent and calcium-dependent signaling mechanisms in realization of tumor cell response to the antioxidant action were studied. Potassium phenosan and BEP-11-K were found to stimulate proliferation and ARE-inducing phenolic antioxidant TS-13 was found to inhibit tumor cell growth in culture. The tumor cell growth rate depended on the rate of intracellular reactive oxygen species production and was decreased by apocynin (a NADPH-oxidase inhibitor) and antimycin A (an ubiquinol-cytochrome c oxidoreductase inhibitor). TS-13 action on tumor cells was accompanied by a transient increase in intracellular reactive oxygen species production and the intracellular calcium concentration, whereas cell incubation with potassium phenosan and BEP-11-K did not influence the reactive oxygen species level and intracellular calcium ions. Cyclosporine A blocked the inhibitory effect of TS-13. Thus, it can be reasonably speculated that phenolic antioxidant TS-13 starts mitochondria-dependent apoptosis in tumor cells by the opening of permeability transition pores.

Mission planning optimization of video satellite for ground multi-object staring imaging

NASA Astrophysics Data System (ADS)

Cui, Kaikai; Xiang, Junhua; Zhang, Yulin

2018-03-01

This study investigates the emergency scheduling problem of ground multi-object staring imaging for a single video satellite. In the proposed mission scenario, the ground objects require a specified duration of staring imaging by the video satellite. The planning horizon is not long, i.e., it is usually shorter than one orbit period. A binary decision variable and the imaging order are used as the design variables, and the total observation revenue combined with the influence of the total attitude maneuvering time is regarded as the optimization objective. Based on the constraints of the observation time windows, satellite attitude adjustment time, and satellite maneuverability, a constraint satisfaction mission planning model is established for ground object staring imaging by a single video satellite. Further, a modified ant colony optimization algorithm with tabu lists (Tabu-ACO) is designed to solve this problem. The proposed algorithm can fully exploit the intelligence and local search ability of ACO. Based on full consideration of the mission characteristics, the design of the tabu lists can reduce the search range of ACO and improve the algorithm efficiency significantly. The simulation results show that the proposed algorithm outperforms the conventional algorithm in terms of optimization performance, and it can obtain satisfactory scheduling results for the mission planning problem.

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 10 2012-07-01 2012-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 10 2013-07-01 2013-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 10 2014-07-01 2014-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

Analysis of the MRPL3, DNAJC13 and OFCC1 variants in Chinese Han patients with TS-CTD.

PubMed

Guo, Yi; Deng, Xiong; Zhang, Jie; Su, Linyan; Xu, Hongbo; Luo, Ziqiang; Deng, Hao

2012-05-23

Tourette syndrome/chronic tic phenotype (TS-CTD) is a neurological disorder manifested particularly by motor and vocal tics and associated with a variety of behavioral abnormalities. Recently, the mitochondrial ribosomal protein L3 gene (MRPL3) S75N, the DnaJ (Hsp40) homolog subfamily C member 13 gene (DNAJC13) A2057S, the orofacial cleft 1 candidate 1 gene (OFCC1) R129G and c.-5A>G variants are reported to be associated with Tourette syndrome/chronic tic phenotype (TS-CTD) in patients of European ancestry. To evaluate whether these variants are associated with TS-CTD in Chinese Han patients, we screened 132 Chinese Han patients from Mainland China. None of the 132 samples from patients with TS-CTD showed the MRPL3 S75N, DNAJC13 A2057S, OFCC1 R129G and c.-5A>G variants, and these variants probably are a rare cause of TS-CTD in a Chinese Han ethnic group. Genetic heterogeneity of TS should be considered and tests designed to detect these variants in Chinese Han ethnic group probably will not have a diagnostic utility in clinical practice. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Determination of the kinetics of guanine nucleotide exchange on EF-Tu and EF-Ts: continuing uncertainties.

PubMed

Manchester, Keith L

2004-01-30

An analysis is made of the rate constants for the reactions involving the interactions of EF-Tu, EF-Ts, GDP, and GTP recently derived by Gromadski et al. [Biochemistry 41 (2002) 162]. Though their measured values appear to allow a reasonable rate of nucleotide exchange sufficient to support rates of protein synthesis in vivo, their data underestimate the thermodynamic barrier involved in nucleotide exchange and therefore cannot be considered definitive. A kinetic scheme consistent with the thermodynamic barrier can be achieved by modification of various rate constants, particularly of those involving the release of EF-Ts from EF-Tu.GTP.EF-Ts, but such constants are markedly different from what are experimentally observed. It thus remains impossible at present satisfactorily to model guanine nucleotide exchange on EF-Tu, catalysed by EF-Ts by a double displacement mechanism, with experimentally derived rate constants. Metabolic control analysis has been applied to determine the degree of flux control of the different steps in the pathway.

Probing the structure of Leishmania donovani chagasi DHFR-TS: comparative protein modeling and protein-ligand interaction studies.

PubMed

Maganti, Lakshmi; Manoharan, Prabu; Ghoshal, Nanda

2010-09-01

Dihydrofolate reductase (DHFR) has been used successfully as a drug target in the area of anti-bacterial, anti-cancer and anti-malarial therapy. It also acts as a drug target for Leishmaniasis. Inhibition of DHFR leads to cell death through lack of thymine (nucleotide metabolism). Although the crystal structures of Leishmania major and Trypanosoma cruzi DHFR-thymidylate synthase (TS) have been resolved, to date there is no three-dimensional (3D)-structural information on DHFR-TS of Leishmania donovani chagasi, which causes visceral leishmaniasis. Our aim in this study was to model the 3D structure of L. donovani chagasi DHFR-TS, and to investigate the structural requirements for its inhibition. In this paper we describe a highly refined homology model of L. donovani chagasi DHFR-TS based on available crystallographic structures by using the Homology module of Insight II. Structural refinement and minimization of the generated L. donovani chagasi DHFR-TS model employed the Discover 3 module of Insight II and molecular dynamic simulations. The model was further validated through use of the PROCHECK, Verify_3D, PROSA, PSQS and ERRAT programs, which confirm that the model is reliable. Superimposition of the model structure with the templates L. major A chain, L. major B chain And T. cruzi A chain showed root mean square deviations of 0.69 A, 0.71 A and 1.11 A, respectively. Docking analysis of the L. donovani chagasi DHFR-TS model with methotrexate enabled us to identify specific residues, viz. Val156, Val30, Lys95, Lys75 and Arg97, within the L. donovani chagasi DHFR-TS binding pocket, that play an important role in ligand or substrate binding. Docking studies clearly indicated that these five residues are important determinants for binding as they have strong hydrogen bonding interactions with the ligand.

Regional Value Analysis at Threat Evaluation

DTIC Science & Technology

2014-06-01

targets based on information entropy and fuzzy optimization theory. in Industrial Engineering and Engineering Management (IEEM), 2011 IEEE...Assignment by Virtual Permutation and Tabu Search Heuristics. Systems, Man, and Cybernetics, Part C: Applications and Reviews, IEEE Transactions on, 2010

Trypanosoma brucei DHFR-TS Revisited: Characterisation of a Bifunctional and Highly Unstable Recombinant Dihydrofolate Reductase-Thymidylate Synthase.

PubMed

Gibson, Marc W; Dewar, Simon; Ong, Han B; Sienkiewicz, Natasha; Fairlamb, Alan H

2016-05-01

Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a chemically and genetically validated target in African trypanosomes, causative agents of sleeping sickness in humans and nagana in cattle. Here we report the kinetic properties and sensitivity of recombinant enzyme to a range of lipophilic and classical antifolate drugs. The purified recombinant enzyme, expressed as a fusion protein with elongation factor Ts (Tsf) in ThyA- Escherichia coli, retains DHFR activity, but lacks any TS activity. TS activity was found to be extremely unstable (half-life of 28 s) following desalting of clarified bacterial lysates to remove small molecules. Stability could be improved 700-fold by inclusion of dUMP, but not by other pyrimidine or purine (deoxy)-nucleosides or nucleotides. Inclusion of dUMP during purification proved insufficient to prevent inactivation during the purification procedure. Methotrexate and trimetrexate were the most potent inhibitors of DHFR (Ki 0.1 and 0.6 nM, respectively) and FdUMP and nolatrexed of TS (Ki 14 and 39 nM, respectively). All inhibitors showed a marked drop-off in potency of 100- to 1,000-fold against trypanosomes grown in low folate medium lacking thymidine. The most potent inhibitors possessed a terminal glutamate moiety suggesting that transport or subsequent retention by polyglutamylation was important for biological activity. Supplementation of culture medium with folate markedly antagonised the potency of these folate-like inhibitors, as did thymidine in the case of the TS inhibitors raltitrexed and pemetrexed.

The Prediction of the Gas Utilization Ratio Based on TS Fuzzy Neural Network and Particle Swarm Optimization

PubMed Central

Jiang, Haihe; Yin, Yixin; Xiao, Wendong; Zhao, Baoyong

2018-01-01

Gas utilization ratio (GUR) is an important indicator that is used to evaluate the energy consumption of blast furnaces (BFs). Currently, the existing methods cannot predict the GUR accurately. In this paper, we present a novel data-driven model for predicting the GUR. The proposed approach utilized both the TS fuzzy neural network (TS-FNN) and the particle swarm algorithm (PSO) to predict the GUR. The particle swarm algorithm (PSO) is applied to optimize the parameters of the TS-FNN in order to decrease the error caused by the inaccurate initial parameter. This paper also applied the box graph (Box-plot) method to eliminate the abnormal value of the raw data during the data preprocessing. This method can deal with the data which does not obey the normal distribution which is caused by the complex industrial environments. The prediction results demonstrate that the optimization model based on PSO and the TS-FNN approach achieves higher prediction accuracy compared with the TS-FNN model and SVM model and the proposed approach can accurately predict the GUR of the blast furnace, providing an effective way for the on-line blast furnace distribution control. PMID:29461469

The Prediction of the Gas Utilization Ratio based on TS Fuzzy Neural Network and Particle Swarm Optimization.

PubMed

Zhang, Sen; Jiang, Haihe; Yin, Yixin; Xiao, Wendong; Zhao, Baoyong

2018-02-20

Gas utilization ratio (GUR) is an important indicator that is used to evaluate the energy consumption of blast furnaces (BFs). Currently, the existing methods cannot predict the GUR accurately. In this paper, we present a novel data-driven model for predicting the GUR. The proposed approach utilized both the TS fuzzy neural network (TS-FNN) and the particle swarm algorithm (PSO) to predict the GUR. The particle swarm algorithm (PSO) is applied to optimize the parameters of the TS-FNN in order to decrease the error caused by the inaccurate initial parameter. This paper also applied the box graph (Box-plot) method to eliminate the abnormal value of the raw data during the data preprocessing. This method can deal with the data which does not obey the normal distribution which is caused by the complex industrial environments. The prediction results demonstrate that the optimization model based on PSO and the TS-FNN approach achieves higher prediction accuracy compared with the TS-FNN model and SVM model and the proposed approach can accurately predict the GUR of the blast furnace, providing an effective way for the on-line blast furnace distribution control.

Effectiveness and safety of tegafur-gimeracil-oteracil potassium (TS-1) for metastatic breast cancer: a single-center retrospective study.

PubMed

Ishizuna, Kazuo; Ninomiya, Jun; Ogawa, Toshihisa; Kojima, Makoto; Tsuji, Eiichi; Kawashima, Miho; Nozaki, Miwako; Yamagishi, Hidetsugu; Ueda, Yoshihiko

2014-12-01

Tegafur-gimeracil-oteracil potassium (TS-1)is a drug that is used mainly as a third-line treatment or beyond for metastatic breast cancer(MBC). However, there is still insufficient evidence on its clinical effectiveness, and there are very few reports on clinical research using TS-1 up front. In this report, we examined the effectiveness and safety of TS-1 therapy for MBC. The subjects were 46 patients with MBC who were treated with TS-1 between January 2005 and January 2013. These patients were retrospectively examined. The objective response rate to TS-1 therapy was 30.4%, clinical benefit rate (CBR)was 50.0%, and the median time to treatment failure was 10.7 months. When examined by site, the CBR was high locally (46.2%), in the lymph nodes (40.7%), in the bone (42.9%), and in the lungs and pleura (44.8%). However it was low in the liver(30.0%). The relationship was examined between clinicopathological factors and the effectiveness of TS-1 therapy. The objective response rate (ORR) was significantly higher for patients with disease-free interval (DFI) of 2 years or more (p=0.039), TS-1 therapy used as third-line treatment or earlier (p=0.022), negative HER2 status (p=0.020), and no history of capecitabine (CAP)therapy (p=0.049). The CBR was significantly higher for patients with no visceral metastasis (p=0.032), TS-1 used as third-line treatment or earlier (p=0.019), negative HER2 status (p= 0.045), no history of CAP therapy (p=0.006), and no history of tegafur-uracil/doxifluridine therapy (p=0.031). Multivariate analysis showed that DFI of 2 years or more (p=0.035, odds ratio:0.104)was an independent predictor of effectiveness assessed by ORR. There were only 4 patients in whom the treatment was discontinued due to adverse event, and TS-1 was generally well tolerated. TS-1 was highly effective and well tolerated by patients with MBC. Its up-front use might enable the maintenance of satisfactory QOL and the enhancement of its clinical effectiveness.

Eastern equatorial Pacific Ocean T-S variations with El Nino

NASA Technical Reports Server (NTRS)

Wang, O.; Fukumori, I.; Lee, T.; Johnson, G. C.

2004-01-01

Temperature-Salinity (T-S) relationship variability in the pycnocline of the eastern equatorial Pacific Ocean (NINO3 region, 5 degrees S ??degrees N, 150 degrees W ?? degrees W) over the last two decades is investigated using observational data and model simulation.

High-resolution empirical geomagnetic field model TS07D: Investigating run-on-request and forecasting modes of operation

NASA Astrophysics Data System (ADS)

Stephens, G. K.; Sitnov, M. I.; Ukhorskiy, A. Y.; Vandegriff, J. D.; Tsyganenko, N. A.

2010-12-01

The dramatic increase of the geomagnetic field data volume available due to many recent missions, including GOES, Polar, Geotail, Cluster, and THEMIS, required at some point the appropriate qualitative transition in the empirical modeling tools. Classical empirical models, such as T96 and T02, used few custom-tailored modules to represent major magnetospheric current systems and simple data binning or loading-unloading inputs for their fitting with data and the subsequent applications. They have been replaced by more systematic expansions of the equatorial and field-aligned current contributions as well as by the advanced data-mining algorithms searching for events with the global activity parameters, such as the Sym-H index, similar to those at the time of interest, as is done in the model TS07D (Tsyganenko and Sitnov, 2007; Sitnov et al., 2008). The necessity to mine and fit data dynamically, with the individual subset of the database being used to reproduce the geomagnetic field pattern at every new moment in time, requires the corresponding transition in the use of the new empirical geomagnetic field models. It becomes more similar to runs-on-request offered by the Community Coordinated Modeling Center for many first principles MHD and kinetic codes. To provide this mode of operation for the TS07D model a new web-based modeling tool has been created and tested at the JHU/APL (http://geomag_field.jhuapl.edu/model/), and we discuss the first results of its performance testing and validation, including in-sample and out-of-sample modeling of a number of CME- and CIR-driven magnetic storms. We also report on the first tests of the forecasting version of the TS07D model, where the magnetospheric part of the macro-parameters involved in the data-binning process (Sym-H index and its trend parameter) are replaced by their solar wind-based analogs obtained using the Burton-McPherron-Russell approach.

Adrenalectomy for Cushing's syndrome: do's and don'ts.

PubMed

Paduraru, D N; Nica, A; Carsote, M; Valea, A

2016-01-01

Aim. To present specific aspects of adrenalectomy for Cushing's syndrome (CS) by introducing well established aspects ("do's") and less known aspects ("don'ts"). Material and Method. This is a narrative review. Results. The "do's" for laparoscopic adrenalectomy (LA) are the following: it represents the "gold standard" for secretor and non-secretor adrenal tumors and the first line therapy for CS with an improvement of cardio-metabolic co-morbidities; the success rate depending on the adequate patients' selection and the surgeon's skills. The "don'ts" are large (>6-8 centimeters), locally invasive, malignant tumors requiring open adrenalectomy (OA). Robotic adrenalectomy is a new alternative for LA, with similar safety and conversion rate and lower pain drugs use. The "don'ts" are the following: lack of randomized controlled studies including oncologic outcome, different availability at surgical centers. Related to the sub-types of CS, the "do's" are the following: adrenal adenomas which are cured by LA, while adrenocortical carcinoma (ACC) requires adrenalectomy as first line therapy and adjuvant mitotane therapy; synchronous bilateral adrenalectomy (SBA) is useful for Cushing's disease (only cases refractory to pituitary targeted therapy), for ectopic Cushing's syndrome (cases with unknown or inoperable primary site), and for bilateral cortisol producing adenomas. The less established aspects are the following: criteria of skilled surgeon to approach ACC; the timing of surgery in subclinical CS; the need for adrenal vein catheterization (which is not available in many centers) to avoid unnecessary SBA. Conclusion. Adrenalectomy for CS is a dynamic domain; LA overstepped the former OA area. The future will improve the knowledge related to RA while the cutting edge is represented by a specific frame of intervention in SCS, children and pregnant women. Abbreviations: ACC = adrenocortical carcinoma, ACTH = Adrenocorticotropic Hormone, CD = Cushing's disease, CS

PLANiTS : structuring and supporting the intelligent transportation systems planning process

DOT National Transportation Integrated Search

1997-01-01

PLANiTS (Planning and Analysis Integration for Intelligent Transportation Systems) is a process-based computer system that supports a series of mutually interdependent steps progressing toward developing and programming transportation improvement pro...

General form of a cooperative gradual maximal covering location problem

NASA Astrophysics Data System (ADS)

Bagherinejad, Jafar; Bashiri, Mahdi; Nikzad, Hamideh

2018-07-01

Cooperative and gradual covering are two new methods for developing covering location models. In this paper, a cooperative maximal covering location-allocation model is developed (CMCLAP). In addition, both cooperative and gradual covering concepts are applied to the maximal covering location simultaneously (CGMCLP). Then, we develop an integrated form of a cooperative gradual maximal covering location problem, which is called a general CGMCLP. By setting the model parameters, the proposed general model can easily be transformed into other existing models, facilitating general comparisons. The proposed models are developed without allocation for physical signals and with allocation for non-physical signals in discrete location space. Comparison of the previously introduced gradual maximal covering location problem (GMCLP) and cooperative maximal covering location problem (CMCLP) models with our proposed CGMCLP model in similar data sets shows that the proposed model can cover more demands and acts more efficiently. Sensitivity analyses are performed to show the effect of related parameters and the model's validity. Simulated annealing (SA) and a tabu search (TS) are proposed as solution algorithms for the developed models for large-sized instances. The results show that the proposed algorithms are efficient solution approaches, considering solution quality and running time.

Interstitial lung disease caused by TS-1: a case of long-term drug retention as a fatal adverse reaction.

PubMed

Park, Joong-Min; Hwang, In Gyu; Suh, Suk-Won; Chi, Kyong-Choun

2011-12-01

TS-1 is an oral anti-cancer agent for gastric cancer with a high response rate and low toxicity. We report a case of long-term drug retention of TS-1 causing interstitial lung disease (ILD) as a fatal adverse reaction. A 65-year-old woman underwent a total gastrectomy with pathologic confirmation of gastric adenocarcinoma. She received 6 cycles of TS-1 and low-dose cisplatin for post-operative adjuvant chemotherapy followed by single-agent maintenance therapy with TS-1. After 8 months, the patient complained of a productive cough with sputum and mild dyspnea. A pulmonary evaluation revealed diffuse ILD in the lung fields, bilaterally. In spite of discontinuing chemotherapy and the administration of corticosteroids, the pulmonary symptoms did not improve, and the patient died of pulmonary failure. TS-1-induced ILD can be caused by long-term drug retention that alters the lung parenchyma irreversibly, the outcome of which can be life-threatening. Pulmonary evaluation for early detection of disease is recommended.

Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodiumfalciparum plastid.

PubMed

Biswas, Subir; Lim, Erin E; Gupta, Ankit; Saqib, Uzma; Mir, Snober S; Siddiqi, Mohammad Imran; Ralph, Stuart A; Habib, Saman

2011-03-01

Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader sequence targeted GFP to the apicoplast, confirming that PfEF-Ts functions in this organelle. Recombinant PfEF-Ts mediated nucleotide exchange on PfEF-Tu and homology modeling of the PfEF-Tu:PfEF-Ts complex revealed PfEF-Ts-induced structural alterations that would expedite GDP release from PfEF-Tu. Our results establish functional interaction between two apicoplast translation factors encoded by genes residing in different cellular compartments and highlight the significance of their sequence/structural differences from bacterial elongation factors in relation to inhibitor activity. These data provide an experimental system to study the effects of novel inhibitors targeting PfEF-Tu and PfEF-Tu.PfEF-Ts interaction. Our finding that apicoplast EF-Tu possesses chaperone-related disulphide reductase activity also provides a rationale for retention of the tufA gene on the plastid genome. Copyright © 2010 Australian Society for Parasitology Inc. All rights reserved.

FHSA-SED: Two-Locus Model Detection for Genome-Wide Association Study with Harmony Search Algorithm.

PubMed

Tuo, Shouheng; Zhang, Junying; Yuan, Xiguo; Zhang, Yuanyuan; Liu, Zhaowen

2016-01-01

Two-locus model is a typical significant disease model to be identified in genome-wide association study (GWAS). Due to intensive computational burden and diversity of disease models, existing methods have drawbacks on low detection power, high computation cost, and preference for some types of disease models. In this study, two scoring functions (Bayesian network based K2-score and Gini-score) are used for characterizing two SNP locus as a candidate model, the two criteria are adopted simultaneously for improving identification power and tackling the preference problem to disease models. Harmony search algorithm (HSA) is improved for quickly finding the most likely candidate models among all two-locus models, in which a local search algorithm with two-dimensional tabu table is presented to avoid repeatedly evaluating some disease models that have strong marginal effect. Finally G-test statistic is used to further test the candidate models. We investigate our method named FHSA-SED on 82 simulated datasets and a real AMD dataset, and compare it with two typical methods (MACOED and CSE) which have been developed recently based on swarm intelligent search algorithm. The results of simulation experiments indicate that our method outperforms the two compared algorithms in terms of detection power, computation time, evaluation times, sensitivity (TPR), specificity (SPC), positive predictive value (PPV) and accuracy (ACC). Our method has identified two SNPs (rs3775652 and rs10511467) that may be also associated with disease in AMD dataset.

FHSA-SED: Two-Locus Model Detection for Genome-Wide Association Study with Harmony Search Algorithm

PubMed Central

Tuo, Shouheng; Zhang, Junying; Yuan, Xiguo; Zhang, Yuanyuan; Liu, Zhaowen

2016-01-01

Motivation Two-locus model is a typical significant disease model to be identified in genome-wide association study (GWAS). Due to intensive computational burden and diversity of disease models, existing methods have drawbacks on low detection power, high computation cost, and preference for some types of disease models. Method In this study, two scoring functions (Bayesian network based K2-score and Gini-score) are used for characterizing two SNP locus as a candidate model, the two criteria are adopted simultaneously for improving identification power and tackling the preference problem to disease models. Harmony search algorithm (HSA) is improved for quickly finding the most likely candidate models among all two-locus models, in which a local search algorithm with two-dimensional tabu table is presented to avoid repeatedly evaluating some disease models that have strong marginal effect. Finally G-test statistic is used to further test the candidate models. Results We investigate our method named FHSA-SED on 82 simulated datasets and a real AMD dataset, and compare it with two typical methods (MACOED and CSE) which have been developed recently based on swarm intelligent search algorithm. The results of simulation experiments indicate that our method outperforms the two compared algorithms in terms of detection power, computation time, evaluation times, sensitivity (TPR), specificity (SPC), positive predictive value (PPV) and accuracy (ACC). Our method has identified two SNPs (rs3775652 and rs10511467) that may be also associated with disease in AMD dataset. PMID:27014873

Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes

PubMed Central

Keck-Wherley, Jennifer; Grover, Deepak; Bhattacharyya, Sharmistha; Xu, Xiufen; Holman, Derek; Lombardini, Eric D.; Verma, Ranjana; Biswas, Roopa; Galdzicki, Zygmunt

2011-01-01

Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21. Elevated levels of several microRNAs (miRNAs) located on chromosome 21 have been reported in human DS heart and brain tissues. The Ts65Dn mouse model is the most investigated DS model with a triplicated segment of mouse chromosome 16 harboring genes orthologous to those on human chromosome 21. Using ABI TaqMan miRNA arrays, we found a set of miRNAs that were significantly up- or downregulated in the Ts65Dn hippocampus compared to euploid controls. Furthermore, miR-155 and miR-802 showed significant overexpression in the Ts65Dn hippocampus, thereby confirming results of previous studies. Interestingly, miR-155 and miR-802 were also overexpressed in the Ts65Dn whole blood but not in lung tissue. We also found overexpression of the miR-155 precursors, pri- and pre-miR-155 derived from the miR-155 host gene, known as B cell integration cluster, suggesting enhanced biogenesis of miR-155. Bioinformatic analysis revealed that neurodevelopment, differentiation of neuroglia, apoptosis, cell cycle, and signaling pathways including ERK/MAPK, protein kinase C, phosphatidylinositol 3-kinase, m-TOR and calcium signaling are likely targets of these miRNAs. We selected some of these potential gene targets and found downregulation of mRNA encoding Ship1, Mecp2 and Ezh2 in Ts65Dn hippocampus. Interestingly, the miR-155 target gene Ship1 (inositol phosphatase) was also downregulated in Ts65Dn whole blood but not in lung tissue. Our findings provide insights into miRNA-mediated gene regulation in Ts65Dn mice and their potential contribution to impaired hippocampal synaptic plasticity and neurogenesis, as well as hemopoietic abnormalities observed in DS. PMID:22042248

Combined Analyses of hENT1, TS, and DPD Predict Outcomes of Borderline-resectable Pancreatic Cancer.

PubMed

Yabushita, Yasuhiro; Mori, Ryutaro; Taniguchi, Koichi; Matsuyama, Ryusei; Kumamoto, Takafumi; Sakamaki, Kentaro; Kubota, Kensuke; Endo, Itaru

2017-05-01

Predicting chemosensitivity to neoadjuvant chemoradiotherapy (NACRT) in pancreatic cancer is desired. The present study aimed to examine the relationship between intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) and the outcomes of NACRT with gemcitabine (GEM) combined with S-1 in patients with borderline-resectable pancreatic cancer (BRPC). Forty-seven patients who underwent NACRT with GEM plus S-1, following curative surgery, were recruited in our Institution between 2009 and 2012. Immunohistochemical expressions of hENT1, TS, and DPD in fine-needle aspiration (FNA) biopsies and resected specimens were examined. The correlation between these enzyme expressions and long-term outcome was analyzed. In 21 FNA specimens, no relationship between clinical responses to NACRT and long-term survival was found. However, in 47 resected specimens, patients were classified according to the number of favorable hENT1, TS, and DPD expression factors (hENT1 positive/TS negative/DPD negative). The presence of three favorable factors was strongly associated with improved partial response rates to NACRT (p=0.002). Patients with 2 or more favorable factors showed a significantly longer overall survival than the other patients (p=0.002). Combined expression analyses of hENT1, TS, and DPD may predict long-term outcomes in patients with BRPC after NACRT. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A finite difference Davidson procedure to sidestep full ab initio hessian calculation: Application to characterization of stationary points and transition state searches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharada, Shaama Mallikarjun; Bell, Alexis T., E-mail: mhg@bastille.cchem.berkeley.edu, E-mail: bell@cchem.berkeley.edu; Head-Gordon, Martin, E-mail: mhg@bastille.cchem.berkeley.edu, E-mail: bell@cchem.berkeley.edu

2014-04-28

The cost of calculating nuclear hessians, either analytically or by finite difference methods, during the course of quantum chemical analyses can be prohibitive for systems containing hundreds of atoms. In many applications, though, only a few eigenvalues and eigenvectors, and not the full hessian, are required. For instance, the lowest one or two eigenvalues of the full hessian are sufficient to characterize a stationary point as a minimum or a transition state (TS), respectively. We describe here a method that can eliminate the need for hessian calculations for both the characterization of stationary points as well as searches for saddlemore » points. A finite differences implementation of the Davidson method that uses only first derivatives of the energy to calculate the lowest eigenvalues and eigenvectors of the hessian is discussed. This method can be implemented in conjunction with geometry optimization methods such as partitioned-rational function optimization (P-RFO) to characterize stationary points on the potential energy surface. With equal ease, it can be combined with interpolation methods that determine TS guess structures, such as the freezing string method, to generate approximate hessian matrices in lieu of full hessians as input to P-RFO for TS optimization. This approach is shown to achieve significant cost savings relative to exact hessian calculation when applied to both stationary point characterization as well as TS optimization. The basic reason is that the present approach scales one power of system size lower since the rate of convergence is approximately independent of the size of the system. Therefore, the finite-difference Davidson method is a viable alternative to full hessian calculation for stationary point characterization and TS search particularly when analytical hessians are not available or require substantial computational effort.« less

Short-lived non-coding transcripts (SLiTs): Clues to regulatory long non-coding RNA.

PubMed

Tani, Hidenori

2017-03-22

Whole transcriptome analyses have revealed a large number of novel long non-coding RNAs (lncRNAs). Although the importance of lncRNAs has been documented in previous reports, the biological and physiological functions of lncRNAs remain largely unknown. The role of lncRNAs seems an elusive problem. Here, I propose a clue to the identification of regulatory lncRNAs. The key point is RNA half-life. RNAs with a long half-life (t 1/2 > 4 h) contain a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short half-life (t 1/2 < 4 h) include known regulatory ncRNAs and regulatory mRNAs. This novel class of ncRNAs with a short half-life can be categorized as Short-Lived non-coding Transcripts (SLiTs). I consider that SLiTs are likely to be rich in functionally uncharacterized regulatory RNAs. This review describes recent progress in research into SLiTs.

CaTs Lab (CHAOS and Thermal Sciences Laboratory)

NASA Technical Reports Server (NTRS)

Teate, Anthony A.

2002-01-01

The CHAOS and Thermal Sciences Laboratory (CaTs) at James Madison University evolved into a noteworthy effort to increase minority representation in the sciences and mathematics. Serving ten students and faculty directly, and nearly 50 students indirectly, CaTs, through recruitment efforts, workshops, mentoring programs, tutorial services and research and computational laboratories, fulfilled its intent to initiate an academically enriched research program aimed at strengthening the academic and self-actualization skills of undergraduate students with potential to pursue doctoral study in the sciences. The stated goal of the program was to increase by 5% the number of enrolled mathematics and science students into the program. Success far exceeded the program goals by producing 100% graduation rate of all supported recipients during its tenure, with 30% of the students subsequently in pursuit of graduate degrees. Student retention in the program exceeded 90% and faculty participation exceeded the three members involved in mentoring and tutoring, gaining multi-disciplinary support. Aggressive marketing of the program resulted in several paid summer internships and commitments from NASA and an ongoing relationship with CHROME, a nationally recognized organization which focuses on developing minority students in the sciences and mathematics. Success of the program was only limited by the limited fiscal resources at NASA which resulted in phasing out of the program.

The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice.

PubMed

Marumo, Toshiyuki; Eto, Kei; Wake, Hiroaki; Omura, Tomohiro; Nabekura, Junichi

2010-11-01

20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. TS-011 (0.3 mg·kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS-011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome

PubMed Central

Powers, Brian E.; Velazquez, Ramon; Kelley, Christy M.; Ash, Jessica A.; Strawderman, Myla S.; Alldred, Melissa J.; Ginsberg, Stephen D.; Mufson, Elliott J.

2016-01-01

Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs. PMID:26719290

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome.

PubMed

Powers, Brian E; Velazquez, Ramon; Kelley, Christy M; Ash, Jessica A; Strawderman, Myla S; Alldred, Melissa J; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2016-12-01

Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs.

A green surfactant-assisted synthesis of hierarchical TS-1 zeolites with excellent catalytic properties for oxidative desulfurization.

PubMed

Du, Shuting; Li, Fen; Sun, Qiming; Wang, Ning; Jia, Mingjun; Yu, Jihong

2016-02-25

Hierarchical TS-1 zeolites with uniform intracrystalline mesopores have been successfully synthesized through the hydrothermal method by using the green and cheap surfactant Triton X-100 as the mesoporous template. The resultant materials exhibit remarkably enhanced catalytic activity in oxidative desulfurization reactions compared to the conventional TS-1 zeolite.

Direct evidence of an elongation factor-Tu/Ts·GTP·Aminoacyl-tRNA quaternary complex.

PubMed

Burnett, Benjamin J; Altman, Roger B; Ferguson, Angelica; Wasserman, Michael R; Zhou, Zhou; Blanchard, Scott C

2014-08-22

During protein synthesis, elongation factor-Tu (EF-Tu) bound to GTP chaperones the entry of aminoacyl-tRNA (aa-tRNA) into actively translating ribosomes. In so doing, EF-Tu increases the rate and fidelity of the translation mechanism. Recent evidence suggests that EF-Ts, the guanosine nucleotide exchange factor for EF-Tu, directly accelerates both the formation and dissociation of the EF-Tu-GTP-Phe-tRNA(Phe) ternary complex (Burnett, B. J., Altman, R. B., Ferrao, R., Alejo, J. L., Kaur, N., Kanji, J., and Blanchard, S. C. (2013) J. Biol. Chem. 288, 13917-13928). A central feature of this model is the existence of a quaternary complex of EF-Tu/Ts·GTP·aa-tRNA(aa). Here, through comparative investigations of phenylalanyl, methionyl, and arginyl ternary complexes, and the development of a strategy to monitor their formation and decay using fluorescence resonance energy transfer, we reveal the generality of this newly described EF-Ts function and the first direct evidence of the transient quaternary complex species. These findings suggest that EF-Ts may regulate ternary complex abundance in the cell through mechanisms that are distinct from its guanosine nucleotide exchange factor functions. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats.

PubMed

Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

2015-12-01

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

PubMed Central

Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

2015-01-01

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats. PMID:26877840

A synergetic combination of small and large neighborhood schemes in developing an effective procedure for solving the job shop scheduling problem.

PubMed

Amirghasemi, Mehrdad; Zamani, Reza

2014-01-01

This paper presents an effective procedure for solving the job shop problem. Synergistically combining small and large neighborhood schemes, the procedure consists of four components, namely (i) a construction method for generating semi-active schedules by a forward-backward mechanism, (ii) a local search for manipulating a small neighborhood structure guided by a tabu list, (iii) a feedback-based mechanism for perturbing the solutions generated, and (iv) a very large-neighborhood local search guided by a forward-backward shifting bottleneck method. The combination of shifting bottleneck mechanism and tabu list is used as a means of the manipulation of neighborhood structures, and the perturbation mechanism employed diversifies the search. A feedback mechanism, called repeat-check, detects consequent repeats and ignites a perturbation when the total number of consecutive repeats for two identical makespan values reaches a given threshold. The results of extensive computational experiments on the benchmark instances indicate that the combination of these four components is synergetic, in the sense that they collectively make the procedure fast and robust.

Down-regulation of Jab1, HIF-1alpha, and VEGF by Moloney murine leukemia virus-ts1 infection: a possible cause of neurodegeneration.

PubMed

Lungu, Gina F; Stoica, George; Wong, Paul K Y

2008-05-01

Moloney murine leukemia virus-temperature sensitive (MoMuLV-ts1)-mediated neuronal death is a result of both loss of glial support and release of cytokines and neurotoxins from ts1-infected glial cells. Here the authors propose vascular endothelial growth factor (VEGF) down-regulation as another contributory factor in neuronal degeneration induced by ts1 infection. To determine how ts1 affects VEGF expression in ts1-infected brain, the authors examined the expression of several proteins that are important in regulating the expression of VEGF. The authors found significant decreases in Jun-activating domain-binding protein 1 (Jab1), hypoxia-inducible factor (HIF)-1alpha, and VEGF levels and increases in p53 protein levels in ts1-infected brains compared to noninfected control brains. The authors suggest that a decrease Jab1 expression in ts1 infection leads to accumulation of p53, which binds to HIF-1alpha to accelerate its degradation. A rapid degradation of HIF-1alpha leads to decreased VEGF production and secretion. Considering that endothelial cells are the most conspicuous in virus replication and production in ts1 infection, but are not killed by the infection, the authors examined the expression of these proteins using infected and noninfected mouse cerebrovascular endothelial (CVE) cells. The ts1- infected CVE cells showed decreased Jab1, HIF-1alpha, and VEGF mRNA and protein levels and increased p53 protein levels compared with noninfected cells, consistent with the results found in vivo. These results confirm that ts1 infection results in insufficient secretion of VEGF from endothelial cells and may result in decreased neuroprotection. This study suggested that ts1-mediated neuropathology in mice may result from changes in expression and activity of Jab1, p53, and HIF-1alpha, with a final target on VEGF expression and neuronal degeneration.

Temperature-sensitive mutants of influenza A virus. XIV. Production and evaluation of influenza A/Georgia/74-ts-1[E] recombinant viruses in human adults.

PubMed

Richman, D D; Murphy, B R; Belshe, R B; Rusten, H M; Chanock, R M; Blacklow, N R; Parrino, T A; Rose, F B; Levine, M M; Caplan, E

1977-08-01

The two temperature-sensitive (ts) lesions present in influenza A/Hong Kong/68-ts-1[E] (H3N2 68) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N2 74) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therfore, the attenuation exhibited by the Georgia/74-ts-1[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-1[E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombination exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinat virus possessing the new surface antigens.

Towards an estimation of water masses formation areas from SMOS-based TS diagrams

NASA Astrophysics Data System (ADS)

Klockmann, Marlene; Sabia, Roberto; Fernandez-Prieto, Diego; Donlon, Craig; Font, Jordi

2014-05-01

Temperature-Salinity (TS) diagrams emphasize the mutual variability of ocean temperature and salinity values, relating them to the corresponding density. Canonically used in oceanography, they provide a means to characterize and trace ocean water masses. In [1], a first attempt to estimate surface-layer TS diagrams based on satellite measurements has been performed, profiting from the recent availability of spaceborne salinity data. In fact, the Soil Moisture and Ocean Salinity (SMOS, [2]) and the Aquarius/SAC-D [3] satellite missions allow to study the dynamical patterns of Sea Surface Salinity (SSS) for the first time on a global scale. In [4], given SMOS and Aquarius salinity estimates, and by also using Sea Surface Temperature (SST) from the Operational Sea Surface Temperature and Sea Ice Analysis (OSTIA, [5]) effort, experimental satellite-based TS diagrams have been routinely derived for the year 2011. They have been compared with those computed from ARGO-buoys interpolated fields, referring to a customised partition of the global ocean into seven regions, according to the water masses classification of [6]. In [7], moreover, besides using TS diagrams as a diagnostic tool to evaluate the temporal variation of SST and SSS (and their corresponding density) as estimated by satellite measurements, the emphasis was on the interpretation of the geographical deviations with respect to the ARGO baseline (aiming at distinguishing between the SSS retrieval errors and the additional information contained in the satellite data with respect to ARGO). In order to relate these mismatches to identifiable oceanographic structures and processes, additional satellite datasets of ocean currents, evaporation/precipitation fluxes, and wind speed have been super-imposed. Currently, the main focus of the study deals with the exploitation of these TS diagrams as a prognostic tool to derive water masses formation areas. Firstly, following the approach described in [8], the surface

Interaction between paliperidone extended release and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative, in a schizophrenic patient.

PubMed

Yasui-Furukori, Norio; Hashimoto, Kojiro; Kubo, Kazutoshi; Tomita, Tetsu

2013-01-01

Until now there has been no information available on drug interaction between paliperidone and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative. The patient in the case presented here was a 39-year-old man with a 15-year history of schizophrenia. The patient's usual treatment of 2 mg/day of risperidone was changed to 3 mg/day of paliperidone extended release. He experienced worsening psychotic symptoms after switching from risperidone to paliperidone while he was also receiving TS-1. Retrospective analyses showed plasma concentration of paliperidone was consistently lower during the treatment with TS-1 than without TS-1. This case suggests there is drug interaction between paliperidone extended-release tablets and TS-1.

[The value of transbronchial lung biopsy findings in the diagnosis of a case of TS-1-induced pulmonary toxicity].

PubMed

Ito, Shunsuke; Yamaguchi, Tomoyoshi; Morisue, Ryo; Ogaw, Yukari; Munakata, Kazuo; Fukuda, Yuh

2011-12-01

We report the case of a 67-year-old man with a diagnosis of stage IV stomach cancer in May 2010 who was treated with outpatient chemotherapy using TS-1, paclitaxel and lentinan. Dyspnea and coughing developed after drug administration in November and the patient was hospitalized on day 5 after the appearance of symptoms due to hypoxemia and the presence of ground-glass opacities in the right middle and lower lung fields. On the same day, bronchoscopy was performed for differentiation from infection and lymphangitic carcinomatosis. A transbronchial lung biopsy suggested drug-induced pulmonary toxicity, and a drug lymphocyte stimulation test was highly positive for TS-1. Discontinuation of TS-1 alone improved his respiratory status and imaging findings. TS-1 is available only in Japan, and because it is administered orally and its toxicity is minimal, its use has been expanded to treat a variety of malignancies. Drug-induced pulmonary toxicity due to TS-1 occurs in only 0.03% of all cases, and there are few reports regarding the histopathological findings of TS-1-related pulmonary toxicity. Although it can be difficult to diagnose drug-induced pulmonary toxicity because it demonstrates a variety of imaging findings, the present case suggests that it is important to proactively perform transbronchial lung biopsy at the early stage of diagnosis and promptly determine a course of treatment.

Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome.

PubMed

Kelley, Christy M; Ash, Jessica A; Powers, Brian E; Velazquez, Ramon; Alldred, Melissa J; Ikonomovic, Milos D; Ginsberg, Stephen D; Strupp, Barbara J; Mufson, Elliott J

2016-01-01

Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer's disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice compared to 2N mice sacrificed at 6-8 and 14-18 months of age. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6-8 and 14-18 mos were used for an aging study and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14-18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in Ts65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS.

Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Kelley, Christy M.; Ash, Jessica A.; Powers, Brian E.; Velazquez, Ramon; Alldred, Melissa J.; Ikonomovic, Milos D.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

2016-01-01

Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer’s disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6–8 and 14–18 mos were used for an aging study, and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14–18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in TS65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS. PMID:26391045

Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks.

PubMed

Wang, Yingying; Chang, Jianhui; Shao, Lijian; Feng, Wei; Luo, Yi; Chow, Marie; Du, Wei; Meng, Aimin; Zhou, Daohong

2016-06-01

Down syndrome (DS) is a genetic disorder caused by the presence of an extra partial or whole copy of chromosome 21. In addition to musculoskeletal and neurodevelopmental abnormalities, children with DS exhibit various hematologic disorders and have an increased risk of developing acute lymphoblastic leukemia and acute megakaryocytic leukemia. Using the Ts65Dn mouse model, we investigated bone marrow defects caused by trisomy for 132 orthologs of the genes on human chromosome 21. The results showed that, although the total bone marrow cellularity as well as the frequency of hematopoietic progenitor cells (HPCs) was comparable between Ts65Dn mice and their age-matched euploid wild-type (WT) control littermates, human chromosome 21 trisomy led to a significant reduction in hematopoietic stem cell (HSC) numbers and clonogenic function in Ts65Dn mice. We also found that spontaneous DNA double-strand breaks (DSBs) were significantly increased in HSCs from the Ts65Dn mice, which was correlated with the significant reduction in HSC clonogenic activity compared to those from WT controls. Moreover, analysis of the repair kinetics of radiation-induced DSBs revealed that HSCs from Ts65Dn mice were less proficient in DSB repair than the cells from WT controls. This deficiency was associated with a higher sensitivity of Ts65Dn HSCs to radiation-induced suppression of HSC clonogenic activity than that of euploid HSCs. These findings suggest that an additional copy of genes on human chromosome 21 may selectively impair the ability of HSCs to repair DSBs, which may contribute to DS-associated hematological abnormalities and malignancies.

Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks

PubMed Central

Wang, Yingying; Chang, Jianhui; Shao, Lijian; Feng, Wei; Luo, Yi; Chow, Marie; Du, Wei; Meng, Aimin; Zhou, Daohong

2016-01-01

Down syndrome (DS) is a genetic disorder caused by the presence of an extra partial or whole copy of chromosome 21. In addition to musculoskeletal and neurodevelopmental abnormalities, children with DS exhibit various hematologic disorders and have an increased risk of developing acute lymphoblastic leukemia and acute megakaryocytic leukemia. Using the Ts65Dn mouse model, we investigated bone marrow defects caused by trisomy for 132 orthologs of the genes on human chromosome 21. The results showed that, although the total bone marrow cellularity as well as the frequency of hematopoietic progenitor cells (HPCs) was comparable between Ts65Dn mice and their age-matched euploid wild-type (WT) control littermates, human chromosome 21 trisomy led to a significant reduction in hematopoietic stem cell (HSC) numbers and clonogenic function in Ts65Dn mice. We also found that spontaneous DNA double-strand breaks (DSBs) were significantly increased in HSCs from the Ts65Dn mice, which was correlated with the significant reduction in HSC clonogenic activity compared to those from WT controls. Moreover, analysis of the repair kinetics of radiation-induced DSBs revealed that HSCs from Ts65Dn mice were less proficient in DSB repair than the cells from WT controls. This deficiency was associated with a higher sensitivity of Ts65Dn HSCs to radiation-induced suppression of HSC clonogenic activity than that of euploid HSCs. These findings suggest that an additional copy of genes on human chromosome 21 may selectively impair the ability of HSCs to repair DSBs, which may contribute to DS-associated hematological abnormalities and malignancies. PMID:27243896

Tips on Mainstreaming: Do's and Don'ts in Activity Programs.

ERIC Educational Resources Information Center

Practical Pointers, 1978

1978-01-01

The document provides 10 brief articles on activities for mainstreamed handicapped students. Included are the following titles: "Tips on Mainstreaminq--Do's and Don'ts for Activity Programs;""Mainstreaming--A Goal and A Process;""What To Do When You Meet a Handicapped Person;""Tips for Dealing with Handicapped Persons;""Relatinq to Orthopedically…

Characterization and Evolution of Tetrameric Photosystem I from the Thermophilic Cyanobacterium Chroococcidiopsis sp TS-821[C][W][OPEN

PubMed Central

Li, Meng; Semchonok, Dmitry A.; Boekema, Egbert J.; Bruce, Barry D.

2014-01-01

Photosystem I (PSI) is a reaction center associated with oxygenic photosynthesis. Unlike the monomeric reaction centers in green and purple bacteria, PSI forms trimeric complexes in most cyanobacteria with a 3-fold rotational symmetry that is primarily stabilized via adjacent PsaL subunits; however, in plants/algae, PSI is monomeric. In this study, we discovered a tetrameric form of PSI in the thermophilic cyanobacterium Chroococcidiopsis sp TS-821 (TS-821). In TS-821, PSI forms tetrameric and dimeric species. We investigated these species by Blue Native PAGE, Suc density gradient centrifugation, 77K fluorescence, circular dichroism, and single-particle analysis. Transmission electron microscopy analysis of native membranes confirms the presence of the tetrameric PSI structure prior to detergent solubilization. To investigate why TS-821 forms tetramers instead of trimers, we cloned and analyzed its psaL gene. Interestingly, this gene product contains a short insert between the second and third predicted transmembrane helices. Phylogenetic analysis based on PsaL protein sequences shows that TS-821 is closely related to heterocyst-forming cyanobacteria, some of which also have a tetrameric form of PSI. These results are discussed in light of chloroplast evolution, and we propose that PSI evolved stepwise from a trimeric form to tetrameric oligomer en route to becoming monomeric in plants/algae. PMID:24681621

Genetic Variation of Methylenetetrahydrofolate Reductase (MTHFR) and Thymidylate Synthase (TS) Genes Is Associated with Idiopathic Recurrent Implantation Failure.

PubMed

Choi, Youngsok; Kim, Jung Oh; Shim, Sung Han; Lee, Yubin; Kim, Ji Hyang; Jeon, Young Joo; Ko, Jung Jae; Lee, Woo Sik; Kim, Nam Keun

2016-01-01

The one-carbon metabolism pathway disorder was important role in successful pregnancy. The MTHFR and TS protein were crucial factor in one-carbon metabolism. To investigate the association between recurrent implantation failure (RIF) and enzymes in the one-carbon metabolism pathway. A total of 120 women diagnosed with RIF and 125 control subjects were genotyped for MTHFR 677C>T, 1298A>C, TSER 2R/3R and TS 1494del/ins by a polymerase chain reaction-restriction fragment length polymorphism assay. According to the gene-gene combination analysis, the MTHFR 677/MTHFR 1298 (TT/AA) and MTHFR 677/TS 1494 (TT/6bp6bp) genetic combinations were associated with relatively higher risks [adjusted odds ratio (AOR), 2.764; 95% CI, 1.065-7.174; P = 0.037 and AOR, 3.186; 95% CI, 1.241-8.178; P = 0.016] in RIF patients compared to the CC/AA (MTHFR 677/MTHFR 1298) and TT/6bp6bp (MTHFR 677/TS 1494) combinations, respectively. The results suggested that the combined MTHFR 677/MTHFR 1298 genotype might be associated with increased risk of RIF. To the best of our knowledge, this study is the first to elucidate the potential association of MTHFR, TS and TSER polymorphisms with RIF risk in Korean patients.

Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Scott-McKean, Jonah J.; Roque, Adriano L.; Surewicz, Krystyna; Johnson, Mark W.; Surewicz, Witold K.

2018-01-01

The Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compared with euploid mouse-derived slices. Additionally, therapeutically relevant doses of the drug memantine were shown to rescue learning and memory deficits in Ts65Dn mice. Here, we observed that 1 μM memantine had no detectable effect on HFS-induced LTP in either Ts65Dn- or control-derived slices, but it rescued TBS-induced LTP in Ts65Dn-derived slices to control euploid levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 μM picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices. PMID:29849573

TS-071 is a novel, potent and selective renal sodium-glucose cotransporter 2 (SGLT2) inhibitor with anti-hyperglycaemic activity.

PubMed

Yamamoto, K; Uchida, S; Kitano, K; Fukuhara, N; Okumura-Kitajima, L; Gunji, E; Kozakai, A; Tomoike, H; Kojima, N; Asami, J; Toyoda, H; Arai, M; Takahashi, T; Takahashi, K

2011-09-01

The renal sodium-glucose cotransporter 2 (SGLT2) plays an important role in the reuptake of filtered glucose in the proximal tubule and therefore may be an attractive target for the treatment of diabetes mellitus. This study characterizes the pharmacological profile of TS-071 ((1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol hydrate), a novel SGLT2 inhibitor in vitro and in vivo. Inhibition of glucose uptake by TS-071 was studied in CHO-K1 cells stably expressing either human SGLT1 or SGLT2. Single oral dosing studies were performed in rats, mice and dogs to assess the abilities of TS-071 to increase urinary glucose excretion and to lower plasma glucose levels. TS-071 inhibited SGLT2 activity in a concentration-dependent manner and was a potent and highly selective inhibitor of SGLT2. Orally administered TS-071 increased urinary glucose excretion in Zucker fatty rats and beagle dogs at doses of 0.3 and 0.03 mg·kg(-1) respectively. TS-071 improved glucose tolerance in Zucker fatty rats without stimulating insulin secretion and reduced hyperglycaemia in streptozotocin (STZ)-induced diabetic rats and db/db mice at a dose of 0.3 mg·kg(-1). These data indicate that TS-071 is a potent and selective SGLT2 inhibitor that improves glucose levels in rodent models of type 1 and 2 diabetes and may be useful for the treatment for diabetes mellitus. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

MEMS startups: disruptive technology and business do's and don'ts

NASA Astrophysics Data System (ADS)

Bryzek, Janusz

2005-02-01

This paper characterizes factors that affect the probability of success for new startups. These guidelines are derived primarily from Venture Capital industry experience in funding disruptive technology companies. It follows with an overview of Silicon Valley MEMS and MOEMS startups and provides with a summary of Do"s and Don"ts for entrepreneurs.

Relapsed cervicomediastinal lymph node carcinoma with an unknown primary site treated with TS-1 alone: a case report.

PubMed

Yajima, Toshiki; Onozato, Ryoichi; Shitara, Yoshinori; Mogi, Akira; Tanaka, Shigebumi; Kuwano, Hiroyuki

2013-12-27

Cervicomediastinal lymph node carcinoma with an unknown primary site is quite rare, and useful treatment of these diseases has not been established. We report here the case of a patient successfully treated with TS-1 alone after the relapse of cervicomediastinal lymph node carcinoma with an unknown primary site. A 62-year-old man was referred to our hospital because of cervicomediastinal lymph node swelling and high serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen. Fluorodeoxyglucose-positron emission tomography/computed tomography revealed an accumulation of fluorodeoxyglucose in the left supraclavicular lymph nodes, mediastinal lymph nodes, and the pelvic cavity. Colonoscopy revealed rectal cancer, which was diagnosed by biopsy as a tubular adenocarcinoma. Because metastases from rectal cancer to the cervicomediastinal lymph nodes are rare, the patient underwent thoracoscopic mediastinal lymphadenectomy. A biopsy specimen from the paraaortic lymph nodes demonstrated papillary adenocarcinoma that was pathologically different from the rectal cancer; therefore, a diagnosis of mediastinal carcinoma with an unknown primary site was established. The patient underwent low anterior resection of the rectum for the rectal cancer, and no abdominal lymph node metastasis (pMP, N0/stage I) was found. Although radiotherapy was performed for the cervicomediastinal lymph nodes, the mediastinal carcinoma relapsed after 6 months. Because the patient desired oral chemotherapy on an outpatient basis, TS-1 was administered at a dosage of 80 mg/day for 2 weeks, followed by a 1-week rest. TS-1 treatment resulted in a decrease in the size of the cervicomediastinal lymph nodes, and the serum tumor marker levels decreased to normal after the fourth course. The patient continued TS-1 treatment without adverse events and is currently alive without recurrence or identification of the primary site at the 32nd month after TS-1 treatment. This is the first reported case of

Elongation factor Ts directly facilitates the formation and disassembly of the Escherichia coli elongation factor Tu·GTP·aminoacyl-tRNA ternary complex.

PubMed

Burnett, Benjamin J; Altman, Roger B; Ferrao, Ryan; Alejo, Jose L; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C

2013-05-10

Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex with the G-protein elongation factor Tu (EF-Tu) and GTP. EF-Tu·GTP·aa-tRNA ternary complex formation and decay rates are accelerated in the presence of the nucleotide exchange factor elongation factor Ts (EF-Ts). EF-Ts directly facilitates the formation and disassociation of ternary complex. This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis.

Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients.

PubMed

Krawczyk, Paweł; Kucharczyk, Tomasz; Kowalski, Dariusz M; Powrózek, Tomasz; Ramlau, Rodryg; Kalinka-Warzocha, Ewa; Winiarczyk, Kinga; Knetki-Wróblewska, Magdalena; Wojas-Krawczyk, Kamila; Kałakucka, Katarzyna; Dyszkiewicz, Wojciech; Krzakowski, Maciej; Milanowski, Janusz

2014-12-01

We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy. The following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5'-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3'-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations' results were correlated with disease control rate, progression-free survival (PFS) and overall survival. Polymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality. The examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients.

Tensile strength/yield strength (TS/YS) ratios of high-strength steel (HSS) reinforcing bars

NASA Astrophysics Data System (ADS)

Tavio, Anggraini, Retno; Raka, I. Gede Putu; Agustiar

2018-05-01

The building codes such as American Concrete Institute (ACI) 318M-14 and Standard National Indonesia (SNI) 2847:2013 require that the ratio of tensile strength (TS) and yield strength (YS) should not less than 1.25. The requirement is based on the assumption that a capability of a structural member to develop inelastic rotation capacity is a function of the length of the yield region. This paper reports an investigation on various steel grades, namely Grades 420, 550, 650, and 700 MPa, to examine the impact of different TS/YS ratios if it is less or greater than the required value. Grades 550, 650, and 700 MPa were purposely selected with the intention to examine if these higher grades are still promising to be implemented in special structural systems since they are prohibited by the building codes for longitudinal reinforcement, whereas Grade 420 MPa bars are the maximum limit of yield strength of reinforcing bars that is allowable for longitudinal reinforcement of special structural systems. Tensile tests of these steel samples were conducted under displacement controlled mode to capture the complete stress-strain curves and particularly the post-yield response of the steel bars. From the study, it can be concluded that Grade 420 performed higher TS/YS ratios and they were able to reach up to more than 1.25. However, the High Strength Still (HSS) bars (Grades 550, 600, and 700 MPa) resulted in lower TS/YS ratios (less than 1.25) compared with those of Grade 420 MPa.

Reproducible Preparation of Au/TS-1 with High Reaction Rate for Gas Phase Epoxidation of Propylene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee W. S.; Stach E.; Akatay, M.C.

2012-03-01

A refined and reliable synthesis procedure for Au/TS-1(Si/Ti molar ratio {approx}100) with high reaction rate for the direct gas phase epoxidation of propylene has been developed by studying the effects of pH of the gold slurry solution, mixing time, and preparation temperature for deposition precipitation (DP) of Au on TS-1 supports. Au/TS-1 catalysts prepared at optimal DP conditions (pH {approx} 7.3, mixing for 9.5 h, room temperature) showed an average PO rate {approx} 160 g{sub PO} h{sup -1} kg{sub Cat}{sup -1} at 200 C at 1 atm. A reproducibility better than {+-}10% was demonstrated by nine independent samples prepared atmore » the same conditions. These are the highest rates yet reported at 200 C. No visible gold particles were observed by the HRTEM analysis in the fresh Au/TS-1 with gold loading up to {approx}0.1 wt%, indicating that the gold species were smaller than 1 nm. Additionally, the rate per gram of Au and the catalyst stability increased as the Au loading decreased, giving a maximum value of 500 g{sub PO} h{sup -1} g{sub Au}{sup -1}, and Si/Ti molar ratios of {approx}100 gave the highest rates.« less

TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed.

PubMed

Uramoto, Hidetaka; Onitsuka, Takamitsu; Shimokawa, Hidehiko; Hanagiri, Takeshi

2010-10-01

Recently, pemetrexed (PEM), a new generation antifolate, has been used for the treatment of patients with advanced non-squamous cell carcinoma (SQ) of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). However, no useful markers for selecting appropriate candidates exist at present. Tumor specimens were collected from 5 lung non-SQ and 8 MPM patients who underwent surgery and received PEM. Real-time PCR and immunohistochemical (IHC) staining of the primary tumor were used to analyze the mRNA and protein expressions of thymidylate synthase (TS)/dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), and to compare the expression status and clinical outcomes. TS, DHFR, and GARFT mRNA levels had a median value of 2.39, 1.70, and 1.40 in non-SQ samples of NSCLC patients. The TS and DHFR protein levels had a mean total score of 2 and 4 in non-SQ of NSCLC patients. TS, DHFR, and GARFT mRNA levels had a median value of 5.55, 3.73, and 3.52 in MPM patients. TS and DHFR protein levels had a mean total expression score of 1 and 3 in MPM patients. No significant correlation was identified between the expression levels of TS/DPD/GARFT mRNA and clinical response for the non-SQ of NSCLC and MPM patients treated with PEM. TS, DHFR, and GARFT mRNA and protein expression may not be useful markers for predicting clinical response in Japanese patients with non-SQ of NSCLC and MPM. Further investigations are necessary in order to develop biomarkers to determine the clinical benefits of PEM treatment.

Evaluation of heparin-induced thrombocytopenia (HIT) laboratory testing and the 4Ts scoring system in the intensive care unit.

PubMed

Pierce, Wesly; Mazur, Joseph; Greenberg, Charles; Mueller, Joan; Foster, Joyce; Lazarchick, John

2013-01-01

Over-diagnosis of heparin-induced thrombocytopenia (HIT) results in costly and unnecessary laboratory screening and treatment with direct thrombin inhibitors. Our aim was to evaluate the utility of the 4Ts scoring system to predict HIT in multiple ICU settings and to characterize our treatment of these cases. Eighty-two patients from multiple ICU settings who underwent laboratory testing for HIT were classified as low-, intermediate-, or high-risk patients based on retrospectively adjudicated 4Ts scores. These results were compared with platelet-factor 4 enzyme-linked immunosorbent assays (PF4 ELISAs), optical density (OD) values, and serotonin-release assays (SRAs) to assess the utility of the 4Ts score to rule out ICU-related HIT and reduce laboratory and drug expenditures. Of the 82 patients reviewed, only 12 (11.4%) were PF4-positive and only 1 (1.2%) was SRA-positive for HIT. Heparin was discontinued in only 63.4% of patients suspected to have HIT. There were no significant differences in mean day of platelet fall, mean platelet nadir, and mean percent fall in platelet count between PF4-positive and negative patients (all p > 0.2). There was, however, a significantly higher proportion of patients with an intermediate to high 4Ts score in the PF4-positive group than in the PF4-negative group (66% vs. 30%, respectively; p = 0.02). The mean PF4 OD value in patients with intermediate to high 4Ts scores was significantly higher than in patients with low 4Ts scores (0.658 vs. 0.258, respectively; p < 0.001). The negative predictive values of the 4Ts score relative to the PF4 and SRA were 92% and 100%, respectively. The estimated laboratory and pharmacologic cost avoidance potential of the scoring system in this cohort was $21,450. Our modified 4Ts scoring system appears to be an effective tool for predicting HIT in the ICU and could avoid significant drug and laboratory expenditures if implemented prospectively. The clinical management of patients suspected of HIT

Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC.

PubMed

Wang, Xia; Wang, Yadi; Wang, Yue; Cheng, Jian; Wang, Yanyun; Ha, Minwen

2013-01-25

Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3'-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival. Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3'-UTR 1494 bp (-6 bp/-6 bp) genotype and the rest had TS gene 3'-UTR 1494 bp (-6 bp/+6 bp). There was no TS 3'-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3'-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (-6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (-6 bp/+6 bp). This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3'-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized

Influence of aerothermoacoustic treatment on the structure and the properties of a TS6 titanium alloy

NASA Astrophysics Data System (ADS)

Remshev, E. Yu.; Danilin, G. A.; Vorob'eva, G. A.; Kuznetsov, V. V.

2017-01-01

The influence of standard heat or aerothermoacoustic treatment on the structure and the properties of a TS6 titanium alloy is considered. The interrelation between variations in the structure, the grain size, and the properties of the alloy has been detected. The possibilities of aerothermoacoustic treatment to provide a simultaneous increase in the strength and the plasticity of a TS6 alloy upon refining of its grain structure in the course of microplastic deformation and recrystallization are demonstrated.

ERCC1 and TS Expression as Prognostic and Predictive Biomarkers in Metastatic Colon Cancer.

PubMed

Choueiri, Michel B; Shen, John Paul; Gross, Andrew M; Huang, Justin K; Ideker, Trey; Fanta, Paul

2015-01-01

In patients with metastatic colon cancer, response to first line chemotherapy is a strong predictor of overall survival (OS). Currently, oncologists lack diagnostic tests to determine which chemotherapy regimen offers the greatest chance for response in an individual patient. Here we present the results of gene expression analysis for two genes, ERCC1 and TS, measured with the commercially available ResponseDX: Colon assay (Response Genetics, Los Angeles, CA) in 41 patients with de novo metastatic colon cancer diagnosed between July 2008 and August 2013 at the University of California, San Diego. In addition ERCC1 and TS expression levels as determined by RNAseq and survival data for patients in TCGA were downloaded from the TCGA data portal. We found that patients with low expression of ERCC1 (n = 33) had significantly longer median OS (36.0 vs. 10.1 mo, HR 0.29, 95% CI .095 to .84, log-rank p = 9.0x10-6) and median time to treatment to failure (TTF) following first line chemotherapy (14.1 vs. 2.4 mo, HR 0.17, 95% CI 0.048 to 0.58, log-rank p = 5.3x10-4) relative to those with high expression (n = 4). After accounting for the covariates age, sex, tumor grade and ECOG performance status in a Cox proportional hazard model the association of low ERCC1 with longer OS (HR 0.18, 95% CI 0.14 to 0.26, p = 0.0448) and TTF (HR 0.16, 95% CI 0.14 to 0.21, p = 0.0053) remained significant. Patients with low TS expression (n = 29) had significantly longer median OS (36.0 vs. 14.8 mo, HR 0.25, 95% CI 0.074 to 0.82, log-rank p = 0.022) relative to those with high expression (n = 12). The combined low expression of ERCC1/TS was predictive of response in patients treated with FOLFOX (40% vs. 91%, RR 2.3, Fisher's exact test p = 0.03, n = 27), but not with FOLFIRI (71% vs. 71%, RR 1.0, Fisher's exact test p = 1, n = 14). Overall, these findings suggest that measurement of ERCC1 and TS expression has potential clinical utility in managing patients with metastatic colorectal cancer.

Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice

PubMed Central

Yan, Jian; Ginsberg, Stephen D.; Powers, Brian; Alldred, Melissa J.; Saltzman, Arthur; Strupp, Barbara J.; Caudill, Marie A.

2014-01-01

Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a trisomic mouse model of Down syndrome and Alzheimer's disease. To gain insight into the mechanisms underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters choline metabolism in adult Ts65Dn offspring. Deuterium-labeled methyl-d9-choline was administered to adult Ts65Dn and disomic (2N) female littermates born to choline-unsupplemented or choline-supplemented Ts65Dn dams. Enrichment of d9-choline metabolites (derived from intact choline) and d3 + d6-choline metabolites [produced when choline-derived methyl groups are used by phosphatidylethanolamine N-methyltransferase (PEMT)] was measured in harvested tissues. Adult offspring (both Ts65Dn and 2N) of choline-supplemented (vs. choline-unsupplemented) dams exhibited 60% greater (P≤0.007) activity of hepatic PEMT, which functions in de novo choline synthesis and produces phosphatidylcholine (PC) enriched in docosahexaenoic acid. Higher (P<0.001) enrichment of PEMT-derived d3 and d6 metabolites was detected in liver, plasma, and brain in both genotypes but to a greater extent in the Ts65Dn adult offspring. MCS also yielded higher (P<0.05) d9 metabolite enrichments in liver, plasma, and brain. These data demonstrate that MCS exerts lasting effects on offspring choline metabolism, including up-regulation of the hepatic PEMT pathway and enhanced provision of choline and PEMT-PC to the brain.—Yan, J., Ginsberg, S. D., Powers, B., Alldred, M. J., Saltzman, A., Strupp, B. J., Caudill, M. A. Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice. PMID:24963152

Correlation between expressions of ERCC1/TS mRNA and effects of gastric cancer to chemotherapy in the short term.

PubMed

Chen, Liqi; Li, Guoli; Li, Jieshou; Fan, Chaogang; Xu, Jian; Wu, Bo; Liu, Kun; Zhang, Caihua

2013-04-01

To study the correlation between expression levels of ERCC1/TS mRNA and the susceptibility of preoperative chemotherapy for patients with gastric cancer. A total of forty cases with advanced gastric cancer of T3-4N1-2M0 were treated with preoperative chemotherapy according to FLEEOX regimen based on endarterial-intravenous coadministration. Sufficient, fresh gastric tissue specimens were obtained with the help of gastroscope, and the expression levels of ERCC1/TS mRNA were detected by qRT-PCR before chemotherapy. The chemotherapeutic response was evaluated with Choi Criteria after chemotherapy, and pathologic remission extent was observed after surgery. The correlation between the expression levels of ERCC1/TS mRNA before chemotherapy and the chemotherapeutic effect based on imageology and pathology was analyzed. The response rate of Chemotherapy in this cohort was 80.0 % based on imageology and 51.43 % based on pathology. The expression levels of ERCC1/TS mRNA were significantly associated with imageology remission extent (P = 0.033, P = 0.025) and pathologic remission extent (P = 0.044, P = 0.016), respectively. The chemotherapeutic effect on patients with low-expression levels of ERCC1/TS mRNA was better. From the perspective of pathology and imageology evaluating the preoperative chemotherapeutic response for patients with gastric cancer, ERCC1 and TS were used as the molecular predictors and provided prognostic information in this study.

Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice.

PubMed

Yan, Jian; Ginsberg, Stephen D; Powers, Brian; Alldred, Melissa J; Saltzman, Arthur; Strupp, Barbara J; Caudill, Marie A

2014-10-01

Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a trisomic mouse model of Down syndrome and Alzheimer's disease. To gain insight into the mechanisms underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters choline metabolism in adult Ts65Dn offspring. Deuterium-labeled methyl-d9-choline was administered to adult Ts65Dn and disomic (2N) female littermates born to choline-unsupplemented or choline-supplemented Ts65Dn dams. Enrichment of d9-choline metabolites (derived from intact choline) and d3 + d6-choline metabolites [produced when choline-derived methyl groups are used by phosphatidylethanolamine N-methyltransferase (PEMT)] was measured in harvested tissues. Adult offspring (both Ts65Dn and 2N) of choline-supplemented (vs. choline-unsupplemented) dams exhibited 60% greater (P≤0.007) activity of hepatic PEMT, which functions in de novo choline synthesis and produces phosphatidylcholine (PC) enriched in docosahexaenoic acid. Higher (P<0.001) enrichment of PEMT-derived d3 and d6 metabolites was detected in liver, plasma, and brain in both genotypes but to a greater extent in the Ts65Dn adult offspring. MCS also yielded higher (P<0.05) d9 metabolite enrichments in liver, plasma, and brain. These data demonstrate that MCS exerts lasting effects on offspring choline metabolism, including up-regulation of the hepatic PEMT pathway and enhanced provision of choline and PEMT-PC to the brain. © FASEB.

Development of High-Field ST Merging Experiment: TS-U for High Power Reconnection Heating

NASA Astrophysics Data System (ADS)

Ono, Y.; Koike, H.; Tanabe, H.; Himeno, S.; Ishida, S.; Kimura, K.; Kawanami, M.; Narita, M.; Takahata, Y.; Yokoyama, T.; Inomoto, M.; Cheng, C. Z.

2016-10-01

We are developing high-magnetic field ST merging/ reconnection experiment TS-U with Brec = 0.3-0.5T, based on our scaling law of reconnection heating energy proportional to square of the reconnecting (poloidal) magnetic field Brec. This scaling law indicates that the high-Brec ST merging will heat ions to the burning plasma regime without using any additional heating facility. Its mechanism is that the reconnection outflow accelerates mainly ions up to the poloidal Alfven speed like the Sweet-Parker model. The shock-like density pileups thermalize the accelerated ions in the down-streams in agreement with recent solar satellite observations and PIC simulation results. We already documented significant ion heating of spheromak and ST mergings up to 0.25keV in TS-3 and 1.2keV in MAST, leading us to the high-Brec merging experiment TS-U. It is noted that high-resolution (>500 channel) 2D measurements of ion and electron temperatures is being developed for the purpose of solving all acceleration and heating effects of magnetic reconnection, such as the huge outflow heating of ions in the downstream and electron heating localized at the X-point.

A highly Conserved Aspartic Acid Residue of the Chitosanase from Bacillus Sp. TS Is Involved in the Substrate Binding.

PubMed

Zhou, Zhanping; Zhao, Shuangzhi; Liu, Yang; Chang, Zhengying; Ma, Yanhe; Li, Jian; Song, Jiangning

2016-11-01

The chitosanase from Bacillus sp. TS (CsnTS) is an enzyme belonging to the glycoside hydrolase family 8. The sequence of CsnTS shares 98 % identity with the chitosanase from Bacillus sp. K17. Crystallography analysis and site-direct mutagenesis of the chitosanase from Bacillus sp. K17 identified the important residues involved in the catalytic interaction and substrate binding. However, despite progress in understanding the catalytic mechanism of the chitosanase from the family GH8, the functional roles of some residues that are highly conserved throughout this family have not been fully elucidated. This study focused on one of these residues, i.e., the aspartic acid residue at position 318. We found that apart from asparagine, mutation of Asp318 resulted in significant loss of enzyme activity. In-depth investigations showed that mutation of this residue not only impaired enzymatic activity but also affected substrate binding. Taken together, our results showed that Asp318 plays an important role in CsnTS activity.

Improved immune response to an attenuated pseudorabies virus vaccine by ginseng stem-leaf saponins (GSLS) in combination with thimerosal (TS).

PubMed

Ni, Jingxuan; Bi, Shicheng; Xu, Wei; Zhang, Cenrong; Lu, Yisong; Zhai, Lijuan; Hu, Songhua

2016-08-01

Vaccination using attenuated vaccines remains an important method to control animal infectious diseases. The present study evaluated ginseng stem-leaf saponins (GSLS) and thimerosal (TS) for their adjuvant effect on an attenuated pseudorabies virus (aPrV) vaccine in mice. Compared to the group immunized with aPrV alone, the co-inoculation of GSLS and/or TS induced a higher antibody response. Particularly, when administered together with GSLS-TS, the aPrV vaccine provoked a higher serum gB-specific antibody, IgG1 and IgG2a levels, lymphocyte proliferative responses, as well as production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) from lymphocytes, and more importantly provided an enhanced cytotoxicity of NK cells and protection against virulent field pseudorabies virus challenge. Additionally, the increased expression of miR-132, miR-146a, miR-147 and miR-155 was found in murine macrophages cultured with GSLS and/or TS. These data suggest that GSLS-TS as adjuvant improve the efficacy of aPrV vaccine in mouse model and have potential for the development of attenuated viral vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

EFFECTS OF LONG-TERM MEMANTINE ON MEMORY AND NEUROPATHOLOGY IN TS65DN MICE, A MODEL FOR DOWN SYNDROME

PubMed Central

Lockrow, Jason; Boger, Heather; Bimonte-Nelson, Heather; Granholm, Ann-Charlotte

2010-01-01

Memantine is a partial NMDA receptor antagonist that has been shown to improve learning and memory in several animal models, and is approved for the treatment of Alzheimer’s disease. Chronic treatments using memantine in animal models of Alzheimer’s disease show disease-modifying effects and suggest a potential neuroprotective function. The present study assessed the effects of both short- and long-term memantine treatment in a mouse model of Down syndrome, the Ts65Dn mouse. The Ts65Dn mouse contains a partial trisomy of murine chromosome 16, and exhibits hippocampal-dependent memory deficits, as well as progressive degeneration of basal forebrain cholinergic neurons. Ts65Dn mice were treated with memantine for a period of six months, beginning at four months of age. At the end of treatment the mice underwent memory testing using novel object recognition and water radial arm maze tasks, and then histologically analyzed for markers of neurodegeneration. Memantine treatment improved spatial and recognition memory performance in the Ts65Dn mice, though not to the level of normosomic littermate controls. Despite these memory improvements, histological analysis found no morphological signs of neuroprotection of basal forebrain cholinergic or locus coeruleus neurons in memantine-treated Ts65Dn mice. However, memantine treatment of Ts65Dn mice gave rise to elevated brain-derived neurotrophic factor expression in the hippocampus and frontal cortex, suggesting a mechanism of behavioral modification. Thus, our findings provide further evidence for memory facilitation of memantine, but suggest pharmacological rather than neuroprotective effects of memantine both after acute and chronic treatment in this mouse model. PMID:20363261

Model predictive controller design for boost DC-DC converter using T-S fuzzy cost function

NASA Astrophysics Data System (ADS)

Seo, Sang-Wha; Kim, Yong; Choi, Han Ho

2017-11-01

This paper proposes a Takagi-Sugeno (T-S) fuzzy method to select cost function weights of finite control set model predictive DC-DC converter control algorithms. The proposed method updates the cost function weights at every sample time by using T-S type fuzzy rules derived from the common optimal control engineering knowledge that a state or input variable with an excessively large magnitude can be penalised by increasing the weight corresponding to the variable. The best control input is determined via the online optimisation of the T-S fuzzy cost function for all the possible control input sequences. This paper implements the proposed model predictive control algorithm in real time on a Texas Instruments TMS320F28335 floating-point Digital Signal Processor (DSP). Some experimental results are given to illuminate the practicality and effectiveness of the proposed control system under several operating conditions. The results verify that our method can yield not only good transient and steady-state responses (fast recovery time, small overshoot, zero steady-state error, etc.) but also insensitiveness to abrupt load or input voltage parameter variations.

A master-slave parallel hybrid multi-objective evolutionary algorithm for groundwater remediation design under general hydrogeological conditions

NASA Astrophysics Data System (ADS)

Wu, J.; Yang, Y.; Luo, Q.; Wu, J.

2012-12-01

This study presents a new hybrid multi-objective evolutionary algorithm, the niched Pareto tabu search combined with a genetic algorithm (NPTSGA), whereby the global search ability of niched Pareto tabu search (NPTS) is improved by the diversification of candidate solutions arose from the evolving nondominated sorting genetic algorithm II (NSGA-II) population. Also, the NPTSGA coupled with the commonly used groundwater flow and transport codes, MODFLOW and MT3DMS, is developed for multi-objective optimal design of groundwater remediation systems. The proposed methodology is then applied to a large-scale field groundwater remediation system for cleanup of large trichloroethylene (TCE) plume at the Massachusetts Military Reservation (MMR) in Cape Cod, Massachusetts. Furthermore, a master-slave (MS) parallelization scheme based on the Message Passing Interface (MPI) is incorporated into the NPTSGA to implement objective function evaluations in distributed processor environment, which can greatly improve the efficiency of the NPTSGA in finding Pareto-optimal solutions to the real-world application. This study shows that the MS parallel NPTSGA in comparison with the original NPTS and NSGA-II can balance the tradeoff between diversity and optimality of solutions during the search process and is an efficient and effective tool for optimizing the multi-objective design of groundwater remediation systems under complicated hydrogeologic conditions.

Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican

PubMed Central

Howell, Matthew D; Gottschall, Paul E

2012-01-01

DS (Down syndrome), resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls). In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs. In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze) and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets), an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits. PMID:22225533

[The expression of thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) protein in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy].

PubMed

Ishibashi, Keiichiro; Okada, Norimichi; Ishiguro, Toru; Kuwabara, Kouki; Ohsawa, Tomonori; Yokoyama, Masaru; Kumamoto, Kensuke; Haga, Norihiro; Mori, Takashi; Yamada, Hirofumi; Miura, Ichiro; Tamaru, Junichi; Itoyama, Shinji; Ishida, Hideyuki

2010-11-01

Thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) were known to be important biomarkers to predict a tumor response to 5-fluorouracil (5-FU) and oxaliplatin, but the relationship between these expressions and tumor response were still unclear. The aim of this study was to determine whether the expression of TS and ERCC-1 protein predict a tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy as first-line treatment. Fifty patients with unresectable colorectal cancer treated with mFOLFOX6 therapy were enrolled in this study. The expression of TS and ERCC-1 protein in primary cancer cells were examined using immunohistochemistry. There were no significant differences between response rate and the expression of TS or ERCC-1 protein (TS: p>0.99, ERCC-1: p= 0.50). There were no significant differences between progression-free survival time and the expression of TS or ERCC-1 protein (TS: p=0.60, ERCC-1: p=0.60). In this study, the expression TS and ERCC-1 protein may not be useful for the prediction of tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy.

Identification and mapping of ts (tender spines), a gene involved in soft spine development in Cucumis sativus.

PubMed

Guo, Chunli; Yang, Xuqin; Wang, Yunli; Nie, Jingtao; Yang, Yi; Sun, Jingxian; Du, Hui; Zhu, Wenying; Pan, Jian; Chen, Yue; Lv, Duo; He, Huanle; Lian, Hongli; Pan, Junsong; Cai, Run

2018-01-01

Using map-based cloning of ts gene, we identified a new sort of gene involved in the initiation of multicellular tender spine in cucumber. The cucumber (Cucumis sativus L.) fruit contains spines on the surface, which is an extremely valuable quality trait affecting the selection of customers. In this study, we elaborated cucumber line NC072 with wild type (WT) hard fruit spines and its spontaneous mutant NC073, possessing tender and soft spines on fruits. The mutant trait was named as tender spines (ts), which is controlled by a single recessive nuclear gene. We identified the gene ts by map-based cloning with an F 2 segregating population of 721 individuals generated from NC073 and WT line SA419-2. It was located between two markers Indel6239679 and Indel6349344, 109.7 kb physical distance on chromosome 1 containing fifteen putative genes. With sequencing and quantitative reverse transcription-polymerase chain reaction analysis, the Csa1G056960 gene was considered as the most possible candidate gene of ts. In the mutant, Csa1G056960 has a nucleotide change in the 5' splicing site of the second intron, which causes different splicing to delete the second exon, resulting in a N-terminal deletion in the predicted amino acid sequence. The gene encodes a C-type lectin receptor-like tyrosine-protein kinase which would play an important role in the formation of cucumber fruit. This is firstly reported of a receptor kinase gene regulating the development of multicellular spines/trichomes in plants. The ts allele could accelerate the molecular breeding of cucumber soft spines.

Performance of the CONTOUR® TS Blood Glucose Monitoring System.

PubMed

Frank, Joy; Wallace, Jane F; Pardo, Scott; Parkes, Joan Lee

2011-01-01

Self-monitoring of blood glucose (SMBG) remains an important component of diabetes management, engendering a need for affordable blood glucose (BG) meters that are accurate, precise, and convenient. The CONTOUR® TS is a BG meter that endeavors to meet this need. It uses glucose dehydrogenase/flavin dinucleotide chemistry, automatic test strip calibration, and autocompensation for hematocrit along with the ease of use that has come to be expected of a modern meter. The objective of this clinical trial was to determine whether the CONTOUR TS system met these criteria. The system was evaluated at a single clinical site with 106 subjects with type 1 or type 2 diabetes. Blood glucose values ranged from 60 to 333 mg/dl over all subjects. Both lay users and health care professionals (HCPs) tested the meters, with test strips from three different lots. Results were compared to a reference analyzer of verified precision and accuracy. Forty-nine of the subjects also participated in a home study of the meter. Lay users learned to use the system without assistance and were surveyed on its use at the end of the study. When used with capillary blood, both subjects and HCPs obtained results that exceeded the International Organization for Standardization 15197:2003 criteria, (i.e., ≥95% of values fell within 20% or 15 mg/dl of the laboratory value for BG levels greater than or less than 75 mg/dl, respectively). Specifically, lay users achieved 97.9% and HCPs 98.6%. When used with venous blood, 99.8% of measurements were within the criteria. All measurements for both capillary and venous blood fell into zones A or B of the Parkes error grid, deemed clinically accurate. Hematocrit was found to have no influence on BG measurements. A large majority of the subjects found the system easy to learn and to use. The CONTOUR TS BG meter system gave accurate and reproducible results with both capillary and venous blood; subjects learned to use the meter system by following the user guide

TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients.

PubMed

Fariña-Sarasqueta, A; Gosens, M J E M; Moerland, E; van Lijnschoten, I; Lemmens, V E P P; Slooter, G D; Rutten, H J T; van den Brule, Adriaan J C

2011-08-01

Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy. 251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5'untranslated region of the TS gene were genotyped. There was a positive association between tumor T stage and the VNTR genotypes (p = 0.05). In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes. We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.

TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients.

PubMed

Fariña-Sarasqueta, A; Gosens, M J E M; Moerland, E; van Lijnschoten, I; Lemmens, V E P P; Slooter, G D; Rutten, H J T; van den Brule, A J C

2010-01-01

Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy. 251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5'-untranslated region of the TS gene were genotyped. There was a positive association between tumor T stage and the VNTR genotypes (p=0.05).In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes. We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.

TS Gene Polymorphisms Are Not Good Markers of Response to 5-FU Therapy in Stage III Colon Cancer Patients

PubMed Central

Fariña-Sarasqueta, A.; Gosens, M. J. E. M.; Moerland, E.; van Lijnschoten, I.; Lemmens, V. E. P. P.; Slooter, G. D.; Rutten, H. J. T.; van den Brule, A. J. C.

2010-01-01

Aim: Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy. Patients and Methods: 251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5′-untranslated region of the TS gene were genotyped. Results: There was a positive association between tumor T stage and the VNTR genotypes (p=0.05). In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes. Conclusion: We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival. PMID:20966539

TsAGI The Center of Aviation Science and Mechanics,

DTIC Science & Technology

1979-10-23

elements and an aircraft as a whole . In December 1925 TsAGI began operation of the largest wind tunnel in the world, at that time, the T-I - T-II wind...analysis methods for aviation structures were developed and the causes of the onset of vibrations in aircraft were investigated. V. N. Belyayev, A. Yu...compressors and other machines and devices were developed and studied in detail. A large number of enterprises, coal mines and the Moscow subway received

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins

PubMed Central

Cremonez, Caroline M.; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A. A.; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M. C.; Arantes, Eliane C.; Tytgat, Jan

2016-01-01

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx. PMID:27706049

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins.

PubMed

Cremonez, Caroline M; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A A; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M C; Arantes, Eliane C; Tytgat, Jan

2016-09-30

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx.

Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism.

PubMed

Shimohata, Atsushi; Ishihara, Keiichi; Hattori, Satoko; Miyamoto, Hiroyuki; Morishita, Hiromasa; Ornthanalai, Guy; Raveau, Matthieu; Ebrahim, Abdul Shukkur; Amano, Kenji; Yamada, Kazuyuki; Sago, Haruhiko; Akiba, Satoshi; Mataga, Nobuko; Murphy, Niall P; Miyakawa, Tsuyoshi; Yamakawa, Kazuhiro

2017-07-01

Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice. Ts1Cje mice showed enhanced locomotor activity in novel environments and increased social contact with unfamiliar partners when compared with wild-type littermates, but a significantly lower activity in familiar environments. Ts1Cje mice also exhibited some signs of decreased depression like-behavior. Furthermore, Ts1Cje mice showed monoamine abnormalities, including increased extracellular dopamine and serotonin, and enhanced catabolism in the striatum and ventral forebrain. This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Polymorphism of TS 3'-UTR predicts survival of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.

PubMed

Gao, J; He, Q; Hua, D; Mao, Y; Li, Y; Shen, L

2013-08-01

Capecitabine-containing chemotherapy was widely used in clinic medication. We investigated the association of the thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD) polymorphisms with the clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. Blood samples were collected prior to treatment from 125 patients with advanced gastric cancer and the TS (two or three repeats of a 28 bp sequence in 5'-untranslated region and 6 bp insertion or deletion in 3'-untranslated region), MTHFR (C677T) and DPD (IVS14+1G > A) polymorphisms were determined using PCR amplification and Sanger sequencing. The median age of 125 patients was 58 years (range, 23-76) with female 42 and male 83, and the response rate, median progression-free survival and overall survival (OS) were 43.2 %, 5.2 and 11.0 months. The median OS in patients with TS ins6/ins6 genotype (6.8 months) was significantly shorter than those in patients with ins6/del6 (11.0 months, P = 0.016) and del6/del6 (11.5 months, P = 0.039) genotypes. Cox multivariate analysis also showed that TS ins6/ins6 genotype was the independent poor OS predictor (P = 0.001, HR = 3.182). No significant associations were found between the polymorphisms of TS 5'-UTR/MTHFR and clinical outcome, and no IVS14+1G > A polymorphism of DPD was found in this study. We first reported that TS 3'-UTR ins6/ins6 genotype could predict the poor survival of advanced gastric cancer patients treated with capecitabine plus paclitaxel, which would be further verified in a large multicenter study.

Treatment with corn oil improves neurogenesis and cognitive performance in the Ts65Dn mouse model of Down syndrome.

PubMed

Giacomini, Andrea; Stagni, Fiorenza; Emili, Marco; Guidi, Sandra; Salvalai, Maria Elisa; Grilli, Mariagrazia; Vidal-Sanchez, Veronica; Martinez-Cué, Carmen; Bartesaghi, Renata

2018-06-20

Individuals with Down syndrome (DS), a genetic condition due to triplication of Chromosome 21, are characterized by intellectual disability that worsens with age. Since impairment of neurogenesis and dendritic maturation are very likely key determinants of intellectual disability in DS, interventions targeted to these defects may translate into a behavioral benefit. While most of the neurogenesis enhancers tested so far in DS mouse models may pose some caveats due to possible side effects, substances naturally present in the human diet may be regarded as therapeutic tools with a high translational impact. Linoleic acid and oleic acid are major constituents of corn oil that positively affect neurogenesis and neuron maturation. Based on these premises, the goal of the current study was to establish whether treatment with corn oil improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn model of DS. Four-month-old Ts65Dn and euploid mice were treated with saline or corn oil for 30 days. Evaluation of behavior at the end of treatment showed that Ts65Dn mice treated with corn oil underwent a large improvement in hippocampus-dependent learning and memory. Evaluation of neurogenesis and dendritogenesis showed that in treated Ts65Dn mice the number of new granule cells of the hippocampal dentate gyrus and their dendritic pattern became similar to those of euploid mice. In addition, treated Ts65Dn mice underwent an increase in body and brain weight. This study shows for the first time that fatty acids have a positive impact on the brain of the Ts65Dn mouse model of DS. These results suggest that a diet that is rich in fatty acids may exert beneficial effects on cognitive performance in individuals with DS without causing adverse effects. Copyright © 2018. Published by Elsevier Inc.

REAC/TS Radiation Accident Registry: An Overview

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doran M. Christensen, DO, REAC /TS Associate Director and Staff Physician Becky Murdock, REAC/TS Registry and Health Physics Technician

2012-12-12

Over the past four years, REAC/TS has presented a number of case reports from its Radiation Accident Registry. Victims of radiological or nuclear incidents must meet certain dose criteria for an incident to be categorized as an “accident” and be included in the registry. Although the greatest numbers of “accidents” in the United States that have been entered into the registry involve radiation devices, the greater percentage of serious accidents have involved sealed sources of one kind or another. But if one looks at the kinds of accident scenarios that have resulted in extreme consequence, i.e., death, the greater sharemore » of deaths has occurred in medical settings.« less

T11TS immunotherapy repairs PI3K-AKT signaling in T-cells: Clues toward enhanced T-cell survival in rat glioma model.

PubMed

Chaudhuri, Suhnrita; Singh, Manoj K; Bhattacharya, Debanjan; Datta, Ankur; Hazra, Iman; Mondal, Somnath; Faruk Sk Md, Omar; Ronsard, Larance; Ghosh, Tushar K; Chaudhuri, Swapna

2018-02-01

Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) blocks T-cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin-NFAT pathway following T11TS immunotherapy of glioma-bearing rats. This lead to investigations whether such T-cell activation upon T11TS therapy translates into activation of downstream PI3K/AKT signals which may be related to observed blockade of T-cell apoptosis. For the purpose, we assessed by flowcytometry and immunoblotting, expressions of PI3K, PDK1, AKT, p-AKT, and PTEN in splenic T-cells of normal, experimentally-induced glioma-bearing rats and glioma-bearing rats receiving first, second and third doses of T11TS. We also determined comparative nuclear translocation of NF-κB across groups. We found significant increases in T-cell expressions of PDK1, PI3K, and p-AKT in T11TS-treated animal groups compared to sharp downregulations in glioma. AKT levels remained unchanged across groups. PTEN levels declined sharply after T11TS immunotherapy. T11TS also caused enhanced NF-κB translocation to the T-cell nucleus compared to glioma group. Results showed heightened activation of the PI3K-AKT pathway in glioma-bearing rats following T11TS immunotherapy. These results illustrate the novel role of T11TS immunotherapy in ameliorating the PI3K pathway in T-cells in glioma-bearing animals to enhance T-cell survival, according greater defense against glioma. The study thus has far-reaching clinical outcomes. © 2017 Wiley Periodicals, Inc.

3Ts--Training, Testing, and Telling: A Guide for Community Partners

ERIC Educational Resources Information Center

US Environmental Protection Agency, 2006

2006-01-01

The United States Environmental Protection Agency (EPA) wants to ensure schools and child care facilities are safe environments for the nation's children. In response to rising public concern over the health risks posed to young children by lead in the drinking water, EPA is launching a "3Ts--Training, Testing, and Telling" program. This…

Protein Dynamics Associated with Failed and Rescued Learning in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Ahmed, Md. Mahiuddin; Dhanasekaran, A. Ranjitha; Block, Aaron; Tong, Suhong; Costa, Alberto C. S.; Stasko, Melissa; Gardiner, Katheleen J.

2015-01-01

Down syndrome (DS) is caused by an extra copy of human chromosome 21 (Hsa21). Although it is the most common genetic cause of intellectual disability (ID), there are, as yet, no effective pharmacotherapies. The Ts65Dn mouse model of DS is trisomic for orthologs of ∼55% of Hsa21 classical protein coding genes. These mice display many features relevant to those seen in DS, including deficits in learning and memory (L/M) tasks requiring a functional hippocampus. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist, memantine, was shown to rescue performance of the Ts65Dn in several L/M tasks. These studies, however, have not been accompanied by molecular analyses. In previous work, we described changes in protein expression induced in hippocampus and cortex in control mice after exposure to context fear conditioning (CFC), with and without memantine treatment. Here, we extend this analysis to Ts65Dn mice, measuring levels of 85 proteins/protein modifications, including components of MAP kinase and MTOR pathways, and subunits of NMDA receptors, in cortex and hippocampus of Ts65Dn mice after failed learning in CFC and after learning was rescued by memantine. We show that, compared with wild type littermate controls, (i) of the dynamic responses seen in control mice in normal learning, >40% also occur in Ts65Dn in failed learning or are compensated by baseline abnormalities, and thus are considered necessary but not sufficient for successful learning, and (ii) treatment with memantine does not in general normalize the initial protein levels but instead induces direct and indirect responses in approximately half the proteins measured and results in normalization of the endpoint protein levels. Together, these datasets provide a first view of the complexities associated with pharmacological rescue of learning in the Ts65Dn. Extending such studies to additional drugs and mouse models of DS will aid in identifying pharmacotherapies for effective clinical trials

Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer.

PubMed

Shen, Xiao-Ming; Zhou, Chong; Lian, Lian; Li, Li-Qun; Li, Wei; Tao, Min

2015-04-01

The aim was to determine changes in dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) mRNAs in the blood of advanced gastric cancer (AGC) patients to see whether these enzymes affected the patients' response to S-1-based chemotherapy and prognosis. For this purpose, pretreatment DPD/TS mRNA expressions were determined in 40 AGC patients using RT-PCR. The patients were then administered with S-1-based regimen (S-1 + cisplatin) and toxicities were recorded. The relationship between the DPD/TS mRNA expressions and the chemotherapy response, drug resistance, and prognosis was analyzed. The data show that DPD mRNA expression correlated significantly with Lauren type while TS mRNA expression correlated with distant metastasis. Patients with higher DPD and/or TS mRNA expression(s) showed poor response, while those with low DPD mRNA expression showed better response to the chemotherapy. Pooled analysis showed that the patients with low DPD/TS mRNA expressions had better therapeutic response. The incidence of bone marrow suppression, diarrhea, and oral mucositis was high in patients with low DPD mRNA expression. Median overall survival (OS) in 40 patients was 13.5 months. It was 17 months for low and 10 months for high DPD (P = 0.044) and TS mRNA expression (P = 0.047). Pooled analysis showed that the patients with both low DPD/TS mRNA expressions had longer OS (P = 0.001). In conclusion, the detection of DPD and/or TS mRNA expression can be used to predict the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC patients as well as to help guide the individualized treatment of gastric cancer.

Combination of TS-021 with metformin improves hyperglycemia and synergistically increases pancreatic β-cell mass in a mouse model of type 2 diabetes.

PubMed

Tajima, Atsushi; Hirata, Takashi; Taniguchi, Kazuo; Kondo, Yukiko; Kato, Sota; Saito-Hori, Masako; Ishimoto, Tsuyoshi; Yamamoto, Koji

2011-10-24

The objectives of this study were to elucidate the effects of a potent dipeptidyl peptidase (DPP)-IV inhibitor, TS-021, combined with/without metformin on glycemic control and pathological changes in pancreatic islets in high-fat diet and streptozotocin-induced (HFD-STZ) diabetic mice. The anti-diabetic effects of TS-021 and/or metformin in HFD-STZ mice were examined in both acute and chronic treatment studies. In addition, we performed immunohistochemical analysis after repeated administration of TS-021 and/or metformin to HFD-STZ mice twice a day for 5 weeks. In the acute treatment study, TS-021 and/or metformin significantly improved glucose tolerance and glucagon-like peptide-1 (GLP-1) level, and TS-021 alone or in combination with metformin significantly increased the plasma insulin level after nutrient ingestion. In the chronic treatment study, TS-021 in combination with metformin significantly lowered the glycosylated hemoglobin level, plasma insulin level, and α-cell-to-β-cell area ratio in pancreatic islets. In particular, the combined treatment synergistically increased the insulin-positive area in pancreatic islets from 32.3% in diabetic mice treated with the vehicle to 51.1% (TS-021 alone, 35.3%; metformin alone, 30.6%). The present study demonstrated that the coadministration of TS-021 and metformin synergistically improved the islet morphology by increasing the circulating level of biologically active GLP-1, which is thought to result from two different mechanisms (namely, an increase in GLP-1 secretion and DPP-IV inhibition). These findings strongly support the rationale for combined treatment with DPP-IV inhibitors plus metformin in clinical practice by clearly demonstrating an anti-diabetic effect associated with the remarkable improvement in pancreatic β-cell morphology. Copyright © 2011 Elsevier Inc. All rights reserved.

Widespread cerebellar transcriptome changes in Ts65Dn Down syndrome mouse model after lifelong running.

PubMed

Walus, Marius; Kida, Elizabeth; Rabe, Ausma; Albertini, Giorgio; Golabek, Adam A

2016-01-01

Our previous study showed an improvement in locomotor deficits after voluntary lifelong running in Ts65Dn mice, an animal model for Down syndrome (DS). In the present study, we employed mouse microarrays printed with 55,681 probes in an attempt to identify molecular changes in the cerebellar transcriptome that might contribute to the observed behavioral benefits of voluntary long-term running in Ts65Dn mice. Euploid mice were processed in parallel for comparative purposes in some analyses. We found that running significantly changed the expression of 4,315 genes in the cerebellum of Ts65Dn mice, over five times more than in euploid animals, up-regulating 1,991 and down-regulating 2,324 genes. Functional analysis of these genes revealed a significant enrichment of 92 terms in the biological process category, including regulation of biosynthesis and metabolism, protein modification, phosphate metabolism, synaptic transmission, development, regulation of cell death/apoptosis, protein transport, development, neurogenesis and neuron differentiation. The KEGG pathway database identified 18 pathways that are up-regulated and two that are down-regulated by running that were associated with learning, memory, cell signaling, proteolysis, regeneration, cell cycle, proliferation, growth, migration, and survival. Of six mRNA protein products we tested by immunoblotting, four showed significant running-associated changes in their levels, the most prominent in glutaminergic receptor metabotropic 1, and two showed changes that were close to significant. Thus, unexpectedly, our data point to the high molecular plasticity of Ts65Dn mouse cerebellum, which translated into humans with DS, suggests that the motor deficits of individuals with DS could markedly benefit from prolonged exercise. Copyright © 2015 Elsevier B.V. All rights reserved.

Search for gamma-ray emission from the nearby dwarf spheroidal galaxies with 9 years of Fermi-LAT data

NASA Astrophysics Data System (ADS)

Li, Shang; Duan, Kai-Kai; Liang, Yun-Feng; Xia, Zi-Qing; Shen, Zhao-Qiang; Li, Xiang; Liao, Neng-Hui; Feng, Lei; Yuan, Qiang; Fan, Yi-Zhong; Chang, Jin

2018-06-01

In this work, we search for γ -ray emission from nearby Milky Way dwarf spheroidal galaxies (dSphs) and candidates with the publicly available Pass 8 data of Fermi-LAT. Our sample includes 12 sources with the distances <50 kpc . Very weak γ -ray excesses (˜2 σ ) are found in some dSphs/candidates, consistent with those reported in the previous literature. Intriguingly, the peak test statistic (TS) value of the weak emission from Reticulum II rises continually. If interpreted as dark matter (DM) annihilation, the peak TS value is 13.5 for the annihilation channel of χ χ →τ+τ- and the DM mass of mχ˜16 GeV . The combination of all these nearby sources yields a more significant (with local significance >4 σ ) γ -ray signal.

TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and -2 clinical trials.

PubMed

Grimminger, P P; Shi, M; Barrett, C; Lebwohl, D; Danenberg, K D; Brabender, J; Vigen, C L P; Danenberg, P V; Winder, T; Lenz, H-J

2012-10-01

To validate established cutoff levels of thymidylate synthase (TS) and excision repair cross-complementing (ERCC-1) intratumoral mRNA expressions in tumor samples from metastatic colorectal cancer (mCRC) patients treated with PTK787/ZK222584 (PTK/ZK). From 122 samples of patients with mCRC enrolled in CONFIRM-1 (Colorectal Oral Novel Therapy for the Inhibition of Angiogenesis and Retarding of Metastases) or CONFIRM-2, mRNA was isolated of microdissected formalin-fixed paraffin-embedded samples and quantitated using TaqMan-based technology. Existing TS and ERCC-1 cutoff levels were tested for their prognostic value in first-line and second-line therapy. TS expression was associated with overall survival (OS) in first-line, but not second-line therapy. ERCC-1 was associated with OS in patients treated with first-line and second-line FOLFOX4. In first-line FOLFOX4, combination of high TS and/or high ERCC-1 was associated with shorter OS. A correlation was observed between ERCC-1 expression and benefit from PTK/ZK+FOLFOX4 treatment. TS and ERCC-1 expression is associated with clinical outcome in mCRC. Baseline TS and ERCC-1 levels may allow the selection of patients who benefit from FOLFOX4 chemotherapy.

Probing the structure of Leishmania major DHFR TS and structure based virtual screening of peptide library for the identification of anti-leishmanial leads.

PubMed

Rajasekaran, Rajalakshmi; Chen, Yi-Ping Phoebe

2012-09-01

Leishmaniasis, a multi-faceted ethereal disease is considered to be one of the World's major communicable diseases that demands exhaustive research and control measures. The substantial data on these protozoan parasites has not been utilized completely to develop potential therapeutic strategies against Leishmaniasis. Dihydrofolate reductase thymidylate synthase (DHFR-TS) plays a major role in the infective state of the parasite and hence the DHFR-TS based drugs remains of much interest to researchers working on Leishmaniasis. Although, crystal structures of DHFR-TS from different species including Plasmodium falciparum and Trypanosoma cruzi are available, the experimentally determined structure of the Leishmania major DHFR-TS has not yet been reported in the Protein Data Bank. A high quality three dimensional structure of L.major DHFR-TS has been modeled through the homology modeling approach. Carefully refined and the energy minimized structure of the modeled protein was validated using a number of structure validation programs to confirm its structure quality. The modeled protein structure was used in the process of structure based virtual screening to figure out a potential lead structure against DHFR TS. The lead molecule identified has a binding affinity of 0.51 nM and clearly follows drug like properties.

Investigating the enhanced Best Performance Algorithm for Annual Crop Planning problem based on economic factors

PubMed Central

2017-01-01

The Annual Crop Planning (ACP) problem was a recently introduced problem in the literature. This study further expounds on this problem by presenting a new mathematical formulation, which is based on market economic factors. To determine solutions, a new local search metaheuristic algorithm is investigated which is called the enhanced Best Performance Algorithm (eBPA). eBPA’s results are compared against two well-known local search metaheuristic algorithms; these include Tabu Search and Simulated Annealing. The results show the potential of the eBPA for continuous optimization problems. PMID:28792495

Investigating the enhanced Best Performance Algorithm for Annual Crop Planning problem based on economic factors.

PubMed

Adewumi, Aderemi Oluyinka; Chetty, Sivashan

2017-01-01

The Annual Crop Planning (ACP) problem was a recently introduced problem in the literature. This study further expounds on this problem by presenting a new mathematical formulation, which is based on market economic factors. To determine solutions, a new local search metaheuristic algorithm is investigated which is called the enhanced Best Performance Algorithm (eBPA). eBPA's results are compared against two well-known local search metaheuristic algorithms; these include Tabu Search and Simulated Annealing. The results show the potential of the eBPA for continuous optimization problems.

A Universal Ts-VI Triangle Method for the Continuous Retrieval of Evaporative Fraction From MODIS Products

NASA Astrophysics Data System (ADS)

Zhu, Wenbin; Jia, Shaofeng; Lv, Aifeng

2017-10-01

The triangle method based on the spatial relationship between remotely sensed land surface temperature (Ts) and vegetation index (VI) has been widely used for the estimates of evaporative fraction (EF). In the present study, a universal triangle method was proposed by transforming the Ts-VI feature space from a regional scale to a pixel scale. The retrieval of EF is only related to the boundary conditions at pixel scale, regardless of the Ts-VI configuration over the spatial domain. The boundary conditions of each pixel are composed of the theoretical dry edge determined by the surface energy balance principle and the wet edge determined by the average air temperature of open water. The universal triangle method was validated using the EF observations collected by the Energy Balance Bowen Ratio systems in the Southern Great Plains of the United States of America (USA). Two parameterization schemes of EF were used to demonstrate their applicability with Terra Moderate Resolution Imaging Spectroradiometer (MODIS) products over the whole year 2004. The results of this study show that the accuracy produced by both of these two parameterization schemes is comparable to that produced by the traditional triangle method, although the universal triangle method seems specifically suited to the parameterization scheme proposed in our previous research. The independence of the universal triangle method from the Ts-VI feature space makes it possible to conduct a continuous monitoring of evapotranspiration and soil moisture. That is just the ability the traditional triangle method does not possess.

Analysis of a commercial small unmanned airborne system (sUAS) in support of the Radiometric Calibration Test Site (RadCaTS) at Railroad Valley

NASA Astrophysics Data System (ADS)

Czapla-Myers, Jeffrey S.; Anderson, Nikolaus J.

2017-09-01

The Radiometric Calibration Test Site (RadCaTS) is an automated facility developed by the Remote Sensing Group (RSG) at the University of Arizona to provide radiometric calibration data for airborne and satellite sensors. RadCaTS uses stationary ground-viewing radiometers (GVRs) to spatially sample the surface reflectance of the site. The number and location of the GVRs is based on previous spatial, spectral, and temporal analyses of Railroad Valley. With the increase in high-resolution satellite sensors, there is renewed interest in examining the spatial uniformity the 1-km2 RadCaTS area at scales smaller than a typical 30-m sensor. RadCaTS is one of the four instrumented sites currently in the CEOS WGCV Radiometric Calibration Network (RadCalNet), which aims to harmonize the post-launch radiometric calibration of satellite sensors through the use of a global network of automated calibration sites. A better understanding of the RadCaTS spatial uniformity as a function of pixel size will also benefit the RadCalNet work. RSG has recently acquired a commercially-available small unmanned airborne system (sUAS) system, with which preliminary spatial homogeneity measurements of the 1-km2 RadCaTS area were made. This work describes an initial assessment of the airborne platform and integrated camera for spatial studies of RadCaTS using data that were collected in 2016 and 2017.

Developmental excitatory-to-inhibitory GABA polarity switch is delayed in Ts65Dn mice, a genetic model of Down syndrome.

PubMed

Lysenko, Larisa V; Kim, Jeesun; Madamba, Francisco; Tyrtyshnaia, Anna A; Ruparelia, Aarti; Kleschevnikov, Alexander M

2018-07-01

Down syndrome (DS) is the most frequent genetic cause of developmental abnormalities leading to intellectual disability. One notable phenomenon affecting the formation of nascent neural circuits during late developmental periods is developmental switch of GABA action from depolarizing to hyperpolarizing mode. We examined properties of this switch in DS using primary cultures and acute hippocampal slices from Ts65Dn mice, a genetic model of DS. Cultures of DIV3-DIV13 Ts65Dn and control normosomic (2 N) neurons were loaded with FURA-2 AM, and GABA action was assessed using local applications. In 2 N cultures, the number of GABA-activated cells dropped from ~100% to 20% between postnatal days 3-13 (P3-P13) reflecting the switch in GABA action polarity. In Ts65Dn cultures, the timing of this switch was delayed by 2-3 days. Next, microelectrode recordings of multi-unit activity (MUA) were performed in CA3 slices during bath application of the GABA A agonist isoguvacine. MUA frequency was increased in P8-P12 and reduced in P14-P22 slices reflecting the switch of GABA action from excitatory to inhibitory mode. The timing of this switch was delayed in Ts65Dn by approximately 2 days. Finally, frequency of giant depolarizing potentials (GDPs), a form of primordial neural activity, was significantly increased in slices from Ts65Dn pups at P12 and P14. These experimental evidences show that GABA action polarity switch is delayed in Ts65Dn model of DS, and that these changes lead to a delay in maturation of nascent neural circuits. These alterations may affect properties of neural circuits in adult animals and, therefore, represent a prospective target for pharmacotherapy of cognitive impairment in DS. Copyright © 2018 Elsevier Inc. All rights reserved.

A non-chemically selective top-down approach towards the preparation of hierarchical TS-1 zeolites with improved oxidative desulfurization catalytic performance.

PubMed

Du, Shuting; Chen, Xiaoxin; Sun, Qiming; Wang, Ning; Jia, Mingjun; Valtchev, Valentin; Yu, Jihong

2016-02-28

Hierarchical TS-1 zeolites with secondary macropores have been successfully prepared by using two different fluoride-containing chemical etching post-treated routes. Hierarchical TS-1 zeolites exhibited a chemical composition similar to that of the parent material and showed remarkably enhanced catalytic activity in oxidative desulfurization reaction.

The joint search for gravitational wave and low energy neutrino signals from core-collapse supernovae: methodology and status report

NASA Astrophysics Data System (ADS)

Gromov, M. B.; Casentini, C.

2017-09-01

The detection of gravitational waves opens a new era in physics. Now it's possible to observe the Universe using a fundamentally new way. Gravitational waves potentially permit getting insight into the physics of Core-Collapse Supernovae (CCSNe). However, due to signi cant uncertainties on the theoretical models of gravitational wave emission associated with CCSNe, bene ts may come from multi-messenger observations of CCSNe. Such bene ts include increased con dence in detection, extending the astrophysical reach of the detectors and allowing deeper understanding of the nature of the phenomenon. Fortunately, CCSNe have a neutrino signature con rmed by the observation of SN1987A. The gravitational and neutrino signals propagate with the speed of light and without signi cant interaction with interstellar matter. So that they must reach an observer on the Earth almost simultaneously. These facts open a way to search for the correlation between the signals. However, this method is limited by the sensitivity of modern neutrino detectors that allow to observe CCSNe only in the Local Group of galaxies. The methodology and status of a proposed joint search for the correlation signals are presented here.

Abnormalities in the meibomian glands in patients with oral administration of anticancer combination drug-capsule TS-1(®): a case report.

PubMed

Mizoguchi, Shin; Okada, Yuka; Kokado, Masahide; Saika, Shizuya

2015-10-24

The anticancer TS-1(®) combination capsules of tegafur, gimeracil, and oteracil potassium (Taiho Pharmaceutical Co. Ltd, Japan) causes side effects, i. e., corneal epithelial disorder and dacryostenosis. However, its side effect on meibomian gland had not been reported. We observed morphological changes in the meibomian gland in patients taking TS-1(®) who exhibited punctate corneal epithelial defects to examine if dysfunction of meibomian glands is involved in the corneal epitheliopathy. Patients comprised two males and one female (age, 59-81 years). After starting oral TS-1(®) administration, patients developed subjective symptoms such as decreased visual acuity. Corneal epithelial disorder was seen in all six eyes of the three subjects exhibited, and lacrimal duct disorder was seen in one eye. Furthermore, meibomian gland loss and contraction were observed in all six eyes that exhibited meibomian gland disorder upon examination by using the MeiboPen(®). Results suggested that oral administration of TS-1(®) may cause meibomian gland disorder which potentially affect corneal epithelial homeostasis.

LIDAR TS for ITER core plasma. Part I: layout & hardware

NASA Astrophysics Data System (ADS)

Salzmann, H.; Gowers, C.; Nielsen, P.

2017-12-01

The original time-of-flight design of the Thomson scattering diagnostic for the ITER core plasma has been shown up by ITER. This decision was justified by insufficiencies of some of the components. In this paper we show that with available, present day technology a LIDAR TS system is feasible which meets all the ITER specifications. As opposed to the conventional TS system the LIDAR TS also measures the high field side of the plasma. The optical layout of the front end has been changed only little in comparison with the latest one considered by ITER. The main change is that it offers an optical collection without any vignetting over the low field side. The throughput of the system is defined only by the size and the angle of acceptance of the detectors. This, in combination with the fact that the LIDAR system uses only one set of spectral channels for the whole line of sight, means that no absolute calibration using Raman or Rayleigh scattering from a non-hydrogen isotope gas fill of the vessel is needed. Alignment of the system is easy since the collection optics view the footprint of the laser on the inner wall. In the described design we use, simultaneously, two different wavelength pulses from a Nd:YAG laser system. Its fundamental wavelength ensures measurements of 2 keV up to more than 40 keV, whereas the injection of the second harmonic enables measurements of low temperatures. As it is the purpose of this paper to show the technological feasibility of the LIDAR system, the hardware is considered in Part I of the paper. In Part II we demonstrate by numerical simulations that the accuracy of the measurements as required by ITER is maintained throughout the given plasma parameter range. The effect of enhanced background radiation in the wavelength range 400 nm-500 nm is considered. In Part III the recovery of calibration in case of changing spectral transmission of the front end is treated. We also investigate how to improve the spatial resolution at the

Synaptic Vesicle Recycling Is Unaffected in the Ts65Dn Mouse Model of Down Syndrome.

PubMed

Marland, Jamie R K; Smillie, Karen J; Cousin, Michael A

2016-01-01

Down syndrome (DS) is the most common genetic cause of intellectual disability, and arises from trisomy of human chromosome 21. Accumulating evidence from studies of both DS patient tissue and mouse models has suggested that synaptic dysfunction is a key factor in the disorder. The presence of several genes within the DS trisomy that are either directly or indirectly linked to synaptic vesicle (SV) endocytosis suggested that presynaptic dysfunction could underlie some of these synaptic defects. Therefore we determined whether SV recycling was altered in neurons from the Ts65Dn mouse, the best characterised model of DS to date. We found that SV exocytosis, the size of the SV recycling pool, clathrin-mediated endocytosis, activity-dependent bulk endocytosis and SV generation from bulk endosomes were all unaffected by the presence of the Ts65Dn trisomy. These results were obtained using battery of complementary assays employing genetically-encoded fluorescent reporters of SV cargo trafficking, and fluorescent and morphological assays of fluid-phase uptake in primary neuronal culture. The absence of presynaptic dysfunction in central nerve terminals of the Ts65Dn mouse suggests that future research should focus on the established alterations in excitatory / inhibitory balance as a potential route for future pharmacotherapy.

Synaptic Vesicle Recycling Is Unaffected in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Marland, Jamie R. K.; Smillie, Karen J.; Cousin, Michael A.

2016-01-01

Down syndrome (DS) is the most common genetic cause of intellectual disability, and arises from trisomy of human chromosome 21. Accumulating evidence from studies of both DS patient tissue and mouse models has suggested that synaptic dysfunction is a key factor in the disorder. The presence of several genes within the DS trisomy that are either directly or indirectly linked to synaptic vesicle (SV) endocytosis suggested that presynaptic dysfunction could underlie some of these synaptic defects. Therefore we determined whether SV recycling was altered in neurons from the Ts65Dn mouse, the best characterised model of DS to date. We found that SV exocytosis, the size of the SV recycling pool, clathrin-mediated endocytosis, activity-dependent bulk endocytosis and SV generation from bulk endosomes were all unaffected by the presence of the Ts65Dn trisomy. These results were obtained using battery of complementary assays employing genetically-encoded fluorescent reporters of SV cargo trafficking, and fluorescent and morphological assays of fluid-phase uptake in primary neuronal culture. The absence of presynaptic dysfunction in central nerve terminals of the Ts65Dn mouse suggests that future research should focus on the established alterations in excitatory / inhibitory balance as a potential route for future pharmacotherapy. PMID:26808141

Association between ERCC1 and TS mRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil (5-FU) adjuvant chemotherapy.

PubMed

Li, Sheng; Zhu, Liangjun; Yao, Li; Xia, Lei; Pan, Liangxi

2014-08-29

Aim was to explore the association of ERCC1 and TS mRNA levels with the disease free survival (DFS) in Chinese colorectal cancer (CRC) patients receiving oxaliplatin and 5-FU based adjuvant chemotherapy. Total 112 Chinese stage II-III CRC patients were respectively treated by four different chemotherapy regimens after curative operation. The TS and ERCC1 mRNA levels in primary tumor were measured by real-time RT-PCR. Kaplan-Meier curves and log-rank tests were used for DFS analysis. The Cox proportional hazards model was used for prognostic analysis. In univariate analysis, the hazard ratio (HR) for the mRNA expression levels of TS and ERCC1 (logTS: HR = 0.820, 95% CI = 0.600 - 1.117, P = 0.210; logERCC1: HR = 1.054, 95% CI = 0.852 - 1.304, P = 0.638) indicated no significant association of DFS with the TS and ERCC1 mRNA levels. In multivariate analyses, tumor stage (IIIc: reference, P = 0.083; IIb: HR = 0.240, 95% CI = 0.080 - 0.724, P = 0.011; IIc: HR < 0.0001, P = 0.977; IIIa: HR = 0.179, 95% CI = 0.012 - 2.593, P = 0.207) was confirmed to be the independent prognostic factor for DFS. Moreover, the Kaplan-Meier DFS curves showed that TS and ERCC1 mRNA levels were not significantly associated with the DFS (TS: P = 0.264; ERCC1: P = 0.484). The mRNA expression of ERCC1 and TS were not applicable to predict the DFS of Chinese stage II-III CRC patients receiving 5-FU and oxaliplatin based adjuvant chemotherapy.

Hybrid Nested Partitions and Math Programming Framework for Large-scale Combinatorial Optimization

DTIC Science & Technology

2010-03-31

optimization problems: 1) exact algorithms and 2) metaheuristic algorithms . This project will integrate concepts from these two technologies to develop...optimal solutions within an acceptable amount of computation time, and 2) metaheuristic algorithms such as genetic algorithms , tabu search, and the...integer programming decomposition approaches, such as Dantzig Wolfe decomposition and Lagrangian relaxation, and metaheuristics such as the Nested

Successful TS-1 monotherapy as the second-line treatment for advanced extramammary Paget's disease: A report of two cases.

PubMed

Kato, Junji; Hida, Tokimasa; Yamashita, Toshiharu; Kamiya, Shiori; Horimoto, Kohei; Sato, Sayuri; Takahashi, Hitomi; Sawada, Masahide; Yamada, Mao; Uhara, Hisashi

2018-01-01

There is no standard chemotherapeutic treatment for advanced extramammary Paget's disease, though the effectiveness of some chemotherapy regimens, including docetaxel, has been reported. In this report, we report that TS-1 monotherapy was effective in two patients with advanced extramammary Paget's disease after docetaxel treatment failure. TS-1 monotherapy may be useful as the second-line treatment for patients with advanced extramammary Paget's disease. © 2017 Japanese Dermatological Association.

Towards Distinctive and Developmental Curricula at UoTs: The STEPS process at CUT

ERIC Educational Resources Information Center

Mthembu, T. Z.; Orkin, M.; Gering, M.

2012-01-01

Universities of technology (UoTs) achieve developmental impact through differentiated curricula, allowing graduates to undertake mid-level occupations in the workplace. This mandate differs from that at traditional universities in six respects: diploma-level entrants, labour market focus, workplace-oriented learning, applied research and…

3Ts for Reducing Lead in Drinking Water in Schools and Child Care Facilities

EPA Pesticide Factsheets

EPA’s 3Ts was developed to assist schools with lead in drinking water prevention programs. It is intended for use by school officials responsible for the maintenance and/or safety of school’s drinking water.

Deleterious Effects of Chronic Folate Deficiency in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Helm, Susan; Blayney, Morgan; Whited, Taylor; Noroozi, Mahjabin; Lin, Sen; Kern, Semira; Green, David; Salehi, Ahmad

2017-01-01

Folate is an important B vitamin naturally found in the human diet and plays a critical role in methylation of nucleic acids. Indeed, abnormalities in this major epigenetic mechanism play a pivotal role in the pathogenesis of cognitive deficit and intellectual disability in humans. The most common cause of cognitive dysfunction in children is Down syndrome (DS). Since folate deficiency is very common among the pediatric population, we questioned whether chronic folate deficiency (CFD) exacerbates cognitive dysfunction in a mouse model of DS. To test this, adult Ts65Dn mice and their disomic littermates were chronically fed a diet free of folic acid while preventing endogenous production of folate in the digestive tract for a period of 8 weeks. Our results show that the Ts65Dn mouse model of DS was significantly more vulnerable to CFD in terms of plasma homocysteine and N5-methyltetrahydrofolate (5-MTHF) levels. Importantly, these changes were linked to degenerative alterations in hippocampal dendritic morphology and impaired nest building behavior in Ts65Dn mice. Based on our results, a rigorous examination of folate intake and its metabolism in individuals with DS is warranted. PMID:28649192

The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis.

PubMed

De Savi, Chris; Pape, Andrew; Cumming, John G; Ting, Attilla; Smith, Peter D; Burrows, Jeremy N; Mills, Mark; Davies, Chris; Lamont, Scott; Milne, David; Cook, Calum; Moore, Peter; Sawyer, Yvonne; Gerhardt, Stefan

2011-03-01

Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described. Copyright © 2011 Elsevier Ltd. All rights reserved.

Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice

PubMed Central

Kelley, Christy M.; Powers, Brian E.; Velazquez, Ramon; Ash, Jessica A.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

2014-01-01

Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer’s disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. While DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3–7.5 mos of age. Ts65Dn dams were maintained on a choline supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; postweaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, brains were sectioned, and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75NTR). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. PMID:24178831

Robust adaptive controller design for a class of uncertain nonlinear systems using online T-S fuzzy-neural modeling approach.

PubMed

Chien, Yi-Hsing; Wang, Wei-Yen; Leu, Yih-Guang; Lee, Tsu-Tian

2011-04-01

This paper proposes a novel method of online modeling and control via the Takagi-Sugeno (T-S) fuzzy-neural model for a class of uncertain nonlinear systems with some kinds of outputs. Although studies about adaptive T-S fuzzy-neural controllers have been made on some nonaffine nonlinear systems, little is known about the more complicated uncertain nonlinear systems. Because the nonlinear functions of the systems are uncertain, traditional T-S fuzzy control methods can model and control them only with great difficulty, if at all. Instead of modeling these uncertain functions directly, we propose that a T-S fuzzy-neural model approximates a so-called virtual linearized system (VLS) of the system, which includes modeling errors and external disturbances. We also propose an online identification algorithm for the VLS and put significant emphasis on robust tracking controller design using an adaptive scheme for the uncertain systems. Moreover, the stability of the closed-loop systems is proven by using strictly positive real Lyapunov theory. The proposed overall scheme guarantees that the outputs of the closed-loop systems asymptotically track the desired output trajectories. To illustrate the effectiveness and applicability of the proposed method, simulation results are given in this paper.

An Advanced Tabu Search Approach to the Airlift Loading Problem

DTIC Science & Technology

2006-12-01

This report specified that analysis of 14,692 strategic airlift missions demonstrated that … more than 86 percent flew with payloads that were lighter...The University of Texas at Austin December, 2006 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection...Information Operations and Reports , 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any

Nonlinear interaction of near-planar TS waves and longitudinal vortices in boundary-layer transition

NASA Technical Reports Server (NTRS)

Smith, F. T.

1988-01-01

The nonlinear interactions that evolve between a planar or nearly planar Tollmien-Schlichting (TS) wave and the associated longitudinal vortices are considered theoretically for a boundary layer at high Reynolds number. The vortex flow is either induced by the TS nonlinear forcing or is input upstream, and similarly for the nonlinear wave development. Three major kinds of nonlinear spatial evolution, Types 1-3, are found. Each can start from secondary instability and then become nonlinear, Type 1 proving to be relatively benign but able to act as a pre-cursor to the Types 2, 3 which turn out to be very powerful nonlinear interactions. Type 2 involves faster stream-wise dependence and leads to a finite-distance blow-up in the amplitudes, which then triggers the full nonlinear 3-D triple-deck response, thus entirely altering the mean-flow profile locally. In contrast, Type 3 involves slower streamwise dependence but a faster spanwise response, with a small TS amplitude thereby causing an enhanced vortex effect which, again, is substantial enough to entirely alter the meanflow profile, on a more global scale. Streak-like formations in which there is localized concentration of streamwise vorticity and/or wave amplitude can appear, and certain of the nonlinear features also suggest by-pass processes for transition and significant changes in the flow structure downstream. The powerful nonlinear 3-D interactions 2, 3 are potentially very relevant to experimental findings in transition.

Dos and Don'ts of Giving OTC Cough and Cold Medicines to Your Child

MedlinePlus

... workers, extended family members, or babysitters) knows what medicines your child is taking and when he or she should ... ts Don’t give OTC cough and cold medicines to a child younger than 4 years of age unless your ...

TS-SRP/PACK - COMPUTER PROGRAMS TO CHARACTERIZE ALLOYS AND PREDICT CYCLIC LIFE USING THE TOTAL STRAIN VERSION OF STRAINRANGE PARTITIONING

NASA Technical Reports Server (NTRS)

Saltsman, J. F.

1994-01-01

TS-SRP/PACK is a set of computer programs for characterizing and predicting fatigue and creep-fatigue resistance of metallic materials in the high-temperature, long-life regime for isothermal and nonisothermal fatigue. The programs use the total strain version of the Strainrange Partitioning (TS-SRP). The user should be thoroughly familiar with the TS-SRP method before attempting to use any of these programs. The document for this program includes a theory manual as well as a detailed user's manual with a tutorial to guide the user in the proper use of TS-SRP. An extensive database has also been developed in a parallel effort. This database is an excellent source of high-temperature, creep-fatigue test data and can be used with other life-prediction methods as well. Five programs are included in TS-SRP/PACK along with the alloy database. The TABLE program is used to print the datasets, which are in NAMELIST format, in a reader friendly format. INDATA is used to create new datasets or add to existing ones. The FAIL program is used to characterize the failure behavior of an alloy as given by the constants in the strainrange-life relations used by the total strain version of SRP (TS-SRP) and the inelastic strainrange-based version of SRP. The program FLOW is used to characterize the flow behavior (the constitutive response) of an alloy as given by the constants in the flow equations used by TS-SRP. Finally, LIFE is used to predict the life of a specified cycle, using the constants characterizing failure and flow behavior determined by FAIL and FLOW. LIFE is written in interpretive BASIC to avoid compiling and linking every time the equation constants are changed. Four out of five programs in this package are written in FORTRAN 77 for IBM PC series and compatible computers running MS-DOS and are designed to read data using the NAMELIST format statement. The fifth is written in BASIC version 3.0 for IBM PC series and compatible computers running MS-DOS version 3.10. The

Global electrostatic potential structures of merging flux tubes in TS-U torus plasma merging experiment

NASA Astrophysics Data System (ADS)

Sawada, Asuka; Hatano, Hironori; Akimitsu, Moe; Cao, Qinghong; Yamasaki, Kotaro; Tanabe, Hiroshi; Ono, Yasushi; TS-Group Team

2017-10-01

We have been investigating 2D potential profile of global merging tokamaks to solve high-power heating of magnetic reconnection in TS-3 and TS-3U (ST, FRC:R =0.2m, 1985-, 2017-) and TS-4 (ST, FRC:R =0.5m, 2000-), UTST (ST:R =0.45m, 2008-) and MAST (ST:R = 0.9m, 2000-) devices. These experiments made clear that the electrostatic potential well is formed not only in the downstream area of magnetic reconnection but also in the whole common (reconnected) flux area of two merging flux tubes: tokamak plasmas. This fact suggests that the ion acceleration/heating occurs in much wider region than the reconnection downstream. We studied how the potential structure depends on key reconnection parameters:guide toroidal field and plasma collisionality. We found the polarity of the guide toroidal field determines those of potential hills and wells, indicating their formation is affected by the Hall effect. The peak value of the electrostatic potential well decreased with gas pressure increasing, suggesting plasma collisionality suppresses the Hall effect. The relationship between the electrostatic potential structure and anomalous ion heating is being studied as a possible cause for the high-power heating of fast magnetic reconnection. This work was supported by JSPS KAKENHI Grant Numbers 15H05750, 15K14279 and 17H04863.

The Feasibility and Acceptability to Service Users of CIRCuiTS, a Computerized Cognitive Remediation Therapy Programme for Schizophrenia.

PubMed

Reeder, Clare; Pile, Victoria; Crawford, Polly; Cella, Matteo; Rose, Diana; Wykes, Til; Watson, Andrew; Huddy, Vyv; Callard, Felicity

2016-05-01

Cognitive remediation (CR) is a psychological therapy, effective in improving cognitive performance and functioning in people with schizophrenia. As the therapy becomes more widely implemented within mental health services its longevity and uptake is likely to depend on its feasibility and acceptability to service users and clinicians. To assess the feasibility and acceptability of a new strategy-based computerized CR programme (CIRCuiTS) for people with psychosis. Four studies were conducted using mixed methods. Perceptions of attractiveness, comprehensibility, acceptability and usability were assessed using self-report questionnaires in 34 non-clinical participants (study 1), and five people with a schizophrenia diagnosis and three experienced CR therapists (studies 2 and 3). The ease with which pre-specified therapy programmes could be assembled was also assessed by three therapists (Study 2). Finally, the satisfaction of 20 service users with a diagnosis of schizophrenia regarding their experience of using CIRCuiTS in the context of a course of the CR therapy was assessed in a qualitative interview study (study 4). Ratings of perceived attractiveness, comprehensibility, acceptability and usability consistently exceeded pre-set high targets by non-clinical, clinical and therapist participants. Qualitative analysis of satisfaction with CIRCuiTS showed that receiving the therapy was generally seen to be a positive experience, leading to perceptions that cognitive functioning had improved and attempts to incorporate new strategy use into daily activities. CIRCuiTS demonstrates high acceptability and ease of use for both service users with a schizophrenia diagnosis and clinicians.

Elongation Factor Ts Directly Facilitates the Formation and Disassembly of the Escherichia coli Elongation Factor Tu·GTP·Aminoacyl-tRNA Ternary Complex*

PubMed Central

Burnett, Benjamin J.; Altman, Roger B.; Ferrao, Ryan; Alejo, Jose L.; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C.

2013-01-01

Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis. PMID:23539628

Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice.

PubMed

Kelley, Christy M; Powers, Brian E; Velazquez, Ramon; Ash, Jessica A; Ginsberg, Stephen D; Strupp, Barbara J; Mufson, Elliott J

2014-04-15

Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer's disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. Although DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3-7.5 months of age. Ts65Dn dams were maintained on a choline-supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; post weaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, and brains were sectioned and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75(NTR) ). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn-unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. Copyright © 2013 Wiley Periodicals, Inc.

Involvement of Potassium and Cation Channels in Hippocampal Abnormalities of Embryonic Ts65Dn and Tc1 Trisomic Mice

PubMed Central

Stern, Shani; Segal, Menahem; Moses, Elisha

2015-01-01

Down syndrome (DS) mouse models exhibit cognitive deficits, and are used for studying the neuronal basis of DS pathology. To understand the differences in the physiology of DS model neurons, we used dissociated neuronal cultures from the hippocampi of Ts65Dn and Tc1 DS mice. Imaging of [Ca2+]i and whole cell patch clamp recordings were used to analyze network activity and single neuron properties, respectively. We found a decrease of ~ 30% in both fast (A-type) and slow (delayed rectifier) outward potassium currents. Depolarization of Ts65Dn and Tc1 cells produced fewer spikes than diploid cells. Their network bursts were smaller and slower than diploids, displaying a 40% reduction in Δf / f0 of the calcium signals, and a 30% reduction in propagation velocity. Additionally, Ts65Dn and Tc1 neurons exhibited changes in the action potential shape compared to diploid neurons, with an increase in the amplitude of the action potential, a lower threshold for spiking, and a sharp decrease of about 65% in the after-hyperpolarization amplitude. Numerical simulations reproduced the DS measured phenotype by variations in the conductance of the delayed rectifier and A-type, but necessitated also changes in inward rectifying and M-type potassium channels and in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. We therefore conducted whole cell patch clamp measurements of M-type potassium currents, which showed a ~ 90% decrease in Ts65Dn neurons, while HCN measurements displayed an increase of ~ 65% in Ts65Dn cells. Quantitative real-time PCR analysis indicates overexpression of 40% of KCNJ15, an inward rectifying potassium channel, contributing to the increased inhibition. We thus find that changes in several types of potassium channels dominate the observed DS model phenotype. PMID:26501103

Kcnj6(GIRK2) trisomy is not sufficient for conferring the susceptibility to infantile spasms seen in the Ts65Dn mouse model of down syndrome.

PubMed

Joshi, Krutika; Shen, Lily; Cao, Feng; Dong, Susan; Jia, Zhengping; Cortez, Miguel A; Snead, O Carter

2018-06-12

Infantile spasms (IS) is a catastrophic childhood seizure disorder that is characterized by extensor and/or flexor spasms, cognitive deterioration and a characteristic EEG abnormality. The latter consists of a pattern of a spike-wave followed by an electrodecremental response (EDR), which is a flattening of the EEG waveform amplitude. The mechanism/circuitry that underpins IS is unknown. Children with Down Syndrome (DS) are particularly vulnerable to IS. The standard mouse model of DS is the Ts65Dn mutant mouse (Ts). Using the Ts mouse, we have created an animal model of IS in DS. This model entails the treatment of Ts mice with a GABA B R agonist with a resultant recapitulation of the semiological, electrographic, and pharmacological phenotype of IS. One of the genes triplicated in Ts mice is the kcnj6 gene which codes for the G-protein inwardly rectifying potassium channel 2 (GIRK2) protein. We have shown that over expression of GIRK2 in Ts brain is necessary for the production of the GABA B R agonist induced IS phenotype in the Ts mouse. Here, we ask the question whether the excess GIRK2 is sufficient for the production of the GABA B R agonist induced IS phenotype. To address this question, we used kcnj6 triploid mice, and compared the number of spasms via video analysis and EDR events via EEG to that of the WT mice. We now show that GABA R R agonist-treated kcnj6 triploid mice failed to show susceptibility to the IS phenotype. Therefore, over expression of GIRK2 in the brain is necessary, but not sufficient to confer susceptibility to the GABA B R agonist-induced IS phenotype in the Ts model of DS. It is therefore likely that GIRK2 is working in concert with another factor or factors that are altered in the Ts brain in the production of the GABA B R agonist-induced IS phenotype. Copyright © 2018. Published by Elsevier B.V.

Biochemical characterization of the triticale TsPAP1, a new type of plant prolyl aminopeptidase, and its impact on proline content and flowering time in transgenic Arabidopsis plants.

PubMed

Zdunek-Zastocka, Edyta; Grabowska, Agnieszka; Branicki, Tomasz; Michniewska, Beata

2017-07-01

Proline aminopeptidase (PAP, EC 3.4.11.5) is the only enzyme that effectively releases proline from the N-termini of peptides. The amino acid sequence of the PAP from Triticosecale, TsPAP1, comprises conserved regions, characteristic of the monomeric forms of PAP found in bacteria but not yet identified in plants. Therefore, we aimed to obtain and biochemically characterize the TsPAP1 protein. The recombinant TsPAP1 protein was received through heterologous expression of the TsPAP1 coding sequence in a bacterial expression system and purified with affinity chromatography. Gel filtration chromatography and SDS electrophoresis revealed that TsPAP1 is a monomer with a molecular mass of 37.5 kDa. TsPAP1 prefers substrates with proline at the N-terminus but is also capable of hydrolyzing β-naphthylamides of hydroxyproline and alanine. Among the peptides tested, the most preferred were di- and tripeptides, especially those with glycine in the Y position. The use of diagnostic inhibitors indicated that TsPAP1 is a serine peptidase; however, further characterization revealed that the SH residues are also important for maintaining its activity. To examine the role of TsPAP1 under physiological conditions, we developed transgenic Arabidopsis plants overexpressing TsPAP1. Compared with wild-type plants, the transgenic lines accumulated more proline, flowered an average of 3.5 days earlier, and developed more siliques than did untransformed controls. Our paper is the first to describe the biochemical properties of a novel monomeric plant PAP and contributes to the functional characterization of PAP proteins in plants. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dynamic output feedback control of a flexible air-breathing hypersonic vehicle via T-S fuzzy approach

NASA Astrophysics Data System (ADS)

Hu, Xiaoxiang; Wu, Ligang; Hu, Changhua; Wang, Zhaoqiang; Gao, Huijun

2014-08-01

By utilising Takagi-Sugeno (T-S) fuzzy set approach, this paper addresses the robust H∞ dynamic output feedback control for the non-linear longitudinal model of flexible air-breathing hypersonic vehicles (FAHVs). The flight control of FAHVs is highly challenging due to the unique dynamic characteristics, and the intricate couplings between the engine and fight dynamics and external disturbance. Because of the dynamics' enormous complexity, currently, only the longitudinal dynamics models of FAHVs have been used for controller design. In this work, T-S fuzzy modelling technique is utilised to approach the non-linear dynamics of FAHVs, then a fuzzy model is developed for the output tracking problem of FAHVs. The fuzzy model contains parameter uncertainties and disturbance, which can approach the non-linear dynamics of FAHVs more exactly. The flexible models of FAHVs are difficult to measure because of the complex dynamics and the strong couplings, thus a full-order dynamic output feedback controller is designed for the fuzzy model. A robust H∞ controller is designed for the obtained closed-loop system. By utilising the Lyapunov functional approach, sufficient solvability conditions for such controllers are established in terms of linear matrix inequalities. Finally, the effectiveness of the proposed T-S fuzzy dynamic output feedback control method is demonstrated by numerical simulations.

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome

PubMed Central

Simoes de Souza, Fabio M.; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N.; Restrepo, Diego

2011-01-01

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities. PMID:22355654

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome.

PubMed

de Souza, Fabio M Simoes; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N; Restrepo, Diego

2011-01-01

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities.

Identification of an anti-sperm auto-monoclonal antibody (Ts4)-recognized molecule in the mouse sperm acrosomal region and its inhibitory effect on fertilization in vitro.

PubMed

Yoshitake, Hiroshi; Oda, Risako; Yanagida, Mitsuaki; Kawasaki, Yu; Sakuraba, Mayumi; Takamori, Kenji; Hasegawa, Akiko; Fujiwara, Hiroshi; Araki, Yoshihiko

2016-06-01

We previously established an anti-mouse sperm auto-monoclonal antibody, Ts4, which shows immunoreactivity against several kinds of glycoproteins in the acrosomal region of epididymal spermatozoa, testicular germ cells, and early embryo, via binding to an epitope containing a common N-linked oligosaccharide (OS) chain on the molecules. In mice, we have already demonstrated that the OS chain in the epitope for Ts4 is a fucosylated agalacto-complex-type biantennary glycan carrying bisecting N-acetylglucosamine. In the testis, one of the specific OS chain-conjugated molecules is TEX101, a germ cell-marker glycoprotein, which is expressed in spermatocytes, spermatids, and testicular spermatozoa, but not in epididymal spermatozoa. In this study, we identified a Ts4-reactive glycoprotein in mouse cauda epididymal sperm. An immunoprecipitation method together with liquid chromatography-tandem mass spectrometry showed that alpha-N-acetylglucosaminidase (Naglu; a degradation enzyme of heparan sulfate) is one of the glycoproteins recognized by Ts4 in the epididymal spermatozoa. Western blot and immunohistochemical analyses revealed that mouse Naglu exists in two forms (82 and 77kDa) and is expressed in the acrosomal region and the flagellum of cauda epididymal sperm. Of the two Naglu-forms expressed in sperm, Ts4 immunoreacted against only the 82-kDa form located on the acrosomal region. The Ts4 mAb and anti-Naglu pAb negatively affected mouse fertilization in vitro. In addition, Ts4 inhibited sperm acrosome reaction induced by heparan sulfate. The Ts4-recognized fucosylated agalactobiantennary complex-type glycan with bisecting N-acetylglucosamine and Naglu on cauda epididymal spermatozoa may play a role in the process of fertilization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Efficacy and safety of TS-1 monotherapy for advanced/metastatic breast cancer - an observational study by the Kumamoto Breast Cancer Cooperative Group(KBCCG)].

PubMed

Yamamoto, Yutaka; Nishimura, Reiki; Tanigawa, Tomio; Kawano, Ichiro; Hayashi, Kyoji; Kuramoto, Masafumi; Yamamoto-Ibusuki, Mutsuko; Iwase, Hirotaka

2014-10-01

TS-1, an oral fluoropyrimidine, is known to be effective for the treatment of various carcinomas including advanced/metastatic breast cancer.The Kumamoto Breast Cancer Cooperative Group(KBCCG)conducted an observational study, wherein, the efficacy and safety of TS-1 monotherapy was analyzed in 35 patients with recurrent or metastatic breast cancer.The median time to cancer progression was 3.7 months, overall response rate was 12%, and clinical benefit rate was 32%. Adverse events were observed in 27 patients(77%), and adverse events of Grade >3 were observed in 7 patients(20%). The rate of treatment-related Grade 3 and 4 adverse events increased, and was associated with poor levels of creatinine clearance(Ccr)ie <60mL/min.This study suggests that TS-1 monotherapy can potentially be used as a salvage treatment for advanced/metastatic breast cancer owing to its safety and efficacy.Measuring the level of Ccr before TS-1 therapy should be considered to avoid severe adverse events.

A federated capability-based access control mechanism for internet of things (IoTs)

NASA Astrophysics Data System (ADS)

Xu, Ronghua; Chen, Yu; Blasch, Erik; Chen, Genshe

2018-05-01

The prevalence of Internet of Things (IoTs) allows heterogeneous embedded smart devices to collaboratively provide intelligent services with or without human intervention. While leveraging the large-scale IoT-based applications like Smart Gird and Smart Cities, IoT also incurs more concerns on privacy and security. Among the top security challenges that IoTs face is that access authorization is critical in resource and information protection over IoTs. Traditional access control approaches, like Access Control Lists (ACL), Role-based Access Control (RBAC) and Attribute-based Access Control (ABAC), are not able to provide a scalable, manageable and efficient mechanisms to meet requirement of IoT systems. The extraordinary large number of nodes, heterogeneity as well as dynamicity, necessitate more fine-grained, lightweight mechanisms for IoT devices. In this paper, a federated capability-based access control (FedCAC) framework is proposed to enable an effective access control processes to devices, services and information in large scale IoT systems. The federated capability delegation mechanism, based on a propagation tree, is illustrated for access permission propagation. An identity-based capability token management strategy is presented, which involves registering, propagation and revocation of the access authorization. Through delegating centralized authorization decision-making policy to local domain delegator, the access authorization process is locally conducted on the service provider that integrates situational awareness (SAW) and customized contextual conditions. Implemented and tested on both resources-constrained devices, like smart sensors and Raspberry PI, and non-resource-constrained devices, like laptops and smart phones, our experimental results demonstrate the feasibility of the proposed FedCAC approach to offer a scalable, lightweight and fine-grained access control solution to IoT systems connected to a system network.

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

PubMed

Corrales, Andrea; Parisotto, Eduardo B; Vidal, Verónica; García-Cerro, Susana; Lantigua, Sara; Diego, Marian; Wilhem Filho, Danilo; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

2017-09-15

Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlation between E-cadherin interactions, survivin expression, and apoptosis in MDCK and ts-Src MDCK cell culture models.

PubMed

Capra, Janne; Eskelinen, Sinikka

2017-12-01

Survivin, a member of inhibitor of apoptosis (IAP) protein family, is a multifunctional protein expressed in most cancers. In addition to inhibition of apoptosis, it regulates proliferation and promotes migration. Its presence and function in cells is strongly regulated via transcription factors, intracellular localization, and degradation. We analyzed the presence of survivin at protein level in various culture environments and under activation of Src tyrosine kinase in epithelial canine kidney MDCK cells in order to elucidate factors controlling survivin 'lifespan'. We used untransformed and temperature sensitive ts-Src MDCK cells as a model and forced them to grow in suspension (1D), in 2D on hard and soft surfaces and in soft 3D Matrigel environment with or without EGTA. In addition, we tested the effect of stressful conditions by cultivating the cells in the presence of an anti-cancer drug and a generator of reactive oxygen species (ROS), piperlongumine (PL) with or without an antioxidant, N-acetylcysteine (NAC). We could confirm that inhibition of apoptosis and simultaneous downregulation of survivin in MDCK cells required both intact cell-cell junctions, trans-interactions of E-cadherin and soft 3D matrix environment. In ts-Src-transformed MDCK cells, survivin was upregulated as soon as the cell-cell junctions were disintegrated. ROS generation with PL-induced cell death of ts-Src MDCK cells concomitantly with survivin downregulation. NAC rescued the ts-Src MDCK cells from ROS-induced apoptosis without upregulation of survivin resulting in a situation resembling untransformed MDCK cells in 3D environment and E-cadherin delineating the lateral cell walls.

Propylene epoxidation over biogenic Au/TS-1 catalysts by Cinnamomum camphora extract in the presence of H2 and O2

NASA Astrophysics Data System (ADS)

Du, Mingming; Huang, Jiale; Sun, Daohua; Li, Qingbiao

2016-03-01

The Au/TS-1 catalysts with different Au nanoparticles (NPs) sizes ranging from 3.1 to 8.4 nm but the same Au loading of 0.5 wt% were prepared by Cinnamomum camphora (CC) extract, and were used for propylene epoxidation. The results showed that the interaction between Au and TS-1 support surface is important for propylene epoxidation and much smaller Au NPs (<3 nm) are the dominant active sites. After reaction of 100 h, there is no decreasing in both the activity and the PO selectivity for the Au/TS-1 catalysts, and only 1.8 wt% of the carbonaceous deposits on the surface of the catalyst after reaction, suggesting that the desorption of the product from the modified catalysts surface by residual biomolecules is much easier.

Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR.

PubMed

Anderson, Karen S

2017-03-01

Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. In contrast, several parasitic protozoa, including Leishmania major (Lm), Plasmodium falciparum (Pf), Toxoplasma gondii (Tg) and Cryptosporidium hominis (Ch), contain a unique bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) having the two sequential catalytic activities contained on a single polypeptide chain. It has been suggested that the bifunctional nature of the two catalytic activities may enable substrate channeling. The 3D structures for each of these enzymes reveals distinct features for each species. While three of the four species (Pf, Tg and Ch) contain a junctional region linking the two domains, this is lacking in Lm. The Lm and Pf contain N-terminal amino acid extensions. A multidisciplinary approach using structural studies and transient kinetic analyses combined with mutational analysis has investigated the roles of these unique structural features for each enzyme. Additionally, the possibility of substrate channeling behavior was explored. These studies have identified unique, functional regions in both the TS and DHFR domains that govern efficient catalysis for each species. Surprisingly, even though there are structural similarities among the species, each is regulated in a distinct manner. This structural and mechanistic information was also used to exploit species-specific inhibitor design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect.

PubMed

Ogawa, Kazuo; Omatsu, Tatsushi; Matsumoto, Chinami; Tsuchiya, Naoko; Yamamoto, Masahiro; Naito, Yuji; Yoshikawa, Toshikazu

2012-08-09

TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of bone marrow suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression using a proteomics approach. Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. This study indicates that bone marrow suppression by treatment with TS-1 in mice might

Oil fuel delivery optimization for multi product and multi depot: the case of petrol station replenishment problem (PSRP)

NASA Astrophysics Data System (ADS)

Surjandari, Isti; Rachman, Amar; Dianawati, Fauzia; Wibowo, R. Pramono

2011-10-01

With the Oil and Gas Law No. 22 of 2001, national and foreign private enterprises can invest in all sectors of Oil and Gas in Indonesia. In anticipation of this free competition, Pertamina, as a state-owned enterprises, which previously had monopolized the oil and gas business activities in Indonesia, should be able to improve services as well as the efficiency in order to compete in the free market, especially in terms of cost efficiency of fuel distribution to gas station (SPBU). To optimize the distribution activity, it is necessary to design a scheduling system and its fuel delivery routes daily to every SPBU. The determination of routes and scheduling delivery of fuel to the SPBU can be modeled as a Petrol Station Replenishment Problem (PSRP) with the multi-depot, multi-product, time windows and split deliveries, which in this study will be completed by the Tabu Search algorithm (TS). This study was conducted in the area of Bandung, the capital of West Java province, which is a big city and the neighboring city of Jakarta, the capital city of Indonesia. By using the fuel delivery data for one day, the results showed a decrease of 16.38% of the distance of the route compared to the current conditions, which impacted on the reduction of distribution costs and decrease the number of total trips by 5.22% and 3.83%.

Monoacylglycerol Lipase Inhibitor JZL184 Improves Behavior and Neural Properties in Ts65Dn Mice, a Model of Down Syndrome

PubMed Central

Lysenko, Larisa V.; Kim, Jeesun; Henry, Cassandra; Tyrtyshnaia, Anna; Kohnz, Rebecca A.; Madamba, Francisco; Simon, Gabriel M.; Kleschevnikova, Natalia E.; Nomura, Daniel K.; Ezekowitz, R . Alan B.; Kleschevnikov, Alexander M.

2014-01-01

Genetic alterations or pharmacological treatments affecting endocannabinoid signaling have profound effects on synaptic and neuronal properties and, under certain conditions, may improve higher brain functions. Down syndrome (DS), a developmental disorder caused by triplication of chromosome 21, is characterized by deficient cognition and inevitable development of the Alzheimer disease (AD) type pathology during aging. Here we used JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL), to examine the effects of chronic MAGL inhibition on the behavioral, biochemical, and synaptic properties of aged Ts65Dn mice, a genetic model of DS. In both Ts65Dn mice and their normosomic (2N) controls, JZL184-treatment increased brain levels of 2-arachidonoylglycerol (2-AG) and decreased levels of its metabolites such as arachidonic acid, prostaglandins PGD2, PGE2, PGFα, and PGJ2. Enhanced spontaneous locomotor activity of Ts65Dn mice was reduced by the JZL184-treatement to the levels observed in 2N animals. Deficient long-term memory was also improved, while short-term and working types of memory were unaffected. Furthermore, reduced hippocampal long-term potentiation (LTP) was increased in the JZL184-treated Ts65Dn mice to the levels observed in 2N mice. Interestingly, changes in synaptic plasticity and behavior were not observed in the JZL184-treated 2N mice suggesting that the treatment specifically attenuated the defects in the trisomic animals. The JZL184-treatment also reduced the levels of Aβ40 and Aβ42, but had no effect on the levels of full length APP and BACE1 in both Ts65Dn and 2N mice. These data show that chronic MAGL inhibition improves the behavior and brain functions in a DS model suggesting that pharmacological targeting of MAGL may be considered as a perspective new approach for improving cognition in DS. PMID:25474204

Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Heinen, Markus; Hettich, Moritz M.; Ryan, Devon P.; Schnell, Susanne; Paesler, Katharina; Ehninger, Dan

2012-01-01

Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAA receptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAA receptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome. PMID:22848851

Observer-Based Non-PDC Control for Networked T-S Fuzzy Systems With an Event-Triggered Communication.

PubMed

Peng, Chen; Ma, Shaodong; Xie, Xiangpeng

2017-02-07

This paper addresses the problem of an event-triggered non-parallel distribution compensation (PDC) control for networked Takagi-Sugeno (T-S) fuzzy systems, under consideration of the limited data transmission bandwidth and the imperfect premise matching membership functions. First, a unified event-triggered T-S fuzzy model is provided, in which: 1) a fuzzy observer with the imperfect premise matching is constructed to estimate the unmeasurable states of the studied system; 2) a fuzzy controller is designed following the same premise as the observer; and 3) an output-based event-triggering transmission scheme is designed to economize the restricted network resources. Different from the traditional PDC method, the synchronous premise between the fuzzy observer and the T-S fuzzy system are no longer needed in this paper. Second, by use of Lyapunov theory, a stability criterion and a stabilization condition are obtained for ensuring asymptotically stable of the studied system. On account of the imperfect premise matching conditions are well considered in the derivation of the above criteria, less conservation can be expected to enhance the design flexibility. Compared with some existing emulation-based methods, the controller gains are no longer required to be known a priori. Finally, the availability of proposed non-PDC design scheme is illustrated by the backing-up control of a truck-trailer system.

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome

PubMed Central

Velazquez, Ramon; Ash, Jessica A.; Powers, Brian E.; Kelley, Christy M.; Strawderman, Myla; Luscher, Zoe I.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

2014-01-01

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer’s disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS. PMID:23643842

Evaluation of Beef by Electronic Tongue System TS-5000Z: Flavor Assessment, Recognition and Chemical Compositions According to Its Correlation with Flavor.

PubMed

Zhang, Xinzhuang; Zhang, Yawei; Meng, Qingxiang; Li, Ning; Ren, Liping

2015-01-01

The aim of this study was to assess the ability of electronic tongue system TS-5000Z to evaluate meat quality based on flavor assessment, recognition and correlation with the meat chemical composition. Meat was sampled from eighteen beef cattle including 6 Wagyu breed cattle, 6 Angus breed cattle and 6 Simmental breed cattle. Chemical composition including dry matter, crude protein, fat, ash, cholesterol and taurine and flavor of the meat were measured. The results showed that different breed cattle had different chemical compositions and flavor, which contains sourness, umami, saltiness, bitterness, astringency, aftertaste from astringency, aftertaste from bitterness and aftertaste from umami, respectively. A principal component analysis (PCA) showed an easily visible separation between different breeds of cattle and indicated that TS-5000Z made a rapid identification of different breeds of cattle. In addition, TS-5000Z seemed to be used to predict the chemical composition according to its correlation with the flavor. In conclusion, TS-5000Z would be used as a rapid analytical tool to evaluate the beef quality both qualitatively and quantitatively, based on flavor assessment, recognition and chemical composition according to its correlation with flavor.

Design, synthesis and antimalarial screening of some hybrid 4-aminoquinoline-triazine derivatives against pf-DHFR-TS.

PubMed

Sahu, Supriya; Ghosh, Surajit Kumar; Kalita, Junmoni; Dutta, Mayurakhi; Bhat, Hans Raj

2016-04-01

Existing antifolate antimalarial drugs have shown resistance due to the mutations at some amino acid positions of Plasmodium falciparum DHFR-TS. In the present study, to overcome this resistance, a new series of hybrid 4-aminoquinoline-triazine derivatives were designed and docked into the active site of Pf-DHFR-TS (PDB i.d. 1J3K) using validated CDOCKER protocol. Binding energy was calculated by applying CHARMm forcefield. Binding energy and the pattern of interaction of the docked compounds were analysed. Fifteen compounds were selected for synthesis based on their binding energy values and docking poses. Synthesized compounds were characterised by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy and were screened for antimalarial activity against 3D7 strain of Plasmodium falciparum. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of methylenetetrahydrofolate reductase (MTHFR 677C>T) and thymidylate synthase (TSER and TS 1494del6) polymorphisms with premature ovarian failure in Korean women.

PubMed

Rah, HyungChul; Jeon, Young Joo; Choi, Youngsok; Shim, Sung Han; Yoon, Tae Ki; Choi, Dong Hee; Cha, Sun Hee; Kim, Nam Keun

2012-11-01

The aim of our study was to investigate whether methylenetetrahydrofolate reductase (MTHFR) gene variant (MTHFR 677C>T) and thymidylate synthase (TS) gene variants (TS enhancer region [TSER] and TS 1494del6) confer a risk for premature ovarian failure (POF). We genotyped 136 POF patients and 236 controls among Korean women for the three single nucleotide polymorphism sites using polymerase chain reaction restriction fragment length polymorphism analysis. Differences in the MTHFR 677C>T, TSER, and TS 1494del6 genotype frequencies between POF patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as a measure of the strength of the association between genotypes and POF. The MTHFR 677CT and CT + TT variant genotypes were more frequent in POF patients than in controls (OR, 2.249; 95% CI, 1.317-3.843; and OR, 2.132; 95% CI, 1.268-3.585, respectively). The combined genotype frequencies of MTHFR 677CT + TT/TSER 3R3R and 677CT + TT/TS 1494del6 del6/del6 were higher in patients than in controls (OR, 2.300; 95% CI, 1.219-4.337; and OR, 3.314; 95% CI, 1.623-6.767, respectively). The T-3R-del6 and T-2R-del6 (MTHFR 677C>T/TSER/TS 1494del6) haplotypes were more frequent in patients (OR, 1.450; 95% CI, 1.050-2.002; and OR, 2.911; 95% CI, 1.191-7.117, respectively), whereas the C-2R-del6 haplotype was less frequent in patients (OR, 0.372; 95% CI, 0.152-0.912). The T-del6 (MTHFR 677/TS 1494del6) haplotype frequency was higher among patients (OR, 1.653; 95% CI, 1.206-2.266), whereas the C-del6 haplotype frequency was lower among patients (OR, 0.700; 95% CI, 0.516-0.950). We did not find an association between TSER or TS 1494del6 polymorphisms and POF. Our data suggest that the MTHFR 677T allele may increase the risk for POF, which could lead to the development of novel genetic markers for predicting the risk of POF in patients.

Development and immunogenicity of recombinant GapA(+) Mycoplasma gallisepticum vaccine strain ts-11 expressing infectious bronchitis virus-S1 glycoprotein and chicken interleukin-6.

PubMed

Shil, Pollob K; Kanci, Anna; Browning, Glenn F; Markham, Philip F

2011-04-12

Mycoplasma gallisepticum (MG) is a major pathogen of poultry that causes chronic respiratory disease in chickens and infectious sinusitis in turkeys. A live attenuated vaccine, ts-11, has been used for the control of MG in several countries. The efficacy of this vaccine is highly dose dependent and the flock antibody response is weak. To improve the functionality of the vaccine and investigate its potential as a delivery vector for foreign antigens and immunomodulatory proteins, we developed a derivative of ts-11 expressing infectious bronchitis virus-S1 glycoprotein (IBV-S1) and releasing chicken interleukin-6 into the extracellular milieu (MG ts-11 C3 (+CS)) using a transposon-based delivery vector. Following administration of MG ts-11 C3 (+CS) to chickens by eye-drop, an antibody response to MG and IBV-S1, as determined by the rapid serum agglutination test (RSA) and Western blotting, respectively, could be detected. Birds inoculated with the recombinant vaccine had significantly enhanced weight gain and were partially protected against damage by pathogenic IBV. These results indicate that the ChIL-6 released by MG ts-11 C3 (+CS) may have had a non-specific effect on growth rate. They also suggest that ts-11 is a promising vaccine vector, capable of delivering heterologous protective antigens, and may also provide non-specific benefits when engineered to express immunomodulatory proteins. With some improvements in the expression system, it could be used to induce a targeted immune response against specific mucosal pathogens, and co-expression of several antigens would allow development of a novel multivalent vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

GRP78 confers the resistance to 5-FU by activating the c-Src/LSF/TS axis in hepatocellular carcinoma.

PubMed

Gu, Yan-jiao; Li, Hong-dan; Zhao, Liang; Zhao, Song; He, Wu-bin; Rui, Li; Su, Chang; Zheng, Hua-chuan; Su, Rong-jian

2015-10-20

5-FU is a common first-line chemotherapeutic drug for the treatment of hepatocellular carcinoma. However the development of acquired resistance to 5-FU confines its clinical usages. Although this phenomenon has been the subject of intense investigation, the exact mechanism of acquired resistance to 5-FU remains elusive. Here, we report that over-expression of GRP78 contributes to acquired resistance to 5-FU in HCC by up-regulating the c-Src/LSF/TS axis. Moreover, we found that the resistance to 5-FU conferred by GRP78 is mediated by its ATPase domain. The ATPase domain differentially increased the expression of LSF, TS and promoted the phosphorylation of ERK and Akt. We further identified that GRP78 interacts physically with c-Src through its ATPase domain and promotes the phosphorylation of c-Src, which in turn increases the expression of LSF in the nucleus. Together, GRP78 confers the resistance to 5-FU by up-regulating the c-Src/LSF/TS axis via its ATPase domain.

The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients.

PubMed

Kucharczyk, Tomasz; Krawczyk, Paweł; Powrózek, Tomasz; Kowalski, Dariusz M; Ramlau, Rodryg; Kalinka-Warzocha, Ewa; Knetki-Wróblewska, Magdalena; Winiarczyk, Kinga; Krzakowski, Maciej; Milanowski, Janusz

2016-01-01

In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes (TS, DHFR and GARFT) involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats (VNTR), the G > C SNP in these repeats and insertion/deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival (OS) of NSCLC patients. Carriers of 2R/3R(G), 3R(C)/3R(G), 3R(G)/3R(G) genotypes showed significantly more frequent early progression than carriers of 2R/2R, 2R/3R(C), 3R(C)/3R(C) genotypes of TS gene (p < 0.05). Among carriers of triple 28 bp tandem repeats (3R) in TS gene and C/C genotype of MTHFR gene a significantly shorter OS was observed (HR = 3.07; p = 0.003). In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R/3R genotype in TS and C/C genotype in 677C > T SNP in MTHFR (HR = 3.85; p < 0.005) as well as in patients with short duration of response to first-line chemotherapy (HR = 2.09; p < 0.005). Results of our study suggested that genetic factors may have a high predictive and prognostic value (even greater than clinical factors) for patients treated with pemetrexed monotherapy.

Correlation between TS, MTHFR, and ERCC1 gene polymorphisms and the efficacy of platinum in combination with pemetrexed first-line chemotherapy in mesothelioma patients.

PubMed

Powrózek, Tomasz; Kowalski, Dariusz M; Krawczyk, Paweł; Ramlau, Rodryg; Kucharczyk, Tomasz; Kalinka-Warzocha, Ewa; Knetki-Wróblewska, Magdalena; Winiarczyk, Kinga; Dyszkiewicz, Wojciech; Krzakowski, Maciej; Milanowski, Janusz

2014-11-01

The combination of pemetrexed and platinum compound represents the standard regimen for first-line chemotherapy in malignant pleural mesothelioma patients. Pemetrexed is a multitarget antifolate agent that inhibits folate-dependent enzymes (eg, thymidylate synthase [TS]) and thus synthesis of nucleotides and DNA. Expression of TS and folate availability, regulated by gene polymorphisms, have implications for effectiveness of chemotherapy and the outcome of mesothelioma patients. The aim of this retrospective multicenter study was to assess the correlation between TS, 5,10-methylenetetrahydrofolate reductase (MTHFR) and excision repair cross-complementing group 1 (ERCC1) gene polymorphisms and the efficacy of pemetrexed-based first-line chemotherapy of mesothelioma patients. Fifty-nine mesothelioma patients (31 men with a median age of 62 years) treated in first-line chemotherapy with platinum in combination with pemetrexed or pemetrexed monotherapy were enrolled. Genomic DNA was isolated from peripheral blood. Using polymerase chain reaction and high resolution melt methods, the variable number of tandem repeat, the G>C single nucleotide polymorphism (SNP) in these repeats, and 6-base pair (bp) insertion/deletion polymorphism of the TS gene, the SNP of 677C>T in MTHFR, and 19007C>T in the ERCC1 gene were analyzed and correlated with disease control rate, progression-free survival (PFS), and overall survival (OS) of mesothelioma patients. Greater risk of early disease progression (PD), and shortening of PFS and OS were associated with several clinical factors (eg, anemia for early PD and OS), weight loss (for PFS and OS), and previous surgical treatment (for early PD, PFS, and OS). Insertion of 6-bp in both alleles of the TS gene (1494del6) was the only genetic factor that increased the incidence of early progression (P = .028) and shortening of median PFS (P = .06) in patients treated with pemetrexed-based chemotherapy. In multivariate analysis, the 1494del6 in the

In situ hydrothermal synthesis of a novel hierarchically porous TS-1/modified-diatomite composite for methylene blue (MB) removal by the synergistic effect of adsorption and photocatalysis.

PubMed

Yuan, Weiwei; Yuan, Peng; Liu, Dong; Yu, Wenbin; Laipan, Minwang; Deng, Liangliang; Chen, Fanrong

2016-01-15

Hierarchically porous TS-1/modified-diatomite composites with high removal efficiency for methylene blue (MB) were prepared via a facile in situ hydrothermal route. The surface charge state of the diatomite was modified to enhance the electrostatic interactions, followed by in situ hydrothermal coating with TS-1 nanoparticles. The zeolite loading amount in the composites could be adjusted by changing the hydrothermal time. The highest specific surface area and micropore volume of the obtained composites were 521.3m(2)/g and 0.254cm(3)/g, respectively, with an optimized zeolite loading amount of 96.8%. Based on the synergistic effect of efficient adsorption and photocatalysis resulting from the newly formed hierarchically porous structure and improved dispersion of TS-1 nanoparticles onto diatomite, the composites' removal efficiency for MB reached 99.1% after 2h of photocatalytic reaction, even higher than that observed using pure TS-1 nanoparticles. Moreover, the superior MB removal kinetics of the composites were well represented by a pseudo-first-order model, with a rate constant (5.28×10(-2)min(-1)) more than twice as high as that of pure TS-1 nanoparticles (2.43×10(-2)min(-1)). The significant dye removal performance of this novel TS-1/modified-diatomite composite indicates that it is a promising candidate for use in waste water treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome.

PubMed

Velazquez, Ramon; Ash, Jessica A; Powers, Brian E; Kelley, Christy M; Strawderman, Myla; Luscher, Zoe I; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2013-10-01

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer's disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS. Copyright © 2013 Elsevier Inc. All rights reserved.

Guidelines: the do's, don'ts and don't knows of feedback for clinical education.

PubMed

Lefroy, Janet; Watling, Chris; Teunissen, Pim W; Brand, Paul

2015-12-01

The guidelines offered in this paper aim to amalgamate the literature on formative feedback into practical Do's, Don'ts and Don't Knows for individual clinical supervisors and for the institutions that support clinical learning. The authors built consensus by an iterative process. Do's and Don'ts were proposed based on authors' individual teaching experience and awareness of the literature, and the amalgamated set of guidelines were then refined by all authors and the evidence was summarized for each guideline. Don't Knows were identified as being important questions to this international group of educators which if answered would change practice. The criteria for inclusion of evidence for these guidelines were not those of a systematic review, so indicators of strength of these recommendations were developed which combine the evidence with the authors' consensus. A set of 32 Do and Don't guidelines with the important Don't Knows was compiled along with a summary of the evidence for each. These are divided into guidelines for the individual clinical supervisor giving feedback to their trainee (recommendations about both the process and the content of feedback) and guidelines for the learning culture (what elements of learning culture support the exchange of meaningful feedback, and what elements constrain it?) Feedback is not easy to get right, but it is essential to learning in medicine, and there is a wealth of evidence supporting the Do's and warning against the Don'ts. Further research into the critical Don't Knows of feedback is required. A new definition is offered: Helpful feedback is a supportive conversation that clarifies the trainee's awareness of their developing competencies, enhances their self-efficacy for making progress, challenges them to set objectives for improvement, and facilitates their development of strategies to enable that improvement to occur.

Biochemical markers of striatal desensitization in cortical-limbic hyperglutamatergic TS- & OCD-like transgenic mice.

PubMed

O'Brien, Kylie B; Sharrief, Anjail Z; Nordstrom, Eric J; Travanty, Anthony J; Huynh, Mailee; Romero, Megan P; Bittner, Katie C; Bowser, Michael T; Burton, Frank H

2018-04-01

Tics and compulsions in comorbid Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD) are associated with chronic hyperactivity of parallel cortico/amygdalo-striato-thalamo-cortical (CSTC) loop circuits. Comorbid TS- & OCD-like behaviors have likewise been observed in D1CT-7 mice, in which an artificial neuropotentiating transgene encoding the cAMP-elevating intracellular subunit of cholera toxin (CT) is chronically expressed selectively in somatosensory cortical & amygdalar dopamine (DA) D1 receptor-expressing neurons that activate cortico/amygdalo-striatal glutamate (GLU) output. We've now examined in D1CT-7 mice whether the chronic GLU output from their potentiated cortical/limbic CSTC subcircuit afferents associated with TS- & OCD-like behaviors elicits desensitizing neurochemical changes in the striatum (STR). Microdialysis-capillary electrophoresis and in situ hybridization reveal that the mice's chronic GLU-excited STR exhibits pharmacodynamic changes in three independently GLU-regulated measures of output neuron activation, co-excitation, and desensitization, signifying hyperactive striatal CSTC output and compensatory striatal glial and neuronal desensitization: 1) Striatal GABA, an output neurotransmitter induced by afferent GLU, is increased. 2) Striatal d-serine, a glial excitatory co-transmitter inhibited by afferent GLU, is decreased. 3) Striatal Period1 (Per1), which plays a non-circadian role in the STR as a GLU + DA D1- (cAMP-) dependent repressor thought to feedback-inhibit GLU + DA- triggered ultradian urges and motions, is transcriptionally abolished. These data imply that chronic cortical/limbic GLU excitation of the STR desensitizes its co-excitatory d-serine & DA inputs while freezing its GABA output in an active state to mediate chronic tics and compulsions - possibly in part by abolishing striatal Per1-dependent ultradian extinction of urges and motions. Copyright © 2018 The Authors. Published by Elsevier B.V. All

(2S,4S)-4-Fluoro-1-{[(2-hydroxy-1,1-dimethylethyl)amino]acetyl}-pyrrolidine-2-carbonitrile monobenzenesulfonate (TS-021) is a selective and reversible dipeptidyl peptidase IV inhibitor.

PubMed

Tajima, Atsushi; Yamamoto, Koji; Kozakai, Akinori; Okumura-Kitajima, Lisa; Mita, Yasuo; Kitano, Kiyokazu; Jingu, Shigeji; Nakaike, Shiro

2011-03-25

The incretin hormone glucagon-like peptide-1 (GLP-1) has significant roles in the regulation of postprandial glucose metabolism, and the active form of GLP-1 is rapidly degraded by dipeptidyl peptidase (DPP)-IV. Therefore, DPP-IV inhibition is a promising approach for the treatment of type 2 diabetes. In the present study, we investigated the character of a DPP-IV inhibitor, TS-021, (2S, 4S)-4-fluoro-1-{[(2-hydroxy-1,1-dimethylethyl)amino]acetyl}-pyrrolidine-2-carbonitrile monobenzenesulfonate both in vitro and in vivo. TS-021 inhibits DPP-IV activity in human plasma with an IC(50) value of 5.34nM. In kinetics experiments, TS-021 had a relatively higher dissociation rate constant, with a k(off) value of 1.09×10(-3)s, despite exhibiting a potent human plasma DPP-IV inhibition activity with a K(i) value of 4.96nM. TS-021 exhibited significant inhibition selectivity against DPP-8 (>600 fold), DPP-9 (>1200 fold) and other peptidases examined (>15,000 fold). In normal rats, dogs and monkeys, a single oral dose of TS-021 exhibited favorable pharmacokinetic profiles. In Zucker fatty (fa/fa) rats, a rat model of obesity and impaired glucose tolerance, the oral administration of TS-021 resulted in the suppression of plasma DPP-IV activity and an increase in the active form of GLP-1. Furthermore, TS-021 exhibited a significant improvement in glucose tolerance by increasing the plasma insulin level during oral glucose tolerance tests at doses of 0.02-0.5mg/kg. These results suggest that TS-021 is a selective and reversible dipeptidyl peptidase IV inhibitor and has excellent characteristics as an oral anti-diabetic agent for postprandial hyperglycemia in patients with impaired glucose tolerance or type 2 diabetes. Copyright © 2011 Elsevier B.V. All rights reserved.

Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

PubMed

Stringer, Megan; Abeysekera, Irushi; Thomas, Jared; LaCombe, Jonathan; Stancombe, Kailey; Stewart, Robert J; Dria, Karl J; Wallace, Joseph M; Goodlett, Charles R; Roper, Randall J

2017-08-01

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis

75 FR 38168 - Hazardous Materials: International Regulations for the Safe Transport of Radioactive Material (TS...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... (IAEA) ``Regulations for the Safe Transport of Radioactive Material'' (TS-R-1), which is scheduled for... comments on the draft document to the IAEA. We are requesting input from the public to assist in developing....gov . SUPPLEMENTARY INFORMATION: I. Background The IAEA works with its Member States and multiple...

Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles.

PubMed

Cocce, Valentina; Balducci, Luigi; Falchetti, Maria L; Pascucci, Luisa; Ciusani, Emilio; Brini, Anna T; Sisto, Francesca; Piovani, Giovanna; Alessandri, Giulio; Parati, Eugenio; Cabeza, Laura; Pessina, Augusto

2017-11-24

A new tool for the drug delivery is based on the use of Mesenchymal Stromal Cells (MSCs) loaded in vitro with anti-cancer drugs. Unfortunately, the restricted lifespan of MSCs represents a significant limitation to produce them in high amounts and for long time studies. Immortalized MSCs from adipose tissue (hASCs) have been generated as good source of cells with stable features. These cells could improve the development of standardized procedures for both in vitro and preclinical studies. Furthermore they facilitate procedures for preparing large amounts of secretome containing microvesicles (MVs). We used human adipose tissue derived MSCs immortalized with hTERT+SV40 (TS) genes and transfected with GFP (hASCs-TS/GFP+). This line was investigated for its ability to uptake and release anticancer drugs. Microvesicles associated to paclitaxel (MVs/PTX) were isolated, quantified, and tested on pancreatic cancer cells. The line hASCs-TS/GFP+ maintained the main mesenchymal characters and was able to uptake and release, in active form, both paclitaxel and gemcitabine. From paclitaxel loaded hASCs-TS/GFP+ cells were isolated microvesicles in sufficient amount to inhibit "in vitro" the proliferation of pancreatic tumor cells. Our study suggests that human immortalized MSCs could be used for a large scale production of cells for mediated drug delivery. Moreover, the secretion of drug-associated MVs could represent a new way for producing new drug formulation by "biogenesis". In the context of the "advanced cell therapy procedure", the MVs/PTX production would use less resource and time and it could possibly contribute to simplification of GMP procedures. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice.

PubMed

Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S; Reeves, Roger H; Richtsmeier, Joan T

2014-08-01

Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. © 2014 Wiley Periodicals, Inc.

Overlapping Trisomies for Human Chromosome 21 Orthologs Produce Similar Effects on Skull and Brain Morphology of Dp(16)1Yey and Ts65Dn Mice

PubMed Central

Ratliff, Tabetha S.; Reeves, Roger H.; Richtsmeier, Joan T.

2014-01-01

Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16) 1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional microcomputed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. PMID:24788405

Robust fuzzy output feedback controller for affine nonlinear systems via T-S fuzzy bilinear model: CSTR benchmark.

PubMed

Hamdy, M; Hamdan, I

2015-07-01

In this paper, a robust H∞ fuzzy output feedback controller is designed for a class of affine nonlinear systems with disturbance via Takagi-Sugeno (T-S) fuzzy bilinear model. The parallel distributed compensation (PDC) technique is utilized to design a fuzzy controller. The stability conditions of the overall closed loop T-S fuzzy bilinear model are formulated in terms of Lyapunov function via linear matrix inequality (LMI). The control law is robustified by H∞ sense to attenuate external disturbance. Moreover, the desired controller gains can be obtained by solving a set of LMI. A continuous stirred tank reactor (CSTR), which is a benchmark problem in nonlinear process control, is discussed in detail to verify the effectiveness of the proposed approach with a comparative study. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Fast-kick-off monotonically convergent algorithm for searching optimal control fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Sheng-Lun; Ho, Tak-San; Rabitz, Herschel

2011-09-15

This Rapid Communication presents a fast-kick-off search algorithm for quickly finding optimal control fields in the state-to-state transition probability control problems, especially those with poorly chosen initial control fields. The algorithm is based on a recently formulated monotonically convergent scheme [T.-S. Ho and H. Rabitz, Phys. Rev. E 82, 026703 (2010)]. Specifically, the local temporal refinement of the control field at each iteration is weighted by a fractional inverse power of the instantaneous overlap of the backward-propagating wave function, associated with the target state and the control field from the previous iteration, and the forward-propagating wave function, associated with themore » initial state and the concurrently refining control field. Extensive numerical simulations for controls of vibrational transitions and ultrafast electron tunneling show that the new algorithm not only greatly improves the search efficiency but also is able to attain good monotonic convergence quality when further frequency constraints are required. The algorithm is particularly effective when the corresponding control dynamics involves a large number of energy levels or ultrashort control pulses.« less

Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice

PubMed Central

Ash, Jessica A.; Velazquez, Ramon; Kelley, Christy M.; Powers, Brian E.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

2014-01-01

Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer’s disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) lessens hippocampal dysfunction and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1 g/kg choline chloride) or choline supplemented (5.0 g/kg choline chloride) diet. Between 13 and 17 months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial learning and memory followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing powerful support for a functional relationship between these behavioral and morphometric effects of MCS for the trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large. PMID:24932939

[Case report: a recurrent gastric cancer in the terminal stage, associated with obstructive jaundice which responded significantly to oral administration of TS-1].

PubMed

Tasaka, K; Tomofuzi, Y; Sugihara, Z; Fukuda, H

2001-10-01

TS-1, a novel oral formation of 5-fluorouracil that consists of 1M tegafur (5-FU), 0.4M CDHP and 1M Oxo, is reported to achieve a higher response rate of 49% in patients with advanced gastric cancer in a late phase II study. We report a case of recurrent gastric cancer that responded significantly to the short-term administration of TS-1. A 73-year-old man, who had undergone a curative distal gastrectomy with D2 lymphadenectomy 2 years earlier, had presented with obstructive jaundice resulting from cancerous lymphadenopathy. PTCD was performed for drainage, but cholestasis disappeared completely through the two courses of oral administration of TS-1. The serum level of transaminase and bilirubin remained within normal limits, even with PTCD unequipped, until the patient died of the original disease. The adverse effects observed with the drug were anemia (grade 1) and skin pigmentation (grade 2), both of which improved soon after discontinuing the medication. In conclusion, TS-1 may be well-tolerable and effective in some cases of terminal-stage and/or recurrent gastric cancer, especially those associated with obstructive jaundice arising from the cancerous lymphadenopathy, in that patient QOL can be maintained to a much greater extent.

Decreasing the Expression of GABAA α5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome.

PubMed

Vidal, Verónica; García-Cerro, Susana; Martínez, Paula; Corrales, Andrea; Lantigua, Sara; Vidal, Rebeca; Rueda, Noemí; Ozmen, Laurence; Hernández, Maria-Clemencia; Martínez-Cué, Carmen

2018-06-01

Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABA-mediated inhibition. Because of the well-known modulatory role of GABA A α5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABA A α5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABA A α5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice. We show that reducing the expression of GABA A α5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved long-term potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABA A α5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS.

[Postural tachycardia syndrome (PoTS): An up-to-date].

PubMed

Astudillo, L; Laure, A; Fabry, V; Pugnet, G; Maury, P; Labrunée, M; Sailler, L; Pavy-Le Traon, A

2018-06-13

Postural tachycardia syndrome (PoTS) is a multifactorial syndrome defined by an increase in heart rate ≥30bpm, within 10minutes of standing (or during a head up tilt test to at least 60°), in absence of orthostatic hypotension. It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve in supine position. Patients have an intense fatigue with a high incidence on quality of life. This syndrome can be explained by many pathophysiological mechanisms. It can be associated with Ehlers-Danlos disease and some autoimmune disorders. The treatment is based on nonpharmacological measures and treatment with propranolol, fludrocortisone or midodrine. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

Intrahippocampal injection of TsTX-I increases the levels of INF-γ in the cerebral tissue but not the levels of glutamate.

PubMed

Rodriguez, Renan Volner; Dorce, Valquiria Abrão Coronado; de Freitas, Lucas Alves; Dorce, Ana Leticia Coronado; Lebrun, Ivo; Sobral, Ana Claudia Martins; Portaro, Fernanda Calheta Vieira; Kuniyoshi, Alexandre Kazuo; Carvalho, Daniela Cajado; Nencioni, Ana Leonor Abrahão

2015-09-01

TsTX-I, isolated from Tityus serrulatus scorpion venom, causes epileptic-like discharges when injected into the central nervous system. The involvement of excitatory amino acids and cytokines in this activity was investigated. Our results have demonstrated that TsTX-I increases the release of IFN-γ but does not alter the intracerebral concentration of the excitatory amino acids in rats. Thus, this cytokine seems to be more important in the convulsive process than glutamate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Co-administration of liposomal l-OHP and PEGylated TS shRNA-lipoplex: A novel approach to enhance anti-tumor efficacy and reduce the immunogenic response to RNAi molecules.

PubMed

Alaaeldin, Eman; Abu Lila, Amr S; Ando, Hidenori; Fukushima, Masakazu; Huang, Cheng-Long; Wada, Hiromi; Sarhan, Hatem A; Khaled, Khaled A; Ishida, Tatsuhiro

2017-06-10

Many therapeutic strategies have been applied in efforts to conquer the development and/or progression of cancer. The combination of chemotherapy and an RNAi-based approach has proven to be an efficient anticancer therapy. However, the feasibility of such a therapeutic strategy has been substantially restricted either by the failure to achieve the efficient delivery of RNAi molecules to tumor tissue or by the immunostimulatory response triggered by RNAi molecules. In this study, therefore, we intended to investigate the efficacy of using liposomal oxaliplatin (liposomal l-OHP) to guarantee the efficient delivery of RNAi molecules, namely shRNA against thymidylate synthase (TS shRNA) complexed with cationic liposome (TS shRNA-lipoplex), to solid tumors, and to suppress the immunostimulatory effect of RNAi molecules, TS shRNA, following intravenous administration. Herein, we describe how liposomal l-OHP enhanced the intra-tumor accumulation of TS shRNA-lipoplex and significantly reduced the immunostimulatory response triggered by TS shRNA. Consequently, such enhanced accumulation of TS shRNA-lipoplex along with the cytotoxic effect of liposomal l-OHP led to a remarkable tumor growth suppression (compared to mono-therapy) following systemic administration. Our results, therefore, may have important implications for the provision of a safer and more applicable combination therapy of RNAi molecules and anti-cancer agents that can produce a more reliable anti-tumor effect. Copyright © 2017 Elsevier B.V. All rights reserved.

A Search for HI Self-Absorption in the SGPS

NASA Astrophysics Data System (ADS)

Kavars, D. W.; Dickey, J. D.; McClure-Griffiths, N. M.; Gaensler, B. M.; Green, A. J.

2003-12-01

Using data from the Southern Galactic Plane Survey(SGPS) we present a routine to search for cold HI clouds in the Galaxy, based on their HI self-absorption(HISA) signature. The data was obtained using the Australia Telescope Compact Array and the Parkes Radio Telescope. The SGPS, because of its good angular and velocity resolution, is excellent for searching for HISA clouds. We have already analyzed a few of the more prominent HISA features, finding spin temperatures, Ts ˜ 20K, column densities, NHI ˜ 2 x 1020}cm{-2, and optical depths of ˜ 1. The next step is to search the entire SGPS. A search by eye is possible, but is biased towards the most pronounced features. To better understand the role HISA plays in the ISM, an automated search technique is required. Our routine takes the first and second derivatives of the HI emission brightness temperature with respect to velocity. Due to the sharp drop in the emission profile through a HISA cloud, the derivative profiles show characteristic positive and/or negative peaks. These peaks represent a population of clouds separate from random HI emission fluctuations. By setting thresholds on the derivative maps and defining HISA only if it passes both derivative tests, we can build an unbiased catalog of HISA candidates in the Galaxy. The number distribution can be used to put constraints on the parameters used to find the spin temperature and optical depth, allowing us to more accurately determine the temperature, column density, and optical depth distribution of HISA clouds. We also compare HISA with 12CO emission. In the Inner Galaxy from l=313 deg to l=338 deg we find 30-50% of HISA is associated with 12CO at a brightness temperature of at least 1K. This work was supported by NSF grant AST 97-32695 to the University of Minnesota.

Self-calibration of a noisy multiple-sensor system with genetic algorithms

NASA Astrophysics Data System (ADS)

Brooks, Richard R.; Iyengar, S. Sitharama; Chen, Jianhua

1996-01-01

This paper explores an image processing application of optimization techniques which entails interpreting noisy sensor data. The application is a generalization of image correlation; we attempt to find the optimal gruence which matches two overlapping gray-scale images corrupted with noise. Both taboo search and genetic algorithms are used to find the parameters which match the two images. A genetic algorithm approach using an elitist reproduction scheme is found to provide significantly superior results. The presentation includes a graphic presentation of the paths taken by tabu search and genetic algorithms when trying to find the best possible match between two corrupted images.

Discipline and the TS Child: A Guide for Parents and Teachers of Children with Tourette Syndrome.

ERIC Educational Resources Information Center

Fisher-Collins, Ramona

This parent and teacher guide considers discipline for children with Tourette Syndrome (TS) who have difficulty with behavioral compliance. Discipline is defined primarily as "training to act in accordance with rules," and is not punishment but involves teaching self-control and observance of societal expectations. Controversy and…

[Automated procedures for microscopic analyses of blood smears: medical testing a MECOS-Ts2 complex].

PubMed

Pliasunova, S A; Balugian, R Sh; Khmel'nitskiĭ, K E; Medovyĭ, V S; Parpara, A A; Piatnitskiĭ, A M; Sokolinskiĭ, B Z; Dem'ianov, V L; Nikolaenko, D S

2006-10-01

The paper presents the results of medical tests of a group of computer-aided procedures for microscopic analysis by means of a MECOS-Ts2 complex (ZAO "MECOS", Russia), which have been conducted at the Republican Children's Clinical Hospital, the Research Institute of Emergency Pediatric Surgery and Traumatology, and Moscow City Clinical Hospital No. 23. Computer-aided procedures for calculating the differential count and for analyzing the morphology of red blood cells were tested on blood smears from a total of 443 patients and donors, computer-aided calculation of the count of reticulocytes was tested on 318 smears. The tests were carried out under the US standard NCCLS-H20A. Manual microscopy (443 smears) and flow blood analysis on a Coulter GEN*S (125 smears) were used as reference methods. The quality of collection of samples and laboriousness were additionally assessed. The certified MECOS-Ts2 subsystems were additionally used as reference tools. The tests indicated the advantage of computer-aided MECOS-Tsl2 complex microscopy over manual microscopy.

Intermittent magnetic reconnection in TS-3 merging experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, Y.; Hayashi, Y.; Ii, T.

2011-11-15

Ejection of current sheet with plasma mass causes impulsive and intermittent magnetic reconnection in the TS-3 spherical tokamak (ST) merging experiment. Under high guide toroidal field, the sheet resistivity is almost classical due to the sheet thickness much longer than the ion gyroradius. Large inflow flux and low current-sheet resistivity result in flux and plasma pileup followed by rapid growth of the current sheet. When the pileup exceeds a critical limit, the sheet is ejected mechanically from the squeezed X-point area. The reconnection (outflow) speed is slow during the flux/plasma pileup and is fast during the ejection, suggesting that intermittentmore » reconnection similar to the solar flare increases the averaged reconnection speed. These transient effects enable the merging tokamaks to have the fast reconnection as well as the high-power reconnection heating, even when their current-sheet resistivity is low under high guide field.« less

Increased efficiency of the GABAA and GABAB receptor–mediated neurotransmission in the Ts65Dn mouse model of Down syndrome

PubMed Central

Kleschevnikov, Alexander M.; Belichenko, Pavel V.; Gall, Jessica; George, Lizzy; Nosheny, Rachel; Maloney, Michael T.; Salehi, Ahmad; Mobley, William C.

2011-01-01

Cognitive impairment in Down syndrome (DS) involves the hippocampus. In the Ts65Dn mouse model of DS, deficits in hippocampus-dependent learning and synaptic plasticity were linked to enhanced inhibition. However, the mechanistic basis of changes in inhibitory efficiency remains largely unexplored, and efficiency of the GABAergic synaptic neurotransmission has not yet been investigated in direct electrophysiological experiments. To investigate this important feature of neurobiology of DS, we examined synaptic and molecular properties of the GABAergic system in the dentate gyrus (DG) of adult Ts65Dn mice. Both GABAA and GABAB receptor-mediated components of evoked inhibitory postsynaptic currents (IPSCs) were significantly increased in Ts65Dn vs. control (2N) DG granule cells. These changes were unaccompanied by alterations in hippocampal levels of GABAA (α1, α2, α3, α5 and γ2) or GABAB (Gbr1a and Gbr1b) receptor subunits. Immunoreactivity for GAD65, a marker for GABAergic terminals, was also unchanged. In contrast, there was a marked change in functional parameters of GABAergic synapses. Paired stimulations showed reduced paired-pulse ratios of both GABAA and GABAB receptor-mediated IPSC components (IPSC2/IPSC1), suggesting an increase in presynaptic release of GABA. Consistent with increased gene dose, the level of the Kir3.2 subunit of potassium channels, effectors for postsynaptic GABAB receptors, was increased. This change was associated with enhanced postsynaptic GABAB/Kir3.2 signaling following application of the GABAB receptor agonist baclofen. Thus, both GABAA and GABAB receptor-mediated synaptic efficiency is increased in the Ts65Dn DG, thus likely contributing to deficient synaptic plasticity and poor learning in DS. PMID:22062771

Environmental Enrichment Rescues Postnatal Neurogenesis Defect in the Male and Female Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Chakrabarti, Lina; Scafidi, Joseph; Gallo, Vittorio; Haydar, Tarik F.

2011-01-01

Down syndrome (DS), the most frequent genetic cause of intellectual disability and developmental delay, results from impaired neural stem cell proliferation and differentiation. Impaired neurogenesis in the neocortex, hippocampus and cerebellum is believed to be the underlying cause of learning and behavioral deficits in the Ts65Dn mouse model of DS. Aggressive sensorimotor and cognitive therapies have shown promise in mitigating the cognitive disabilities in DS but these behavioral therapies have not yet been investigated at the cellular level. Here, using the Ts65Dn mouse model of DS, we demonstrate that a combination of environmental enrichment and physical exercise starting in juvenile mice (postnatal day 18) markedly increases cell proliferation, neurogenesis and gliogenesis in the hippocampal dentate gyrus (DG) and the forebrain subventricular zone (SVZ) of both male and female mice. Enrichment and exercise increased the rate of Ts65Dn DG neurogenesis to be comparable to that of the nonenriched euploid group, while the effect on SVZ neurogenesis was reduced and seen only after prolonged exposure. These results clearly indicate that in a comprehensive stimulatory environment, the postnatal DS brain has the intrinsic capability of improving neurogenesis and gliogenesis to the levels of normal matched controls and that this cellular response underlies the cognitive improvement seen following behavioral therapies. PMID:21865665

Long-term effect of neonatal inhibition of APP gamma-secretase on hippocampal development in the Ts65Dn mouse model of Down syndrome.

PubMed

Stagni, Fiorenza; Raspanti, Alessandra; Giacomini, Andrea; Guidi, Sandra; Emili, Marco; Ciani, Elisabetta; Giuliani, Alessandro; Bighinati, Andrea; Calzà, Laura; Magistretti, Jacopo; Bartesaghi, Renata

2017-07-01

Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed. Previous evidence showed that neonatal treatment with ELND006, an inhibitor of gamma-secretase, reinstates the Shh pathway and fully restores neurogenesis in Ts65Dn pups. In the framework of potential therapies for DS, it is extremely important to establish whether the positive effects of early intervention are retained after treatment cessation. Therefore, the goal of the current study was to establish whether early treatment with ELND006 leaves an enduring trace in the brain of Ts65Dn mice. Ts65Dn and euploid pups were treated with ELND006 in the postnatal period P3-P15 and the outcome of treatment was examined at ~one month after treatment cessation. We found that in treated Ts65Dn mice the pool of proliferating cells in the hippocampal dentate gyrus (DG) and total number of granule neurons were still restored as was the number of pre- and postsynaptic terminals in the stratum lucidum of CA3, the site of termination of the mossy fibers from the DG. Accordingly, patch-clamp recording from field CA3 showed functional normalization of the input to CA3. Unlike in field CA3, the number of pre- and postsynaptic terminals in the DG of treated Ts65Dn mice was no longer fully restored. The finding that many of the positive effects of neonatal treatment were retained after treatment cessation provides proof of principle demonstration of the efficacy of early

CES2, ABCG2, TS and Topo-I primary and synchronous metastasis expression and clinical outcome in metastatic colorectal cancer patients treated with first-line FOLFIRI regimen.

PubMed

Silvestris, Nicola; Simone, Giovanni; Partipilo, Giulia; Scarpi, Emanuela; Lorusso, Vito; Brunetti, Anna Elisabetta; Maiello, Evaristo; Paradiso, Angelo; Mangia, Anita

2014-09-05

Enzymatic activation of irinotecan (CPT-11) is due to carboxylesterase (CES), and its pharmacological behavior is influenced by drug resistance-related proteins. We previously reported that the clinical response and prognosis of metastatic colorectal cancer (mCRC) patients did not differ in tumors with different thymidylate synthase (TS) or topoisomerase-I (Topo-I) expression. Using immunohistochemistry (IHC), we evaluated the biological role of CES2 and the expression of breast cancer resistance protein (BCRP/ABCG2) in 58 consecutive mCRC patients, who had undergone a first-line CPT-11/5-FU/leucovirin (FOLFIRI) regimen. The expression of these proteins was also examined in a group of synchronous lymph nodes and liver metastases. Furthermore, all samples were revaluated for TS and Topo-I expression. High expression of CES2, ABCG2, TS and Topo-I was observed in 55%, 56%, 38% and 49% of patients, respectively. There was a significant association between high TS and high ABCG2 expression (p = 0.049). Univariate analysis showed that only TS expression significantly impacted on time to progression (p = 0.005). Moreover, Cox' multivariate analysis revealed that TS expression was significantly associated with overall survival (p = 0.01). No significant correlation was found between investigated markers expression and clinical response. Topo-I expression resulted in being significantly higher in liver metastases with respect to the corresponding primary tumors (p < 0.0001), emphasizing the role of Topo-I expression in metastatic cancer biology. In primary tumor tissues, CES2 expression tended to be higher than that observed in liver metastasis tissues (p = 0.05). These preliminary data may suggest CES2 over-expression as a potential marker of malignant phenotype. In light of these findings, we suggest that Topo-I expression together with TS expression could be associated with metastatic progression of CRC. Further studies are warranted with the aim of evaluating the

Real-life GH dosing patterns in children with GHD, TS or born SGA: a report from the NordiNet® International Outcome Study.

PubMed

Blankenstein, Oliver; Snajderova, Marta; Blair, Jo; Pournara, Effie; Pedersen, Birgitte Tønnes; Petit, Isabelle Oliver

2017-08-01

To describe real-life dosing patterns in children with growth hormone deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) receiving growth hormone (GH) and enrolled in the NordiNet International Outcome Study (IOS; Nbib960128) between 2006 and 2016. This non-interventional, multicentre study included paediatric patients diagnosed with GHD (isolated (IGHD) or multiple pituitary hormone deficiency (MPHD)), born SGA or with TS and treated according to everyday clinical practice from the Czech Republic (IGHD/MPHD/SGA/TS: n  = 425/61/316/119), France ( n  = 1404/188/970/206), Germany ( n  = 2603/351/1387/411) and the UK ( n  = 259/60/87/35). GH dosing was compared descriptively across countries and indications. Proportions of patients by GH dose group (low/medium/high) or GH dose change (decrease/increase/no change) during years 1 and 2 were also evaluated across countries and indications. In the Czech Republic, GH dosing was generally within recommended levels. In France, average GH doses were higher for patients with IGHD, MPHD and SGA than in other countries. GH doses in TS tended to be at the lower end of the recommended label range, especially in Germany and the UK; the majority of patients were in the low-dose group. A significant inverse association between baseline height standard deviation score and GH dose was shown ( P  < 0.05); shorter patients received higher doses. Changes in GH dose, particularly increases, were more common in the second (40%) than in the first year (25%). GH dosing varies considerably across countries and indications. In particular, almost half of girls with TS received GH doses below practice guidelines and label recommendations. © 2017 The authors.

Real-life GH dosing patterns in children with GHD, TS or born SGA: a report from the NordiNet® International Outcome Study

PubMed Central

Snajderova, Marta; Blair, Jo; Pournara, Effie; Pedersen, Birgitte Tønnes; Petit, Isabelle Oliver

2017-01-01

Objective To describe real-life dosing patterns in children with growth hormone deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) receiving growth hormone (GH) and enrolled in the NordiNet International Outcome Study (IOS; Nbib960128) between 2006 and 2016. Design This non-interventional, multicentre study included paediatric patients diagnosed with GHD (isolated (IGHD) or multiple pituitary hormone deficiency (MPHD)), born SGA or with TS and treated according to everyday clinical practice from the Czech Republic (IGHD/MPHD/SGA/TS: n = 425/61/316/119), France (n = 1404/188/970/206), Germany (n = 2603/351/1387/411) and the UK (n = 259/60/87/35). Methods GH dosing was compared descriptively across countries and indications. Proportions of patients by GH dose group (low/medium/high) or GH dose change (decrease/increase/no change) during years 1 and 2 were also evaluated across countries and indications. Results In the Czech Republic, GH dosing was generally within recommended levels. In France, average GH doses were higher for patients with IGHD, MPHD and SGA than in other countries. GH doses in TS tended to be at the lower end of the recommended label range, especially in Germany and the UK; the majority of patients were in the low-dose group. A significant inverse association between baseline height standard deviation score and GH dose was shown (P < 0.05); shorter patients received higher doses. Changes in GH dose, particularly increases, were more common in the second (40%) than in the first year (25%). Conclusions GH dosing varies considerably across countries and indications. In particular, almost half of girls with TS received GH doses below practice guidelines and label recommendations. PMID:28522645

Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.

PubMed

Ash, Jessica A; Velazquez, Ramon; Kelley, Christy M; Powers, Brian E; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2014-10-01

Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer's disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) improves spatial mapping and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1g/kg choline chloride) or choline supplemented (5.0g/kg choline chloride) diet. Between 13 and 17months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial mapping followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing support for a functional relationship between these behavioral and morphometric effects of MCS for trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhancement by Nalidixic Acid of the Thermal Susceptibility of the Ts-7 Mutant of Escherichia Coli TAU-Bar

PubMed Central

Nishida, Mikio; Mishima, Yukio; Kawada, Jun; Yielding, K. Lemone

1975-01-01

Nadilidixic acid at 5 × 10−6 M produced a substantial increase in thermal susceptibility of Ts-7, suggesting either that the thermal and nalidixic acid targets are identical or closely interdependent. PMID:1101825

[Effect of TUBB3, TS and ERCC1 mRNA expression on chemoresponse and clinical outcome of advanced gastric cancer by multiplex branched-DNA liquid chip technology].

PubMed

Huang, Jin; Hu, Huabin; Xie, Yangchun; Tang, Youhong; Liu, Wei; Zhong, Meizuo

2013-06-01

To analyze the impact of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU (DCF) regimen chemotherapy. The study population consisted of 48 patients with advanced gastric cancer. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology. The patients with low TUBB3 mRNA expression had higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that ECOG (Eastern Cooperative Oncology Group)≥2 (HR=2.42, P=0.009) and TUBB3 (HR=2.34, P=0.036) mRNA expression significantly impacted on OS. High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.

Deletions in the tetracycline resistance determinant reduce the thermosensitivity of a trfA(Ts) derivative of plasmid RP1 in Pseudomonas aeruginosa.

PubMed

Rella, M; Watson, J M; Thomas, C M; Haas, D

1987-01-01

A derivative of the broad-host-range plasmid RP1, pME301, was temperature-sensitive (Ts) at 43 degrees C for maintenance in Pseudomonas aeruginosa, P. mendocina, Klebsiella aerogenes and Escherichia coli. In E. coli, the Ts defect of pME301 could be complemented in trans by the cloned trfA gene, which is known to be essential for RP1 replication in E. coli and P. aeruginosa. Because pME301 expressed a Ts phenotype in P. mendocina and K. aerogenes, we assume that the trfA function is also vital in these organisms. When plasmid-encoded carbenicillin resistance (on transposon Tn801) was selected at non-permissive temperatures in P. aeruginosa strain PAO carrying pME301, we obtained either Tn801 insertions into the chromosome or pME301 derivatives having a deletion (or point mutation) in their tet genes, which determine resistance to tetracycline and are not transposable. From cloning experiments, we infer that the tet gene product(s) destabilize the pME301 replicon in P. aeruginosa at 40-43 degrees C.

Pharmacotherapy with Fluoxetine Restores Functional Connectivity from the Dentate Gyrus to Field CA3 in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Guidi, Sandra; Ciani, Elisabetta; Mangano, Chiara; Calzà, Laura; Bartesaghi, Renata

2013-01-01

Down syndrome (DS) is a high-incidence genetic pathology characterized by severe impairment of cognitive functions, including declarative memory. Impairment of hippocampus-dependent long-term memory in DS appears to be related to anatomo-functional alterations of the hippocampal trisynaptic circuit formed by the dentate gyrus (DG) granule cells - CA3 pyramidal neurons - CA1 pyramidal neurons. No therapies exist to improve cognitive disability in individuals with DS. In previous studies we demonstrated that pharmacotherapy with fluoxetine restores neurogenesis, granule cell number and dendritic morphology in the DG of the Ts65Dn mouse model of DS. The goal of the current study was to establish whether treatment rescues the impairment of synaptic connectivity between the DG and CA3 that characterizes the trisomic condition. Euploid and Ts65Dn mice were treated with fluoxetine during the first two postnatal weeks and examined 45–60 days after treatment cessation. Untreated Ts65Dn mice had a hypotrophyc mossy fiber bundle, fewer synaptic contacts, fewer glutamatergic contacts, and fewer dendritic spines in the stratum lucidum of CA3, the terminal field of the granule cell projections. Electrophysiological recordings from CA3 pyramidal neurons showed that in Ts65Dn mice the frequency of both mEPSCs and mIPSCs was reduced, indicating an overall impairment of excitatory and inhibitory inputs to CA3 pyramidal neurons. In treated Ts65Dn mice all these aberrant features were fully normalized, indicating that fluoxetine can rescue functional connectivity between the DG and CA3. The positive effects of fluoxetine on the DG-CA3 system suggest that early treatment with this drug could be a suitable therapy, possibly usable in humans, to restore the physiology of the hippocampal networks and, hence, memory functions. PMID:23620781

A comparative analysis of immunorestoration and recovery with conventional and immunotherapeutic protocols in canine generalized demodicosis: a newer insight of immunotherapeutic efficacy of T11TS.

PubMed

Sarkar, P; Mukherjee, J; Ghosh, A; Bhattacharjee, M; Mahato, S; Chakraborty, A; Mondal, M; Banerjee, C; Chaudhuri, Swapna

2004-01-01

Demodex canis is a natural inhabiting mite of canine skin. Immunological disorder or genetic disorder induces the Demodex population to proliferate vigorously resulting in generalized demodicosis with consequent chronic immunosuppression. Signs of generalized demodicosis include alopecia, crysting, erythema, secondary pyoderma etc. Amitraz, an acaricide, is used conventionally for the treatment of generalized demodicosis. In many instances, the disease relapses due to the residual immunosuppression. The need of an immunorestorative therapy has been urged in generalized demodicosis. Two immunorestorative drugs, namely, Immuplus, a herbal drug, and T11TS, a sheep erythrocyte surface glycoprotein, has been used in two separate groups of dogs having generalized demodicosis and receiving Amitraz treatment. It was observed that though Amitraz treated group responded to the therapy showing increased E-rosettes and nonspecific cytotoxic efficacy of T-lymphocytes and decrease in phagocytic potential of macrophages, the groups treated with the immunotherapeutics like Immuplus and T11TS, responded better. However, the group treated with T11TS showed best recovery. These results emphasize the need for an immunorestorative therapy in generalized demodicosis and provide data in favor of T11TS as a better immunomodulator in comparison to Immuplus.

Psychometric properties of the Portuguese version of the Acceptance and Action Questionnaire-Trauma Specific (AAQ-TS): A study with Portuguese Colonial War Veterans.

PubMed

Pinto-Gouveia, José; Carvalho, Teresa; Cunha, Marina; Duarte, Joana; Walser, Robyn D

2015-10-01

The Acceptance and Action Questionnaire-Trauma Specific (AAQ-TS) is a self-report measure designed to assess-trauma-related psychological (in)flexibility, as conceptualized in Acceptance and Commitment Therapy. However, there are no studies to date regarding its psychometric properties. This study explores such properties in the Portuguese version of the AAQ-TS, in Portuguese Colonial War Veterans. A Principal Components Analysis (PCA) was conducted in a sample from the general population of war Veterans (N=371). Confirmatory Factor Analysis (CFA) as well as reliability and convergent validity studies were performed in a different sample from the same population (N=312). For the discriminant validity a clinical sample with a war-related PTSD (N=42) and a non-clinical sample without PTSD (N=44) were used. The CFA suggested a re-specified 15-item model with good global adjustment and factorial validity. The AAQ-TS showed internal consistency, a good temporal reliability, convergent validity with psychopathological symptoms (related to PTSD, anxiety, depression and stress) and peritraumatic dissociation (altered awareness and depersonalization/derealization). The questionnaire also discriminates between war Veterans with and without a PTSD diagnosis. The major limitation relates to the samples' characteristics and sampling methods, which can limit the generalization of results. The Portuguese version of the AAQ-TS is a reliable and valid measure to assess experiential avoidance related to trauma in Portuguese Colonial War Veterans. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimal Spatial Design of Capacity and Quantity of Rainwater Catchment Systems for Urban Flood Mitigation

NASA Astrophysics Data System (ADS)

Huang, C.; Hsu, N.

2013-12-01

This study imports Low-Impact Development (LID) technology of rainwater catchment systems into a Storm-Water runoff Management Model (SWMM) to design the spatial capacity and quantity of rain barrel for urban flood mitigation. This study proposes a simulation-optimization model for effectively searching the optimal design. In simulation method, we design a series of regular spatial distributions of capacity and quantity of rainwater catchment facilities, and thus the reduced flooding circumstances using a variety of design forms could be simulated by SWMM. Moreover, we further calculate the net benefit that is equal to subtract facility cost from decreasing inundation loss and the best solution of simulation method would be the initial searching solution of the optimization model. In optimizing method, first we apply the outcome of simulation method and Back-Propagation Neural Network (BPNN) for developing a water level simulation model of urban drainage system in order to replace SWMM which the operating is based on a graphical user interface and is hard to combine with optimization model and method. After that we embed the BPNN-based simulation model into the developed optimization model which the objective function is minimizing the negative net benefit. Finally, we establish a tabu search-based algorithm to optimize the planning solution. This study applies the developed method in Zhonghe Dist., Taiwan. Results showed that application of tabu search and BPNN-based simulation model into the optimization model not only can find better solutions than simulation method in 12.75%, but also can resolve the limitations of previous studies. Furthermore, the optimized spatial rain barrel design can reduce 72% of inundation loss according to historical flood events.

Molecular Cloning of a cDNA Encoding for Taenia solium TATA-Box Binding Protein 1 (TsTBP1) and Study of Its Interactions with the TATA-Box of Actin 5 and Typical 2-Cys Peroxiredoxin Genes.

PubMed

Rodríguez-Lima, Oscar; García-Gutierrez, Ponciano; Jiménez, Lucía; Zarain-Herzberg, Ángel; Lazzarini, Roberto; Landa, Abraham

2015-01-01

TATA-box binding protein (TBP) is an essential regulatory transcription factor for the TATA-box and TATA-box-less gene promoters. We report the cloning and characterization of a full-length cDNA that encodes a Taenia solium TATA-box binding protein 1 (TsTBP1). Deduced amino acid composition from its nucleotide sequence revealed that encodes a protein of 238 residues with a predicted molecular weight of 26.7 kDa, and a theoretical pI of 10.6. The NH2-terminal domain shows no conservation when compared with to pig and human TBP1s. However, it shows high conservation in size and amino acid identity with taeniids TBP1s. In contrast, the TsTBP1 COOH-terminal domain is highly conserved among organisms, and contains the amino acids involved in interactions with the TATA-box, as well as with TFIIA and TFIIB. In silico TsTBP1 modeling reveals that the COOH-terminal domain forms the classical saddle structure of the TBP family, with one α-helix at the end, not present in pig and human. Native TsTBP1 was detected in T. solium cysticerci´s nuclear extract by western blot using rabbit antibodies generated against two synthetic peptides located in the NH2 and COOH-terminal domains of TsTBP1. These antibodies, through immunofluorescence technique, identified the TBP1 in the nucleus of cells that form the bladder wall of cysticerci of Taenia crassiceps, an organism close related to T. solium. Electrophoretic mobility shift assays using nuclear extracts from T. solium cysticerci and antibodies against the NH2-terminal domain of TsTBP1 showed the interaction of native TsTBP1 with the TATA-box present in T. solium actin 5 (pAT5) and 2-Cys peroxiredoxin (Ts2-CysPrx) gene promoters; in contrast, when antibodies against the anti-COOH-terminal domain of TsTBP1 were used, they inhibited the binding of TsTBP1 to the TATA-box of the pAT5 promoter gene.

Molecular Cloning of a cDNA Encoding for Taenia solium TATA-Box Binding Protein 1 (TsTBP1) and Study of Its Interactions with the TATA-Box of Actin 5 and Typical 2-Cys Peroxiredoxin Genes

PubMed Central

Rodríguez-Lima, Oscar; García-Gutierrez, Ponciano; Jiménez, Lucía; Zarain-Herzberg, Ángel; Lazzarini, Roberto; Landa, Abraham

2015-01-01

TATA-box binding protein (TBP) is an essential regulatory transcription factor for the TATA-box and TATA-box-less gene promoters. We report the cloning and characterization of a full-length cDNA that encodes a Taenia solium TATA-box binding protein 1 (TsTBP1). Deduced amino acid composition from its nucleotide sequence revealed that encodes a protein of 238 residues with a predicted molecular weight of 26.7 kDa, and a theoretical pI of 10.6. The NH2-terminal domain shows no conservation when compared with to pig and human TBP1s. However, it shows high conservation in size and amino acid identity with taeniids TBP1s. In contrast, the TsTBP1 COOH-terminal domain is highly conserved among organisms, and contains the amino acids involved in interactions with the TATA-box, as well as with TFIIA and TFIIB. In silico TsTBP1 modeling reveals that the COOH-terminal domain forms the classical saddle structure of the TBP family, with one α-helix at the end, not present in pig and human. Native TsTBP1 was detected in T. solium cysticerci´s nuclear extract by western blot using rabbit antibodies generated against two synthetic peptides located in the NH2 and COOH-terminal domains of TsTBP1. These antibodies, through immunofluorescence technique, identified the TBP1 in the nucleus of cells that form the bladder wall of cysticerci of Taenia crassiceps, an organism close related to T. solium. Electrophoretic mobility shift assays using nuclear extracts from T. solium cysticerci and antibodies against the NH2-terminal domain of TsTBP1 showed the interaction of native TsTBP1 with the TATA-box present in T. solium actin 5 (pAT5) and 2-Cys peroxiredoxin (Ts2-CysPrx) gene promoters; in contrast, when antibodies against the anti-COOH-terminal domain of TsTBP1 were used, they inhibited the binding of TsTBP1 to the TATA-box of the pAT5 promoter gene. PMID:26529408

[Two Cases of Urachal Carcinoma Treated by TS-1/CDDP as Adjuvant Chemotherapy].

PubMed

Ozawa, Michinobu; Kuromoto, Akito; Morozumi, Kento; Satou, Masahiko; Hoshi, Senji; Numahata, Kenji

2017-10-01

Case 1 : A 48-year-old man presenting with gross hematuria was suspected to have a tumor located in the bladder dome. He was referred to our department for further examination and treatment. Cystoscopy showed a dome-shaped mass in the supravesical region. Computed tomography and magnetic resonance imaging indicated the possibility of urachal carcinoma and peritoneal dissemination. Therefore, partial cystectomy with urachal resection was performed. The intraoperative findings were disseminated peritoneal nodules and mucus entering the peritoneal cavity from the tumor. On pathological examination, the tumor was classified as a mucinous-type adenocarcinoma, and 6 courses of TS-1/cisplatin (CDDP) therapy were administered to the patient as adjuvant chemotherapy. To date (10 months since the surgery), there has been no disease progression. Case 2 : A 76-year-old woman was referred to our department with a finding of a tumor in the bladder dome during her detailed examination for lung tumors. Cystoscopy showed nodular tumors, indicating lung metastases of the urachal carcinoma. Therefore, partial cystectomy with urachal resection was performed. On pathological examination, the tumor was classified as an enteric-type adenocarcinoma, and 2 courses of TS-1/CDDP therapy were administered to the patient as adjuvant chemotherapy. However, due to the development of marked bone marrow depression, the drugs had to be discontinued. Nonetheless, the lung metastases markedly diminished in size. To date (9 months since the discontinuation of chemotherapy), there has been no disease progression.

Optimizing Sensor and Actuator Arrays for ASAC Noise Control

NASA Technical Reports Server (NTRS)

Palumbo, Dan; Cabell, Ran

2000-01-01

This paper summarizes the development of an approach to optimizing the locations for arrays of sensors and actuators in active noise control systems. A type of directed combinatorial search, called Tabu Search, is used to select an optimal configuration from a much larger set of candidate locations. The benefit of using an optimized set is demonstrated. The importance of limiting actuator forces to realistic levels when evaluating the cost function is discussed. Results of flight testing an optimized system are presented. Although the technique has been applied primarily to Active Structural Acoustic Control systems, it can be adapted for use in other active noise control implementations.

Touchscreen learning deficits in Ube3a, Ts65Dn and Mecp2 mouse models of neurodevelopmental disorders with intellectual disabilities.

PubMed

Leach, P T; Crawley, J N

2017-12-20

Mutant mouse models of neurodevelopmental disorders with intellectual disabilities provide useful translational research tools, especially in cases where robust cognitive deficits are reproducibly detected. However, motor, sensory and/or health issues consequent to the mutation may introduce artifacts that preclude testing in some standard cognitive assays. Touchscreen learning and memory tasks in small operant chambers have the potential to circumvent these confounds. Here we use touchscreen visual discrimination learning to evaluate performance in the maternally derived Ube3a mouse model of Angelman syndrome, the Ts65Dn trisomy mouse model of Down syndrome, and the Mecp2 Bird mouse model of Rett syndrome. Significant deficits in acquisition of a 2-choice visual discrimination task were detected in both Ube3a and Ts65Dn mice. Procedural control measures showed no genotype differences during pretraining phases or during acquisition. Mecp2 males did not survive long enough for touchscreen training, consistent with previous reports. Most Mecp2 females failed on pretraining criteria. Significant impairments on Morris water maze spatial learning were detected in both Ube3a and Ts65Dn, replicating previous findings. Abnormalities on rotarod in Ube3a, and on open field in Ts65Dn, replicating previous findings, may have contributed to the observed acquisition deficits and swim speed abnormalities during water maze performance. In contrast, these motor phenotypes do not appear to have affected touchscreen procedural abilities during pretraining or visual discrimination training. Our findings of slower touchscreen learning in 2 mouse models of neurodevelopmental disorders with intellectual disabilities indicate that operant tasks offer promising outcome measures for the preclinical discovery of effective pharmacological therapeutics. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Incident angle dependence of proton response of CR-39 (TS-16) track detector

NASA Technical Reports Server (NTRS)

Oda, K.; Csige, I.; Yamauchi, T.; Miyake, H.; Benton, E. V.

1993-01-01

The proton response of the TS-16 type of CR-39 plastic nuclear track detector has been studied with accelerated and fast neutron induced protons in vacuum and in air. The diameters of etched tracks were measured as a function of etching time and the etch rate ratio and the etch induction layer were determined from the growth curve of the diameter using a variable etch rate ratio model. In the case of the accelerated protons in vacuum an anomalous incident angle dependence of the response is observed.

Chiral discrimination of α-hydroxy acids and N-Ts-α-amino acids induced by tetraaza macrocyclic chiral solvating agents by using 1H NMR spectroscopy.

PubMed

Lv, Caixia; Feng, Lei; Zhao, Hongmei; Wang, Guo; Stavropoulos, Pericles; Ai, Lin

2017-02-21

In the field of chiral recognition, reported chiral discrimination by 1 H NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate the chiral discriminating abilities of a chiral auxiliary. Among them, chiral α-hydroxy acids, α-amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes, and also play an important role in the area of preparation of pharmaceuticals, as they are part of the synthetic process in the production of chiral drug intermediates and protein-based drugs. In this paper, several α-hydroxy acids and N-Ts-α-amino acids were used to evaluate the chiral discriminating abilities of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d by 1 H NMR spectroscopy. The results indicate that α-hydroxy acids and N-Ts-α-amino acids were successfully discriminated in the presence of TAMCSAs 1a-1d by 1 H NMR spectroscopy in most cases. The enantiomers of the α-hydroxy acids and N-Ts-α-amino acids were assigned based on the change of integration of the 1 H NMR signals of the corresponding protons. The enantiomeric excesses (ee) of N-Ts-α-amino acids 11 with different optical compositions were calculated based on the integration of the 1 H NMR signals of the CH 3 protons (Ts group) of the enantiomers of (R)- and (S)-11 in the presence of TAMCSA 1b. At the same time, the possible chiral discriminating behaviors have been discussed by means of the Job plots of (±)-2 with TAMCSAs 1b and proposed theoretical models of the enantiomers of 2 and 6 with TAMCSA 1a, respectively.

Remote sensing monitoring the spatio-temporal changes of aridification in the Mongolian Plateau based on the general Ts-NDVI space, 1981-2012

NASA Astrophysics Data System (ADS)

Cao, Xiaoming; Feng, Yiming; Wang, Juanle

2017-06-01

This paper has developed a general Ts-NDVI triangle space with vegetation index time-series data from AVHRR and MODIS to monitor soil moisture in the Mongolian Plateau during 1981-2012, and studied the spatio-temporal variations of drought based on the temperature vegetation dryness index (TVDI). The results indicated that (1) the developed general Ts-NDVI space extracted from the AVHRR and MODIS remote sensing data would be an effective method to monitor regional drought, moreover, it would be more meaningful if the single time Ts-NDVI space showed an unstable condition; (2) the inverted TVDI was expected to reflect the water deficit in the study area. It was found to be in close negative agreement with precipitation and 10 cm soil moisture; (3) in the Mongolian Plateau, TVDI presented a zonal distribution with changes in land use/land cover types, vegetation cover and latitude. The soil moisture is low in bare land, construction land and grassland. During 1981-2012, drought was widely spread throughout the plateau, and aridification was obvious in the study period. Vegetation degradation, overgrazing, and climate warming could be considered as the main reasons.

Ectopic Mineralization in the Middle Ear and Chronic Otitis Media with Effusion Caused by RPL38 Deficiency in the Tail-short (Ts) Mouse*

PubMed Central

Noben-Trauth, Konrad; Latoche, Joseph R.

2011-01-01

Inflammation of the middle ear cavity (otitis media) and the abnormal deposition of bone at the otic capsule are common causes of conductive hearing impairment in children and adults. Although a host of environmental factors can contribute to these conditions, a genetic predisposition has an important role as well. Here, we analyze the Tail-short (Ts) mouse, which harbors a spontaneous semi-dominant mutation that causes skeletal defects and hearing loss. By genetic means, we show that the Ts phenotypes arise from an 18-kb deletion/insertion of the Rpl38 gene, encoding a ribosomal protein of the large subunit. We show that Ts mutants exhibit significantly elevated auditory-brain stem response thresholds and reduced distortion-product otoacoustic emissions, in the presence of normal endocochlear potentials and typical inner ear histology suggestive of a conductive hearing impairment. We locate the cause of the hearing impairment to the middle ear, demonstrating over-ossification at the round window ridge, ectopic deposition of cholesterol crystals in the middle ear cavity, enlarged Eustachian tube, and chronic otitis media with effusion all beginning at around 3 weeks after birth. Using specific antisera, we demonstrate that Rpl38 is an ∼8-kDa protein that is predominantly expressed in mature erythrocytes. Finally, using an Rpl38 cDNA transgene, we rescue the Ts phenotypes. Together, these data present a previously uncharacterized combination of interrelated middle ear pathologies and suggest Rpl38 deficiency as a model to dissect the causative relationships between neo-ossification, cholesterol crystal deposition, and Eustachian tubes in the etiology of otitis media. PMID:21062742

Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome.

PubMed

Olmos-Serrano, J Luis; Tyler, William A; Cabral, Howard J; Haydar, Tarik F

2016-05-01

Mouse models have provided insights into adult changes in learning and memory in Down syndrome, but an in-depth assessment of how these abnormalities develop over time has never been conducted. To address this shortcoming, we conducted a longitudinal behavioral study from birth until late adulthood in the Ts65Dn mouse model to measure the emergence and continuity of learning and memory deficits in individuals with a broad array of tests. Our results demonstrate for the first time that the pace at which neonatal and perinatal milestones are acquired is correlated with later cognitive performance as an adult. In addition, we find that life-long behavioral indexing stratifies mice within each genotype. Our expanded assessment reveals that diminished cognitive flexibility, as measured by reversal learning, is the most robust learning and memory impairment in both young and old Ts65Dn mice. Moreover, we find that reversal learning degrades with age and is therefore a useful biomarker for studying age-related decline in cognitive ability. Altogether, our results indicate that preclinical studies aiming to restore cognitive function in Ts65Dn should target both neonatal milestones and reversal learning in adulthood. Here we provide the quantitative framework for this type of approach. Copyright © 2016 Elsevier Inc. All rights reserved.

Longitudinal measures of cognition in the Ts65Dn mouse: refining windows and defining modalities for therapeutic intervention in Down syndrome

PubMed Central

Olmos-Serrano, J. Luis; Tyler, William A.; Cabral, Howard J.; Haydar, Tarik F.

2016-01-01

Mouse models have provided insights into adult changes in learning and memory in Down syndrome, but an in-depth assessment of how these abnormalities develop over time has never been conducted. To address this shortcoming, we conducted a longitudinal behavioral study from birth until late adulthood in the Ts65Dn mouse model to measure the emergence and continuity of learning and memory deficits in individuals with a broad array of tests. Our results demonstrate for the first time that the pace at which neonatal and perinatal milestones are acquired is correlated with later cognitive performance as an adult. In addition, we find that lifelong behavioral indexing stratifies mice within each genotype. Our expanded assessment reveals that diminished cognitive flexibility, as measured by reversal learning, is the most robust learning and memory impairment in both young and old Ts65Dn mice. Moreover, we find that reversal learning degrades with age and is therefore a useful biomarker for studying age-related decline in cognitive ability. Altogether, our results indicate that preclinical studies aiming to restore cognitive function in Ts65Dn should target both neonatal milestones and reversal learning in adulthood. Here we provide the quantitative framework for this type of approach. PMID:26854932

SU-F-BRD-13: Quantum Annealing Applied to IMRT Beamlet Intensity Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nazareth, D; Spaans, J

Purpose: We report on the first application of quantum annealing (QA) to the process of beamlet intensity optimization for IMRT. QA is a new technology, which employs novel hardware and software techniques to address various discrete optimization problems in many fields. Methods: We apply the D-Wave Inc. proprietary hardware, which natively exploits quantum mechanical effects for improved optimization. The new QA algorithm, running on this hardware, is most similar to simulated annealing, but relies on natural processes to directly minimize the free energy of a system. A simple quantum system is slowly evolved into a classical system, representing the objectivemore » function. To apply QA to IMRT-type optimization, two prostate cases were considered. A reduced number of beamlets were employed, due to the current QA hardware limitation of ∼500 binary variables. The beamlet dose matrices were computed using CERR, and an objective function was defined based on typical clinical constraints, including dose-volume objectives. The objective function was discretized, and the QA method was compared to two standard optimization Methods: simulated annealing and Tabu search, run on a conventional computing cluster. Results: Based on several runs, the average final objective function value achieved by the QA was 16.9 for the first patient, compared with 10.0 for Tabu and 6.7 for the SA. For the second patient, the values were 70.7 for the QA, 120.0 for Tabu, and 22.9 for the SA. The QA algorithm required 27–38% of the time required by the other two methods. Conclusion: In terms of objective function value, the QA performance was similar to Tabu but less effective than the SA. However, its speed was 3–4 times faster than the other two methods. This initial experiment suggests that QA-based heuristics may offer significant speedup over conventional clinical optimization methods, as quantum annealing hardware scales to larger sizes.« less

Ways for improving the properties of semiproducts from V96Ts-3-type high-strength aluminum alloys of the Al - Zn - Mg - Cu system

NASA Astrophysics Data System (ADS)

Elagin, V. I.; Samarina, M. V.; Zakharov, V. V.

2009-11-01

The effect of different modes of three-stage aging on the structure and properties of hot-deformed semiproducts (pressed shapes and rolled plates) from high-strength aluminum alloy V96Ts-3 of the Al - Zn - Mg - Cu system is studied with the aim of optimizing the hardening heat treatment. Amode of three-stage aging convenient for commercial production and ensuring hot-deformed semiproducts from alloy V96Ts-3 with high strength at the state T1 level in combination with satisfactory corrosion resistance corresponding to state T2 is suggested.

Bax and Bid act in synergy to bring about T11TS-mediated glioma apoptosis via the release of mitochondrial cytochrome c and subsequent caspase activation.

PubMed

Bhattacharjee, M; Acharya, S; Ghosh, A; Sarkar, P; Chatterjee, S; Kumar, P; Chaudhuri, S

2008-12-01

The specific apoptotic role of T11TS has been well established in glioma animal models. T11TS specifically induces the glioma cells to die an apoptotic death via immune cross-talk with the two intracranial immune competent cells-microglia and the brain-infiltrating lymphocytes. To unearth the molecular cascades operative within the glioma cells and to some extent in the two interacting immunocytes, we had initiated studies where preliminary findings not only had indicated the involvement of death receptors but had also hinted to the involvement of other apoptotic regulators. Hence, to identify the molecular pathway of apoptosis involving other apoptotic regulators in the three cell types, the cells were studied for the intrinsic apoptotic death regulators that were engaged to maintain the mitochondrial membrane integrity. The proteins that were selected could be divided into three broad classes-the Bcl-2 family of proteins-Bid, Bax and Bcl-2; the guardian of the genome p53 and the proteins downstream of mitochondria-Apaf-1, cytochrome c, caspase-9 and caspase-3. Activated Bid as well as maximal p53 expression was observed in the first dose of T11TS thus dually activating the pro-apoptotic Bax in the first and second dose in the glioma cells. Concurrently, the pro-survival protein Bcl-2's expression level was very much down-regulated in the same two doses favoring the internal microenvironment to proceed for apoptosis. High expression of cytochrome c and Apaf-1 and the presence of active caspase-9 and active caspase-3 in all the T11TS-treated tumor-bearing groups further adjudicated apoptosis of the glioma cells with clear involvement of mitochondrial death pathway in the T11TS-treated animals. Even though expression of the apoptotic regulators remained more or less the same indicating the involvement of mitochondria in the two interacting immunocytes, the intensity of expression of these proteins was much lower than the tumor cells. The present work focuses on the

Lessons Learned from Sleep Education in Schools: A Review of Dos and Don'ts

PubMed Central

Blunden, Sarah; Rigney, Gabrielle

2015-01-01

Study Objectives: Sleep duration and quality are associated with negative neuropsychological and psychosocial outcomes in children and adolescents. However, community awareness of this is low and sleep education programs in schools are attempting to address this issue. Several studies now exist assessing the efficacy of these sleep education programs for improving sleep knowledge, sleep hygiene and sleep patterns. This paper presents these sleep education programs, most particularly, it presents the strengths and weaknesses of the current available studies in the hope that this can identify areas where future sleep education programs can improve. Methods: A systematic search of all school-based sleep education studies in adolescents was undertaken. Studies were scrutinized for author, teacher and participant comment regarding strengths and limitations of each study, which were then extracted and summarized. Results: Two specific types of sleep education programs emerged from the review, those that sought to change sleep behavior and those that sought simply to disseminate information. Issues that dictated the strength or weakness of a particular study including who delivers the program, the theoretical basis, the tools utilized to measure sleep patterns, the content, and their capacity to engage students were assessed. Sleep education was considered important by teachers, students and parents alike. Conclusions: Future sleep education programs need to take into account lessons learned from previous sleep education efforts in order to maximize the potential for sleep education programs to improve the sleep health of our young people. Commentary: A commentary on this article appears in this issue on page 595. Citation: Blunden S, Rigney G. Lessons learned from sleep education in schools: a review of dos and don'ts. J Clin Sleep Med 2015;11(6):671–680. PMID:25766709

Morphological alterations in the hippocampus of the Ts65Dn mouse model for Down Syndrome correlate with structural plasticity markers.

PubMed

Villarroya, Olga; Ballestín, Raúl; López-Hidalgo, Rosa; Mulet, Maria; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan; Gilabert-Juan, Javier; Varea, Emilio

2018-01-01

Down syndrome (DS) is the most common chromosomal aneuploidy. Although trisomy on chromosome 21 can display variable phenotypes, there is a common feature among all DS individuals: the presence of intellectual disability. This condition is partially attributed to abnormalities found in the hippocampus of individuals with DS and in the murine model for DS, Ts65Dn. To check if all hippocampal areas were equally affected in 4-5 month adult Ts65Dn mice, we analysed the morphology of dentate gyrus granule cells and cornu ammonis pyramidal neurons using Sholl method on Golgi-Cox impregnated neurons. Structural plasticity has been analysed using immunohistochemistry for plasticity molecules followed by densitometric analysis (Brain Derived Neurotrophic Factor (BDNF), Polysialylated form of the Neural Cell Adhesion Molecule (PSA-NCAM) and the Growth Associated Protein 43 (GAP43)). We observed an impairment in the dendritic arborisation of granule cells, but not in the pyramidal neurons in the Ts65Dn mice. When we analysed the expression of molecules related to structural plasticity in trisomic mouse hippocampus, we observed a reduction in the expression of BDNF and PSA-NCAM, and an increment in the expression of GAP43. These alterations were restricted to the regions related to dentate granule cells suggesting an interrelation. Therefore the impairment in dendritic arborisation and molecular plasticity is not a general feature of all Down syndrome principal neurons. Pharmacological manipulations of the levels of plasticity molecules could provide a way to restore granule cell morphology and function.

MTHFR, TS and XRCC1 genetic variants may affect survival in patients with myelodysplastic syndromes treated with supportive care or azacitidine.

PubMed

Visani, G; Loscocco, F; Ruzzo, A; Galimberti, S; Graziano, F; Voso, M T; Giacomini, E; Finelli, C; Ciabatti, E; Fabiani, E; Barulli, S; Volpe, A; Magro, D; Piccaluga, P; Fuligni, F; Vignetti, M; Fazi, P; Piciocchi, A; Gabucci, E; Rocchi, M; Magnani, M; Isidori, A

2017-12-05

We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0.001; P=0.026; P=0.058; P=0.024). MTHFR 677T/T, TS 3'-UTR -6 bp/-6 bp and XRCC1 399G/G genotypes were associated with short survival in patients receiving azacitidine by multivariate analysis (P<0.001; P=0.004; P=0.002). We then performed an exploratory analysis to evaluate the effect of the simultaneous presence of multiple adverse variant genotypes. Interestingly, patients with ⩾1 adverse genetic variants had a short survival, independently from their International Prognostic Scoring System (IPSS) and therapy received. To our knowledge, this is the first study showing that polymorphisms in folate-metabolizing pathway, DNA synthesis and DNA repair genes could influence survival of MDS patients.The Pharmacogenomics Journal advance online publication, 5 December 2017; doi:10.1038/tpj.2017.48.

PiTS-1: Carbon Partitioning in Loblolly Pine after 13C Labeling and Shade Treatments

DOE Data Explorer

Warren, J. M.; Iversen, C. M.; Garten, Jr., C. T.; Norby, R. J.; Childs, J.; Brice, D.; Evans, R. M.; Gu, L.; Thornton, P.; Weston, D. J.

2013-01-01

The PiTS task was established with the objective of improving the C partitioning routines in existing ecosystem models by exploring mechanistic model representations of partitioning tested against field observations. We used short-term field manipulations of C flow, through 13CO2 labeling, canopy shading and stem girdling, to dramatically alter C partitioning, and resultant data are being used to test model representation of C partitioning processes in the Community Land Model (CLM4 or CLM4.5).

Factors Influencing the Transition to a New Leadership Position in Serbian Armed Forces Organizational Units

DTIC Science & Technology

2014-12-12

staff group/section to be efficient?) 3. Koji unutršnji faktori najviše utiču na rad grupe/odseka u Generalštabu? (What, within the command, most...influences the staff group/section’s performance?) 4. Koji spoljni faktori najviše utiču na rad grupe/odseka u Generalštabu? (What, from...dužnosti načelnika grupe/odseka u Generalštabu uspešan? (What are the indicators that successful transition has occurred?) 7. Koji unutrašnji

BiGGEsTS: integrated environment for biclustering analysis of time series gene expression data

PubMed Central

Gonçalves, Joana P; Madeira, Sara C; Oliveira, Arlindo L

2009-01-01

Background The ability to monitor changes in expression patterns over time, and to observe the emergence of coherent temporal responses using expression time series, is critical to advance our understanding of complex biological processes. Biclustering has been recognized as an effective method for discovering local temporal expression patterns and unraveling potential regulatory mechanisms. The general biclustering problem is NP-hard. In the case of time series this problem is tractable, and efficient algorithms can be used. However, there is still a need for specialized applications able to take advantage of the temporal properties inherent to expression time series, both from a computational and a biological perspective. Findings BiGGEsTS makes available state-of-the-art biclustering algorithms for analyzing expression time series. Gene Ontology (GO) annotations are used to assess the biological relevance of the biclusters. Methods for preprocessing expression time series and post-processing results are also included. The analysis is additionally supported by a visualization module capable of displaying informative representations of the data, including heatmaps, dendrograms, expression charts and graphs of enriched GO terms. Conclusion BiGGEsTS is a free open source graphical software tool for revealing local coexpression of genes in specific intervals of time, while integrating meaningful information on gene annotations. It is freely available at: . We present a case study on the discovery of transcriptional regulatory modules in the response of Saccharomyces cerevisiae to heat stress. PMID:19583847

Opuntia in México: Identifying Priority Areas for Conserving Biodiversity in a Multi-Use Landscape

PubMed Central

Illoldi-Rangel, Patricia; Ciarleglio, Michael; Sheinvar, Leia; Linaje, Miguel; Sánchez-Cordero, Victor; Sarkar, Sahotra

2012-01-01

Background México is one of the world's centers of species diversity (richness) for Opuntia cacti. Yet, in spite of their economic and ecological importance, Opuntia species remain poorly studied and protected in México. Many of the species are sparsely but widely distributed across the landscape and are subject to a variety of human uses, so devising implementable conservation plans for them presents formidable difficulties. Multi–criteria analysis can be used to design a spatially coherent conservation area network while permitting sustainable human usage. Methods and Findings Species distribution models were created for 60 Opuntia species using MaxEnt. Targets of representation within conservation area networks were assigned at 100% for the geographically rarest species and 10% for the most common ones. Three different conservation plans were developed to represent the species within these networks using total area, shape, and connectivity as relevant criteria. Multi–criteria analysis and a metaheuristic adaptive tabu search algorithm were used to search for optimal solutions. The plans were built on the existing protected areas of México and prioritized additional areas for management for the persistence of Opuntia species. All plans required around one–third of México's total area to be prioritized for attention for Opuntia conservation, underscoring the implausibility of Opuntia conservation through traditional land reservation. Tabu search turned out to be both computationally tractable and easily implementable for search problems of this kind. Conclusions Opuntia conservation in México require the management of large areas of land for multiple uses. The multi-criteria analyses identified priority areas and organized them in large contiguous blocks that can be effectively managed. A high level of connectivity was established among the prioritized areas resulting in the enhancement of possible modes of plant dispersal as well as only a small number

Cast Care: Do's and Don'ts

MedlinePlus

... the healing process. Derby R, et al. General principles of acute fracture management. https://uptodate.com/contents/search. Accessed Jan. 25, 2018. Eiff MP, et al. General principles of fracture care. In: Fracture Management for Primary Care, Updated Edition. 3rd ed. Philadelphia, ...

Searching for new scalar bosons via triple-top signature in cg → tS0 → tt t bar

NASA Astrophysics Data System (ADS)

Kohda, Masaya; Modak, Tanmoy; Hou, Wei-Shu

2018-01-01

The alignment phenomenon, that the 125 GeV h0 boson so resembles the Standard Model Higgs boson, can be understood in a two Higgs doublet model without discrete symmetry. New Yukawa couplings ρtt and ρtc offer new avenues to discover the extra scalar H0 and pseudoscalar A0. We propose to search for cg → tH0, tA0 followed by H0, A0 → t t bar , t c bar , where same-sign dileptons could be the harbinger, with triple-top, in the signature of three leptons plus three b-jets, as confirmation. Discovery could touch upon the origin of baryon asymmetry of the Universe.

Role of Hemidivisional Corneal Topographic Astigmatisms (CorTs) in the Regularization and Reduction of Irregular Astigmatism.

PubMed

Alpins, Noel; Ong, James K Y; Stamatelatos, George

2018-03-01

To demonstrate how the concept of hemidivisional corneal topographic astigmatism (hemiCorT) enables the planning of hemidivisional corneal treatments to reduce irregularity and overall astigmatism. Whole-of-cornea corneal topographic astigmatism (CorT) is calculated from topography data derived from a corneal topographer or tomographer. The cornea is conceptually divided into 2 hemidivisions along the flat meridian of the CorT. For each hemidivision, hemiCorTs are calculated. The regularization treatment for each hemidivision is the treatment required to target the whole-of-cornea CorT, which is a symmetrical orthogonal corneal astigmatism. The regularization is then combined with astigmatism reduction treatment, which could be a conventional refractive treatment or a vector-planned treatment. For each hemidivision, the combined astigmatic effect of the regularization treatment and reduction treatment can be determined through double-angle vector summation. The 2 hemidivisional treatments together regularize and reduce corneal astigmatism. A theoretical pair of hemidivisional treatments is derived from an actual example of a cornea displaying idiopathic asymmetric nonorthogonal astigmatism. HemiCorTs allow for the design of hemidivisional corneal treatments of asymmetric nonorthogonal astigmatism. Such treatments should be suitable in the routine treatment of commonly occurring irregular astigmatism, while also allowing the spherical refractive error to be treated concurrently.

Effective management of an advanced gastric cancer patient by TS-1 combined chemotherapy using nasojejunal tube and successful transfer to home care after percutaneous transesophageal gastro-tubing (PTEG): a case report.

PubMed

Okita, Atsushi; Miyade, Yoshio; Okano, Kazuo

2010-02-01

A 67-year-old woman with debilitation and massive ascites was admitted to our hospital and diagnosed with stage IV scirrhous gastric cancer with peritoneal dissemination. After successful nasojejunal tube feeding because of oral intake disability, TS-1 combined with paclitaxel chemotherapy was selected. TS-1 at 80mg/m2 was given daily via nasojejunal tube for 2 weeks, followed by a 1-week rest, and paclitaxel at 50mg/m2 was administered intravenously on day 1 and 8. There were no serious side effects. After 4 cycles, a partial response was observed and percutaneous transesophageal gastrotubing (PTEG) was placed. After the fifth cycle, she was transferred to her home and received chemotherapy in an outpatient clinic. After 7 cycles, the disease progressed, and TS-1 combined with low-dose cisplatin was administered for 3 cycles. However, the patient died 16 weeks after discharge. PTEG was useful not only for a route of TS-1 administration, but also for receiving chemotherapy at home to maintain her quality.

Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

PubMed

Stimac, Monika; Dolinsek, Tanja; Lampreht, Ursa; Cemazar, Maja; Sersa, Gregor

2015-01-01

Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β) co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET) (TS plasmid), in comparison to the plasmid with constitutive promoter (CON plasmid), in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET) of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

Parent's perceptions of interactions with health professionals in the pathway to gaining a diagnosis of tuberous sclerosis (TS) and beyond.

PubMed

Whitehead, Lisa C; Gosling, Vashti

2003-01-01

This paper presents selected findings from a qualitative study on the lived experience of young people with tuberous sclerosis (TS) and their families. In-depth interviews with 109 participants from 40 families were undertaken. This paper presents the findings in relation to parents' interactions with health professionals before, during and after a diagnosis of TS was given. The majority of parents recalled examples of both positive and negative experiences with health professionals. Negative experiences included having to 'fight' for the recognition of symptoms and the reluctance of doctors to move on beyond a diagnosis of epilepsy. Attributes valued by parents pre-diagnosis included health professionals showing understanding at diagnosis, flexibility, support, accessibility, time and attention, honesty, reliability, sensitivity and post-diagnosis a willingness to find out and share information and to consult colleagues and other professionals. The interviews indicated that these were not always demonstrated by professionals.

Can "Sensibility" Be Re-"Associated"? Reflections on T.S. Eliot and the Possibility of Educating for a Sustainable Environment

ERIC Educational Resources Information Center

Stables, Andrew

2008-01-01

The paper considers T.S. Eliot's "dissociation of sensibility" thesis, considering its philosophical value and attempting to defend it against published objections. While accepting some of the criticisms, it is argued that Eliot's argument is sound to a significant extent. Eliot's account retains explanatory power with regard to an enduring…

Teacher Salary Comparisons--Inter-City Differences: 2010-11 and 2011-12. BCTF Research Report. Section I. 2012-TS-02

ERIC Educational Resources Information Center

White, Margaret

2012-01-01

This research report, which is an update of research report 2011-TS-03, shows the salary difference for each step of British Columbia's (BC) Category 5 or comparable qualifications. Salaries for Vancouver public school teachers are compared to teacher salaries in Toronto (elementary), Ottawa (secondary), and Edmonton. Salaries for Prince George…

Hypoxia-inducible factor-targeting prodrug TOP3 combined with gemcitabine or TS-1 improves pancreatic cancer survival in an orthotopic model.

PubMed

Hoang, Ngoc Thi Hong; Kadonosono, Tetsuya; Kuchimaru, Takahiro; Kizaka-Kondoh, Shinae

2016-08-01

Pancreatic cancer is one of the most lethal digestive system cancers with a 5-year survival rate of 4-7%. Despite extensive efforts, recent chemotherapeutic regimens have provided only limited benefits to pancreatic cancer patients. Gemcitabine and TS-1, the current standard-of-care chemotherapeutic drugs for treatment of this severe cancer, have a low response rate. Hypoxia is one of the factors contributing to treatment resistance. Specifically, overexpression of hypoxia-inducible factor, a master transcriptional regulator of cell adaption to hypoxia, is strongly correlated with poor prognosis in many human cancers. TAT-ODD-procaspase-3 (TOP3) is a protein prodrug that is specifically processed and activated in hypoxia-inducible factor-active cells in cancers, leading to cell death. Here, we report combination therapies in which TOP3 was combined with gemcitabine or TS-1. As monotherapy, gemcitabine and TS-1 showed a limited effect on hypoxic and starved pancreatic cancer cells, whereas co-treatment with TOP3 successfully overcame this limitation in vitro. Furthermore, combination therapies of TOP3 with these drugs resulted in a significant improvement in survival of orthotopic pancreatic cancer models involving the human pancreatic cancer cell line SUIT-2. Overall, our study indicates that the combination of TOP3 with current chemotherapeutic drugs can significantly improve treatment outcome, offering a promising new therapeutic option for patients with pancreatic cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome

PubMed Central

Kazim, Syed Faraz; Blanchard, Julie; Bianchi, Riccardo; Iqbal, Khalid

2017-01-01

Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model. PMID:28368015

An expert protocol for immunofluorescent detection of calcium channels in tsA-201 cells.

PubMed

Koch, Peter; Herzig, Stefan; Matthes, Jan

Pore-forming subunits of voltage gated calcium channels (VGCC) are large membrane proteins (260kDa) containing 24 transmembrane domains. Despite transfection with viral promoter driven vectors, biochemical analysis of VGCC is often hampered by rather low expression levels in heterologous systems rendering VGCC challenging targets. Especially in immunofluorescent detection, calcium channels are demanding proteins. We provide an expert step-by-step protocol with adapted conditions for handling procedures (tsA-201 cell culture, transient transfection, incubation time and temperature at 28°C or 37°C and immunostaining) to address the L-type calcium-channel pore Ca v 1.2 in an immunofluorescent approach. We performed immunocytochemical analysis of Ca v 1.2 expression at single-cell level in combination with detection of different markers for cellular organelles. We show confluency levels and shapes of tsA-201 cells at different time points during an experiment. Our experiments reveal sufficient levels of Ca v 1.2 protein and a correct Ca v 1.2 expression pattern in polygonal shaped cells already 12h after transfection. A sequence of elaborated protocol modifications allows subcellular localization analysis of Ca v 1.2 in an immunocytochemical approach. We provide a protocol that may be used to achieve insights into physiological and pathophysiological processes involving voltage gated calcium channels. Our protocol may be used for expression analysis of other challenging proteins and efficient overexpression may be exploited in related biochemical techniques requiring immunolabels. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic evolutionary taboo search for optimal marker placement in infrared patient setup

NASA Astrophysics Data System (ADS)

Riboldi, M.; Baroni, G.; Spadea, M. F.; Tagaste, B.; Garibaldi, C.; Cambria, R.; Orecchia, R.; Pedotti, A.

2007-09-01

In infrared patient setup adequate selection of the external fiducial configuration is required for compensating inner target displacements (target registration error, TRE). Genetic algorithms (GA) and taboo search (TS) were applied in a newly designed approach to optimal marker placement: the genetic evolutionary taboo search (GETS) algorithm. In the GETS paradigm, multiple solutions are simultaneously tested in a stochastic evolutionary scheme, where taboo-based decision making and adaptive memory guide the optimization process. The GETS algorithm was tested on a group of ten prostate patients, to be compared to standard optimization and to randomly selected configurations. The changes in the optimal marker configuration, when TRE is minimized for OARs, were specifically examined. Optimal GETS configurations ensured a 26.5% mean decrease in the TRE value, versus 19.4% for conventional quasi-Newton optimization. Common features in GETS marker configurations were highlighted in the dataset of ten patients, even when multiple runs of the stochastic algorithm were performed. Including OARs in TRE minimization did not considerably affect the spatial distribution of GETS marker configurations. In conclusion, the GETS algorithm proved to be highly effective in solving the optimal marker placement problem. Further work is needed to embed site-specific deformation models in the optimization process.

Thermal Power Of The TS-300B Refrigerator in the Aspects of Statistical Research / Moc Cieplna Chłodziarki TS-300B W Aspekcie Badań Statystycznych

NASA Astrophysics Data System (ADS)

Nowak, Bernard; Łuczak, Rafał

2015-09-01

The article discusses the improvement of thermal working conditions in underground mine workings, using local refrigeration systems. It considers the efficiency of air cooling with direct action air compression refrigerator of the TS-300B type. As a result of a failure to meet the required operating conditions of the aforementioned air cooling system, frequently there are discrepancies between the predicted (and thus the expected) effects of its work and the reality. Therefore, to improve the operating efficiency of this system, in terms of effective use of the evaporator cooling capacity, quality criteria were developed, which are easy in practical application. They were obtained in the form of statistical models, describing the effect of independent variables, i.e. the parameters of the inlet air to the evaporator (temperature, humidity and volumetric flow rate), as well as the parameters of the water cooling the condenser (temperature and volumetric flow rate), on the thermal power of air cooler, treated as the dependent variable. Statistical equations describing the performance of the analyzed air cooling system were determined, based on the linear and nonlinear multiple regression. The obtained functions were modified by changing the values of the coefficients in the case of linear regression, and of the coefficients and exponents in the case of non-linear regression, with the independent variables. As a result, functions were obtained, which were more convenient in practical applications. Using classical statistics methods, the quality of fitting the regression function to the experimental data was evaluated. Also, the values of the evaporator thermal power of the refrigerator, which were obtained on the basis of the measured air parameters, were compared with the calculated ones, by using the obtained regression functions. These statistical models were built on the basis of the results of measurements in different operating conditions of the TS-300B

A Tabu-Search Heuristic for Deterministic Two-Mode Blockmodeling of Binary Network Matrices

ERIC Educational Resources Information Center

Brusco, Michael; Steinley, Douglas

2011-01-01

Two-mode binary data matrices arise in a variety of social network contexts, such as the attendance or non-attendance of individuals at events, the participation or lack of participation of groups in projects, and the votes of judges on cases. A popular method for analyzing such data is two-mode blockmodeling based on structural equivalence, where…

[Actuator placement for active sound and vibration control

NASA Technical Reports Server (NTRS)

1997-01-01

Two refereed journal publications and ten talks given at conferences, seminars, and colloquia resulted from research supported by NASA. They are itemized in this report. The two publications were entitled "Reactive Tabu and Search Sensor Selection in Active Structural Acoustic Control Problems" and "Quelling Cabin Noise in Turboprop Aircraft via Active Control." The conference presentations covered various aspects of actuator placement, including location problems, for active sound and vibration control of cylinders, of commuter jets, of propeller driven or turboprop aircraft, and for quelling aircraft cabin or interior noise.

Comparison of the Protective Effects of Individual Components of Particulated trans-Sialidase (PTCTS), PTC and TS, against High Cholesterol Diet-Induced Atherosclerosis in Rabbits.

PubMed

Garavelo, Shérrira M; Higuchi, Maria de Lourdes; Pereira, Jaqueline J; Reis, Marcia M; Kawakami, Joyce T; Ikegami, Renata N; Palomino, Suely A P; Wadt, Nilsa S Y; Agouni, Abdelali

2017-01-01

Previous studies showed the presence of Mycoplasma pneumoniae ( M. pneumoniae ) and membrane-shed microparticles (MPs) in vulnerable atherosclerotic plaques. H&S Science and Biotechnology developed PTCTS, composed by natural particles from medicinal plants (PTC) combined with trans -Sialidase (TS), to combat MPs and Mycoplasma pneumoniae . Our aim was to determine the effects of the different components of PTCTS in a rabbit model of atherosclerosis. Rabbits were fed with high cholesterol diet for 12 weeks and treated during the last 6 weeks with either vehicle, PTC, TS, or PTCTS. Lipid profile and quantification of MPs positive for Mycoplasma pneumoniae and oxidized LDL antigens were carried out. Aortas and organs were then histologically analyzed. PTCTS reduced circulating MPs positive for Mycoplasma pneumoniae and oxidized LDL antigens, reduced the plaque area in the abdominal aorta, and caused positive remodeling of the ascendant aorta. PTC caused positive remodeling and reduced plaque area in the abdominal aorta; however, TS had a lipid lowering effect. PTCTS components combined were more effective against atherosclerosis than individual components. Our data reinforce the infectious theory of atherosclerosis and underscore the potential role of circulating MPs. Therefore, the removal of Mycoplasma -derived MPs could be a new therapeutic approach in the treatment of atherosclerosis.

Making Home Sweet and Sturdy: Toxoplasma gondii ppGalNAc-Ts Glycosylate in Hierarchical Order and Confer Cyst Wall Rigidity

PubMed Central

Tomita, Tadakimi; Sugi, Tatsuki; Yakubu, Rama; Tu, Vincent; Ma, Yanfen

2017-01-01

ABSTRACT The protozoan intracellular parasite Toxoplasma gondii forms latent cysts in the central nervous system (CNS) and persists for the lifetime of the host. This cyst is cloaked with a glycosylated structure called the cyst wall. Previously, we demonstrated that a mucin-like glycoprotein, CST1, localizes to the cyst wall and confers structural rigidity on brain cysts in a mucin-like domain-dependent manner. The mucin-like domain of CST1 is composed of 20 units of threonine-rich tandem repeats that are O-GalNAc glycosylated. A family of enzymes termed polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) initiates O-GalNAc glycosylation. To identify which isoforms of ppGalNAc-Ts are responsible for the glycosylation of the CST1 mucin-like domain and to evaluate the function of each ppGalNAc-T in the overall glycosylation of the cyst wall, all five ppGalNAc-T isoforms were deleted individually from the T. gondii genome. The ppGalNAc-T2 and -T3 deletion mutants produced various glycosylation defects on the cyst wall, implying that many cyst wall glycoproteins are glycosylated by T2 and T3. Both T2 and T3 glycosylate the CST1 mucin-like domain, and this glycosylation is necessary for CST1 to confer structural rigidity on the cyst wall. We established that T2 is required for the initial glycosylation of the mucin-like domain and that T3 is responsible for the sequential glycosylation on neighboring acceptor sites, demonstrating hierarchical glycosylation by two distinct initiating and filling-in ppGalNAc-Ts in an intact organism. PMID:28074022

ssaD1, a suppressor of secA51(Ts) that renders growth of Escherichia coli cold sensitive, is an early amber mutation in the transcription factor gene nusB.

PubMed Central

Rajapandi, T.; Oliver, D.

1994-01-01

Complementation analysis of the ssaD1 mutation, isolated as a suppressor of the secA51(Ts) mutation that renders growth of Escherichia coli cold sensitive, was used to show that ssaD corresponds to nusB, a gene known to be important in transcription antitermination. DNA sequence analysis of the ssaD1 allele showed that it creates an amber mutation in the 15th codon of nusB. Analysis of the effect of different levels of NusB protein on secA transcription and translation suggested that NusB plays little or no role in the control of secA expression. Accordingly, mechanisms by which nusB inactivation can lead to suppression of secA51(Ts) and secY24(Ts) mutations without affecting secA expression need to be considered. PMID:8021230

Bactericidal activity of culture fluid components of Lactobacillus fermentum strain 90 TS-4 (21) clone 3, and their capacity to modulate adhesion of Candida albicans yeast-like fungi to vaginal epithelial cells.

PubMed

Anokhina, I V; Kravtsov, E G; Protsenko, A V; Yashina, N V; Yermolaev, A V; Chesnokova, V L; Dalin, M V

2007-03-01

Antagonistic activities of L. fermentum strain 90 TS-4 (21), L. casei ATCC 27216, and L. acidophilus ATCC 4356 and bactericidal activity of lactobacillus culture fluid towards E. coli strain K12, S. aureus, and S. epidermidis test cultures were studied. The bactericidal effect of L. fermentum strain 90 TS-4 (21) clone 3 culture fluid preparation (pH 6.0) on the test cultures was dose-dependent. Adhesion of C. albicans yeast-like fungi to vaginal epitheliocytes was more pronounced for strains isolated from women with asymptomatic infection than for strains isolated from women with manifest forms. L. fermentum strain 90 TS-4 (21) clone 3 culture fluid preparation modulated adhesion of yeast-like fungi only if the fungal strain was initially highly adherent.

Influence of TS (rs34743033) and RUNX1 (rs2014300) gene polymorphisms on survival outcomes of fluorouracil-based chemotherapy in Chinese advanced gastric cancer patients.

PubMed

Han, Rongbo; Wei, Jingsun; Zhang, Honghong; Su, Xinyu; Chu, Xia; Chen, Yuetong; Gong, Yang; Wang, Xiujuan; Shi, Junfeng; Chen, Jinfei

2018-01-01

This study aimed to explore the clinical correlation of single-nucleotide polymorphisms of thymidylate synthase (TS) and runt-related transcription factor 1 (RUNX1) in patients with postoperative stage II and III gastric cancer (GC). Samples were obtained from 661 patients with postoperative stage II and III GC. TS (rs34743033) and RUNX1 (rs2014300) were genotyped in 261 patients who received postoperative basic platinum and fluorouracil chemotherapy regimens and 400 patients who did not accept chemotherapy. TS (rs34743033) variant genotypes significantly prolonged the median overall survival (OS) time compared to the patients who only received adjuvant chemotherapy (HR 1.604, 95% CI 1.068-2.410, p =0.021). Moreover, 3R/3R variant genotypes were demonstrated to have a positive effect on the OS of patients who received chemotherapy based on cisplatin (HR 1.754, 95% CI 1.041-2.954, p =0.031) compared to oxaliplatin. A stratification analysis indicated that 2R/3R and 2R/2R variant genotypes were associated with inferior survival in GC patients with intestinal-type tumors, tumor less than 5 cm in size, and poorly differentiated tumors ( p <0.05). However, RUNX1 (rs2014300) AA genotypes markedly increased the risk of death in GC patients compared with the GG/GA genotypes ( p =0.007), but no significant difference was observed between chemotherapy based on platinum. The stratification analysis showed that the GA/AA genotype was significantly associated with inferior survival in well to moderately differentiated tumors (HR 2.001, 95% CI 1.082-3.703, p =0.023). These preliminary results indicated that the two polymorphisms had a significant effect on postoperative adjuvant chemotherapy. TS (rs34743033) and RUNX1 (rs2014300) may be used as biomarkers to predict prognosis and select chemotherapy regimens in GC patients.

Light-cone reduction vs. TsT transformations: a fluid dynamics perspective

NASA Astrophysics Data System (ADS)

Dutta, Suvankar; Krishna, Hare

2018-05-01

We compute constitutive relations for a charged (2+1) dimensional Schrödinger fluid up to first order in derivative expansion, using holographic techniques. Starting with a locally boosted, asymptotically AdS, 4 + 1 dimensional charged black brane geometry, we uplift that to ten dimensions and perform TsT transformations to obtain an effective five dimensional local black brane solution with asymptotically Schrödinger isometries. By suitably implementing the holographic techniques, we compute the constitutive relations for the effective fluid living on the boundary of this space-time and extract first order transport coefficients from these relations. Schrödinger fluid can also be obtained by reducing a charged relativistic conformal fluid over light-cone. It turns out that both the approaches result the same system at the end. Fluid obtained by light-cone reduction satisfies a restricted class of thermodynamics. Here, we see that the charged fluid obtained holographically also belongs to the same restricted class.

Ethnicity, development and gender: Tsáchila indigenous women in Ecuador.

PubMed

Radcliffe, Sarah; Pequeño, Andrea

2010-01-01

In recent decades, indigenous populations have become the subjects and agents of development in national and international multicultural policy that acknowledges poverty among indigenous peoples and their historic marginalization from power over development. Although the impact of these legal and programmatic efforts is growing, one persistent axis of disadvantage, male–female difference, is rarely taken into account in ethno-development policy and practice. This article argues that assumptions that inform policy related to indigenous women fail to engage with indigenous women's development concerns. The institutional separation between gender and development policy (GAD) and multiculturalism means that provisions for gender in multicultural policies are inadequate, and ethnic rights in GAD policies are invisible. Drawing on post-colonial feminism, the paper examines ethnicity and gender as interlocking systems that structure indigenous women's development experiences. These arguments are illustrated in relation to the case of the Tsáchila ethno-cultural group in the South American country of Ecuador.

Uncovering key patterns in self-harm in adolescents: Sequence analysis using the Card Sort Task for Self-harm (CaTS).

PubMed

Townsend, E; Wadman, R; Sayal, K; Armstrong, M; Harroe, C; Majumder, P; Vostanis, P; Clarke, D

2016-12-01

Self-harm is a significant clinical issue in adolescence. There is little research on the interplay of key factors in the months, weeks, days and hours leading to self-harm. We developed the Card Sort Task for Self-harm (CaTS) to investigate the pattern of thoughts, feelings, events and behaviours leading to self-harm. Forty-five young people (aged 13-21 years) with recent repeated self-harm completed the CaTS to describe their first ever/most recent self-harm episode. Lag sequential analysis determined significant transitions in factors leading to self-harm (presented in state transition diagrams). A significant sequential structure to the card sequences produced was observed demonstrating similarities and important differences in antecedents to first and most recent self-harm. Life-events were distal in the self-harm pathway and more heterogeneous. Of significant clinical concern was that the wish to die and hopelessness emerged as important antecedents in the most recent episode. First ever self-harm was associated with feeling better afterward, but this disappeared for the most recent episode. Larger sample sizes are necessary to examine longer chains of sequences and differences in genders, age and type of self-harm. The sample was self-selected with 53% having experience of living in care. The CaTs offers a systematic approach to understanding the dynamic interplay of factors that lead to self-harm in young people. It offers a method to target key points for intervention in the self-harm pathway. Crucially the factors most proximal to self-harm (negative emotions, impulsivity and access to means) are modifiable with existing clinical interventions. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

On the Cause of Eastern Equatorial Pacific Ocean T-S Variations Associated with El Nino

NASA Technical Reports Server (NTRS)

Wang, Ou; Fukumori, Ichiro; Lee, Tong; Cheng, Benny

2004-01-01

The nature of observed variations in temperature-salinity (T-S) relationship between El Nino and non-El Nino years in the pycnocline of the eastern equatorial Pacific Ocean (NINO3 region, 5(deg)S-5(deg)N, 150(deg)W-90(deg)W) is investigated using an ocean general circulation model. The origin of the subject water mass is identified using the adjoint of a simulated passive tracer. The higher salinity during El Nino is attributed to larger convergence of saltier water from the Southern Hemisphere and smaller convergence of fresher water from the Northern Hemisphere.

On the asymptotic optimality and improved strategies of SPTB heuristic for open-shop scheduling problem

NASA Astrophysics Data System (ADS)

Bai, Danyu; Zhang, Zhihai

2014-08-01

This article investigates the open-shop scheduling problem with the optimal criterion of minimising the sum of quadratic completion times. For this NP-hard problem, the asymptotic optimality of the shortest processing time block (SPTB) heuristic is proven in the sense of limit. Moreover, three different improvements, namely, the job-insert scheme, tabu search and genetic algorithm, are introduced to enhance the quality of the original solution generated by the SPTB heuristic. At the end of the article, a series of numerical experiments demonstrate the convergence of the heuristic, the performance of the improvements and the effectiveness of the quadratic objective.

Development and validation of the functional assessment of chronic illness therapy treatment satisfaction (FACIT TS) measures.

PubMed

Peipert, John D; Beaumont, Jennifer L; Bode, Rita; Cella, Dave; Garcia, Sofia F; Hahn, Elizabeth A

2014-04-01

To develop and validate a new functional assessment of chronic illness therapy (FACIT) measure of satisfaction with treatment for chronic illnesses such as cancer and HIV/AIDS. To define domains and generate items, a literature review informed creation of semi-structured interview guides for patients and an international expert panel of clinicians and researchers. Patients and experts also rated 15 areas of satisfaction for relevance. The final list of items underwent further refinement by the original expert panel and a new group of clinical experts. Items were tested in four studies (primarily lung cancer) and data were pooled for analysis. Exploratory and confirmatory factor analyses (CFA), and item response theory modeling were conducted to evaluate dimensionality. Internal consistency reliability and test-retest reliability were both evaluated. Validity was evaluated by correlating the FACIT subscale scores and measures of comparable concepts and by testing the scales' ability to distinguish people according to their overall treatment satisfaction. Two instruments were created: the FACIT TS-general (G), an overall evaluation of current treatment, and the FACIT TS-patient satisfaction (PS), a measure of patient satisfaction. CFA results were not optimal for a five-factor solution for PS. Internal consistency reliability met psychometric standards (≥0.70) for all PS subscales. Construct validity was established for the PS subscales: Physician Communication, Treatment Staff Communication, Technical Competence, Confidence and Trust, and Nurse Communication. The two instruments generated here offer a new way to assess several key dimensions of patient satisfaction with treatment, especially for people with lung cancer.

Defective Hematopoietic Stem Cell and Lymphoid Progenitor Development in the Ts65Dn Mouse Model of Down Syndrome: Potential Role of Oxidative Stress

PubMed Central

Lorenzo, Laureanne Pilar E.; Chen, Haiyan; Shatynski, Kristen E.; Clark, Sarah; Yuan, Rong; Harrison, David E.; Yarowsky, Paul J.

2011-01-01

Abstract Aims Down Syndrome (DS), a genetic disease caused by a triplication of chromosome 21, is characterized by increased markers of oxidative stress. In addition to cognitive defects, patients with DS also display hematologic disorders and increased incidence of infections and leukemia. Using the Ts65Dn mouse model of DS, the goal of this study was to examine hematopoietic stem and lymphoid progenitor cell function in DS. Results Analysis of hematopoietic progenitor populations showed that Ts65Dn mice possessed fewer functional hematopoietic stem cells and a significantly decreased percentage of bone marrow lymphoid progenitors. Increased reactive oxygen species and markers of oxidative stress were detected in hematopoietic stem cell populations and were associated with a loss of quiescence. Bone marrow progenitor populations expressed diminished levels of the IL-7Rα chain, which was associated with decreased proliferation and increased apoptosis. Modulating oxidative stress in vitro suggested that oxidative stress selectively leads to decreased IL-7Rα expression, and inhibits the survival of IL-7Rα-expressing hematopoietic progenitors, potentially linking increased reactive oxygen species and immunopathology. Innovation The study results identify a link between oxidative stress and diminished IL-7Rα expression and function. Further, the data suggest that this decrease in IL-7Rα is associated with defective hematopoietic development in Down Syndrome. Conclusion The data suggest that hematopoietic stem and lymphoid progenitor cell defects underlie immune dysfunction in DS and that increased oxidative stress and reduced cytokine signaling may alter hematologic development in Ts65Dn mice. Antioxid. Redox Signal. 15, 2083–2094. PMID:21504363

A hybrid approach for integrated healthcare cooperative purchasing and supply chain configuration.

PubMed

Rego, Nazaré; Claro, João; Pinho de Sousa, Jorge

2014-12-01

This paper presents an innovative and flexible approach for recommending the number, size and composition of purchasing groups, for a set of hospitals willing to cooperate, while minimising their shared supply chain costs. This approach makes the financial impact of the various cooperation alternatives transparent to the group and the individual participants, opening way to a negotiation process concerning the allocation of the cooperation costs and gains. The approach was developed around a hybrid Variable Neighbourhood Search (VNS)/Tabu Search metaheuristic, resulting in a flexible tool that can be applied to purchasing groups with different characteristics, namely different operative and market circumstances, and to supply chains with different topologies and atypical cost characteristics. Preliminary computational results show the potential of the approach in solving a broad range of problems.

High-beta spherical tokamak startup in TS-4 merging experiment by use of toroidal field ramp-up

NASA Astrophysics Data System (ADS)

Kaminou, Yasuhiro; , Toru, II; Kato, Joji; Inomoto, Michiaki; Ono, Yasushi; TS Group Team; National InstituteFusion Science Collaboration

2014-10-01

We demonstrated the formation method of an ultrahigh-beta spherical tokamak by use of a field-reversed configuration and a spheromak in TS-4 device (R ~ 0.5 m, A ~ 1.5, Ip ~ 30-100 kA, B ~ 100 mT). This method is composed of the following steps: 1. Two spheromaks are merged together and a high-beta spheromak or FRC is formed by reconnection heating. 2. External toroidal magnetic field is added (current rising time ~50 μs), and spherical tokamak-like configuration is formed. In this way, the ultrahigh-beta ST is formed. The ultrahigh-beta ST formed by FRC has a diamagnetic toroidal field, and it presumed to be in a second-stable state for ballooning stability, and the one formed by spheromak has a weak paramagnetic toroidal magnetic field, while a spheormak has a strong paramagnetic toroidal magnetic field. This diamagnetic current derives from inductive electric field by ramping up the external toroidal magnetic field, and the diamagnetic current sustains high thermal pressure of the ultrahigh-beta spherical tokamak. And the beta of the ultrahigh-beta ST formed by FRC reaches about 50%. To sustain the high-beta state, 0.6 MW neutral beam injection and center solenoid coils are installed to the TS-4 device. In the poster, we report the experimental results of ultrahigh-beta spherical tokamak startup and sustainment by NBI and CS current driving experiment.

Mechanistic insights into heterogeneous methane activation

DOE PAGES

Latimer, Allegra A.; Aljama, Hassan; Kakekhani, Arvin; ...

2017-01-11

While natural gas is an abundant chemical fuel, its low volumetric energy density has prompted a search for catalysts able to transform methane into more useful chemicals. This search has often been aided through the use of transition state (TS) scaling relationships, which estimate methane activation TS energies as a linear function of a more easily calculated descriptor, such as final state energy, thus avoiding tedious TS energy calculations. It has been shown that methane can be activated via a radical or surface-stabilized pathway, both of which possess a unique TS scaling relationship. Herein, we present a simple model tomore » aid in the prediction of methane activation barriers on heterogeneous catalysts. Analogous to the universal radical TS scaling relationship introduced in a previous publication, we show that a universal TS scaling relationship that transcends catalysts classes also seems to exist for surface-stabilized methane activation if the relevant final state energy is used. We demonstrate that this scaling relationship holds for several reducible and irreducible oxides, promoted metals, and sulfides. By combining the universal scaling relationships for both radical and surface-stabilized methane activation pathways, we show that catalyst reactivity must be considered in addition to catalyst geometry to obtain an accurate estimation for the TS energy. Here, this model can yield fast and accurate predictions of methane activation barriers on a wide range of catalysts, thus accelerating the discovery of more active catalysts for methane conversion.« less

Mechanistic insights into heterogeneous methane activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latimer, Allegra A.; Aljama, Hassan; Kakekhani, Arvin

While natural gas is an abundant chemical fuel, its low volumetric energy density has prompted a search for catalysts able to transform methane into more useful chemicals. This search has often been aided through the use of transition state (TS) scaling relationships, which estimate methane activation TS energies as a linear function of a more easily calculated descriptor, such as final state energy, thus avoiding tedious TS energy calculations. It has been shown that methane can be activated via a radical or surface-stabilized pathway, both of which possess a unique TS scaling relationship. Herein, we present a simple model tomore » aid in the prediction of methane activation barriers on heterogeneous catalysts. Analogous to the universal radical TS scaling relationship introduced in a previous publication, we show that a universal TS scaling relationship that transcends catalysts classes also seems to exist for surface-stabilized methane activation if the relevant final state energy is used. We demonstrate that this scaling relationship holds for several reducible and irreducible oxides, promoted metals, and sulfides. By combining the universal scaling relationships for both radical and surface-stabilized methane activation pathways, we show that catalyst reactivity must be considered in addition to catalyst geometry to obtain an accurate estimation for the TS energy. Here, this model can yield fast and accurate predictions of methane activation barriers on a wide range of catalysts, thus accelerating the discovery of more active catalysts for methane conversion.« less

Use of Tabu Search in a Solver to Map Complex Networks onto Emulab Testbeds

DTIC Science & Technology

2007-03-01

for. Our PF Chang dinners and Starbuck coffee breaks were pivotal in reconstituting me to take on another day at AFIT. I don’t know how I would’ve done...performance of assign. Option Description Value -s <seed> Random Number Generator Seed varies -P Prune Unsuable Pclasses n/a -H <float> Branching

An Advanced Tabu Search Approach to Solving the Mixed Payload Airlift Load Planning Problem

DTIC Science & Technology

2009-03-01

cargo, and the problem therefore becomes trivial. 3. Shoring: Some cargo requires shoring which is small planks of plywood stacked on top of each...Integer Programming Method In 1989, Kevin Ng examined the bin-packing MPALP for Canada’s C-130 aircraft (Ng 1992). His goal was to move a set of... leadership & ethics [ ] warfighting [ ] international security [ ] doctrine [X] other (specify): Military Airlift

VisSearch: A Collaborative Web Searching Environment

ERIC Educational Resources Information Center

Lee, Young-Jin

2005-01-01

VisSearch is a collaborative Web searching environment intended for sharing Web search results among people with similar interests, such as college students taking the same course. It facilitates students' Web searches by visualizing various Web searching processes. It also collects the visualized Web search results and applies an association rule…

Parameter optimization of differential evolution algorithm for automatic playlist generation problem

NASA Astrophysics Data System (ADS)

Alamag, Kaye Melina Natividad B.; Addawe, Joel M.

2017-11-01

With the digitalization of music, the number of collection of music increased largely and there is a need to create lists of music that filter the collection according to user preferences, thus giving rise to the Automatic Playlist Generation Problem (APGP). Previous attempts to solve this problem include the use of search and optimization algorithms. If a music database is very large, the algorithm to be used must be able to search the lists thoroughly taking into account the quality of the playlist given a set of user constraints. In this paper we perform an evolutionary meta-heuristic optimization algorithm, Differential Evolution (DE) using different combination of parameter values and select the best performing set when used to solve four standard test functions. Performance of the proposed algorithm is then compared with normal Genetic Algorithm (GA) and a hybrid GA with Tabu Search. Numerical simulations are carried out to show better results from Differential Evolution approach with the optimized parameter values.

Potassium N-Iodo p-Toluenesulfonamide (TsNIK, Iodamine-T): A New Reagent for the Oxidation of Hydrazones to Diazo Compounds

PubMed Central

Nicolle, Simon M; Moody, Christopher J

2014-01-01

A new reagent for the oxidation of hydrazones to diazo compounds is described. N-Iodo p-toluenesulfonamide (TsNIK, iodamine-T) allows the preparation of α-diazoesters, α-diazoamides, α-diazoketones and α-diazophosphonates in good yield and in high purity after a simple extractive work-up. α-Diazoesters were also obtained in high yield from the corresponding ketones through a one-pot process of hydrazone formation/oxidation. PMID:24615944

Introducing Online Bibliographic Service to its Users: The Online Presentation

ERIC Educational Resources Information Center

Crane, Nancy B.; Pilachowski, David M.

1978-01-01

A description of techniques for introducing online services to new user groups includes discussion of terms and their definitions, evolution of online searching, advantages and disadvantages of online searching, production of the data bases, search strategies, Boolean logic, costs and charges, "do's and don'ts," and a user search questionnaire. (J…

Combining the bi-Yang-Baxter deformation, the Wess-Zumino term and TsT transformations in one integrable σ-model

NASA Astrophysics Data System (ADS)

Delduc, F.; Hoare, B.; Kameyama, T.; Magro, M.

2017-10-01

A multi-parameter integrable deformation of the principal chiral model is presented. The Yang-Baxter and bi-Yang-Baxter σ-models, the principal chiral model plus a Wess-Zumino term and the TsT transformation of the principal chiral model are all recovered when the appropriate deformation parameters vanish. When the Lie group is SU(2), we show that this four-parameter integrable deformation of the SU(2) principal chiral model corresponds to the Lukyanov model.

The role of polymerase III in conjugation between E. coli K12 donor and recipient strains carrying dnaE ts mutation.

PubMed

Blinkowa, A

1976-01-01

The possible role of DNA polimerase III in conjugation was studied in a series of mutants temperature-sensitive for DNA polymerase III synthesis. The temperature-sensitive DNA mutation called dnaE 486 (ts) prohibits vegetative DNA replication at 41-45 degrees. Transfer of episome and chromosome from temperature-sensitive donor, carrying dnaE mutation to wild-type recipient strains, revertants and dnaE recipients was investigated. In the first two cases the number of Lac+ sexductants being even slightly higher at 43 degrees. Conjugational synthesis accompanying transfer involving the combination of dnaE (ts) thymine dependent and thymine independent donor and recipient strains measured by incorporation of 14C thymine was observed at the restrictive temperature. In the case of conjugation with temperaturesensitive recipient strains a drop of Lac+ sexductants and Pro+ recombinants may be as a result of disturbances in the synthesis of complementary strand in recipient, known to be dependent on pol III. However, the episome investigated by centrifugation in neutral CsC1 gradient after its transfer to the recipient with faulty polymerase III was double stranded (replicated) at the restrictive temperature.

Solderability study of RABiTS-based YBCO coated conductors

NASA Astrophysics Data System (ADS)

Zhang, Yifei; Duckworth, Robert C.; Ha, Tam T.; Gouge, Michael J.

2011-08-01

The solderability of commercially available YBa2Cu3O7-x (YBCO) coated conductors that were made from Rolling Assisted Biaxially Textured Substrates (RABiTS)-based templates was studied. The coated conductors, also known as second-generation (2G) high temperature superconductor (HTS) wires (in the geometry of flat tapes about 4 mm wide), were laminated with copper, brass, or stainless steel strips as stabilizers. To understand the factors that influence their solderability, surface profilometry and scanning electron microscopy were used to characterize the wire surfaces. The solderability of three solders, 52In48Sn, 67Bi33In, and 100In (wt.%), was evaluated using a standard test (IPC/ECA J-STD-002) and with two different commercial fluxes. It was found that the solderability varied with the solder and flux but the three different wires showed similar solderability for a fixed combination of solder and flux. Solder joints of the 2G wires were fabricated using the tools and the procedures recommended by the HTS wire manufacturer. The solder joints were made in a lap-joint geometry and with the superconducting sides of the two wires face-to-face. The electrical resistances of the solder joints were measured at 77 K, and the results were analyzed to qualify the soldering materials and evaluate the soldering process. It was concluded that although the selection of soldering materials affected the resistance of a solder joint, the resistivity of the stabilizer was the dominant factor.

TheoReTS - An information system for theoretical spectra based on variational predictions from molecular potential energy and dipole moment surfaces

NASA Astrophysics Data System (ADS)

Rey, Michaël; Nikitin, Andrei V.; Babikov, Yurii L.; Tyuterev, Vladimir G.

2016-09-01

Knowledge of intensities of rovibrational transitions of various molecules and theirs isotopic species in wide spectral and temperature ranges is essential for the modeling of optical properties of planetary atmospheres, brown dwarfs and for other astrophysical applications. TheoReTS ("Theoretical Reims-Tomsk Spectral data") is an Internet accessible information system devoted to ab initio based rotationally resolved spectra predictions for some relevant molecular species. All data were generated from potential energy and dipole moment surfaces computed via high-level electronic structure calculations using variational methods for vibration-rotation energy levels and transitions. When available, empirical corrections to band centers were applied, all line intensities remaining purely ab initio. The current TheoReTS implementation contains information on four-to-six atomic molecules, including phosphine, methane, ethylene, silane, methyl-fluoride, and their isotopic species 13CH4 , 12CH3D , 12CH2D2 , 12CD4 , 13C2H4, … . Predicted hot methane line lists up to T = 2000 K are included. The information system provides the associated software for spectra simulation including absorption coefficient, absorption and emission cross-sections, transmittance and radiance. The simulations allow Lorentz, Gauss and Voight line shapes. Rectangular, triangular, Lorentzian, Gaussian, sinc and sinc squared apparatus function can be used with user-defined specifications for broadening parameters and spectral resolution. All information is organized as a relational database with the user-friendly graphical interface according to Model-View-Controller architectural tools. The full-featured web application is written on PHP using Yii framework and C++ software modules. In case of very large high-temperature line lists, a data compression is implemented for fast interactive spectra simulations of a quasi-continual absorption due to big line density. Applications for the TheoReTS may

Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a prospective longitudinal test accuracy study to validate new risk scores in women with symptoms of suspected ovarian cancer

PubMed Central

Sundar, Sudha; Rick, Caroline; Dowling, Francis; Au, Pui; Rai, Nirmala; Champaneria, Rita; Stobart, Hilary; Neal, Richard; Davenport, Clare; Mallett, Susan; Sutton, Andrew; Kehoe, Sean; Timmerman, Dirk; Bourne, Tom; Van Calster, Ben; Gentry-Maharaj, Aleksandra; Deeks, Jon

2016-01-01

Introduction Ovarian cancer (OC) is associated with non-specific symptoms such as bloating, making accurate diagnosis challenging: only 1 in 3 women with OC presents through primary care referral. National Institute for Health and Care Excellence guidelines recommends sequential testing with CA125 and routine ultrasound in primary care. However, these diagnostic tests have limited sensitivity or specificity. Improving accurate triage in women with vague symptoms is likely to improve mortality by streamlining referral and care pathways. The Refining Ovarian Cancer Test Accuracy Scores (ROCkeTS; HTA 13/13/01) project will derive and validate new tests/risk prediction models that estimate the probability of having OC in women with symptoms. This protocol refers to the prospective study only (phase III). Methods and analysis ROCkeTS comprises four parallel phases. The full ROCkeTS protocol can be found at http://www.birmingham.ac.uk/ROCKETS. Phase III is a prospective test accuracy study. The study will recruit 2450 patients from 15 UK sites. Recruited patients complete symptom and anxiety questionnaires, donate a serum sample and undergo ultrasound scored as per International Ovarian Tumour Analysis (IOTA) criteria. Recruitment is at rapid access clinics, emergency departments and elective clinics. Models to be evaluated include those based on ultrasound derived by the IOTA group and novel models derived from analysis of existing data sets. Estimates of sensitivity, specificity, c-statistic (area under receiver operating curve), positive predictive value and negative predictive value of diagnostic tests are evaluated and a calibration plot for models will be presented. ROCkeTS has received ethical approval from the NHS West Midlands REC (14/WM/1241) and is registered on the controlled trials website (ISRCTN17160843) and the National Institute of Health Research Cancer and Reproductive Health portfolios. PMID:27507231

Topology optimisation of micro fluidic mixers considering fluid-structure interactions with a coupled Lattice Boltzmann algorithm

NASA Astrophysics Data System (ADS)

Munk, David J.; Kipouros, Timoleon; Vio, Gareth A.; Steven, Grant P.; Parks, Geoffrey T.

2017-11-01

Recently, the study of micro fluidic devices has gained much interest in various fields from biology to engineering. In the constant development cycle, the need to optimise the topology of the interior of these devices, where there are two or more optimality criteria, is always present. In this work, twin physical situations, whereby optimal fluid mixing in the form of vorticity maximisation is accompanied by the requirement that the casing in which the mixing takes place has the best structural performance in terms of the greatest specific stiffness, are considered. In the steady state of mixing this also means that the stresses in the casing are as uniform as possible, thus giving a desired operating life with minimum weight. The ultimate aim of this research is to couple two key disciplines, fluids and structures, into a topology optimisation framework, which shows fast convergence for multidisciplinary optimisation problems. This is achieved by developing a bi-directional evolutionary structural optimisation algorithm that is directly coupled to the Lattice Boltzmann method, used for simulating the flow in the micro fluidic device, for the objectives of minimum compliance and maximum vorticity. The needs for the exploration of larger design spaces and to produce innovative designs make meta-heuristic algorithms, such as genetic algorithms, particle swarms and Tabu Searches, less efficient for this task. The multidisciplinary topology optimisation framework presented in this article is shown to increase the stiffness of the structure from the datum case and produce physically acceptable designs. Furthermore, the topology optimisation method outperforms a Tabu Search algorithm in designing the baffle to maximise the mixing of the two fluids.

A novel heuristic algorithm for capacitated vehicle routing problem

NASA Astrophysics Data System (ADS)

Kır, Sena; Yazgan, Harun Reşit; Tüncel, Emre

2017-09-01

The vehicle routing problem with the capacity constraints was considered in this paper. It is quite difficult to achieve an optimal solution with traditional optimization methods by reason of the high computational complexity for large-scale problems. Consequently, new heuristic or metaheuristic approaches have been developed to solve this problem. In this paper, we constructed a new heuristic algorithm based on the tabu search and adaptive large neighborhood search (ALNS) with several specifically designed operators and features to solve the capacitated vehicle routing problem (CVRP). The effectiveness of the proposed algorithm was illustrated on the benchmark problems. The algorithm provides a better performance on large-scaled instances and gained advantage in terms of CPU time. In addition, we solved a real-life CVRP using the proposed algorithm and found the encouraging results by comparison with the current situation that the company is in.

In Search of Speedier Searches.

ERIC Educational Resources Information Center

Peterson, Ivars

1984-01-01

Methods to make computer searching as simple and efficient as possible have led to the development of various data structures. Data structures specify the items involved in searching and what can be done to them. The nature and advantages of using "self-adjusting" data structures (self-adjusting binary search trees) are discussed. (JN)

Competitive Facility Location with Random Demands

NASA Astrophysics Data System (ADS)

Uno, Takeshi; Katagiri, Hideki; Kato, Kosuke

2009-10-01

This paper proposes a new location problem of competitive facilities, e.g. shops and stores, with uncertain demands in the plane. By representing the demands for facilities as random variables, the location problem is formulated to a stochastic programming problem, and for finding its solution, three deterministic programming problems: expectation maximizing problem, probability maximizing problem, and satisfying level maximizing problem are considered. After showing that one of their optimal solutions can be found by solving 0-1 programming problems, their solution method is proposed by improving the tabu search algorithm with strategic vibration. Efficiency of the solution method is shown by applying to numerical examples of the facility location problems.

Pre-compensation combined with TS-aided and ISFA-enhanced scheme for UWB system

NASA Astrophysics Data System (ADS)

He, Jing; Xiang, Changqing; Long, Fengting; Wu, Kaiquan; Chen, Lin

2017-08-01

In this paper, a pre-compensation combined with training sequence (TS)-aided and intra-symbol frequency-domain averaging (ISFA)-enhanced scheme is proposed to improve the transmission performance in 64-quadrature amplitude modulation multiband orthogonal-frequency-division-multiplexing ultra-wide band over fiber (64QAM MB-OFDM UWBoF) system. We theoretically analyze and experimentally demonstrate that the proposed scheme is suitable for the 64QAM MB-OFDM UWBoF system in contrast with two other cases: (I) only pilot-aided channel estimation and (II) pilot-aided and pre-compensation combined with ISFA-enhanced channel estimation. The experimental results demonstrate that the performance of system with the proposed scheme can be improved by about 1.25 dB and 0.37 dB compared with the case I and the case II, respectively, at the BER of 3.8×10-3 after 70 km transmission in standard single mode fiber (SSMF).

Making Home Sweet and Sturdy: Toxoplasma gondii ppGalNAc-Ts Glycosylate in Hierarchical Order and Confer Cyst Wall Rigidity.

PubMed

Tomita, Tadakimi; Sugi, Tatsuki; Yakubu, Rama; Tu, Vincent; Ma, Yanfen; Weiss, Louis M

2017-01-10

The protozoan intracellular parasite Toxoplasma gondii forms latent cysts in the central nervous system (CNS) and persists for the lifetime of the host. This cyst is cloaked with a glycosylated structure called the cyst wall. Previously, we demonstrated that a mucin-like glycoprotein, CST1, localizes to the cyst wall and confers structural rigidity on brain cysts in a mucin-like domain-dependent manner. The mucin-like domain of CST1 is composed of 20 units of threonine-rich tandem repeats that are O-GalNAc glycosylated. A family of enzymes termed polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) initiates O-GalNAc glycosylation. To identify which isoforms of ppGalNAc-Ts are responsible for the glycosylation of the CST1 mucin-like domain and to evaluate the function of each ppGalNAc-T in the overall glycosylation of the cyst wall, all five ppGalNAc-T isoforms were deleted individually from the T. gondii genome. The ppGalNAc-T2 and -T3 deletion mutants produced various glycosylation defects on the cyst wall, implying that many cyst wall glycoproteins are glycosylated by T2 and T3. Both T2 and T3 glycosylate the CST1 mucin-like domain, and this glycosylation is necessary for CST1 to confer structural rigidity on the cyst wall. We established that T2 is required for the initial glycosylation of the mucin-like domain and that T3 is responsible for the sequential glycosylation on neighboring acceptor sites, demonstrating hierarchical glycosylation by two distinct initiating and filling-in ppGalNAc-Ts in an intact organism. Toxoplasma gondii is an obligate intracellular parasite that infects a third of the world's population. It can cause severe congenital disease and devastating encephalitis in immunocompromised individuals. We identified two glycosyltransferases, ppGalNAc-T2 and -T3, which are responsible for glycosylating cyst wall proteins in a hierarchical fashion. This glycosylation confers structural rigidity on the brain cyst. Our studies provide new

Scientific Communication for Positive Action: Do's and Don'ts

NASA Astrophysics Data System (ADS)

Sanquini, A.; Wood, M. M.

2015-12-01

Natural hazard presentations often highlight disasters that may ensue from natural processes when mitigation or preparedness actions are not taken. Examples include images of raging fires, collapsed buildings, and flooded urban areas. Research has shown that this makes presentations more interesting and more memorable. Such images are the stock and trade of disaster reporting by the media. Unfortunately, it may also trigger avoidance and denial in the audience, resulting in preparedness reduction; the opposite effect of what may have been intended by the speaker. Recent social research has provided insight into a better approach. The theory of communicating actionable risk posits that people will take action against hazards when they know what to do, think it would work, and know someone who did it. This approach was recently applied in an intervention designed to motivate earthquake-resistant construction in Kathmandu Valley, Nepal. Social theory further suggests that a tendency towards action is strengthened by hearing a consistent message over time, and by providing the audience with an appropriate opportunity to seek out relevant information. This presentation shows how, by taking this transdisciplinary step, scientists can make small changes in their hazard communication, thereby acting as positive influencers of change. A summary of "do's" and "don'ts" is given for reference. 1. Show examples of what to do. 2. Show effectiveness of actions. 3. Give sense of knowing someone who did it. 4. Deliver consistent message, repeatedly. 5. Give opportunity for more information. DON'T: 1. Make the disaster the star. 2. Contradict other communications.

Solderability Study of RABiTS-Based YBCO Coated Conductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yifei; Duckworth, Robert C; Ha, Tam T

2011-01-01

The solderability of commercially available YBa{sub 2}Cu{sub 3}O{sub 7-x} (YBCO) coated conductors that were made from Rolling Assisted Biaxially Textured Substrates (RABiTS)-based templates was studied. The coated conductors, also known as second-generation (2G) high temperature superconductor (HTS) wires (in the geometry of flat tapes about 4 mm wide), were laminated with copper, brass, or stainless steel strips as stabilizers. To understand the factors that influence their solderability, surface profilometry and scanning electron microscopy were used to characterize the wire surfaces. The solderability of three solders, 52In48Sn, 67Bi33In, and 100In (wt.%), was evaluated using a standard test (IPC/ECA J-STD-002) and withmore » two different commercial fluxes. It was found that the solderability varied with the solder and flux but the three different wires showed similar solderability for a fixed combination of solder and flux. Solder joints of the 2G wires were fabricated using the tools and the procedures recommended by the HTS wire manufacturer. The solder joints were made in a lap-joint geometry and with the superconducting sides of the two wires face-to-face. The electrical resistances of the solder joints were measured at 77 K, and the results were analyzed to qualify the soldering materials and evaluate the soldering process. It was concluded that although the selection of soldering materials affected the resistance of a solder joint, the resistivity of the stabilizer was the dominant factor.« less

Interrupted Visual Searches Reveal Volatile Search Memory

ERIC Educational Resources Information Center

Shen, Y. Jeremy; Jiang, Yuhong V.

2006-01-01

This study investigated memory from interrupted visual searches. Participants conducted a change detection search task on polygons overlaid on scenes. Search was interrupted by various disruptions, including unfilled delay, passive viewing of other scenes, and additional search on new displays. Results showed that performance was unaffected by…

TS-1 supported highly dispersed sub-5 nm gold nanoparticles toward direct propylene epoxidation using H2 and O2

NASA Astrophysics Data System (ADS)

Li, Naixu; Chen, Yong; Shen, Quanhao; Yang, Bin; Liu, Ming; Wei, Lingfei; Tian, Wei; Zhou, Jiancheng

2018-05-01

We report a simple and efficient method for the preparation of highly dispersed Au nanoparticles (< 5 nm) on TS-1 substrate. The synthesis relies on the use of NaBH4 as a reductant for rapid Au atom generation, as well as PVA as a capping agent confining the particle size and dispersion. The samples were characterized by N2 physisorption, inductively coupled plasma mass spectrometry, power X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, CO pulse chemisorption and thermogravimetric analysis. The size of Au particles can be controlled in the range of 3-5 nm. The supported catalyst shows both good activity and selectivity for propylene oxide (PO) generation from direct propylene epoxidation. An optimal performance with PO formation rate of 102.94 gPO h-1 kg-1cat and selectivity of 84.83% is achieved over 2.0 wt% Au/TS-1 catalyst, which is prepared by controlling PVA/Au3+ mass ratio of 1.5/1 and NaBH4/Au3+ mole ratio of 5/1. After 50 h test at 200 °C, no significant decrement of both catalytic activity and PO selectivity can be observed, indicating the excellent thermally stability of the catalyst. Furthermore, a possible reaction mechanism is described on basis of the previous researches and our experimental results.

Combination TS-1 plus EGFR-tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer after progression on first-line or further EGFR-TKIs: A phase II, single-arm trial.

PubMed

Yang, Lu; Yang, Sheng; Liu, Yutao; Li, Junling; Hu, Xingsheng; Wang, Yalei; Zhang, Yan; Wang, Yan

2018-06-01

EGFR-tyrosine kinase inhibitors (TKIs) combined with TS-1 might overcome EGFR-TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR-TKIs and TS-1 in non-small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR-TKI therapy. This was a phase II, single-arm and single-center prospective study. Stage IIIB-IV NSCLC patients with acquired resistance to prior EGFR-TKI treatment were enrolled. All patients were administered combination therapy of TS-1 and continuing EGFR-TKIs in this study. The primary endpoints were progression-free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints. A total of 42 patients with acquired resistance to EGFR-TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6-5.4). The OS and DCR were 31.9 (95% CI 17.8-46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin. The combination treatment of TS-1 and EGFR-TKIs was effective and well tolerated by patients who had experienced prior EGFR-TKI treatment failure. Our results need to be validated by larger prospective clinical trials. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Maximizing algebraic connectivity in air transportation networks

NASA Astrophysics Data System (ADS)

Wei, Peng

In air transportation networks the robustness of a network regarding node and link failures is a key factor for its design. An experiment based on the real air transportation network is performed to show that the algebraic connectivity is a good measure for network robustness. Three optimization problems of algebraic connectivity maximization are then formulated in order to find the most robust network design under different constraints. The algebraic connectivity maximization problem with flight routes addition or deletion is first formulated. Three methods to optimize and analyze the network algebraic connectivity are proposed. The Modified Greedy Perturbation Algorithm (MGP) provides a sub-optimal solution in a fast iterative manner. The Weighted Tabu Search (WTS) is designed to offer a near optimal solution with longer running time. The relaxed semi-definite programming (SDP) is used to set a performance upper bound and three rounding techniques are discussed to find the feasible solution. The simulation results present the trade-off among the three methods. The case study on two air transportation networks of Virgin America and Southwest Airlines show that the developed methods can be applied in real world large scale networks. The algebraic connectivity maximization problem is extended by adding the leg number constraint, which considers the traveler's tolerance for the total connecting stops. The Binary Semi-Definite Programming (BSDP) with cutting plane method provides the optimal solution. The tabu search and 2-opt search heuristics can find the optimal solution in small scale networks and the near optimal solution in large scale networks. The third algebraic connectivity maximization problem with operating cost constraint is formulated. When the total operating cost budget is given, the number of the edges to be added is not fixed. Each edge weight needs to be calculated instead of being pre-determined. It is illustrated that the edge addition and the

Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a prospective longitudinal test accuracy study to validate new risk scores in women with symptoms of suspected ovarian cancer.

PubMed

Sundar, Sudha; Rick, Caroline; Dowling, Francis; Au, Pui; Snell, Kym; Rai, Nirmala; Champaneria, Rita; Stobart, Hilary; Neal, Richard; Davenport, Clare; Mallett, Susan; Sutton, Andrew; Kehoe, Sean; Timmerman, Dirk; Bourne, Tom; Van Calster, Ben; Gentry-Maharaj, Aleksandra; Menon, Usha; Deeks, Jon

2016-08-09

Ovarian cancer (OC) is associated with non-specific symptoms such as bloating, making accurate diagnosis challenging: only 1 in 3 women with OC presents through primary care referral. National Institute for Health and Care Excellence guidelines recommends sequential testing with CA125 and routine ultrasound in primary care. However, these diagnostic tests have limited sensitivity or specificity. Improving accurate triage in women with vague symptoms is likely to improve mortality by streamlining referral and care pathways. The Refining Ovarian Cancer Test Accuracy Scores (ROCkeTS; HTA 13/13/01) project will derive and validate new tests/risk prediction models that estimate the probability of having OC in women with symptoms. This protocol refers to the prospective study only (phase III). ROCkeTS comprises four parallel phases. The full ROCkeTS protocol can be found at http://www.birmingham.ac.uk/ROCKETS. Phase III is a prospective test accuracy study. The study will recruit 2450 patients from 15 UK sites. Recruited patients complete symptom and anxiety questionnaires, donate a serum sample and undergo ultrasound scored as per International Ovarian Tumour Analysis (IOTA) criteria. Recruitment is at rapid access clinics, emergency departments and elective clinics. Models to be evaluated include those based on ultrasound derived by the IOTA group and novel models derived from analysis of existing data sets. Estimates of sensitivity, specificity, c-statistic (area under receiver operating curve), positive predictive value and negative predictive value of diagnostic tests are evaluated and a calibration plot for models will be presented. ROCkeTS has received ethical approval from the NHS West Midlands REC (14/WM/1241) and is registered on the controlled trials website (ISRCTN17160843) and the National Institute of Health Research Cancer and Reproductive Health portfolios. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

Branching Search

NASA Astrophysics Data System (ADS)

Eliazar, Iddo

2017-12-01

Search processes play key roles in various scientific fields. A widespread and effective search-process scheme, which we term Restart Search, is based on the following restart algorithm: i) set a timer and initiate a search task; ii) if the task was completed before the timer expired, then stop; iii) if the timer expired before the task was completed, then go back to the first step and restart the search process anew. In this paper a branching feature is added to the restart algorithm: at every transition from the algorithm's third step to its first step branching takes place, thus multiplying the search effort. This branching feature yields a search-process scheme which we term Branching Search. The running time of Branching Search is analyzed, closed-form results are established, and these results are compared to the coresponding running-time results of Restart Search.

Solving the flexible job shop problem by hybrid metaheuristics-based multiagent model

NASA Astrophysics Data System (ADS)

Nouri, Houssem Eddine; Belkahla Driss, Olfa; Ghédira, Khaled

2018-03-01

The flexible job shop scheduling problem (FJSP) is a generalization of the classical job shop scheduling problem that allows to process operations on one machine out of a set of alternative machines. The FJSP is an NP-hard problem consisting of two sub-problems, which are the assignment and the scheduling problems. In this paper, we propose how to solve the FJSP by hybrid metaheuristics-based clustered holonic multiagent model. First, a neighborhood-based genetic algorithm (NGA) is applied by a scheduler agent for a global exploration of the search space. Second, a local search technique is used by a set of cluster agents to guide the research in promising regions of the search space and to improve the quality of the NGA final population. The efficiency of our approach is explained by the flexible selection of the promising parts of the search space by the clustering operator after the genetic algorithm process, and by applying the intensification technique of the tabu search allowing to restart the search from a set of elite solutions to attain new dominant scheduling solutions. Computational results are presented using four sets of well-known benchmark literature instances. New upper bounds are found, showing the effectiveness of the presented approach.

CAST: a new program package for the accurate characterization of large and flexible molecular systems.

PubMed

Grebner, Christoph; Becker, Johannes; Weber, Daniel; Bellinger, Daniel; Tafipolski, Maxim; Brückner, Charlotte; Engels, Bernd

2014-09-15

The presented program package, Conformational Analysis and Search Tool (CAST) allows the accurate treatment of large and flexible (macro) molecular systems. For the determination of thermally accessible minima CAST offers the newly developed TabuSearch algorithm, but algorithms such as Monte Carlo (MC), MC with minimization, and molecular dynamics are implemented as well. For the determination of reaction paths, CAST provides the PathOpt, the Nudge Elastic band, and the umbrella sampling approach. Access to free energies is possible through the free energy perturbation approach. Along with a number of standard force fields, a newly developed symmetry-adapted perturbation theory-based force field is included. Semiempirical computations are possible through DFTB+ and MOPAC interfaces. For calculations based on density functional theory, a Message Passing Interface (MPI) interface to the Graphics Processing Unit (GPU)-accelerated TeraChem program is available. The program is available on request. Copyright © 2014 Wiley Periodicals, Inc.

Optimizing an Actuator Array for the Control of Multi-Frequency Noise in Aircraft Interiors

NASA Technical Reports Server (NTRS)

Palumbo, D. L.; Padula, S. L.

1997-01-01

Techniques developed for selecting an optimized actuator array for interior noise reduction at a single frequency are extended to the multi-frequency case. Transfer functions for 64 actuators were obtained at 5 frequencies from ground testing the rear section of a fully trimmed DC-9 fuselage. A single loudspeaker facing the left side of the aircraft was the primary source. A combinatorial search procedure (tabu search) was employed to find optimum actuator subsets of from 2 to 16 actuators. Noise reduction predictions derived from the transfer functions were used as a basis for evaluating actuator subsets during optimization. Results indicate that it is necessary to constrain actuator forces during optimization. Unconstrained optimizations selected actuators which require unrealistically large forces. Two methods of constraint are evaluated. It is shown that a fast, but approximate, method yields results equivalent to an accurate, but computationally expensive, method.

Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down’s syndrome

PubMed Central

2013-01-01

Background Down’s syndrome (DS) is caused by triplication of all or part of human chromosome 21 and is characterized by a decrease in the overall size of the brain. One of the brain regions most affected is the cerebellum, in which the number of granule cells (GCs) is markedly decreased. GCs process sensory information entering the cerebellum via mossy fibres and pass it on to Purkinje cells and inhibitory interneurons. How GCs transform incoming signals depends on their input–output relationship, which is adjusted by tonically active GABAA receptor channels. Results We report that in the Ts65Dn mouse model of DS, in which cerebellar volume and GC number are decreased as in DS, the tonic GABAA receptor current in GCs is smaller than in wild-type mice and is less effective in moderating input resistance and raising the minimum current required for action potential firing. We also find that tonically active GABAA receptors curb the height and broaden the width of action potentials in wild-type GCs but not in Ts65Dn GCs. Single-cell real-time quantitative PCR reveals that these electrical differences are accompanied by decreased expression of the gene encoding the GABAA receptor β3 subunit but not genes coding for some of the other GABAA receptor subunits expressed in GCs (α1, α6, β2 and δ). Conclusions Weaker moderation of excitability and action potential waveform in GCs of the Ts65Dn mouse by tonically active GABAA receptors is likely to contribute to atypical transfer of information through the cerebellum. Similar changes may occur in DS. PMID:23870245

Study of B to X \\gamma Decays and Determination of |V_{td}/V_{ts}|

DOE Office of Scientific and Technical Information (OSTI.GOV)

del Amo Sanchez, P.; Lees, J.P.; Poireau, V.

2011-08-22

Using a sample of 471 million B{bar B} events collected with the BABAR detector, we study the sum of seven exclusive final states B {yields} X{sub s(d){gamma}}, where X{sub s(d)} is a strange (non-strange) hadronic system with a mass of up to 2.0 GeV/c{sup 2}. After correcting for unobserved decay modes, we obtain a branching fraction for b {yields} d{gamma} of (9.2 {+-} 2.0(stat.) {+-} 2.3(syst.)) x 10{sup -6} in this mass range, and a branching fraction for b {yields} s{gamma} of (23.0 {+-} 0.8(stat.) {+-} 3.0(syst.)) x 10{sup -5} in the same mass range. We find {Beta}(b{yields}d{gamma})/{Beta}(b{yields}s{gamma}) = 0.040more » {+-} 0.009(stat.) {+-} 0.010(syst.), from which we determine |V{sub td}/V{sub ts}| = 0.199 {+-} 0.022(stat.) {+-} 0.024(syst.) {+-} 0.002(th.).« less

A pragmatic definition of therapeutic synergy suitable for clinically relevant in vitro multicompound analyses.

PubMed

Kashif, Muhammad; Andersson, Claes; Åberg, Magnus; Nygren, Peter; Sjöblom, Tobias; Hammerling, Ulf; Larsson, Rolf; Gustafsson, Mats G

2014-07-01

For decades, the standard procedure when screening for candidate anticancer drug combinations has been to search for synergy, defined as any positive deviation from trivial cases like when the drugs are regarded as diluted versions of each other (Loewe additivity), independent actions (Bliss independence), or no interaction terms in a response surface model (no interaction). Here, we show that this kind of conventional synergy analysis may be completely misleading when the goal is to detect if there is a promising in vitro therapeutic window. Motivated by this result, and the fact that a drug combination offering a promising therapeutic window seldom is interesting if one of its constituent drugs can provide the same window alone, the largely overlooked concept of therapeutic synergy (TS) is reintroduced. In vitro TS is said to occur when the largest therapeutic window obtained by the best drug combination cannot be achieved by any single drug within the concentration range studied. Using this definition of TS, we introduce a procedure that enables its use in modern massively parallel experiments supported by a statistical omnibus test for TS designed to avoid the multiple testing problem. Finally, we suggest how one may perform TS analysis, via computational predictions of the reference cell responses, when only the target cell responses are available. In conclusion, the conventional error-prone search for promising drug combinations may be improved by replacing conventional (toxicology-rooted) synergy analysis with an analysis focused on (clinically motivated) TS. ©2014 American Association for Cancer Research.

QM/MM Free Energy Simulations of Salicylic Acid Methyltransferase: Effects of Stabilization of TS-like Structures on Substrate Specificity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Jianzhuang; Xu, Qin; Chen, Feng

2010-01-01

Salicylic acid methyltransferases (SAMTs) synthesize methyl salicylate (MeSA) using salicylate as the substrate. MeSA synthesized in plants may function as an airborne signal to activate the expression of defense-related genes and could also be a critical mobile signaling molecule that travels from the site of plant infection to establish systemic immunity in the induction of disease resistance. Here the results of QM/MM free energy simulations for the methyl transfer process in Clarkia breweri SAMT (CbSAMT) are reported to determine the origin of the substrate specificity of SAMTs. The free energy barrier for the methyl transfer from S-adenosyl-l-methionine (AdoMet) to 4-hydroxybenzoatemore » in CbSAMT is found to be about 5 kcal/mol higher than that from AdoMet to salicylate, consistent with the experimental observations. It is suggested that the relatively high efficiency for the methylation of salicylate compared to 4-hydroxybenzoate is due, at least in part, to the reason that a part of the stabilization of the transition state (TS) configuration is already reflected in the reactant complex, presumably, through the binding. The results seem to indicate that the creation of the substrate complex (e.g., through mutagenesis and substrate modifications) with its structure closely resembling TS might be fruitful for improving the catalytic efficiency for some enzymes. The results show that the computer simulations may provide important insights into the origin of the substrate specificity for the SABATH family and could be used to help experimental efforts in generating engineered enzymes with altered substrate specificity.« less

Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature

PubMed Central

Carlson, M; Silberbach, M

2009-01-01

Patients with Turner syndrome (TS) are at risk for aortic dissection, but the clinical profile for those at risk is not well described. In addition to reporting two new cases, we performed an electronic search to identify all reported cases of aortic dissection associated with TS. In total, 85 cases of aortic dissection in TS were reported between 1961 and 2006. Dissection occurred at a young age, 30.7 (range 4–64) years, which is significantly earlier than its occurrence in the general female population (68 years). Importantly, in 11% of the cases, neither hypertension nor congenital heart disease were identified, suggesting that TS alone is an independent risk factor for aortic dissection; however, the cases where no risk factors were identified were very poorly documented. A TS aortic dissection registry has been established to determine the natural history and risk factors better (http://www.turnersyndrome.org/). PMID:21731587

Analysis of the performance of the CONTOUR® TS Blood Glucose Monitoring System: when regulatory performance criteria are met, should we have confidence to use a medical device with all patients?

PubMed

Lyon, Martha E; Lyon, Andrew W

2011-01-01

The article entitled, Performance of the CONTOUR® TS Blood Glucose Monitoring System, by Frank and colleagues in this issue of Journal of Diabetes Science and Technology, demonstrates that the CONTOUR® TS glucose meter exceeds current regulatory expectations for glucose meter performance. However, the appropriateness of current regulatory expectations, such as International Organization for Standardization (ISO) 15197:2003, is being reevaluated because of increasing concern regarding the reliability of glucose meters in ambulatory and hospitalized environments. Between 2004 and 2008, 12,673 serious adverse events with glucose meters that met the ISO 15197 expectations were reported in the Food and Drug Administration-Manufacturer and User Facility Device Experience surveillance database. Should different glucose meter performance criteria be applied to ambulatory versus critical care patients? © 2010 Diabetes Technology Society.

THE DOUBLE-DEGENERATE NUCLEUS OF THE PLANETARY NEBULA TS 01: A CLOSE BINARY EVOLUTION SHOWCASE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tovmassian, Gagik; Richer, Michael G.; Yungelson, Lev

2010-05-01

We present a detailed investigation of SBS 1150+599A, a close binary star hosted by the planetary nebula PN G135.9+55.9 (TS 01). The nebula, located in the Galactic halo, is the most oxygen-poor known to date and is the only one known to harbor a double degenerate core. We present XMM-Newton observations of this object, which allowed the detection of the previously invisible component of the binary core, whose existence was inferred so far only from radial velocity (RV) and photometric variations. The parameters of the binary system were deduced from a wealth of information via three independent routes using themore » spectral energy distribution (from the infrared to X-rays), the light and RV curves, and a detailed model atmosphere fitting of the stellar absorption features of the optical/UV component. We find that the cool component must have a mass of 0.54 {+-} 0.2 M{sub sun}, an average effective temperature, T{sub eff}, of 58,000 {+-} 3000 K, a mean radius of 0.43 {+-} 0.3 R{sub sun}, a gravity, log g = 5.0 {+-} 0.3, and that it nearly fills its Roche lobe. Its surface elemental abundances are found to be: 12 + log He/H = 10.95 {+-} 0.04 dex, 12 + log C/H = 7.20 {+-} 0.3 dex, 12 + log N/H < 6.92, and 12 + log O/H < 6.80, in overall agreement with the chemical composition of the planetary nebula. The hot component has T{sub eff} = 160-180 kK, a luminosity of about {approx}10{sup 4} L{sub sun} and a radius slightly larger than that of a white dwarf. It is probably bloated and heated as a result of intense accretion and nuclear burning on its surface in the past. The total mass of the binary system is very close to the Chandrasekhar limit. This makes TS 01 one of the best Type Ia supernova progenitor candidates. We propose two possible scenarios for the evolution of the system up to its present stage.« less

Comprehensive Behavioral Phenotyping of Ts65Dn Mouse Model of Down Syndrome: Activation of β1-Adrenergic Receptor by Xamoterol as a Potential Cognitive Enhancer

PubMed Central

Faizi, Mehrdad; Bader, Patrick L.; Tun, Christine; Encarnacion, Angelo; Kleschevnikov, Alexander; Belichenko, Pavel; Saw, Nay; Priestley, Matthew; Tsien, Richard W; Mobley, William C; Shamloo, Mehrdad

2012-01-01

Down Syndrome (DS) is the most prevalent form of mental retardation caused by genetic abnormalities in humans. This has been successfully modeled in mice to generate the Ts65Dn mouse, a genetic model of DS. This transgenic mouse model shares a number of physical and functional abnormalities with people with DS, including changes in the structure and function of neuronal circuits. Significant abnormalities in noradrenergic (NE-ergic) afferents from the locus coeruleus to the hippocampus, as well as deficits in NE-ergic neurotransmission are detected in these animals. In the current study we characterized in detail the behavioral phenotype of Ts65Dn mice, in addition to using pharmacological tools for identification of target receptors mediating the learning and memory deficits observed in this model of DS. We undertook a comprehensive approach to mouse phenotyping using a battery of standard and novel tests encompassing: i) locomotion (Activity Chamber, PhenoTyper, and CatWalk), ii) learning and memory (spontaneous alternation, delayed matching-to-place water maze, fear conditioning, and Intellicage), and iii) social behavior. Ts65Dn mice showed increased locomotor activity in novel and home cage environments. There were significant and reproducible deficits in learning and memory tests including spontaneous alternation, delayed matching-to-place water maze, Intellicage place avoidance and contextual fear conditioning. Although Ts65Dn mice showed no deficit in sociability in the 3-chamber test, a marked impairment in social memory was detected. Xamoterol, a β1-adrenergic receptor (β1-ADR) agonist, effectively restored the memory deficit in contextual fear conditioning, spontaneous alternation and novel object recognition. These behavioral improvements were reversed by betaxolol, a selective β1-ADR antagonist. In conclusion, our results demonstrate that this mouse model of Down Syndrome display cognitive deficits which is mediated by imbalance in noradrenergic

End-user search behaviors and their relationship to search effectiveness.

PubMed Central

Wildemuth, B M; Moore, M E

1995-01-01

One hundred sixty-one MEDLINE searches conducted by third-year medical students were analyzed and evaluated to determine which search moves were used, whether those individual moves were effective, and whether there was a relationship between specific search behaviors and the effectiveness of the search strategy as a whole. The typical search included fourteen search statements, used seven terms or "limit" commands, and resulted in the display of eleven citations. The most common moves were selection of a database, entering single-word terms and free-text term phrases, and combining sets of terms. Syntactic errors were also common. Overall, librarians judged the searches to be adequate, and students were quite satisfied with their own searches. However, librarians also identified many missed opportunities in the search strategies, including underutilization of the controlled vocabulary, subheadings, and synonyms for search concepts. No strong relationships were found between specific search behaviors and search effectiveness (as measured by the librarians' or students' evaluations). Implications of these findings for system design and user education are discussed. PMID:7581185

Pharmacokinetic Properties of Memantine after a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down's Syndrome.

PubMed

Victorino, Daniella B; Bederman, Ilya R; Costa, Alberto C S

2017-11-01

Memantine is a drug approved for the treatment of moderate-to-severe Alzheimer's disease (AD), and there is ongoing research on the potential expansion of its clinical applicability. Published data on the pharmacokinetics of memantine in the mouse are still incomplete, particularly for chronic administration regimens and mouse models of specific genetic disorders. Down's syndrome (DS) is a genetic disorder known to affect multiple organs and systems, with the potential to alter significantly drug pharmacokinetics. Here, we describe a simple, efficient and sensitive GC/MS-based procedure for the determination of memantine concentrations in murine blood and tissue samples. We analysed pharmacokinetic properties of memantine, particularly its distribution in blood, brain and liver in the Ts65Dn mouse model of DS and euploid F1 hybrid mice after single intraperitoneal administrations of increasing doses of this drug. We also determined steady-state memantine concentrations in plasma, brain and liver after chronic oral administration of this drug in adult male Ts65Dn mice, euploid littermate controls and nursing or pregnant Ts65Dn mice. Our results revalidated the acute dose of memantine used in previously published work, determined the appropriate amount of memantine to be mixed into mouse chow to achieve steady and pharmacologically relevant plasma and tissue levels of this drug and demonstrated that memantine can be transferred from mother to offspring via maternal milk and placenta. Most of these findings are potentially applicable not only to the study of DS but also to other neurodevelopmental and neurodegenerative disorders. © 2017 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Search for Gravitational Wave Ringdowns from Perturbed Intermediate Mass Black Holes in LIGO-Virgo Data from 2005-2010

NASA Technical Reports Server (NTRS)

Aasi, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Acernese, F.; Blackburn, Lindy L.; Camp, J. B.; Gehrels, N.; Graff, P. B.

2014-01-01

We report results from a search for gravitational waves produced by perturbed intermediate mass black holes (IMBH) in data collected by LIGO and Virgo between 2005 and 2010. The search was sensitive to astrophysical sources that produced damped sinusoid gravitational wave signals, also known as ringdowns, with frequency 50 less than or equal to italic f0/Hz less than or equal to 2000 and decay timescale 0.0001 approximately less than t/s approximately less than 0.1 characteristic of those produced in mergers of IMBH pairs. No significant gravitational wave candidate was detected. We report upper limits on the astrophysical coalescence rates of IMBHs with total binary mass 50 less than or equal to M/solar mass less than or equal to 450 and component mass ratios of either 1:1 or 4:1. For systems with total mass 100 less than or equal to M/solar mass 150, we report a 90%-confidence upper limit on the rate of binary IMBH mergers with non-spinning and equal mass components of 6:9 x 10(exp 8) Mpc(exp -3)yr(exp -1). We also report a rate upper limit for ringdown waveforms from perturbed IMBHs, radiating 1% of their mass as gravitational waves in the fundamental, l=m=2, oscillation mode, that is nearly three orders of magnitude more stringent than previous results.

Tourette syndrome and other neurodevelopmental disorders: a comprehensive review.

PubMed

Cravedi, Elena; Deniau, Emmanuelle; Giannitelli, Marianna; Xavier, Jean; Hartmann, Andreas; Cohen, David

2017-01-01

Gilles de la Tourette syndrome (TS) is a complex developmental neuropsychiatric condition in which motor manifestations are often accompanied by comorbid conditions that impact the patient's quality of life. In the DSM-5, TS belongs to the "neurodevelopmental disorders" group, together with other neurodevelopmental conditions, frequently co-occurring. In this study, we searched the PubMed database using a combination of keywords associating TS and all neurodevelopmental diagnoses. From 1009 original reports, we identified 36 studies addressing TS and neurodevelopmental comorbidities. The available evidence suggests the following: (1) neurodevelopmental comorbidities in TS are the rule, rather than the exception; (2) attention deficit/hyperactivity disorder (ADHD) is the most frequent; (3) there is a continuum from a simple (TS + ADHD or/and learning disorder) to a more complex phenotype (TS + autism spectrum disorder). We conclude that a prompt diagnosis and a detailed description of TS comorbidities are necessary not only to understand the aetiological basis of neurodevelopmental disorders but also to address specific rehabilitative and therapeutic approaches.

The portrayal of Tourette Syndrome in film and television.

PubMed

Calder-Sprackman, Samantha; Sutherland, Stephanie; Doja, Asif

2014-03-01

To determine the representation of Tourette Syndrome (TS) in fictional movies and television programs by investigating recurrent themes and depictions. Television and film can be a source of information and misinformation about medical disorders. Tourette Syndrome has received attention in the popular media, but no studies have been done on the accuracy of the depiction of the disorder. International internet movie databases were searched using the terms "Tourette's", "Tourette's Syndrome", and "tics" to generate all movies, shorts, and television programs featuring a character or scene with TS or a person imitating TS. Using a grounded theory approach, we identified the types of characters, tics, and co-morbidities depicted as well as the overall representation of TS. Thirty-seven television programs and films were reviewed dating from 1976 to 2010. Fictional movies and television shows gave overall misrepresentations of TS. Coprolalia was overrepresented as a tic manifestation, characters were depicted having autism spectrum disorder symptoms rather than TS, and physicians were portrayed as unsympathetic and only focusing on medical therapies. School and family relationships were frequently depicted as being negatively impacted by TS, leading to poor quality of life. Film and television are easily accessible resources for patients and the public that may influence their beliefs about TS. Physicians should be aware that TS is often inaccurately represented in television programs and film and acknowledge misrepresentations in order to counsel patients accordingly.

[Advanced online search techniques and dedicated search engines for physicians].

PubMed

Nahum, Yoav

2008-02-01

In recent years search engines have become an essential tool in the work of physicians. This article will review advanced search techniques from the world of information specialists, as well as some advanced search engine operators that may help physicians improve their online search capabilities, and maximize the yield of their searches. This article also reviews popular dedicated scientific and biomedical literature search engines.

Children's Search Engines from an Information Search Process Perspective.

ERIC Educational Resources Information Center

Broch, Elana

2000-01-01

Describes cognitive and affective characteristics of children and teenagers that may affect their Web searching behavior. Reviews literature on children's searching in online public access catalogs (OPACs) and using digital libraries. Profiles two Web search engines. Discusses some of the difficulties children have searching the Web, in the…

How Users Search the Library from a Single Search Box

ERIC Educational Resources Information Center

Lown, Cory; Sierra, Tito; Boyer, Josh

2013-01-01

Academic libraries are turning increasingly to unified search solutions to simplify search and discovery of library resources. Unfortunately, very little research has been published on library user search behavior in single search box environments. This study examines how users search a large public university library using a prominent, single…

Experience-dependent reduction of soluble β-amyloid oligomers and rescue of cognitive abilities in middle-age Ts65Dn mice, a model of Down syndrome.

PubMed

Sansevero, Gabriele; Begenisic, Tatjana; Mainardi, Marco; Sale, Alessandro

2016-09-01

Down syndrome (DS) is the most diffused genetic cause of intellectual disability and, after the age of forty, is invariantly associated with Alzheimer's disease (AD). In the last years, the prolongation of life expectancy in people with DS renders the need for intervention paradigms aimed at improving mental disability and counteracting AD pathology particularly urgent. At present, however, there are no effective therapeutic strategies for DS and concomitant AD in mid-life people. The most intensively studied mouse model of DS is the Ts65Dn line, which summarizes the main hallmarks of the DS phenotype, included severe learning and memory deficits and age-dependent AD-like pathology. Here we report for the first time that middle-age Ts65Dn mice display a marked increase in soluble Aβ oligomer levels in their hippocampus. Moreover, we found that long-term exposure to environmental enrichment (EE), a widely used paradigm that increases sensory-motor stimulation, reduces Aβ oligomers and rescues spatial memory abilities in trisomic mice. Our findings underscore the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes in DS subjects. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimization in optical systems revisited: Beyond genetic algorithms

NASA Astrophysics Data System (ADS)

Gagnon, Denis; Dumont, Joey; Dubé, Louis

2013-05-01

Designing integrated photonic devices such as waveguides, beam-splitters and beam-shapers often requires optimization of a cost function over a large solution space. Metaheuristics - algorithms based on empirical rules for exploring the solution space - are specifically tailored to those problems. One of the most widely used metaheuristics is the standard genetic algorithm (SGA), based on the evolution of a population of candidate solutions. However, the stochastic nature of the SGA sometimes prevents access to the optimal solution. Our goal is to show that a parallel tabu search (PTS) algorithm is more suited to optimization problems in general, and to photonics in particular. PTS is based on several search processes using a pool of diversified initial solutions. To assess the performance of both algorithms (SGA and PTS), we consider an integrated photonics design problem, the generation of arbitrary beam profiles using a two-dimensional waveguide-based dielectric structure. The authors acknowledge financial support from the Natural Sciences and Engineering Research Council of Canada (NSERC).

Trapping or tethering stones (TS): A multifunctional device in the Pastoral Neolithic of the Sahara

PubMed Central

di Lernia, Savino

2018-01-01

The Pierres de Ben Barour, also known as trapping or tethering stones (TS), are stone artefacts with notches or grooves usually interpreted as hunting devices on the basis of rock art engravings. Though their presence is a peculiar feature of desert landscapes from the Sahara to the Arabian Peninsula, we know little about their age, context and function. Here we present a new approach to the study of these artefacts based on a large dataset (837 items) recorded in the Messak plateau (SW Libya). A statistically-based geoarchaeological survey carried out between 2007 and 2011 in Libya, alongside landscape and intra-site analyses of specific archaeological features (such as rock art, settlement and ceremonial contexts), reveal that these artefacts were used for a prolonged period, probably from the early Holocene. This was followed by a multifunctional use of these devices, particularly during the Pastoral Neolithic phase (ca. 6400–3000 cal BC), with the highest concentrations being found near ceremonial contexts related to cattle burials. PMID:29370242

Search times and probability of detection in time-limited search

NASA Astrophysics Data System (ADS)

Wilson, David; Devitt, Nicole; Maurer, Tana

2005-05-01

When modeling the search and target acquisition process, probability of detection as a function of time is important to war games and physical entity simulations. Recent US Army RDECOM CERDEC Night Vision and Electronics Sensor Directorate modeling of search and detection has focused on time-limited search. Developing the relationship between detection probability and time of search as a differential equation is explored. One of the parameters in the current formula for probability of detection in time-limited search corresponds to the mean time to detect in time-unlimited search. However, the mean time to detect in time-limited search is shorter than the mean time to detect in time-unlimited search and the relationship between them is a mathematical relationship between these two mean times. This simple relationship is derived.

Search Parameter Optimization for Discrete, Bayesian, and Continuous Search Algorithms

DTIC Science & Technology

2017-09-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS SEARCH PARAMETER OPTIMIZATION FOR DISCRETE , BAYESIAN, AND CONTINUOUS SEARCH ALGORITHMS by...to 09-22-2017 4. TITLE AND SUBTITLE SEARCH PARAMETER OPTIMIZATION FOR DISCRETE , BAYESIAN, AND CON- TINUOUS SEARCH ALGORITHMS 5. FUNDING NUMBERS 6...simple search and rescue acts to prosecuting aerial/surface/submersible targets on mission. This research looks at varying the known discrete and

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krityakierne, Tipaluck; Akhtar, Taimoor; Shoemaker, Christine A.

This paper presents a parallel surrogate-based global optimization method for computationally expensive objective functions that is more effective for larger numbers of processors. To reach this goal, we integrated concepts from multi-objective optimization and tabu search into, single objective, surrogate optimization. Our proposed derivative-free algorithm, called SOP, uses non-dominated sorting of points for which the expensive function has been previously evaluated. The two objectives are the expensive function value of the point and the minimum distance of the point to previously evaluated points. Based on the results of non-dominated sorting, P points from the sorted fronts are selected as centersmore » from which many candidate points are generated by random perturbations. Based on surrogate approximation, the best candidate point is subsequently selected for expensive evaluation for each of the P centers, with simultaneous computation on P processors. Centers that previously did not generate good solutions are tabu with a given tenure. We show almost sure convergence of this algorithm under some conditions. The performance of SOP is compared with two RBF based methods. The test results show that SOP is an efficient method that can reduce time required to find a good near optimal solution. In a number of cases the efficiency of SOP is so good that SOP with 8 processors found an accurate answer in less wall-clock time than the other algorithms did with 32 processors.« less

SOP: parallel surrogate global optimization with Pareto center selection for computationally expensive single objective problems

DOE PAGES

Krityakierne, Tipaluck; Akhtar, Taimoor; Shoemaker, Christine A.

2016-02-02

This paper presents a parallel surrogate-based global optimization method for computationally expensive objective functions that is more effective for larger numbers of processors. To reach this goal, we integrated concepts from multi-objective optimization and tabu search into, single objective, surrogate optimization. Our proposed derivative-free algorithm, called SOP, uses non-dominated sorting of points for which the expensive function has been previously evaluated. The two objectives are the expensive function value of the point and the minimum distance of the point to previously evaluated points. Based on the results of non-dominated sorting, P points from the sorted fronts are selected as centersmore » from which many candidate points are generated by random perturbations. Based on surrogate approximation, the best candidate point is subsequently selected for expensive evaluation for each of the P centers, with simultaneous computation on P processors. Centers that previously did not generate good solutions are tabu with a given tenure. We show almost sure convergence of this algorithm under some conditions. The performance of SOP is compared with two RBF based methods. The test results show that SOP is an efficient method that can reduce time required to find a good near optimal solution. In a number of cases the efficiency of SOP is so good that SOP with 8 processors found an accurate answer in less wall-clock time than the other algorithms did with 32 processors.« less

Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome.

PubMed

Stagni, Fiorenza; Giacomini, Andrea; Emili, Marco; Trazzi, Stefania; Guidi, Sandra; Sassi, Martina; Ciani, Elisabetta; Rimondini, Roberto; Bartesaghi, Renata

2016-10-01

Cognitive disability is an unavoidable feature of Down syndrome (DS), a genetic disorder due to the triplication of human chromosome 21. DS is associated with alterations of neurogenesis, neuron maturation and connectivity that are already present at prenatal life stages. Recent evidence shows that pharmacotherapies can have a large impact on the trisomic brain provided that they are administered perinatally. Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, performs many actions in the brain, including inhibition of DYRK1A, a kinase that is over-expressed in the DS brain and contributes to the DS phenotype. Young adults with DS treated with EGCG exhibit some cognitive benefits, although these effects disappear with time. We deemed it extremely important, however, to establish whether treatment with EGCG at the initial stages of brain development leads to plastic changes that outlast treatment cessation. In the current study, we exploited the Ts65Dn mouse model of DS in order to establish whether pharmacotherapy with EGCG during peak of neurogenesis in the hippocampal dentate gyrus (DG) enduringly restores hippocampal development and memory performance. Euploid and Ts65Dn mice were treated with EGCG from postnatal day 3 (P3) to P15. The effects of treatment were examined at its cessation (at P15) or after one month (at P45). We found that at P15 treated trisomic pups exhibited restoration of neurogenesis, total hippocampal granule cell number and levels of pre- and postsynaptic proteins in the DG, hippocampus and neocortex. However, at P45 none of these effects were still present, nor did treated Ts65Dn mice exhibit any improvement in hippocampus-dependent tasks. These findings show that treatment with EGCG carried out in the neonatal period rescues numerous trisomy-linked brain alterations. However, even during this, the most critical time window for hippocampal development, EGCG does not elicit enduring effects on the hippocampal physiology

Experimental verification of a GPC-LPV method with RLS and P1-TS fuzzy-based estimation for limiting the transient and residual vibration of a crane system

NASA Astrophysics Data System (ADS)

Smoczek, Jaroslaw

2015-10-01

The paper deals with the problem of reducing the residual vibration and limiting the transient oscillations of a flexible and underactuated system with respect to the variation of operating conditions. The comparative study of generalized predictive control (GPC) and fuzzy scheduling scheme developed based on the P1-TS fuzzy theory, local pole placement method and interval analysis of closed-loop system polynomial coefficients is addressed to the problem of flexible crane control. The two alternatives of a GPC-based method are proposed that enable to realize this technique either with or without a sensor of payload deflection. The first control technique is based on the recursive least squares (RLS) method applied to on-line estimate the parameters of a linear parameter varying (LPV) model of a crane dynamic system. The second GPC-based approach is based on a payload deflection feedback estimated using a pendulum model with the parameters interpolated using the P1-TS fuzzy system. Feasibility and applicability of the developed methods were confirmed through experimental verification performed on a laboratory scaled overhead crane.

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Evidence-based Medicine Search: a customizable federated search engine.

PubMed

Bracke, Paul J; Howse, David K; Keim, Samuel M

2008-04-01

This paper reports on the development of a tool by the Arizona Health Sciences Library (AHSL) for searching clinical evidence that can be customized for different user groups. The AHSL provides services to the University of Arizona's (UA's) health sciences programs and to the University Medical Center. Librarians at AHSL collaborated with UA College of Medicine faculty to create an innovative search engine, Evidence-based Medicine (EBM) Search, that provides users with a simple search interface to EBM resources and presents results organized according to an evidence pyramid. EBM Search was developed with a web-based configuration component that allows the tool to be customized for different specialties. Informal and anecdotal feedback from physicians indicates that EBM Search is a useful tool with potential in teaching evidence-based decision making. While formal evaluation is still being planned, a tool such as EBM Search, which can be configured for specific user populations, may help lower barriers to information resources in an academic health sciences center.

Clinician search behaviors may be influenced by search engine design.

PubMed

Lau, Annie Y S; Coiera, Enrico; Zrimec, Tatjana; Compton, Paul

2010-06-30

Searching the Web for documents using information retrieval systems plays an important part in clinicians' practice of evidence-based medicine. While much research focuses on the design of methods to retrieve documents, there has been little examination of the way different search engine capabilities influence clinician search behaviors. Previous studies have shown that use of task-based search engines allows for faster searches with no loss of decision accuracy compared with resource-based engines. We hypothesized that changes in search behaviors may explain these differences. In all, 75 clinicians (44 doctors and 31 clinical nurse consultants) were randomized to use either a resource-based or a task-based version of a clinical information retrieval system to answer questions about 8 clinical scenarios in a controlled setting in a university computer laboratory. Clinicians using the resource-based system could select 1 of 6 resources, such as PubMed; clinicians using the task-based system could select 1 of 6 clinical tasks, such as diagnosis. Clinicians in both systems could reformulate search queries. System logs unobtrusively capturing clinicians' interactions with the systems were coded and analyzed for clinicians' search actions and query reformulation strategies. The most frequent search action of clinicians using the resource-based system was to explore a new resource with the same query, that is, these clinicians exhibited a "breadth-first" search behaviour. Of 1398 search actions, clinicians using the resource-based system conducted 401 (28.7%, 95% confidence interval [CI] 26.37-31.11) in this way. In contrast, the majority of clinicians using the task-based system exhibited a "depth-first" search behavior in which they reformulated query keywords while keeping to the same task profiles. Of 585 search actions conducted by clinicians using the task-based system, 379 (64.8%, 95% CI 60.83-68.55) were conducted in this way. This study provides evidence that

Cube search, revisited.

PubMed

Zhang, Xuetao; Huang, Jie; Yigit-Elliott, Serap; Rosenholtz, Ruth

2015-03-16

Observers can quickly search among shaded cubes for one lit from a unique direction. However, replace the cubes with similar 2-D patterns that do not appear to have a 3-D shape, and search difficulty increases. These results have challenged models of visual search and attention. We demonstrate that cube search displays differ from those with "equivalent" 2-D search items in terms of the informativeness of fairly low-level image statistics. This informativeness predicts peripheral discriminability of target-present from target-absent patches, which in turn predicts visual search performance, across a wide range of conditions. Comparing model performance on a number of classic search tasks, cube search does not appear unexpectedly easy. Easy cube search, per se, does not provide evidence for preattentive computation of 3-D scene properties. However, search asymmetries derived from rotating and/or flipping the cube search displays cannot be explained by the information in our current set of image statistics. This may merely suggest a need to modify the model's set of 2-D image statistics. Alternatively, it may be difficult cube search that provides evidence for preattentive computation of 3-D scene properties. By attributing 2-D luminance variations to a shaded 3-D shape, 3-D scene understanding may slow search for 2-D features of the target. © 2015 ARVO.

Cube search, revisited

PubMed Central

Zhang, Xuetao; Huang, Jie; Yigit-Elliott, Serap; Rosenholtz, Ruth

2015-01-01

Observers can quickly search among shaded cubes for one lit from a unique direction. However, replace the cubes with similar 2-D patterns that do not appear to have a 3-D shape, and search difficulty increases. These results have challenged models of visual search and attention. We demonstrate that cube search displays differ from those with “equivalent” 2-D search items in terms of the informativeness of fairly low-level image statistics. This informativeness predicts peripheral discriminability of target-present from target-absent patches, which in turn predicts visual search performance, across a wide range of conditions. Comparing model performance on a number of classic search tasks, cube search does not appear unexpectedly easy. Easy cube search, per se, does not provide evidence for preattentive computation of 3-D scene properties. However, search asymmetries derived from rotating and/or flipping the cube search displays cannot be explained by the information in our current set of image statistics. This may merely suggest a need to modify the model's set of 2-D image statistics. Alternatively, it may be difficult cube search that provides evidence for preattentive computation of 3-D scene properties. By attributing 2-D luminance variations to a shaded 3-D shape, 3-D scene understanding may slow search for 2-D features of the target. PMID:25780063

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Science.gov Websites

with Search To search for a document, type a few descriptive words in the search box, and press the Enter key or click the search button. A results page appears with a list of documents and web pages that are related to your search terms, with the most relevant search results appearing at the top of the

Searching the ASRS Database Using QUORUM Keyword Search, Phrase Search, Phrase Generation, and Phrase Discovery

NASA Technical Reports Server (NTRS)

McGreevy, Michael W.; Connors, Mary M. (Technical Monitor)

2001-01-01

To support Search Requests and Quick Responses at the Aviation Safety Reporting System (ASRS), four new QUORUM methods have been developed: keyword search, phrase search, phrase generation, and phrase discovery. These methods build upon the core QUORUM methods of text analysis, modeling, and relevance-ranking. QUORUM keyword search retrieves ASRS incident narratives that contain one or more user-specified keywords in typical or selected contexts, and ranks the narratives on their relevance to the keywords in context. QUORUM phrase search retrieves narratives that contain one or more user-specified phrases, and ranks the narratives on their relevance to the phrases. QUORUM phrase generation produces a list of phrases from the ASRS database that contain a user-specified word or phrase. QUORUM phrase discovery finds phrases that are related to topics of interest. Phrase generation and phrase discovery are particularly useful for finding query phrases for input to QUORUM phrase search. The presentation of the new QUORUM methods includes: a brief review of the underlying core QUORUM methods; an overview of the new methods; numerous, concrete examples of ASRS database searches using the new methods; discussion of related methods; and, in the appendices, detailed descriptions of the new methods.

A Hybrid Search Algorithm for Swarm Robots Searching in an Unknown Environment

PubMed Central

Li, Shoutao; Li, Lina; Lee, Gordon; Zhang, Hao

2014-01-01

This paper proposes a novel method to improve the efficiency of a swarm of robots searching in an unknown environment. The approach focuses on the process of feeding and individual coordination characteristics inspired by the foraging behavior in nature. A predatory strategy was used for searching; hence, this hybrid approach integrated a random search technique with a dynamic particle swarm optimization (DPSO) search algorithm. If a search robot could not find any target information, it used a random search algorithm for a global search. If the robot found any target information in a region, the DPSO search algorithm was used for a local search. This particle swarm optimization search algorithm is dynamic as all the parameters in the algorithm are refreshed synchronously through a communication mechanism until the robots find the target position, after which, the robots fall back to a random searching mode. Thus, in this searching strategy, the robots alternated between two searching algorithms until the whole area was covered. During the searching process, the robots used a local communication mechanism to share map information and DPSO parameters to reduce the communication burden and overcome hardware limitations. If the search area is very large, search efficiency may be greatly reduced if only one robot searches an entire region given the limited resources available and time constraints. In this research we divided the entire search area into several subregions, selected a target utility function to determine which subregion should be initially searched and thereby reduced the residence time of the target to improve search efficiency. PMID:25386855

A hybrid search algorithm for swarm robots searching in an unknown environment.

PubMed

Li, Shoutao; Li, Lina; Lee, Gordon; Zhang, Hao

2014-01-01

This paper proposes a novel method to improve the efficiency of a swarm of robots searching in an unknown environment. The approach focuses on the process of feeding and individual coordination characteristics inspired by the foraging behavior in nature. A predatory strategy was used for searching; hence, this hybrid approach integrated a random search technique with a dynamic particle swarm optimization (DPSO) search algorithm. If a search robot could not find any target information, it used a random search algorithm for a global search. If the robot found any target information in a region, the DPSO search algorithm was used for a local search. This particle swarm optimization search algorithm is dynamic as all the parameters in the algorithm are refreshed synchronously through a communication mechanism until the robots find the target position, after which, the robots fall back to a random searching mode. Thus, in this searching strategy, the robots alternated between two searching algorithms until the whole area was covered. During the searching process, the robots used a local communication mechanism to share map information and DPSO parameters to reduce the communication burden and overcome hardware limitations. If the search area is very large, search efficiency may be greatly reduced if only one robot searches an entire region given the limited resources available and time constraints. In this research we divided the entire search area into several subregions, selected a target utility function to determine which subregion should be initially searched and thereby reduced the residence time of the target to improve search efficiency.

[Profile of a systematic search. Search areas, databases and reports].

PubMed

Korsbek, Lisa; Bendix, Ane Friis; Kidholm, Kristian

2006-04-03

Systematic literature search is a fundamental in evidence-based medicine. But systematic literature search is not yet a very well used way of retrieving evidence-based information. This article profiles a systematic literature search for evidence-based literature. It goes through the most central databases and gives an example of how to document the literature search. The article also sums up the literature search in all reviews in Ugeskrift for Laeger in the year 2004.

Evidence-based Medicine Search: a customizable federated search engine

PubMed Central

Bracke, Paul J.; Howse, David K.; Keim, Samuel M.

2008-01-01

Purpose: This paper reports on the development of a tool by the Arizona Health Sciences Library (AHSL) for searching clinical evidence that can be customized for different user groups. Brief Description: The AHSL provides services to the University of Arizona's (UA's) health sciences programs and to the University Medical Center. Librarians at AHSL collaborated with UA College of Medicine faculty to create an innovative search engine, Evidence-based Medicine (EBM) Search, that provides users with a simple search interface to EBM resources and presents results organized according to an evidence pyramid. EBM Search was developed with a web-based configuration component that allows the tool to be customized for different specialties. Outcomes/Conclusion: Informal and anecdotal feedback from physicians indicates that EBM Search is a useful tool with potential in teaching evidence-based decision making. While formal evaluation is still being planned, a tool such as EBM Search, which can be configured for specific user populations, may help lower barriers to information resources in an academic health sciences center. PMID:18379665

Asymmetry in search.

PubMed

Kaindl, H; Kainz, G; Radda, K

2001-01-01

Most of the work on search in artificial intelligence (AI) deals with one search direction only-mostly forward search-although it is known that a structural asymmetry of the search graph causes differences in the efficiency of searching in the forward or the backward direction, respectively. In the case of symmetrical graph structure, however, current theory would not predict such differences in efficiency. In several classes of job sequencing problems, we observed a phenomenon of asymmetry in search that relates to the distribution of the are costs in the search graph. This phenomenon can be utilized for improving the search efficiency by a new algorithm that automatically selects the search direction. We demonstrate fur a class of job sequencing problems that, through the utilization of this phenomenon, much more difficult problems can be solved-according to our best knowledge-than by the best published approach, and on the same problems, the running time is much reduced. As a consequence, we propose to check given problems for asymmetrical distribution of are costs that may cause asymmetry in search.

Replacing -CH2CH2- with -CONH- does not significantly change rates of charge transport through Ag(TS)-SAM//Ga2O3/EGaIn junctions.

PubMed

Thuo, Martin M; Reus, William F; Simeone, Felice C; Kim, Choongik; Schulz, Michael D; Yoon, Hyo Jae; Whitesides, George M

2012-07-04

This paper describes physical-organic studies of charge transport by tunneling through self-assembled monolayers (SAMs), based on systematic variations of the structure of the molecules constituting the SAM. Replacing a -CH(2)CH(2)- group with a -CONH- group changes the dipole moment and polarizability of a portion of the molecule and has, in principle, the potential to change the rate of charge transport through the SAM. In practice, this substitution produces no significant change in the rate of charge transport across junctions of the structure Ag(TS)-S(CH(2))(m)X(CH(2))(n)H//Ga(2)O(3)/EGaIn (TS = template stripped, X = -CH(2)CH(2)- or -CONH-, and EGaIn = eutectic alloy of gallium and indium). Incorporation of the amide group does, however, increase the yields of working (non-shorting) junctions (when compared to n-alkanethiolates of the same length). These results suggest that synthetic schemes that combine a thiol group on one end of a molecule with a group, R, to be tested, on the other (e.g., HS~CONH~R) using an amide-based coupling provide practical routes to molecules useful in studies of molecular electronics.

Search systems and computer-implemented search methods

DOEpatents

Payne, Deborah A.; Burtner, Edwin R.; Hampton, Shawn D.; Gillen, David S.; Henry, Michael J.

2017-03-07

Search systems and computer-implemented search methods are described. In one aspect, a search system includes a communications interface configured to access a plurality of data items of a collection, wherein the data items include a plurality of image objects individually comprising image data utilized to generate an image of the respective data item. The search system may include processing circuitry coupled with the communications interface and configured to process the image data of the data items of the collection to identify a plurality of image content facets which are indicative of image content contained within the images and to associate the image objects with the image content facets and a display coupled with the processing circuitry and configured to depict the image objects associated with the image content facets.

Search systems and computer-implemented search methods

DOEpatents

Payne, Deborah A.; Burtner, Edwin R.; Bohn, Shawn J.; Hampton, Shawn D.; Gillen, David S.; Henry, Michael J.

2015-12-22

Search systems and computer-implemented search methods are described. In one aspect, a search system includes a communications interface configured to access a plurality of data items of a collection, wherein the data items include a plurality of image objects individually comprising image data utilized to generate an image of the respective data item. The search system may include processing circuitry coupled with the communications interface and configured to process the image data of the data items of the collection to identify a plurality of image content facets which are indicative of image content contained within the images and to associate the image objects with the image content facets and a display coupled with the processing circuitry and configured to depict the image objects associated with the image content facets.

A Bell-Curved Based Algorithm for Mixed Continuous and Discrete Structural Optimization

NASA Technical Reports Server (NTRS)

Kincaid, Rex K.; Weber, Michael; Sobieszczanski-Sobieski, Jaroslaw

2001-01-01

An evolutionary based strategy utilizing two normal distributions to generate children is developed to solve mixed integer nonlinear programming problems. This Bell-Curve Based (BCB) evolutionary algorithm is similar in spirit to (mu + mu) evolutionary strategies and evolutionary programs but with fewer parameters to adjust and no mechanism for self adaptation. First, a new version of BCB to solve purely discrete optimization problems is described and its performance tested against a tabu search code for an actuator placement problem. Next, the performance of a combined version of discrete and continuous BCB is tested on 2-dimensional shape problems and on a minimum weight hub design problem. In the latter case the discrete portion is the choice of the underlying beam shape (I, triangular, circular, rectangular, or U).

Methods for finding transition states on reduced potential energy surfaces

NASA Astrophysics Data System (ADS)

Burger, Steven K.; Ayers, Paul W.

2010-06-01

Three new algorithms are presented for determining transition state (TS) structures on the reduced potential energy surface, that is, for problems in which a few important degrees of freedom can be isolated. All three methods use constrained optimization to rapidly find the TS without an initial Hessian evaluation. The algorithms highlight how efficiently the TS can be located on a reduced surface, where the rest of the degrees of freedom are minimized. The first method uses a nonpositive definite quasi-Newton update for the reduced degrees of freedom. The second uses Shepard interpolation to fit the Hessian and starts from a set of points that bound the TS. The third directly uses a finite difference scheme to calculate the reduced degrees of freedom of the Hessian of the entire system, and searches for the TS on the full potential energy surface. All three methods are tested on an epoxide hydrolase cluster, and the ring formations of cyclohexane and cyclobutenone. The results indicate that all the methods are able to converge quite rapidly to the correct TS, but that the finite difference approach is the most efficient.

Methods for finding transition states on reduced potential energy surfaces.

PubMed

Burger, Steven K; Ayers, Paul W

2010-06-21

Three new algorithms are presented for determining transition state (TS) structures on the reduced potential energy surface, that is, for problems in which a few important degrees of freedom can be isolated. All three methods use constrained optimization to rapidly find the TS without an initial Hessian evaluation. The algorithms highlight how efficiently the TS can be located on a reduced surface, where the rest of the degrees of freedom are minimized. The first method uses a nonpositive definite quasi-Newton update for the reduced degrees of freedom. The second uses Shepard interpolation to fit the Hessian and starts from a set of points that bound the TS. The third directly uses a finite difference scheme to calculate the reduced degrees of freedom of the Hessian of the entire system, and searches for the TS on the full potential energy surface. All three methods are tested on an epoxide hydrolase cluster, and the ring formations of cyclohexane and cyclobutenone. The results indicate that all the methods are able to converge quite rapidly to the correct TS, but that the finite difference approach is the most efficient.

The epoxidation of limonene over the TS-1 and Ti-SBA-15 catalysts.

PubMed

Wróblewska, Agnieszka

2014-11-28

Limonene belongs to a group of very important intermediates used in the production of fine chemicals. This monoterpene compound can be obtained from peels of oranges or lemon which are a (biomass) waste from the orange juice industry. Thus, limonene is a renewable, easy available and a relatively cheap compound. This work presents preliminary studies on the process of limonene epoxidation over zeolite type catalysts such as: TS-1 and Ti-SBA-15. In these studies methanol was used as a solvent and as an oxidizing agent a 60 wt % hydrogen peroxide solution was applied. The activity of each catalyst was investigated for four chosen temperatures (0 °C, 40 °C, 80 °C and 120 °C). The reaction time was changed from 0.5 to 24 h. For each catalyst the most beneficial conditions (the appropriate temperature and the reaction time) have been established. The obtained results were compared and the most active catalyst was chosen. These studies have also shown different possible ways of limonene transformation, not only in the direction of 1,2-epoxylimonene and its corresponding diol, but also in direction of carveol, carvone and perillyl alcohol-compounds with a lot of applications. The possible mechanisms of formation of the allylic oxidation products were proposed.

Suspicionless Searches.

ERIC Educational Resources Information Center

Zirkel, Perry A.

2000-01-01

In a federal case involving a vice-principal's pat-down search of middle-school students in a cafeteria (for a missing pizza knife), the court upheld the search, saying it was relatively unintrusive and met "TLO's" reasonable-suspicion standards. Principals need reasonable justification for searching a group. (Contains 18 references.)…

Meta Search Engines.

ERIC Educational Resources Information Center

Garman, Nancy

1999-01-01

Describes common options and features to consider in evaluating which meta search engine will best meet a searcher's needs. Discusses number and names of engines searched; other sources and specialty engines; search queries; other search options; and results options. (AEF)

Micro-matrix solid-phase dispersion coupled with MEEKC for quantitative analysis of lignans in Schisandrae Chinensis Fructus using molecular sieve TS-1 as a sorbent.

PubMed

Chu, Chu; Wei, Mengmeng; Wang, Shan; Zheng, Liqiong; He, Zheng; Cao, Jun; Yan, Jizhong

2017-09-15

A simple and effective method was developed for determining lignans in Schisandrae Chinensis Fructus by using a micro-matrix solid phase dispersion (MSPD) technique coupled with microemulsion electrokinetic chromatography (MEEKC). Molecular sieve, TS-1, was applied as a solid supporting material in micro MSPD extraction for the first time. Parameters that affect extraction efficiency, such as type of dispersant, mass ratio of the sample to the dispersant, grinding time, elution solvent and volume were optimized. The optimal extraction conditions involve dispersing 25mg of powdered Schisandrae samples with 50mg of TS-1 by a mortar and pestle. A grinding time of 150s was adopted. The blend was then transferred to a solid-phase extraction cartridge and the target analytes were eluted with 500μL of methanol. Moreover, several parameters affecting MEEKC separation were studied, including the type of oil, SDS concentration, type and concentration of cosurfactant, and concentration of organic modifier. A satisfactory linearity (R>0.9998) was obtained, and the calculated limits of quantitation were less than 2.77μg/mL. Finally, the micro MSPD-MEEKC method was successfully applied to the analysis of lignans in complex Schisandrae fructus samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Beyond the search surface: visual search and attentional engagement.

PubMed

Duncan, J; Humphreys, G

1992-05-01

Treisman (1991) described a series of visual search studies testing feature integration theory against an alternative (Duncan & Humphreys, 1989) in which feature and conjunction search are basically similar. Here the latter account is noted to have 2 distinct levels: (a) a summary of search findings in terms of stimulus similarities, and (b) a theory of how visual attention is brought to bear on relevant objects. Working at the 1st level, Treisman found that even when similarities were calibrated and controlled, conjunction search was much harder than feature search. The theory, however, can only really be tested at the 2nd level, because the 1st is an approximation. An account of the findings is developed at the 2nd level, based on the 2 processes of input-template matching and spreading suppression. New data show that, when both of these factors are controlled, feature and conjunction search are equally difficult. Possibilities for unification of the alternative views are considered.

Interest in Anesthesia as Reflected by Keyword Searches using Common Search Engines.

PubMed

Liu, Renyu; García, Paul S; Fleisher, Lee A

2012-01-23

Since current general interest in anesthesia is unknown, we analyzed internet keyword searches to gauge general interest in anesthesia in comparison with surgery and pain. The trend of keyword searches from 2004 to 2010 related to anesthesia and anaesthesia was investigated using Google Insights for Search. The trend of number of peer reviewed articles on anesthesia cited on PubMed and Medline from 2004 to 2010 was investigated. The average cost on advertising on anesthesia, surgery and pain was estimated using Google AdWords. Searching results in other common search engines were also analyzed. Correlation between year and relative number of searches was determined with p< 0.05 considered statistically significant. Searches for the keyword "anesthesia" or "anaesthesia" diminished since 2004 reflected by Google Insights for Search (p< 0.05). The search for "anesthesia side effects" is trending up over the same time period while the search for "anesthesia and safety" is trending down. The search phrase "before anesthesia" is searched more frequently than "preanesthesia" and the search for "before anesthesia" is trending up. Using "pain" as a keyword is steadily increasing over the years indicated. While different search engines may provide different total number of searching results (available posts), the ratios of searching results between some common keywords related to perioperative care are comparable, indicating similar trend. The peer reviewed manuscripts on "anesthesia" and the proportion of papers on "anesthesia and outcome" are trending up. Estimates for spending of advertising dollars are less for anesthesia-related terms when compared to that for pain or surgery due to relative smaller number of searching traffic. General interest in anesthesia (anaesthesia) as measured by internet searches appears to be decreasing. Pain, preanesthesia evaluation, anesthesia and outcome and side effects of anesthesia are the critical areas that anesthesiologists should

Study of B{yields}X{gamma} decays and determination of |V{sub td}/V{sub ts}|

DOE Office of Scientific and Technical Information (OSTI.GOV)

del Amo Sanchez, P.; Lees, J. P.; Poireau, V.

2010-09-01

Using a sample of 471x10{sup 6} BB events collected with the BABAR detector, we study the sum of seven exclusive final states B{yields}X{sub s(d){gamma}}, where X{sub s(d)} is a strange (nonstrange) hadronic system with a mass of up to 2.0 GeV/c{sup 2}. After correcting for unobserved decay modes, we obtain a branching fraction for b{yields}d{gamma} of (9.2{+-}2.0(stat){+-}2.3(syst))x10{sup -6} in this mass range, and a branching fraction for b{yields}s{gamma} of (23.0{+-}0.8(stat){+-}3.0(syst))x10{sup -5} in the same mass range. We find (B(b{yields}d{gamma})/B(b{yields}s{gamma}))=0.040{+-}0.009(stat){+-}0.010(syst), from which we determine |V{sub td}/V{sub ts}|=0.199{+-}0.022(stat){+-}0.024(syst){+-}0.002(th).

MIS High-Purity Plutonium Oxide Metal Oxidation Product TS707001 (SSR123): Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veirs, Douglas Kirk; Stroud, Mary Ann; Berg, John M.

A high-purity plutonium dioxide material from the Material Identification and Surveillance (MIS) Program inventory has been studied with regard to gas generation and corrosion in a storage environment. Sample TS707001 represents process plutonium oxides from several metal oxidation operations as well as impure and scrap plutonium from Hanford that are currently stored in 3013 containers. After calcination to 950°C, the material contained 86.98% plutonium with no major impurities. This study followed over time, the gas pressure of a sample with nominally 0.5 wt% water in a sealed container with an internal volume scaled to 1/500th of the volume of amore » 3013 container. Gas compositions were measured periodically over a six year period. The maximum observed gas pressure was 138 kPa. The increase over the initial pressure of 80 kPa was primarily due to generation of nitrogen and carbon dioxide gas in the first six months. Hydrogen and oxygen were minor components of the headspace gas. At the completion of the study, the internal components of the sealed container showed signs of corrosion, including pitting.« less

Using single top rapidity to measure V{sub td}, V{sub ts}, V{sub tb} at hadron colliders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aguilar-Saavedra, J. A.; Onofre, A.; Departamento de Fisica, Universidade do Minho, P-4710-057 Braga

2011-04-01

Single top production processes are usually regarded as the ones in which V{sub tb} can be directly measured at hadron colliders. We show that the analysis of the single top rapidity distribution in t-channel and tW production can also set direct limits on V{sub td}. At LHC with 10 fb{sup -1} at 14 TeV, the combined limits on V{sub td} may be reduced by almost a factor of 2 when the top rapidity distribution is used. This also implies that the limits on V{sub tb} can also be reduced by 15%, since both parameters, as well as V{sub ts}, mustmore » be simultaneously obtained from a global fit to data. At Tevatron, the exploitation of this distribution would require very high statistics.« less

Interest in Anesthesia as Reflected by Keyword Searches using Common Search Engines

PubMed Central