Sample records for optimize analyze repeat

  1. Ethanol production from glycerol using immobilized Pachysolen tannophilus during microaerated repeated-batch fermentor culture.

    PubMed

    Cha, Hye-Geun; Kim, Yi-Ok; Choi, Woon Yong; Kang, Do-Hyung; Lee, Hyeon-Yong; Jung, Kyung-Hwan

    2015-03-01

    Herein, we established a repeated-batch process for ethanol production from glycerol by immobilized Pachysolen tannophilus. The aim of this study was to develop a more practical and applicable ethanol production process for biofuel. In particular, using industrial-grade medium ingredients, the microaeration rate was optimized for maximization of the ethanol production, and the relevant metabolic parameters were then analyzed. The microaeration rate of 0.11 vvm, which is far lower than those occurring in a shaking flask culture, was found to be the optimal value for ethanol production from glycerol. In addition, it was found that, among those tested, Celite was a more appropriate carrier for the immobilization of P. tannophilus to induce production of ethanol from glycerol. Finally, through a repeated-batch culture, the ethanol yield (Ye/g) of 0.126 ± 0.017 g-ethanol/g-glycerol (n = 4) was obtained, and this value was remarkably comparable with a previous report. In the future, it is expected that the results of this study will be applied for the development of a more practical and profitable long-term ethanol production process, thanks to the industrial-grade medium preparation, simple immobilization method, and easy repeated-batch operation.

  2. 40 CFR 90.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Recheck the zero response. If it has changed by more than ±one percent of full scale, repeat the test. (6... operating adjustment using the appropriate fuel (see § 90.312) and purified synthetic air or zero-grade nitrogen. (2) Use of one of the following procedures is required for FID or HFID optimization: (i) The...

  3. An effective model for ergonomic optimization applied to a new automotive assembly line

    NASA Astrophysics Data System (ADS)

    Duraccio, Vincenzo; Elia, Valerio; Forcina, Antonio

    2016-06-01

    An efficient ergonomic optimization can lead to a significant improvement in production performance and a considerable reduction of costs. In the present paper new model for ergonomic optimization is proposed. The new approach is based on the criteria defined by National Institute of Occupational Safety and Health and, adapted to Italian legislation. The proposed model provides an ergonomic optimization, by analyzing ergonomic relations between manual work in correct conditions. The model includes a schematic and systematic analysis method of the operations, and identifies all possible ergonomic aspects to be evaluated. The proposed approach has been applied to an automotive assembly line, where the operation repeatability makes the optimization fundamental. The proposed application clearly demonstrates the effectiveness of the new approach.

  4. Compression of strings with approximate repeats.

    PubMed

    Allison, L; Edgoose, T; Dix, T I

    1998-01-01

    We describe a model for strings of characters that is loosely based on the Lempel Ziv model with the addition that a repeated substring can be an approximate match to the original substring; this is close to the situation of DNA, for example. Typically there are many explanations for a given string under the model, some optimal and many suboptimal. Rather than commit to one optimal explanation, we sum the probabilities over all explanations under the model because this gives the probability of the data under the model. The model has a small number of parameters and these can be estimated from the given string by an expectation-maximization (EM) algorithm. Each iteration of the EM algorithm takes O(n2) time and a few iterations are typically sufficient. O(n2) complexity is impractical for strings of more than a few tens of thousands of characters and a faster approximation algorithm is also given. The model is further extended to include approximate reverse complementary repeats when analyzing DNA strings. Tests include the recovery of parameter estimates from known sources and applications to real DNA strings.

  5. An effective model for ergonomic optimization applied to a new automotive assembly line

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

    Duraccio, Vincenzo; Elia, Valerio; Forcina, Antonio

    2016-06-08

    An efficient ergonomic optimization can lead to a significant improvement in production performance and a considerable reduction of costs. In the present paper new model for ergonomic optimization is proposed. The new approach is based on the criteria defined by National Institute of Occupational Safety and Health and, adapted to Italian legislation. The proposed model provides an ergonomic optimization, by analyzing ergonomic relations between manual work in correct conditions. The model includes a schematic and systematic analysis method of the operations, and identifies all possible ergonomic aspects to be evaluated. The proposed approach has been applied to an automotive assemblymore » line, where the operation repeatability makes the optimization fundamental. The proposed application clearly demonstrates the effectiveness of the new approach.« less

  6. Innovative Multimodal Physical Therapy Reduces Incidence of Repeat Manipulation under Anesthesia in Post-Total Knee Arthroplasty Patients Who Had an Initial Manipulation under Anesthesia.

    PubMed

    Chughtai, Morad; McGinn, Tanner; Bhave, Anil; Khan, Sabahat; Vashist, Megha; Khlopas, Anton; Mont, Michael A

    2016-11-01

    Manipulation under anesthesia (MUA) is performed for knee stiffness following a total knee arthroplasty (TKA) when nonoperative treatments fail. It is important to develop an optimal outpatient physical therapy protocol following an MUA, to avoid a repeat procedure. The purpose of this study was to evaluate and compare: (1) range of motion and (2) the rate of repeat MUA in patients who either underwent innovative multimodal physical therapy (IMMPT) or standard-of-care physical therapy (standard) following an MUA after a TKA. We performed a retrospective database study of patients who underwent an MUA following a TKA between January 2013 to December 2014 ( N  = 57). There were 16 (28%) men and 41 (72%) women who had a mean age of 59 years (range, 32-81 years). The patients were stratified into those who underwent IMMPT ( n  = 22) and those who underwent standard physical therapy ( n  = 35). The 6-month range of motion and rate of repeat manipulation between the two cohorts was analyzed by using Student t-test and Chi-square tests. In addition, we performed a Kaplan-Meier analysis of time to repeat MUA. The IMMPT cohort had a statistically significant higher proportion of TKAs with an optimal range of motion as compared with the standard cohort. There was statistically significant lower proportion of patients who underwent a repeat MUA in the IMMPT as compared with the standard cohort. There was also a significantly lower incidence and longer time to MUA in the IMMPT cohort as compared with the standard cohort in the Kaplan-Meier analysis. The group who underwent IMMPT utilizing Astym therapy had a significantly higher proportion of patients with optimal range of motion, which implies the potential efficacy of this regimen to improve range of motion. Furthermore, the IMMPT cohort had a significantly lower proportion of repeat manipulations as compared with the standard cohort, which implies that an IMMPT approach could potentially reduce the need for a repeat MUA. These findings warrant further investigation into outcomes of different rehab approaches. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Resource allocation for error resilient video coding over AWGN using optimization approach.

    PubMed

    An, Cheolhong; Nguyen, Truong Q

    2008-12-01

    The number of slices for error resilient video coding is jointly optimized with 802.11a-like media access control and the physical layers with automatic repeat request and rate compatible punctured convolutional code over additive white gaussian noise channel as well as channel times allocation for time division multiple access. For error resilient video coding, the relation between the number of slices and coding efficiency is analyzed and formulated as a mathematical model. It is applied for the joint optimization problem, and the problem is solved by a convex optimization method such as the primal-dual decomposition method. We compare the performance of a video communication system which uses the optimal number of slices with one that codes a picture as one slice. From numerical examples, end-to-end distortion of utility functions can be significantly reduced with the optimal slices of a picture especially at low signal-to-noise ratio.

  8. Device-independent secret-key-rate analysis for quantum repeaters

    NASA Astrophysics Data System (ADS)

    Holz, Timo; Kampermann, Hermann; Bruß, Dagmar

    2018-01-01

    The device-independent approach to quantum key distribution (QKD) aims to establish a secret key between two or more parties with untrusted devices, potentially under full control of a quantum adversary. The performance of a QKD protocol can be quantified by the secret key rate, which can be lower bounded via the violation of an appropriate Bell inequality in a setup with untrusted devices. We study secret key rates in the device-independent scenario for different quantum repeater setups and compare them to their device-dependent analogon. The quantum repeater setups under consideration are the original protocol by Briegel et al. [Phys. Rev. Lett. 81, 5932 (1998), 10.1103/PhysRevLett.81.5932] and the hybrid quantum repeater protocol by van Loock et al. [Phys. Rev. Lett. 96, 240501 (2006), 10.1103/PhysRevLett.96.240501]. For a given repeater scheme and a given QKD protocol, the secret key rate depends on a variety of parameters, such as the gate quality or the detector efficiency. We systematically analyze the impact of these parameters and suggest optimized strategies.

  9. Optimization of laser-induced breakdown spectroscopy for coal powder analysis with different particle flow diameters

    NASA Astrophysics Data System (ADS)

    Yao, Shunchun; Xu, Jialong; Dong, Xuan; Zhang, Bo; Zheng, Jianping; Lu, Jidong

    2015-08-01

    The on-line measurement of coal is extremely useful for emission control and combustion process optimization in coal-fired plant. Laser-induced breakdown spectroscopy was employed to directly analyze coal particle flow. A set of tapered tubes were proposed for beam-focusing the coal particle flow to different diameters. For optimizing the measurement of coal particle flow, the characteristics of laser-induced plasma, including optical breakdown, the relative standard deviation of repeated measurement, partial breakdown spectra ratio and line intensity, were carefully analyzed. The comparison of the plasma characteristics among coal particle flow with different diameters showed that air breakdown and the random change in plasma position relative to the collection optics could significantly influence on the line intensity and the reproducibility of measurement. It is demonstrated that the tapered tube with a diameter of 5.5 mm was particularly useful to enrich the coal particles in laser focus spot as well as to reduce the influence of air breakdown and random changes of plasma in the experiment.

  10. Decreased risk of prematurity after elective repeat cesarean delivery in Hispanics.

    PubMed

    Vilchez, Gustavo; Chelliah, Anushka; Bratley, Elaine; Bahado-Singh, Ray; Sokol, Robert

    2015-01-01

    The current recommendation is to delay elective repeat cesarean deliveries (ERCD) until 39 weeks to decrease prematurity risks. Prior reports suggest accelerated maturity of fetuses according to race (African-Americans and Asians). To analyze the effect of the Hispanic ethnicity on the prematurity risk after ERCD. The US Natality Database from 2004 to 2008 was reviewed. Inclusion criteria were singleton delivery, no trial of labor, repeat cesarean. Exclusion criteria were fetal anomalies, history of diabetes/hypertension related disorders. Outcomes analyzed were Apgar score, assisted ventilation, intensive care admission, surfactant/antibiotic use and seizures. Two groups were identified: non-Hispanic Whites (NHW) and Hispanic Whites (HW). Regression analysis was performed to calculate adjusted odds ratios. Deliveries at 36-40 weeks were studied with 40 weeks as the reference group. A total of 930421 ERCDs were identified, 396823 NHW and 236733 HW. For NHW, the risk of prematurity was lower at 39 weeks. For HW, there was no difference in the risks of prematurity at/beyond 38 weeks. There appears to be accelerated maturity with no increase in prematurity risk at 38 weeks in HW delivered by ERCD. Ethnicity can be considered for patient counseling and decision making regarding optimal timing of elective interventions.

  11. ConvAn: a convergence analyzing tool for optimization of biochemical networks.

    PubMed

    Kostromins, Andrejs; Mozga, Ivars; Stalidzans, Egils

    2012-01-01

    Dynamic models of biochemical networks usually are described as a system of nonlinear differential equations. In case of optimization of models for purpose of parameter estimation or design of new properties mainly numerical methods are used. That causes problems of optimization predictability as most of numerical optimization methods have stochastic properties and the convergence of the objective function to the global optimum is hardly predictable. Determination of suitable optimization method and necessary duration of optimization becomes critical in case of evaluation of high number of combinations of adjustable parameters or in case of large dynamic models. This task is complex due to variety of optimization methods, software tools and nonlinearity features of models in different parameter spaces. A software tool ConvAn is developed to analyze statistical properties of convergence dynamics for optimization runs with particular optimization method, model, software tool, set of optimization method parameters and number of adjustable parameters of the model. The convergence curves can be normalized automatically to enable comparison of different methods and models in the same scale. By the help of the biochemistry adapted graphical user interface of ConvAn it is possible to compare different optimization methods in terms of ability to find the global optima or values close to that as well as the necessary computational time to reach them. It is possible to estimate the optimization performance for different number of adjustable parameters. The functionality of ConvAn enables statistical assessment of necessary optimization time depending on the necessary optimization accuracy. Optimization methods, which are not suitable for a particular optimization task, can be rejected if they have poor repeatability or convergence properties. The software ConvAn is freely available on www.biosystems.lv/convan. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. [Discriminatory power of variable number on tandem repeats loci for genotyping Mycobacterium tuberculosis strains in China].

    PubMed

    Chen, H X; Cai, C; Liu, J Y; Zhang, Z G; Yuan, M; Jia, J N; Sun, Z G; Huang, H R; Gao, J M; Li, W M

    2017-06-10

    Objective: Using the standard genotype method, variable number of tandem repeats (VNTR), we constructed a VNTR database to cover all provinces and proposed a set of optimized VNTR loci combinations for each province, in order to improve the preventive and control programs on tuberculosis, in China. Methods: A total of 15 loci VNTR was used to analyze 4 116 Mycobacterium tuberculosis strains, isolated from national survey of Drug Resistant Tuberculosis, in 2007. Hunter-Gaston Index (HGI) was also used to analyze the discriminatory power of each VNTR site. A set combination of 12-VNTR, 10-VNTR, 8-VNTR and 5-VNTR was respectively constructed for each province, based on 1) epidemic characteristics of M. tuberculosis lineages in China, with high discriminatory power and genetic stability. Results: Through the completed 15 loci VNTR patterns of 3 966 strains under 96.36 % (3 966/4 116) coverage, we found seven high HGI loci (including QUB11b and MIRU26) as well as low stable loci (including QUB26, MIRU16, Mtub21 and QUB11b) in several areas. In all the 31 provinces, we found an optimization VNTR combination as 10-VNTR loci in Inner Mongolia, Chongqing and Heilongjiang, but with 8-VNTR combination shared in other provinces. Conclusions: It is necessary to not only use the VNTR database for tracing the source of infection and cluster of M. tuberculosis in the nation but also using the set of optimized VNTR combinations in monitoring those local epidemics and M. tuberculosis (genetics in local) population.

  13. Bioresorbable scaffolds for bone tissue engineering: optimal design, fabrication, mechanical testing and scale-size effects analysis.

    PubMed

    Coelho, Pedro G; Hollister, Scott J; Flanagan, Colleen L; Fernandes, Paulo R

    2015-03-01

    Bone scaffolds for tissue regeneration require an optimal trade-off between biological and mechanical criteria. Optimal designs may be obtained using topology optimization (homogenization approach) and prototypes produced using additive manufacturing techniques. However, the process from design to manufacture remains a research challenge and will be a requirement of FDA design controls to engineering scaffolds. This work investigates how the design to manufacture chain affects the reproducibility of complex optimized design characteristics in the manufactured product. The design and prototypes are analyzed taking into account the computational assumptions and the final mechanical properties determined through mechanical tests. The scaffold is an assembly of unit-cells, and thus scale size effects on the mechanical response considering finite periodicity are investigated and compared with the predictions from the homogenization method which assumes in the limit infinitely repeated unit cells. Results show that a limited number of unit-cells (3-5 repeated on a side) introduce some scale-effects but the discrepancies are below 10%. Higher discrepancies are found when comparing the experimental data to numerical simulations due to differences between the manufactured and designed scaffold feature shapes and sizes as well as micro-porosities introduced by the manufacturing process. However good regression correlations (R(2) > 0.85) were found between numerical and experimental values, with slopes close to 1 for 2 out of 3 designs. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

  14. Cuckoo Search Algorithm Based on Repeat-Cycle Asymptotic Self-Learning and Self-Evolving Disturbance for Function Optimization

    PubMed Central

    Wang, Jie-sheng; Li, Shu-xia; Song, Jiang-di

    2015-01-01

    In order to improve convergence velocity and optimization accuracy of the cuckoo search (CS) algorithm for solving the function optimization problems, a new improved cuckoo search algorithm based on the repeat-cycle asymptotic self-learning and self-evolving disturbance (RC-SSCS) is proposed. A disturbance operation is added into the algorithm by constructing a disturbance factor to make a more careful and thorough search near the bird's nests location. In order to select a reasonable repeat-cycled disturbance number, a further study on the choice of disturbance times is made. Finally, six typical test functions are adopted to carry out simulation experiments, meanwhile, compare algorithms of this paper with two typical swarm intelligence algorithms particle swarm optimization (PSO) algorithm and artificial bee colony (ABC) algorithm. The results show that the improved cuckoo search algorithm has better convergence velocity and optimization accuracy. PMID:26366164

  15. Evaluation of microextraction by packed sorbent, liquid-liquid microextraction and derivatization pretreatment of diet-derived phenolic acids in plasma by gas chromatography with triple quadrupole mass spectrometry.

    PubMed

    Bustamante, Luis; Cárdenas, Diana; von Baer, Dietrich; Pastene, Edgar; Duran-Sandoval, Daniel; Vergara, Carola; Mardones, Claudia

    2017-09-01

    Miniaturized sample pretreatments for the analysis of phenolic metabolites in plasma, involving protein precipitation, enzymatic deconjugation, extraction procedures, and different derivatization reactions were systematically evaluated. The analyses were conducted by gas chromatography with mass spectrometry for the evaluation of 40 diet-derived phenolic compounds. Enzyme purification was necessary for the phenolic deconjugation before extraction. Trimethylsilanization reagent and two different tetrabutylammonium salts for derivatization reactions were compared. The optimum reaction conditions were 50 μL of trimethylsilanization reagent at 90°C for 30 min, while tetrabutylammonium salts were associated with loss of sensitivity due to rapid activation of the inert gas chromatograph liner. Phenolic acids extractions from plasma were optimized. Optimal microextraction by packed sorbent performance was achieved using an octadecylsilyl packed bed and better recoveries for less polar compounds, such as methoxylated derivatives, were observed. Despite the low recovery for many analytes, repeatability using an automated extraction procedure in the gas chromatograph inlet was 2.5%. Instead, using liquid-liquid microextraction, better recoveries (80-110%) for all analytes were observed at the expense of repeatability (3.8-18.4%). The phenolic compounds in gerbil plasma samples, collected before and 4 h after the administration of a calafate extract, were analyzed with the optimized methodology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Comparison of three methods to assess individual skeletal maturity.

    PubMed

    Pasciuti, Enzo; Franchi, Lorenzo; Baccetti, Tiziano; Milani, Silvano; Farronato, Giampietro

    2013-09-01

    The knowledge of facial growth and development is fundamental to determine the optimal timing for different treatment procedures in the growing patient. To analyze the reproducibility of three methods in assessing individual skeletal maturity, and to evaluate any degree of concordance among them. In all, 100 growing subjects were enrolled to test three methods: the hand-wrist, cervical vertebral maturation (CVM), and medial phalanges of the third finger method (MP3). Four operators determined the skeletal maturity of the subjects to evaluate the reproducibility of each method. After 30 days the operators repeated the analysis to assess the repeatability of each method. Finally, one operator examined all subjects' radiographs to detect any concordance among the three methods. The weighted kappa values for inter-operator variability were 0.94, 0.91, and 0.90, for the WRI, CVM, and MP3 methods, respectively. The weighted kappa values for intra-operator variability were 0.92, 0.91, and 0.92, for the WRI, CVM, and MP3 methods, respectively. The three methods revealed a high degree of repeatability and reproducibility. Complete agreement among the three methods was observed in 70% of the analyzed samples. The CVM method has the advantage of not necessitating an additional radiograph. The MP3 method is a simple and practical alternative as it requires only a standard dental x-ray device.

  17. Novel protein domains and repeats in Drosophila melanogaster: insights into structure, function, and evolution.

    PubMed

    Ponting, C P; Mott, R; Bork, P; Copley, R R

    2001-12-01

    Sequence database searching methods such as BLAST, are invaluable for predicting molecular function on the basis of sequence similarities among single regions of proteins. Searches of whole databases however, are not optimized to detect multiple homologous regions within a single polypeptide. Here we have used the prospero algorithm to perform self-comparisons of all predicted Drosophila melanogaster gene products. Predicted repeats, and their homologs from all species, were analyzed further to detect hitherto unappreciated evolutionary relationships. Results included the identification of novel tandem repeats in the human X-linked retinitis pigmentosa type-2 gene product, repeated segments in cystinosin, associated with a defect in cystine transport, and 'nested' homologous domains in dysferlin, whose gene is mutated in limb girdle muscular dystrophy. Novel signaling domain families were found that may regulate the microtubule-based cytoskeleton and ubiquitin-mediated proteolysis, respectively. Two families of glycosyl hydrolases were shown to contain internal repetitions that hint at their evolution via a piecemeal, modular approach. In addition, three examples of fruit fly genes were detected with tandem exons that appear to have arisen via internal duplication. These findings demonstrate how completely sequenced genomes can be exploited to further understand the relationships between molecular structure, function, and evolution.

  18. Based Upon Repeat Pattern (BURP): an algorithm to characterize the long-term evolution of Staphylococcus aureus populations based on spa polymorphisms.

    PubMed

    Mellmann, Alexander; Weniger, Thomas; Berssenbrügge, Christoph; Rothgänger, Jörg; Sammeth, Michael; Stoye, Jens; Harmsen, Dag

    2007-10-29

    For typing of Staphylococcus aureus, DNA sequencing of the repeat region of the protein A (spa) gene is a well established discriminatory method for outbreak investigations. Recently, it was hypothesized that this region also reflects long-term epidemiology. However, no automated and objective algorithm existed to cluster different repeat regions. In this study, the Based Upon Repeat Pattern (BURP) implementation that is a heuristic variant of the newly described EDSI algorithm was investigated to infer the clonal relatedness of different spa types. For calibration of BURP parameters, 400 representative S. aureus strains with different spa types were characterized by MLST and clustered using eBURST as "gold standard" for their phylogeny. Typing concordance analysis between eBURST and BURP clustering (spa-CC) were performed using all possible BURP parameters to determine their optimal combination. BURP was subsequently evaluated with a strain collection reflecting the breadth of diversity of S. aureus (JCM 2002; 40:4544). In total, the 400 strains exhibited 122 different MLST types. eBURST grouped them into 23 clonal complexes (CC; 354 isolates) and 33 singletons (46 isolates). BURP clustering of spa types using all possible parameter combinations and subsequent comparison with eBURST CCs resulted in concordances ranging from 8.2 to 96.2%. However, 96.2% concordance was reached only if spa types shorter than 8 repeats were excluded, which resulted in 37% excluded spa types. Therefore, the optimal combination of the BURP parameters was "exclude spa types shorter than 5 repeats" and "cluster spa types into spa-CC if cost distances are less than 4" exhibiting 95.3% concordance to eBURST. This algorithm identified 24 spa-CCs, 40 singletons, and excluded only 7.8% spa types. Analyzing the natural population with these parameters, the comparison of whole-genome micro-array groupings (at the level of 0.31 Pearson correlation index) and spa-CCs gave a concordance of 87.1%; BURP spa-CCs vs. manually grouped spa types resulted in 95.7% concordance. BURP is the first automated and objective tool to infer clonal relatedness from spa repeat regions. It is able to extract an evolutionary signal rather congruent to MLST and micro-array data.

  19. Leaner and greener analysis of cannabinoids.

    PubMed

    Mudge, Elizabeth M; Murch, Susan J; Brown, Paula N

    2017-05-01

    There is an explosion in the number of labs analyzing cannabinoids in marijuana (Cannabis sativa L., Cannabaceae) but existing methods are inefficient, require expert analysts, and use large volumes of potentially environmentally damaging solvents. The objective of this work was to develop and validate an accurate method for analyzing cannabinoids in cannabis raw materials and finished products that is more efficient and uses fewer toxic solvents. An HPLC-DAD method was developed for eight cannabinoids in cannabis flowers and oils using a statistically guided optimization plan based on the principles of green chemistry. A single-laboratory validation determined the linearity, selectivity, accuracy, repeatability, intermediate precision, limit of detection, and limit of quantitation of the method. Amounts of individual cannabinoids above the limit of quantitation in the flowers ranged from 0.02 to 14.9% w/w, with repeatability ranging from 0.78 to 10.08% relative standard deviation. The intermediate precision determined using HorRat ratios ranged from 0.3 to 2.0. The LOQs for individual cannabinoids in flowers ranged from 0.02 to 0.17% w/w. This is a significant improvement over previous methods and is suitable for a wide range of applications including regulatory compliance, clinical studies, direct patient medical services, and commercial suppliers.

  20. Optimization of b-value distribution for biexponential diffusion-weighted MR imaging of normal prostate.

    PubMed

    Jambor, Ivan; Merisaari, Harri; Aronen, Hannu J; Järvinen, Jukka; Saunavaara, Jani; Kauko, Tommi; Borra, Ronald; Pesola, Marko

    2014-05-01

    To determine the optimal b-value distribution for biexponential diffusion-weighted imaging (DWI) of normal prostate using both a computer modeling approach and in vivo measurements. Optimal b-value distributions for the fit of three parameters (fast diffusion Df, slow diffusion Ds, and fraction of fast diffusion f) were determined using Monte-Carlo simulations. The optimal b-value distribution was calculated using four individual optimization methods. Eight healthy volunteers underwent four repeated 3 Tesla prostate DWI scans using both 16 equally distributed b-values and an optimized b-value distribution obtained from the simulations. The b-value distributions were compared in terms of measurement reliability and repeatability using Shrout-Fleiss analysis. Using low noise levels, the optimal b-value distribution formed three separate clusters at low (0-400 s/mm2), mid-range (650-1200 s/mm2), and high b-values (1700-2000 s/mm2). Higher noise levels resulted into less pronounced clustering of b-values. The clustered optimized b-value distribution demonstrated better measurement reliability and repeatability in Shrout-Fleiss analysis compared with 16 equally distributed b-values. The optimal b-value distribution was found to be a clustered distribution with b-values concentrated in the low, mid, and high ranges and was shown to improve the estimation quality of biexponential DWI parameters of in vivo experiments. Copyright © 2013 Wiley Periodicals, Inc.

  1. Genome-wide characterization and selection of expressed sequence tag simple sequence repeat primers for optimized marker distribution and reliability in peach

    USDA-ARS?s Scientific Manuscript database

    Expressed sequence tag (EST) simple sequence repeats (SSRs) in Prunus were mined, and flanking primers designed and used for genome-wide characterization and selection of primers to optimize marker distribution and reliability. A total of 12,618 contigs were assembled from 84,727 ESTs, along with 34...

  2. Precise and rapid isotopomic analysis by (1)H-(13)C 2D NMR: Application to triacylglycerol matrices.

    PubMed

    Merchak, Noelle; Silvestre, Virginie; Rouger, Laetitia; Giraudeau, Patrick; Rizk, Toufic; Bejjani, Joseph; Akoka, Serge

    2016-08-15

    An optimized HSQC sequence was tested and applied to triacylglycerol matrices to determine their isotopic and metabolomic profiles. Spectral aliasing and non-uniform sampling approaches were used to decrease the experimental time and to improve the resolution, respectively. An excellent long-term repeatability of signal integrals was achieved enabling to perform isotopic measurements. Thirty-two commercial vegetable oils were analyzed by this methodology. The results show that this method can be used to classify oil samples according to their geographical and botanical origins. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Optimum periodicity of repeated contractile actions applied in mass transport

    NASA Astrophysics Data System (ADS)

    Ahn, Sungsook; Lee, Sang Joon

    2015-01-01

    Dynamically repeated periodic patterns are abundant in natural and artificial systems, such as tides, heart beats, stock prices, and the like. The characteristic repeatability and periodicity are expected to be optimized in effective system-specific functions. In this study, such optimum periodicity is experimentally evaluated in terms of effective mass transport using one-valve and multi-valve systems working in contractile fluid flows. A set of nanoscale gating functions is utilized, operating in nanocomposite networks through which permeates selectively pass under characteristic contractile actions. Optimized contractile periodicity exists for effective energy impartment to flow in a one-valve system. In the sequential contractile actions for a multi-valve system, synchronization with the fluid flow is critical for effective mass transport. This study provides fundamental understanding on the various repeated periodic patterns and dynamic repeatability occurring in nature and mechanical systems, which are useful for broad applications.

  4. Test-Retest Repeatability of Myocardial Blood Flow Measurements using Rubidium-82 Positron Emission Tomography

    NASA Astrophysics Data System (ADS)

    Efseaff, Matthew

    Rubidium-82 positron emission tomography (PET) imaging has been proposed for routine myocardial blood flow (MBF) quantification. Few studies have investigated the test-retest repeatability of this method. Same-day repeatability of rest MBF imaging was optimized with a highly automated analysis program using image-derived input functions and a dual spillover correction (SOC). The effects of heterogeneous tracer infusion profiles and subject hemodynamics on test-retest repeatability were investigated at rest and during hyperemic stress. Factors affecting rest MBF repeatability included gender, suspected coronary artery disease, and dual SOC (p < 0.001). The best repeatability coefficient for same-day rest MBF was 0.20 mL/min/g using a six-minute scan-time, iterative reconstruction, dual SOC, resting rate-pressure-product (RPP) adjustment, and a left atrium image-derived input function. The serial study repeatabilities of the optimized protocol in subjects with homogeneous RPPs and tracer infusion profiles was 0.19 and 0.53 mL/min/g at rest and stress, and 0.95 for stress / rest myocardial flow reserve (MFR). Subjects with heterogeneous tracer infusion profiles and hemodynamic conditions had significantly less repeatable MBF measurements at rest, stress, and stress/rest flow reserve (p < 0.05).

  5. Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

    PubMed Central

    Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B.; Swartz, Harold

    2011-01-01

    Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO2 could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO2 during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO2 by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO2 at more than one site in the glioma and contralateral cerebral tissue. The pO2 of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO2 of 27 - 36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO2 of 7 - 12 mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO2 was investigated in rats breathing 100% O2. A significant increase in F98 tumor and contralateral brain pO2 was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO2. This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO2. PMID:22079559

  6. Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.

    PubMed

    Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B; Swartz, Harold

    2012-02-15

    Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO(2) could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO(2) during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO(2) by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO(2) at more than one site in the glioma and contralateral cerebral tissue. The pO(2) of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO(2) of 27-36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO(2) of 7-12mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO(2) was investigated in rats breathing 100% O(2). A significant increase in F98 tumor and contralateral brain pO(2) was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO(2). This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO(2). Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Investigation of vinegar production using a novel shaken repeated batch culture system.

    PubMed

    Schlepütz, Tino; Büchs, Jochen

    2013-01-01

    Nowadays, bioprocesses are developed or optimized on small scale. Also, vinegar industry is motivated to reinvestigate the established repeated batch fermentation process. As yet, there is no small-scale culture system for optimizing fermentation conditions for repeated batch bioprocesses. Thus, the aim of this study is to propose a new shaken culture system for parallel repeated batch vinegar fermentation. A new operation mode - the flushing repeated batch - was developed. Parallel repeated batch vinegar production could be established in shaken overflow vessels in a completely automated operation with only one pump per vessel. This flushing repeated batch was first theoretically investigated and then empirically tested. The ethanol concentration was online monitored during repeated batch fermentation by semiconductor gas sensors. It was shown that the switch from one ethanol substrate quality to different ethanol substrate qualities resulted in prolonged lag phases and durations of the first batches. In the subsequent batches the length of the fermentations decreased considerably. This decrease in the respective lag phases indicates an adaptation of the acetic acid bacteria mixed culture to the specific ethanol substrate quality. Consequently, flushing repeated batch fermentations on small scale are valuable for screening fermentation conditions and, thereby, improving industrial-scale bioprocesses such as vinegar production in terms of process robustness, stability, and productivity. Copyright © 2013 American Institute of Chemical Engineers.

  8. A novel method for repeatedly generating speckle patterns used in digital image correlation

    NASA Astrophysics Data System (ADS)

    Zhang, Juan; Sweedy, Ahmed; Gitzhofer, François; Baroud, Gamal

    2018-01-01

    Speckle patterns play a key role in Digital Image Correlation (DIC) measurement, and generating an optimal speckle pattern has been the goal for decades now. The usual method of generating a speckle pattern is by manually spraying the paint on the specimen. However, this makes it difficult to reproduce the optimal pattern for maintaining identical testing conditions and achieving consistent DIC results. This study proposed and evaluated a novel method using an atomization system to repeatedly generate speckle patterns. To verify the repeatability of the speckle patterns generated by this system, simulation and experimental studies were systematically performed. The results from both studies showed that the speckle patterns and, accordingly, the DIC measurements become highly accurate and repeatable using the proposed atomization system.

  9. Alcohol warnings in TV beer advertisements.

    PubMed

    Slater, M D; Domenech, M M

    1995-05-01

    Mandated warnings are among the few steps Congress has taken to influence the use of legal substances such as alcohol. The usefulness of such warnings in discouraging abuse of alcohol is, however, controversial. This study examines the impact of televised warnings on probable antecedents of belief change not examined in previous research: confidence in beliefs about beer risks or benefits, and cognitive responses to the advertisements. The present study (N = 75 male and female college students) tests four of the warnings recommended in Senate Bill 674 (1993--the "Thurmond bill") edited into randomly sampled television beer advertisements, using a between-subjects treatment-and-control experimental design. The four advertisements or advertisement/warning pairs were counterbalanced and analyzed as a repeated measures factor. The study indicated, as hypothesized, that subjects exposed to warnings tended to have less confidence in their generally skeptical assessments of beer risks--a likely precursor to belief change in resistant populations. Repeated exposure to the advertisements alone also appeared to lead to increased confidence in generally positive assessments of beer benefits, whereas repeated exposure to warnings led to decreased confidence in such assessments. Repeated exposure to warnings also may have primed negative reactions to subsequent beer advertisements. These results suggest mechanisms by which alcohol warnings may over time influence beliefs. Measures used here may serve as useful criterion variables in future studies on warnings. Further attention to optimizing warning content and presentation is recommended.

  10. Simultaneous separation/enrichment and detection of trace ciprofloxacin and lomefloxacin in food samples using thermosensitive smart polymers aqueous two-phase flotation system combined with HPLC.

    PubMed

    Lu, Yang; Chen, Bo; Yu, Miao; Han, Juan; Wang, Yun; Tan, Zhenjiang; Yan, Yongsheng

    2016-11-01

    Smart polymer aqueous two phase flotation system (SPATPF) is a new separation and enrichment technology that integrated the advantages of the three technologies, i.e., aqueous two phase system, smart polymer and flotation sublation. Ethylene oxide and propylene oxide copolymer (EOPO)-(NH4)2SO4 SPATPF is a pretreatment technique, and it is coupled with high-performance liquid chromatography to analyze the trace ciprofloxacin and lomefloxacin in real food samples. The optimized conditions of experiment were determined in the multi-factor experiment by using response surface methodology. The flotation efficiency of lomefloxacin and ciprofloxacin was 94.50% and 98.23% under the optimized conditions. The recycling experimentsshowed that the smart polymer EOPO could use repeatedly, which will reduce the cost in the future application. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Upper limb strength estimation of physically impaired persons using a musculoskeletal model: A sensitivity analysis.

    PubMed

    Carmichael, Marc G; Liu, Dikai

    2015-01-01

    Sensitivity of upper limb strength calculated from a musculoskeletal model was analyzed, with focus on how the sensitivity is affected when the model is adapted to represent a person with physical impairment. Sensitivity was calculated with respect to four muscle-tendon parameters: muscle peak isometric force, muscle optimal length, muscle pennation, and tendon slack length. Results obtained from a musculoskeletal model of average strength showed highest sensitivity to tendon slack length, followed by muscle optimal length and peak isometric force, which is consistent with existing studies. Muscle pennation angle was relatively insensitive. The analysis was repeated after adapting the musculoskeletal model to represent persons with varying severities of physical impairment. Results showed that utilizing the weakened model significantly increased the sensitivity of the calculated strength at the hand, with parameters previously insensitive becoming highly sensitive. This increased sensitivity presents a significant challenge in applications utilizing musculoskeletal models to represent impaired individuals.

  12. Optimal spatio-temporal design of water quality monitoring networks for reservoirs: Application of the concept of value of information

    NASA Astrophysics Data System (ADS)

    Maymandi, Nahal; Kerachian, Reza; Nikoo, Mohammad Reza

    2018-03-01

    This paper presents a new methodology for optimizing Water Quality Monitoring (WQM) networks of reservoirs and lakes using the concept of the value of information (VOI) and utilizing results of a calibrated numerical water quality simulation model. With reference to the value of information theory, water quality of every checkpoint with a specific prior probability differs in time. After analyzing water quality samples taken from potential monitoring points, the posterior probabilities are updated using the Baye's theorem, and VOI of the samples is calculated. In the next step, the stations with maximum VOI is selected as optimal stations. This process is repeated for each sampling interval to obtain optimal monitoring network locations for each interval. The results of the proposed VOI-based methodology is compared with those obtained using an entropy theoretic approach. As the results of the two methodologies would be partially different, in the next step, the results are combined using a weighting method. Finally, the optimal sampling interval and location of WQM stations are chosen using the Evidential Reasoning (ER) decision making method. The efficiency and applicability of the methodology are evaluated using available water quantity and quality data of the Karkheh Reservoir in the southwestern part of Iran.

  13. Dynamic airway pressure-time curve profile (Stress Index): a systematic review.

    PubMed

    Terragni, Pierpaolo; Bussone, Guido; Mascia, Luciana

    2016-01-01

    The assessment of respiratory mechanics at the bedside is necessary in order to identify the most protective ventilatory strategy. Indeed in the last 20 years, adverse effects of positive ventilation to the lung structures have led to a reappraisal of the objectives of mechanical ventilation. The ventilator setting requires repeated readjustment over the period of mechanical ventilation dependency and careful respiratory monitoring to minimize the risks, preventing further injury and permitting the lung and airways healing. Among the different methods that have been proposed and validated, the analysis of dynamic P-t curve (named Stress Index, SI) represents an adequate tool available at the bedside, repeatable and, therefore, able to identify the amount of overdistension occurring in the daily clinical practice, when modifying positive end-expiratory pressure. In this review we will analyze the evidence that supports respiratory mechanics assessment at the bedside and the application of the dynamic P/t curve profile (SI) to optimize protective ventilation in patients with acute respiratory failure.

  14. Microsatellites evolve more rapidly in humans than in chimpanzees

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

    Rubinsztein, D.C.; Leggo, J.; Amos, W.

    1995-12-10

    Microsatellites are highly polymorphic markers consisting of varying numbers of tandem repeats. At different loci, these repeats can consist of one to five nucleotides. Microsatellites have been used in many fields of genetics, including genetic mapping, linkage disequilibrium analyses, forensic studies, and population genetics. It is important that we understand their mutational processes better so that they can be exploited optimally for studies of human diversity and evolutionary genetics. We have analyzed 24 microsatellite loci in chimpanzees, East Anglians, and Sub-Saharan Africans. The stepwise-weighted genetic distances between the humans and the chimpanzees and between the two human populations were calculatedmore » according to the method described by Deka et al. The ratio of the genetic distances between the chimpanzees and the humans relative to that between the Africans and the East Anglians was more than 10 times smaller than expected. This suggests that microsatellites have evolved more rapidly in humans than in chimpanzees. 12 refs., 1 tab.« less

  15. A Feasability Study of the Wheel Electrostatic Spectrometer

    NASA Technical Reports Server (NTRS)

    Johansen, Michael Ryan; Phillips, James Ralph; Kelley, Joshua David; Mackey, Paul J.; Holbert, Eirik; Clements, Gregory R.; Calle, Carlos I.

    2014-01-01

    Mars rover missions rely on time-consuming, power-exhausting processes to analyze the Martian regolith. A low power electrostatic sensor in the wheels of a future Mars rover could be used to quickly determine when the rover is driving over a different type of regolith. The Electrostatics and Surface Physics Laboratory at NASA's Kennedy Space Center developed the Wheel Electrostatic Spectrometer as a feasibility study to investigate this option. In this paper, we discuss recent advances in this technology to increase the repeatability of the tribocharging experiments, along with supporting data. In addition, we discuss the development of a static elimination tool optimized for Martian conditions.

  16. Cognitive load in distributed and massed practice in virtual reality mastoidectomy simulation.

    PubMed

    Andersen, Steven Arild Wuyts; Mikkelsen, Peter Trier; Konge, Lars; Cayé-Thomasen, Per; Sørensen, Mads Sølvsten

    2016-02-01

    Cognitive load theory states that working memory is limited. This has implications for learning and suggests that reducing cognitive load (CL) could promote learning and skills acquisition. This study aims to explore the effect of repeated practice and simulator-integrated tutoring on CL in virtual reality (VR) mastoidectomy simulation. Prospective trial. Forty novice medical students performed 12 repeated virtual mastoidectomy procedures in the Visible Ear Simulator: 21 completed distributed practice with practice blocks spaced in time and 19 participants completed massed practice (all practices performed in 1 day). Participants were randomized for tutoring with the simulator-integrated tutor function. Cognitive load was estimated by measuring reaction time in a secondary task. Data were analyzed using linear mixed models for repeated measurements. The mean reaction time increased by 37% during the procedure compared with baseline, demonstrating that the procedure placed substantial cognitive demands. Repeated practice significantly lowered CL in the distributed practice group but not in massed practice group. In addition, CL was found to be further increased by 10.3% in the later and more complex stages of the procedure. The simulator-integrated tutor function did not have an impact on CL. Distributed practice decreased CL in repeated VR mastoidectomy training more consistently than was seen in massed practice. This suggests a possible effect of skills and memory consolidation occurring over time. To optimize technical skills learning, training should be organized as time-distributed practice rather than as a massed block of practice, which is common in skills-training courses. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Optimization and validation of a method using UHPLC-fluorescence for the analysis of polycyclic aromatic hydrocarbons in cold-pressed vegetable oils.

    PubMed

    Silva, Simone Alves da; Sampaio, Geni Rodrigues; Torres, Elizabeth Aparecida Ferraz da Silva

    2017-04-15

    Among the different food categories, the oils and fats are important sources of exposure to polycyclic aromatic hydrocarbons (PAHs), a group of organic chemical contaminants. The use of a validated method is essential to obtain reliable analytical results since the legislation establishes maximum limits in different foods. The objective of this study was to optimize and validate a method for the quantification of four PAHs [benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(a)pyrene] in vegetable oils. The samples were submitted to liquid-liquid extraction, followed by solid-phase extraction, and analyzed by ultra-high performance liquid chromatography. Under the optimized conditions, the validation parameters were evaluated according to the INMETRO Guidelines: linearity (r2 >0.99), selectivity (no matrix interference), limits of detection (0.08-0.30μgkg -1 ) and quantification (0.25-1.00μgkg -1 ), recovery (80.13-100.04%), repeatability and intermediate precision (<10% RSD). The method was found to be adequate for routine analysis of PAHs in the vegetable oils evaluated. Copyright © 2016. Published by Elsevier Ltd.

  18. CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons.

    PubMed

    Zhou, Yifan; Kumari, Daman; Sciascia, Nicholas; Usdin, Karen

    2016-01-01

    Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats.

  19. Optimization and validation of liquid chromatography and headspace-gas chromatography based methods for the quantitative determination of capsaicinoids, salicylic acid, glycol monosalicylate, methyl salicylate, ethyl salicylate, camphor and l-menthol in a topical formulation.

    PubMed

    Pauwels, Jochen; D'Autry, Ward; Van den Bossche, Larissa; Dewever, Cédric; Forier, Michel; Vandenwaeyenberg, Stephanie; Wolfs, Kris; Hoogmartens, Jos; Van Schepdael, Ann; Adams, Erwin

    2012-02-23

    Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace-gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R² values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks). Copyright © 2011 Elsevier B.V. All rights reserved.

  20. DNA analysis using an integrated microchip for multiplex PCR amplification and electrophoresis for reference samples.

    PubMed

    Le Roux, Delphine; Root, Brian E; Reedy, Carmen R; Hickey, Jeffrey A; Scott, Orion N; Bienvenue, Joan M; Landers, James P; Chassagne, Luc; de Mazancourt, Philippe

    2014-08-19

    A system that automatically performs the PCR amplification and microchip electrophoretic (ME) separation for rapid forensic short tandem repeat (STR) forensic profiling in a single disposable plastic chip is demonstrated. The microchip subassays were optimized to deliver results comparable to conventional benchtop methods. The microchip process was accomplished in sub-90 min compared with >2.5 h for the conventional approach. An infrared laser with a noncontact temperature sensing system was optimized for a 45 min PCR compared with the conventional 90 min amplification time. The separation conditions were optimized using LPA-co-dihexylacrylamide block copolymers specifically designed for microchip separations to achieve accurate DNA size calling in an effective length of 7 cm in a plastic microchip. This effective separation length is less than half of other reports for integrated STR analysis and allows a compact, inexpensive microchip design. This separation quality was maintained when integrated with microchip PCR. Thirty samples were analyzed conventionally and then compared with data generated by the microfluidic chip system. The microfluidic system allele calling was 100% concordant with the conventional process. This study also investigated allelic ladder consistency over time. The PCR-ME genetic profiles were analyzed using binning palettes generated from two sets of allelic ladders run three and six months apart. Using these binning palettes, no allele calling errors were detected in the 30 samples demonstrating that a microfluidic platform can be highly consistent over long periods of time.

  1. Measuring the level of agreement between a veterinary and a human point-of-care glucometer and a laboratory blood analyzer in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Acierno, Mark J; Schnellbacher, Rodney; Tully, Thomas N

    2012-12-01

    Although abnormalities in blood glucose concentrations in avian species are not as common as they are in mammals, the inability to provide point-of-care glucose measurement likely results in underreporting and missed treatment opportunities. A veterinary glucometer that uses different optimization codes for specific groups of animals has been produced. To obtain data for a psittacine bird-specific optimization code, as well as to calculate agreement between the veterinary glucometer, a standard human glucometer, and a laboratory analyzer, blood samples were obtained from 25 Hispaniolan Amazon parrots (Amazona ventralis) in a 2-phase study. In the initial phase, blood samples were obtained from 20 parrots twice at a 2-week interval. For each sample, the packed cell volume was determined, and the blood glucose concentration was measured by the veterinary glucometer. The rest of each sample was placed into a lithium heparin microtainer tube and centrifuged, and plasma was removed and frozen at -30 degrees C. Within 5 days, tubes were thawed, and blood glucose concentrations were measured with a laboratory analyzer. The data from both procedures were used to develop a psittacine bird-specific code. For the second phase of the study, the same procedure was repeated twice at a 2-week interval in 25 birds to determine agreement between the veterinary glucometer, a standard human glucometer, and a laboratory analyzer. Neither glucometer was in good agreement with the laboratory analyzer (veterinary glucometer bias, 9.0; level of agreement, -38.1 to 56.2; standard glucometer bias, 69.4; level of agreement -17.8 to 156.7). Based on these results, the use of handheld glucometers in the diagnostic testing of Hispaniolan Amazon parrots and other psittacine birds cannot be recommended.

  2. [The role of a single PCA3 test before a first negative prostate biopsy: 5-year follow-up].

    PubMed

    Bernardeau, S; Charles, T; Fromont-Hankard, G; Irani, J

    2017-04-01

    We report a 5-year follow-up of a cohort of patients who underwent a first prostate biopsy following a prostate cancer antigen 3 (PCA3) test. We reviewed consecutive patients who had in 2008 a single urinary PCA3 test using the Gen-Probe ® assay before a first prostate biopsy for a prostate-specific antigen (PSA) between 3 and 20ng/mL and/or a suspicious digital rectal examination. PCA3 performances were analyzed in 2008 and then in 2013 after taking into account the results of repeat biopsies. At initial biopsy in 2008, among the 125 patients study cohort, prostate cancer was diagnosed in 47 patients (37.6%). Abnormal digital rectal exam, PSA density, prostate volume and PCA3 score were significantly associated with prostate cancer diagnosis. PCA3 area under the curve of the receiver operating curve was 0.67 [95%CI: 0.57-0.76] with an optimal threshold of PCA3 in this sample of 24 units. During the 5-year follow-up, among the 78 patients with a negative prostate biopsy in 2008, 23 (29.5%) had a repeat prostate biopsy of whom 14 were diagnosed with prostate cancer. PCA3 score measured in 2008 was associated with prostate cancer diagnosis (P=0.002). All 9 patients with a negative repeat prostate biopsy had a PCA3 score below the cut-off while this was the case in only 2 patients among the 14 with a positive repeat prostate biopsy. The results of a single PCA3 test before a first prostate biopsy seems to be a useful aid in deciding whether to perform a repeat biopsy. 4. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE).

    PubMed

    Nekkanti, Vijaykumar; Marwah, Ashwani; Pillai, Raviraj

    2015-01-01

    Design of experiments (DOE), a component of Quality by Design (QbD), is systematic and simultaneous evaluation of process variables to develop a product with predetermined quality attributes. This article presents a case study to understand the effects of process variables in a bead milling process used for manufacture of drug nanoparticles. Experiments were designed and results were computed according to a 3-factor, 3-level face-centered central composite design (CCD). The factors investigated were motor speed, pump speed and bead volume. Responses analyzed for evaluating these effects and interactions were milling time, particle size and process yield. Process validation batches were executed using the optimum process conditions obtained from software Design-Expert® to evaluate both the repeatability and reproducibility of bead milling technique. Milling time was optimized to <5 h to obtain the desired particle size (d90 < 400 nm). The desirability function used to optimize the response variables and observed responses were in agreement with experimental values. These results demonstrated the reliability of selected model for manufacture of drug nanoparticles with predictable quality attributes. The optimization of bead milling process variables by applying DOE resulted in considerable decrease in milling time to achieve the desired particle size. The study indicates the applicability of DOE approach to optimize critical process parameters in the manufacture of drug nanoparticles.

  4. Addressing forecast uncertainty impact on CSP annual performance

    NASA Astrophysics Data System (ADS)

    Ferretti, Fabio; Hogendijk, Christopher; Aga, Vipluv; Ehrsam, Andreas

    2017-06-01

    This work analyzes the impact of weather forecast uncertainty on the annual performance of a Concentrated Solar Power (CSP) plant. Forecast time series has been produced by a commercial forecast provider using the technique of hindcasting for the full year 2011 in hourly resolution for Ouarzazate, Morocco. Impact of forecast uncertainty has been measured on three case studies, representing typical tariff schemes observed in recent CSP projects plus a spot market price scenario. The analysis has been carried out using an annual performance model and a standard dispatch optimization algorithm based on dynamic programming. The dispatch optimizer has been demonstrated to be a key requisite to maximize the annual revenues depending on the price scenario, harvesting the maximum potential out of the CSP plant. Forecasting uncertainty affects the revenue enhancement outcome of a dispatch optimizer depending on the error level and the price function. Results show that forecasting accuracy of direct solar irradiance (DNI) is important to make best use of an optimized dispatch but also that a higher number of calculation updates can partially compensate this uncertainty. Improvement in revenues can be significant depending on the price profile and the optimal operation strategy. Pathways to achieve better performance are presented by having more updates both by repeatedly generating new optimized trajectories but also more often updating weather forecasts. This study shows the importance of working on DNI weather forecasting for revenue enhancement as well as selecting weather services that can provide multiple updates a day and probabilistic forecast information.

  5. Trace DNA Sampling Success from Evidence Items Commonly Encountered in Forensic Casework.

    PubMed

    Dziak, Renata; Peneder, Amy; Buetter, Alicia; Hageman, Cecilia

    2018-05-01

    Trace DNA analysis is a significant part of a forensic laboratory's workload. Knowing optimal sampling strategies and item success rates for particular item types can assist in evidence selection and examination processes and shorten turnaround times. In this study, forensic short tandem repeat (STR) casework results were reviewed to determine how often STR profiles suitable for comparison were obtained from "handler" and "wearer" areas of 764 items commonly submitted for examination. One hundred and fifty-five (155) items obtained from volunteers were also sampled. Items were analyzed for best sampling location and strategy. For casework items, headwear and gloves provided the highest success rates. Experimentally, eyeglasses and earphones, T-shirts, fabric gloves and watches provided the highest success rates. Eyeglasses and latex gloves provided optimal results if the entire surfaces were swabbed. In general, at least 10%, and up to 88% of all trace DNA analyses resulted in suitable STR profiles for comparison. © 2017 American Academy of Forensic Sciences.

  6. High-throughput STR analysis for DNA database using direct PCR.

    PubMed

    Sim, Jeong Eun; Park, Su Jeong; Lee, Han Chul; Kim, Se-Yong; Kim, Jong Yeol; Lee, Seung Hwan

    2013-07-01

    Since the Korean criminal DNA database was launched in 2010, we have focused on establishing an automated DNA database profiling system that analyzes short tandem repeat loci in a high-throughput and cost-effective manner. We established a DNA database profiling system without DNA purification using a direct PCR buffer system. The quality of direct PCR procedures was compared with that of conventional PCR system under their respective optimized conditions. The results revealed not only perfect concordance but also an excellent PCR success rate, good electropherogram quality, and an optimal intra/inter-loci peak height ratio. In particular, the proportion of DNA extraction required due to direct PCR failure could be minimized to <3%. In conclusion, the newly developed direct PCR system can be adopted for automated DNA database profiling systems to replace or supplement conventional PCR system in a time- and cost-saving manner. © 2013 American Academy of Forensic Sciences Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.

  7. Direct liquid chromatography method for the simultaneous quantification of hydroxytyrosol and tyrosol in red wines.

    PubMed

    Piñeiro, Zulema; Cantos-Villar, Emma; Palma, Miguel; Puertas, Belen

    2011-11-09

    A validated HPLC method with fluorescence detection for the simultaneous quantification of hydroxytyrosol and tyrosol in red wines is described. Detection conditions for both compounds were optimized (excitation at 279 and 278 and emission at 631 and 598 nm for hydroxytyrosol and tyrosol, respectively). The validation of the analytical method was based on selectivity, linearity, robustness, detection and quantification limits, repeatability, and recovery. The detection and quantification limits in red wines were set at 0.023 and 0.076 mg L(-1) for hydroxytyrosol and at 0.007 and 0.024 mg L(-1) for tyrosol determination, respectively. Precision values, both within-day and between-day (n = 5), remained below 3% for both compounds. In addition, a fractional factorial experimental design was developed to analyze the influence of six different conditions on analysis. The final optimized HPLC-fluorescence method allowed the analysis of 30 nonpretreated Spanish red wines to evaluate their hydroxytyrosol and tyrosol contents.

  8. Detection of the ice assertion on aircraft using empirical mode decomposition enhanced by multi-objective optimization

    NASA Astrophysics Data System (ADS)

    Bagherzadeh, Seyed Amin; Asadi, Davood

    2017-05-01

    In search of a precise method for analyzing nonlinear and non-stationary flight data of an aircraft in the icing condition, an Empirical Mode Decomposition (EMD) algorithm enhanced by multi-objective optimization is introduced. In the proposed method, dissimilar IMF definitions are considered by the Genetic Algorithm (GA) in order to find the best decision parameters of the signal trend. To resolve disadvantages of the classical algorithm caused by the envelope concept, the signal trend is estimated directly in the proposed method. Furthermore, in order to simplify the performance and understanding of the EMD algorithm, the proposed method obviates the need for a repeated sifting process. The proposed enhanced EMD algorithm is verified by some benchmark signals. Afterwards, the enhanced algorithm is applied to simulated flight data in the icing condition in order to detect the ice assertion on the aircraft. The results demonstrate the effectiveness of the proposed EMD algorithm in aircraft ice detection by providing a figure of merit for the icing severity.

  9. Heritability of targeted gene modifications induced by plant-optimized CRISPR systems.

    PubMed

    Mao, Yanfei; Botella, Jose Ramon; Zhu, Jian-Kang

    2017-03-01

    The Streptococcus-derived CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated protein 9) system has emerged as a very powerful tool for targeted gene modifications in many living organisms including plants. Since the first application of this system for plant gene modification in 2013, this RNA-guided DNA endonuclease system has been extensively engineered to meet the requirements of functional genomics and crop trait improvement in a number of plant species. Given its short history, the emphasis of many studies has been the optimization of the technology to improve its reliability and efficiency to generate heritable gene modifications in plants. Here we review and analyze the features of customized CRISPR/Cas9 systems developed for plant genetic studies and crop breeding. We focus on two essential aspects: the heritability of gene modifications induced by CRISPR/Cas9 and the factors affecting its efficiency, and we provide strategies for future design of systems with improved activity and heritability in plants.

  10. Meeting the nutritional requirements of hospitalized patients: an interdisciplinary approach to hospital catering.

    PubMed

    Iff, S; Leuenberger, M; Rösch, S; Knecht, G; Tanner, B; Stanga, Z

    2008-12-01

    The study served to assure the quality of our catering, to locate problems, and to define further optimization measures at the Bern University Hospital. The main objective was to investigate whether the macronutrient and energy content of the hospital food complies with the nutritional value calculated from recipes as well as with the recommendations issued by the German Nutrition Society (DGE). Prospective, randomized, single-center quality study. Complete standard meals were analyzed over seven consecutive days for each seasonal menu plan in one year. The quantitative and qualitative chemical content of a randomly chosen menu was determined by an external laboratory. Sixty meals were analyzed. The amount of food served and the ratio of macronutrients contained in the food satisfactorily reflected all recipes. Not surprisingly, the energy and carbohydrate content of our meals was lower than in the German recommendations, because the report of the DGE is based on the sum of meals, snacks and beverages consumed over the whole day and not only on the main meals, as we analyzed. Periodic quality control is essential in order to meet recommendations and patients' expectations in hospital catering. Members of the catering service should undergo regularly repeated skills training, and continuous efforts should be made to ensure portion size for all delivered meals. Food provision in the hospital setting needs to be tailored to meet the demands of the different patient groups, to optimize nutritional support, and to minimize food waste.

  11. Laplace Inversion of Low-Resolution NMR Relaxometry Data Using Sparse Representation Methods

    PubMed Central

    Berman, Paula; Levi, Ofer; Parmet, Yisrael; Saunders, Michael; Wiesman, Zeev

    2013-01-01

    Low-resolution nuclear magnetic resonance (LR-NMR) relaxometry is a powerful tool that can be harnessed for characterizing constituents in complex materials. Conversion of the relaxation signal into a continuous distribution of relaxation components is an ill-posed inverse Laplace transform problem. The most common numerical method implemented today for dealing with this kind of problem is based on L2-norm regularization. However, sparse representation methods via L1 regularization and convex optimization are a relatively new approach for effective analysis and processing of digital images and signals. In this article, a numerical optimization method for analyzing LR-NMR data by including non-negativity constraints and L1 regularization and by applying a convex optimization solver PDCO, a primal-dual interior method for convex objectives, that allows general linear constraints to be treated as linear operators is presented. The integrated approach includes validation of analyses by simulations, testing repeatability of experiments, and validation of the model and its statistical assumptions. The proposed method provides better resolved and more accurate solutions when compared with those suggested by existing tools. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 72–88, 2013. PMID:23847452

  12. Laplace Inversion of Low-Resolution NMR Relaxometry Data Using Sparse Representation Methods.

    PubMed

    Berman, Paula; Levi, Ofer; Parmet, Yisrael; Saunders, Michael; Wiesman, Zeev

    2013-05-01

    Low-resolution nuclear magnetic resonance (LR-NMR) relaxometry is a powerful tool that can be harnessed for characterizing constituents in complex materials. Conversion of the relaxation signal into a continuous distribution of relaxation components is an ill-posed inverse Laplace transform problem. The most common numerical method implemented today for dealing with this kind of problem is based on L 2 -norm regularization. However, sparse representation methods via L 1 regularization and convex optimization are a relatively new approach for effective analysis and processing of digital images and signals. In this article, a numerical optimization method for analyzing LR-NMR data by including non-negativity constraints and L 1 regularization and by applying a convex optimization solver PDCO, a primal-dual interior method for convex objectives, that allows general linear constraints to be treated as linear operators is presented. The integrated approach includes validation of analyses by simulations, testing repeatability of experiments, and validation of the model and its statistical assumptions. The proposed method provides better resolved and more accurate solutions when compared with those suggested by existing tools. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 72-88, 2013.

  13. Comparative Robustness of Recent Methods for Analyzing Multivariate Repeated Measures Designs

    ERIC Educational Resources Information Center

    Seco, Guillermo Vallejo; Gras, Jaime Arnau; Garcia, Manuel Ato

    2007-01-01

    This study evaluated the robustness of two recent methods for analyzing multivariate repeated measures when the assumptions of covariance homogeneity and multivariate normality are violated. Specifically, the authors' work compares the performance of the modified Brown-Forsythe (MBF) procedure and the mixed-model procedure adjusted by the…

  14. Optimal architectures for long distance quantum communication.

    PubMed

    Muralidharan, Sreraman; Li, Linshu; Kim, Jungsang; Lütkenhaus, Norbert; Lukin, Mikhail D; Jiang, Liang

    2016-02-15

    Despite the tremendous progress of quantum cryptography, efficient quantum communication over long distances (≥ 1000 km) remains an outstanding challenge due to fiber attenuation and operation errors accumulated over the entire communication distance. Quantum repeaters (QRs), as a promising approach, can overcome both photon loss and operation errors, and hence significantly speedup the communication rate. Depending on the methods used to correct loss and operation errors, all the proposed QR schemes can be classified into three categories (generations). Here we present the first systematic comparison of three generations of quantum repeaters by evaluating the cost of both temporal and physical resources, and identify the optimized quantum repeater architecture for a given set of experimental parameters for use in quantum key distribution. Our work provides a roadmap for the experimental realizations of highly efficient quantum networks over transcontinental distances.

  15. Optimal architectures for long distance quantum communication

    PubMed Central

    Muralidharan, Sreraman; Li, Linshu; Kim, Jungsang; Lütkenhaus, Norbert; Lukin, Mikhail D.; Jiang, Liang

    2016-01-01

    Despite the tremendous progress of quantum cryptography, efficient quantum communication over long distances (≥1000 km) remains an outstanding challenge due to fiber attenuation and operation errors accumulated over the entire communication distance. Quantum repeaters (QRs), as a promising approach, can overcome both photon loss and operation errors, and hence significantly speedup the communication rate. Depending on the methods used to correct loss and operation errors, all the proposed QR schemes can be classified into three categories (generations). Here we present the first systematic comparison of three generations of quantum repeaters by evaluating the cost of both temporal and physical resources, and identify the optimized quantum repeater architecture for a given set of experimental parameters for use in quantum key distribution. Our work provides a roadmap for the experimental realizations of highly efficient quantum networks over transcontinental distances. PMID:26876670

  16. Optimal architectures for long distance quantum communication

    NASA Astrophysics Data System (ADS)

    Muralidharan, Sreraman; Li, Linshu; Kim, Jungsang; Lütkenhaus, Norbert; Lukin, Mikhail D.; Jiang, Liang

    2016-02-01

    Despite the tremendous progress of quantum cryptography, efficient quantum communication over long distances (≥1000 km) remains an outstanding challenge due to fiber attenuation and operation errors accumulated over the entire communication distance. Quantum repeaters (QRs), as a promising approach, can overcome both photon loss and operation errors, and hence significantly speedup the communication rate. Depending on the methods used to correct loss and operation errors, all the proposed QR schemes can be classified into three categories (generations). Here we present the first systematic comparison of three generations of quantum repeaters by evaluating the cost of both temporal and physical resources, and identify the optimized quantum repeater architecture for a given set of experimental parameters for use in quantum key distribution. Our work provides a roadmap for the experimental realizations of highly efficient quantum networks over transcontinental distances.

  17. A new implementation of the programming system for structural synthesis (PROSSS-2)

    NASA Technical Reports Server (NTRS)

    Rogers, James L., Jr.

    1984-01-01

    This new implementation of the PROgramming System for Structural Synthesis (PROSSS-2) combines a general-purpose finite element computer program for structural analysis, a state-of-the-art optimization program, and several user-supplied, problem-dependent computer programs. The results are flexibility of the optimization procedure, organization, and versatility of the formulation of constraints and design variables. The analysis-optimization process results in a minimized objective function, typically the mass. The analysis and optimization programs are executed repeatedly by looping through the system until the process is stopped by a user-defined termination criterion. However, some of the analysis, such as model definition, need only be one time and the results are saved for future use. The user must write some small, simple FORTRAN programs to interface between the analysis and optimization programs. One of these programs, the front processor, converts the design variables output from the optimizer into the suitable format for input into the analyzer. Another, the end processor, retrieves the behavior variables and, optionally, their gradients from the analysis program and evaluates the objective function and constraints and optionally their gradients. These quantities are output in a format suitable for input into the optimizer. These user-supplied programs are problem-dependent because they depend primarily upon which finite elements are being used in the model. PROSSS-2 differs from the original PROSSS in that the optimizer and front and end processors have been integrated into the finite element computer program. This was done to reduce the complexity and increase portability of the system, and to take advantage of the data handling features found in the finite element program.

  18. Results of repeated transsphenoidal surgery in Cushing's disease. Long-term follow-up.

    PubMed

    Valderrábano, Pablo; Aller, Javier; García-Valdecasas, Leopoldo; García-Uría, José; Martín, Laura; Palacios, Nuria; Estrada, Javier

    2014-04-01

    Transsphenoidal surgery (TSS) is the treatment of choice for Cushing's disease (CD). However, the best treatment option when hypercortisolism persists or recurs remains unknown. The aim of this study was to analyze the short and long-term outcome of repeat TSS in this situation and to search for response predictors. Data from 26 patients with persistent (n=11) or recurrent (n=15) hypercortisolism who underwent repeat surgery by a single neurosurgeon between 1982 and 2009 were retrospectively analyzed. Remission was defined as normalization of urinary free cortisol (UFC) levels, and recurrence as presence of elevated UFC levels after having achieved remission. The following potential outcome predictors were analyzed: adrenal status (persistence or recurrence) after initial TSS, tumor identification in imaging tests, degree of hypercortisolism before repeat TSS, same/different surgeon in both TSS, and time to repeat surgery. Immediate postoperative remission was achieved in 12 patients (46.2%). Five of the 10 patients with available follow-up data relapsed after surgery (median time to recurrence, 13 months). New hormone deficiencies were seen in seven patients (37%), and two patients had cerebrospinal fluid leakage. No other major complications occurred. None of the preoperative factors analyzed was predictive of surgical outcome. When compared to initial surgery, repeat TSS for CD is associated to a lower remission rate and a higher risk of recurrence and complications. Further studies are needed to define outcome predictors. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  19. Comparison of Two Procedures for Analyzing Small Sets of Repeated Measures Data

    ERIC Educational Resources Information Center

    Vallejo, Guillermo; Livacic-Rojas, Pablo

    2005-01-01

    This article compares two methods for analyzing small sets of repeated measures data under normal and non-normal heteroscedastic conditions: a mixed model approach with the Kenward-Roger correction and a multivariate extension of the modified Brown-Forsythe (BF) test. These procedures differ in their assumptions about the covariance structure of…

  20. Design and optimization of interplanetary spacecraft trajectories

    NASA Astrophysics Data System (ADS)

    McConaghy, Thomas Troy

    Scientists involved in space exploration are always looking for ways to accomplish more with their limited budgets. Mission designers can decrease operational costs by crafting trajectories with low launch costs, short time-of-flight, or low propellant requirements. Gravity-assist maneuvers and low-thrust, high-efficiency ion propulsion can be of great help. This dissertation describes advances in methods to design and optimize interplanetary spacecraft trajectories. particularly for missions using gravity-assist maneuvers or low-thrust engines (or both). The first part of this dissertation describes a new, efficient, two-step methodology to design and optimize low-thrust gravity-assist trajectories. Models for the launch vehicle, solar arrays, and engines are introduced and several examples of optimized trajectories are presented. For example, a 3.7-year Earth-Venus-Earth-Mars-Jupiter flyby trajectory with maximized final mass is described. The way that the parameterization of the optimization problem affects convergence speed and reliability is also investigated. The choice of coordinate system is shown to make a significant difference. The second part of this dissertation describes a way to construct Earth-Mars cycler trajectories---periodic orbits that repeatedly encounter Earth and Mars, yet require little or no propellant. We find that well-known cyclers, such as the Aldrin cycler, are special cases of a much larger family of cyclers. In fact, so many new cyclers are found that a comprehensive naming system (nomenclature) is proposed. One particularly promising new cycler, the "ballistic S1L1 cycler" is analyzed in greater detail.

  1. Exposing Students to Repeat Photography: Increasing Cultural Understanding on a Short-Term Study Abroad

    ERIC Educational Resources Information Center

    Lemmons, Kelly K.; Brannstrom, Christian; Hurd, Danielle

    2014-01-01

    Traditionally, repeat photography has been used to analyze land cover change. This paper describes how repeat photography may be used as a tool to enhance the short-term study abroad experience by facilitating cultural interaction and understanding. We present evidence from two cases and suggest a five-step repeat photography method for educators…

  2. Improving cellulase productivity of Penicillium oxalicum RE-10 by repeated fed-batch fermentation strategy.

    PubMed

    Han, Xiaolong; Song, Wenxia; Liu, Guodong; Li, Zhonghai; Yang, Piao; Qu, Yinbo

    2017-03-01

    Medium optimization and repeated fed-batch fermentation were performed to improve the cellulase productivity by P. oxalicum RE-10 in submerged fermentation. First, Plackett-Burman design (PBD) and central composite design (CCD) were used to optimize the medium for cellulase production. PBD demonstrated wheat bran and NaNO 3 had significant influences on cellulase production. The CCD results showed the maximum filter paper activity (FPA) production of 8.61U/mL could be achieved in Erlenmeyer flasks. The maximal FPA reached 12.69U/mL by submerged batch fermentation in a 7.5-L stirred tank, 1.76-fold higher than that on the original medium. Then, the repeated fed-batch fermentation strategy was performed successfully for increasing the cellulase productivity from 105.75U/L/h in batch fermentation to 158.38U/L/h. The cellulase activity and the glucan conversion of delignined corn cob residue hydrolysis had no significant difference between the enzymes sampled from different cycles of the repeated fed-batch fermentation and that from batch culture. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Cascade Optimization Strategy for Aircraft and Air-Breathing Propulsion System Concepts

    NASA Technical Reports Server (NTRS)

    Patnaik, Surya N.; Lavelle, Thomas M.; Hopkins, Dale A.; Coroneos, Rula M.

    1996-01-01

    Design optimization for subsonic and supersonic aircraft and for air-breathing propulsion engine concepts has been accomplished by soft-coupling the Flight Optimization System (FLOPS) and the NASA Engine Performance Program analyzer (NEPP), to the NASA Lewis multidisciplinary optimization tool COMETBOARDS. Aircraft and engine design problems, with their associated constraints and design variables, were cast as nonlinear optimization problems with aircraft weight and engine thrust as the respective merit functions. Because of the diversity of constraint types and the overall distortion of the design space, the most reliable single optimization algorithm available in COMETBOARDS could not produce a satisfactory feasible optimum solution. Some of COMETBOARDS' unique features, which include a cascade strategy, variable and constraint formulations, and scaling devised especially for difficult multidisciplinary applications, successfully optimized the performance of both aircraft and engines. The cascade method has two principal steps: In the first, the solution initiates from a user-specified design and optimizer, in the second, the optimum design obtained in the first step with some random perturbation is used to begin the next specified optimizer. The second step is repeated for a specified sequence of optimizers or until a successful solution of the problem is achieved. A successful solution should satisfy the specified convergence criteria and have several active constraints but no violated constraints. The cascade strategy available in the combined COMETBOARDS, FLOPS, and NEPP design tool converges to the same global optimum solution even when it starts from different design points. This reliable and robust design tool eliminates manual intervention in the design of aircraft and of air-breathing propulsion engines where it eases the cycle analysis procedures. The combined code is also much easier to use, which is an added benefit. This paper describes COMETBOARDS and its cascade strategy and illustrates the capability of the combined design tool through the optimization of a subsonic aircraft and a high-bypass-turbofan wave-rotor-topped engine.

  4. Multi-Target Tracking via Mixed Integer Optimization

    DTIC Science & Technology

    2016-05-13

    solving these two problems separately, however few algorithms attempt to solve these simultaneously and even fewer utilize optimization. In this paper we...introduce a new mixed integer optimization (MIO) model which solves the data association and trajectory estimation problems simultaneously by minimizing...Kalman filter [5], which updates the trajectory estimates before the algorithm progresses forward to the next scan. This process repeats sequentially

  5. Breast Radiotherapy with Mixed Energy Photons; a Model for Optimal Beam Weighting.

    PubMed

    Birgani, Mohammadjavad Tahmasebi; Fatahiasl, Jafar; Hosseini, Seyed Mohammad; Bagheri, Ali; Behrooz, Mohammad Ali; Zabiehzadeh, Mansour; Meskani, Reza; Gomari, Maryam Talaei

    2015-01-01

    Utilization of high energy photons (>10 MV) with an optimal weight using a mixed energy technique is a practical way to generate a homogenous dose distribution while maintaining adequate target coverage in intact breast radiotherapy. This study represents a model for estimation of this optimal weight for day to day clinical usage. For this purpose, treatment planning computed tomography scans of thirty-three consecutive early stage breast cancer patients following breast conservation surgery were analyzed. After delineation of the breast clinical target volume (CTV) and placing opposed wedge paired isocenteric tangential portals, dosimeteric calculations were conducted and dose volume histograms (DVHs) were generated, first with pure 6 MV photons and then these calculations were repeated ten times with incorporating 18 MV photons (ten percent increase in weight per step) in each individual patient. For each calculation two indexes including maximum dose in the breast CTV (Dmax) and the volume of CTV which covered with 95% Isodose line (VCTV, 95%IDL) were measured according to the DVH data and then normalized values were plotted in a graph. The optimal weight of 18 MV photons was defined as the intersection point of Dmax and VCTV, 95%IDL graphs. For creating a model to predict this optimal weight multiple linear regression analysis was used based on some of the breast and tangential field parameters. The best fitting model for prediction of 18 MV photons optimal weight in breast radiotherapy using mixed energy technique, incorporated chest wall separation plus central lung distance (Adjusted R2=0.776). In conclusion, this study represents a model for the estimation of optimal beam weighting in breast radiotherapy using mixed photon energy technique for routine day to day clinical usage.

  6. Production of laccase by Coriolus versicolor and its application in decolorization of dyestuffs: (I). Production of laccase by batch and repeated-batch processes.

    PubMed

    Lin, Jian-Ping; Wei, Lian; Xia, Li-Ming; Cen, Pei-Lin

    2003-01-01

    The production of laccase by Coriolus versicolor was studied. The effect of cultivation conditions on laccase production by Coriolus versicolor was examined to obtain optimal medium and cultivation conditions. Both batch and repeated-batch processes were performed for laccase production. In repeated-batch fermentation with self-immobilized mycelia, total of 14 cycles were performed with laccase activity in the range between 3.4 and 14.8 U/ml.

  7. Effects of Covariance Heterogeneity on Three Procedures for Analyzing Multivariate Repeated Measures Designs.

    ERIC Educational Resources Information Center

    Vallejo, Guillermo; Fidalgo, Angel; Fernandez, Paula

    2001-01-01

    Estimated empirical Type I error rate and power rate for three procedures for analyzing multivariate repeated measures designs: (1) the doubly multivariate model; (2) the Welch-James multivariate solution (H. Keselman, M. Carriere, a nd L. Lix, 1993); and (3) the multivariate version of the modified Brown-Forsythe procedure (M. Brown and A.…

  8. [Analysis of binary classification repeated measurement data with GEE and GLMMs using SPSS software].

    PubMed

    An, Shengli; Zhang, Yanhong; Chen, Zheng

    2012-12-01

    To analyze binary classification repeated measurement data with generalized estimating equations (GEE) and generalized linear mixed models (GLMMs) using SPSS19.0. GEE and GLMMs models were tested using binary classification repeated measurement data sample using SPSS19.0. Compared with SAS, SPSS19.0 allowed convenient analysis of categorical repeated measurement data using GEE and GLMMs.

  9. Structural Analysis Using Computer Based Methods

    NASA Technical Reports Server (NTRS)

    Dietz, Matthew R.

    2013-01-01

    The stiffness of a flex hose that will be used in the umbilical arms of the Space Launch Systems mobile launcher needed to be determined in order to properly qualify ground umbilical plate behavior during vehicle separation post T-0. This data is also necessary to properly size and design the motors used to retract the umbilical arms. Therefore an experiment was created to determine the stiffness of the hose. Before the test apparatus for the experiment could be built, the structure had to be analyzed to ensure it would not fail under given loading conditions. The design model was imported into the analysis software and optimized to decrease runtime while still providing accurate restlts and allow for seamless meshing. Areas exceeding the allowable stresses in the structure were located and modified before submitting the design for fabrication. In addition, a mock up of a deep space habitat and the support frame was designed and needed to be analyzed for structural integrity under different loading conditions. The load cases were provided by the customer and were applied to the structure after optimizing the geometry. Once again, weak points in the structure were located and recommended design changes were made to the customer and the process was repeated until the load conditions were met without exceeding the allowable stresses. After the stresses met the required factors of safety the designs were released for fabrication.

  10. Pediatric Emergency Department Suicidal Patients: Two-Site Evaluation of Suicide Ideators, Single Attempters, and Repeat Attempters

    ERIC Educational Resources Information Center

    Asarnow, Joan Rosenbaum; Baraff, Larry J.; Berk, Michele; Grob, Charles; Devich-Navarro, Mona; Suddath, Robert; Piacentini, John; Tang, Lingqi

    2008-01-01

    The study examines ideators, single attempters, and repeats attempters of suicide to clarify optimal strategies for emergency department management and risk assessment to help them in reducing youth suicide and suicide attempts. Depression was found to be a strong predictor of suicide/suicide attempts along with substance use, externalizing…

  11. Fully Automated Sample Preparation for Ultrafast N-Glycosylation Analysis of Antibody Therapeutics.

    PubMed

    Szigeti, Marton; Lew, Clarence; Roby, Keith; Guttman, Andras

    2016-04-01

    There is a growing demand in the biopharmaceutical industry for high-throughput, large-scale N-glycosylation profiling of therapeutic antibodies in all phases of product development, but especially during clone selection when hundreds of samples should be analyzed in a short period of time to assure their glycosylation-based biological activity. Our group has recently developed a magnetic bead-based protocol for N-glycosylation analysis of glycoproteins to alleviate the hard-to-automate centrifugation and vacuum-centrifugation steps of the currently used protocols. Glycan release, fluorophore labeling, and cleanup were all optimized, resulting in a <4 h magnetic bead-based process with excellent yield and good repeatability. This article demonstrates the next level of this work by automating all steps of the optimized magnetic bead-based protocol from endoglycosidase digestion, through fluorophore labeling and cleanup with high-throughput sample processing in 96-well plate format, using an automated laboratory workstation. Capillary electrophoresis analysis of the fluorophore-labeled glycans was also optimized for rapid (<3 min) separation to accommodate the high-throughput processing of the automated sample preparation workflow. Ultrafast N-glycosylation analyses of several commercially relevant antibody therapeutics are also shown and compared to their biosimilar counterparts, addressing the biological significance of the differences. © 2015 Society for Laboratory Automation and Screening.

  12. The algorithm for duration acceleration of repetitive projects considering the learning effect

    NASA Astrophysics Data System (ADS)

    Chen, Hongtao; Wang, Keke; Du, Yang; Wang, Liwan

    2018-03-01

    Repetitive project optimization problem is common in project scheduling. Repetitive Scheduling Method (RSM) has many irreplaceable advantages in the field of repetitive projects. As the same or similar work is repeated, the proficiency of workers will be correspondingly low to high, and workers will gain experience and improve the efficiency of operations. This is learning effect. Learning effect is one of the important factors affecting the optimization results in repetitive project scheduling. This paper analyzes the influence of the learning effect on the controlling path in RSM from two aspects: one is that the learning effect changes the controlling path, the other is that the learning effect doesn't change the controlling path. This paper proposes corresponding methods to accelerate duration for different types of critical activities and proposes the algorithm for duration acceleration based on the learning effect in RSM. And the paper chooses graphical method to identity activities' types and considers the impacts of the learning effect on duration. The method meets the requirement of duration while ensuring the lowest acceleration cost. A concrete bridge construction project is given to verify the effectiveness of the method. The results of this study will help project managers understand the impacts of the learning effect on repetitive projects, and use the learning effect to optimize project scheduling.

  13. Ultrathin-shell boron nitride hollow spheres as sorbent for dispersive solid-phase extraction of polychlorinated biphenyls from environmental water samples.

    PubMed

    Fu, Meizhen; Xing, Hanzhu; Chen, Xiangfeng; Chen, Fan; Wu, Chi-Man Lawrence; Zhao, Rusong; Cheng, Chuange

    2014-11-21

    Boron nitride hollow spheres with ultrathin-shells were synthesized and used as sorbents for dispersive solid-phase extraction of aromatic pollutants at trace levels from environmental water samples. Polychlorinated biphenyls (PCBs) were selected as target compounds. Sample quantification and detection were performed by gas chromatography-tandem mass spectrometry. Extraction parameters influencing the extraction efficiency were optimized through response surface methodology using the Box-Behnken design. The proposed method achieved good linearity within the concentration range of 0.15-250 ng L(-1) PCBs, low limits of detection (0.04-0.09 ng L(-1), S/N=3:1), good repeatability of the extractions (relative standard deviation, <12%, n=6), and satisfactory recoveries between 84.9% and 101.0% under optimal conditions. Real environmental samples collected from rivers, local lakes, rain and spring waters were analyzed using the developed method. Results demonstrated that the hexagonal boron nitride-based material has significant potential as a sorbent for organic pollutant extraction from environmental water samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Analysis and discussion on the experimental data of electrolyte analyzer

    NASA Astrophysics Data System (ADS)

    Dong, XinYu; Jiang, JunJie; Liu, MengJun; Li, Weiwei

    2018-06-01

    In the subsequent verification of electrolyte analyzer, we found that the instrument can achieve good repeatability and stability in repeated measurements with a short period of time, in line with the requirements of verification regulation of linear error and cross contamination rate, but the phenomenon of large indication error is very common, the measurement results of different manufacturers have great difference, in order to find and solve this problem, help enterprises to improve quality of product, to obtain accurate and reliable measurement data, we conducted the experimental evaluation of electrolyte analyzer, and the data were analyzed by statistical analysis.

  15. The Contribution of Short Repeats of Low Sequence Complexity to Large Conifer Genomes

    Treesearch

    A. Schmidt; R.L. Doudrick; J.S. Heslop-Harrison; T. Schmidt

    2000-01-01

    Abstract: The abundance and genomic organization of six simple sequence repeats, consisting of di-, tri-, and tetranucleotide sequence motifs, and a minisatellite repeat have been analyzed in different gymnosperms by Southern hybridization. Within the gymnosperm genomes investigated, the abundance and genomic organization of micro- and...

  16. Detecting communities using asymptotical surprise

    NASA Astrophysics Data System (ADS)

    Traag, V. A.; Aldecoa, R.; Delvenne, J.-C.

    2015-08-01

    Nodes in real-world networks are repeatedly observed to form dense clusters, often referred to as communities. Methods to detect these groups of nodes usually maximize an objective function, which implicitly contains the definition of a community. We here analyze a recently proposed measure called surprise, which assesses the quality of the partition of a network into communities. In its current form, the formulation of surprise is rather difficult to analyze. We here therefore develop an accurate asymptotic approximation. This allows for the development of an efficient algorithm for optimizing surprise. Incidentally, this leads to a straightforward extension of surprise to weighted graphs. Additionally, the approximation makes it possible to analyze surprise more closely and compare it to other methods, especially modularity. We show that surprise is (nearly) unaffected by the well-known resolution limit, a particular problem for modularity. However, surprise may tend to overestimate the number of communities, whereas they may be underestimated by modularity. In short, surprise works well in the limit of many small communities, whereas modularity works better in the limit of few large communities. In this sense, surprise is more discriminative than modularity and may find communities where modularity fails to discern any structure.

  17. Interactions between Signaling and Repeated Play with Borrower Default.

    DTIC Science & Technology

    1985-10-01

    is costly in terms of social welfare. Education yields a higher personal gain than socie- tal gain; consequently, more than the socially optimal...Lexington Books. Harris, M., and A. Raviv 119791, "Optimal Incentive Contracts with Imperfect Information," Journal of Economic Theory, Vol. 20, No. 2, pp

  18. Global Optimization of Interplanetary Trajectories in the Presence of Realistic Mission Constraints

    NASA Technical Reports Server (NTRS)

    Hinckley, David; Englander, Jacob; Hitt, Darren

    2015-01-01

    Single trial evaluations Trial creation by Phase-wise GA-style or DE-inspired recombination Bin repository structure requires an initialization period Non-exclusionary Kill Distance Population collapse mechanic Main loop Creation Probabilistic switch between GA and DE creation types Locally optimize Submit to repository Repeat.

  19. Evaluation of the Nova StatSensor® XpressTM Creatinine Point-Of-Care Handheld Analyzer

    PubMed Central

    Kosack, Cara Simone; de Kieviet, Wim; Bayrak, Kubra; Milovic, Anastacija; Page, Anne Laure

    2015-01-01

    Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification. PMID:25886375

  20. Evaluation of the Nova StatSensor® Xpress(TM) Creatinine point-of-care handheld analyzer.

    PubMed

    Kosack, Cara Simone; de Kieviet, Wim; Bayrak, Kubra; Milovic, Anastacija; Page, Anne Laure

    2015-01-01

    Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification.

  1. Approximate analysis for repeated eigenvalue problems with applications to controls-structure integrated design

    NASA Technical Reports Server (NTRS)

    Kenny, Sean P.; Hou, Gene J. W.

    1994-01-01

    A method for eigenvalue and eigenvector approximate analysis for the case of repeated eigenvalues with distinct first derivatives is presented. The approximate analysis method developed involves a reparameterization of the multivariable structural eigenvalue problem in terms of a single positive-valued parameter. The resulting equations yield first-order approximations to changes in the eigenvalues and the eigenvectors associated with the repeated eigenvalue problem. This work also presents a numerical technique that facilitates the definition of an eigenvector derivative for the case of repeated eigenvalues with repeated eigenvalue derivatives (of all orders). Examples are given which demonstrate the application of such equations for sensitivity and approximate analysis. Emphasis is placed on the application of sensitivity analysis to large-scale structural and controls-structures optimization problems.

  2. The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract

    PubMed Central

    Seneca, Sara; De Rademaeker, Marjan; Sermon, Karen; De Rycke, Martine; De Vos, Michel; Haentjens, Patrick; Devroey, Paul; Liebaers, Ingeborg

    2010-01-01

    Purpose This study aims to analyze the relationship between trinucleotide repeat length and reproductive outcome in a large cohort of DM1 patients undergoing ICSI and PGD. Methods Prospective cohort study. The effect of trinucleotide repeat length on reproductive outcome per patient was analyzed using bivariate analysis (T-test) and multivariate analysis using Kaplan-Meier and Cox regression analysis. Results Between 1995 and 2005, 205 cycles of ICSI and PGD were carried out for DM1 in 78 couples. The number of trinucleotide repeats does not have an influence on reproductive outcome when adjusted for age, BMI, basal FSH values, parity, infertility status and male or female affected. Cox regression analysis indicates that cumulative live birth rate is not influenced by the number of trinucleotide repeats. The only factor with a significant effect is age (p < 0.05). Conclusion There is no evidence of an effect of trinucleotide repeat length on reproductive outcome in patients undergoing ICSI and PGD. PMID:20221684

  3. [Comparative analysis of clustered regularly interspaced short palindromic repeats (CRISPRs) loci in the genomes of halophilic archaea].

    PubMed

    Zhang, Fan; Zhang, Bing; Xiang, Hua; Hu, Songnian

    2009-11-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a widespread system that provides acquired resistance against phages in bacteria and archaea. Here we aim to genome-widely analyze the CRISPR in extreme halophilic archaea, of which the whole genome sequences are available at present time. We used bioinformatics methods including alignment, conservation analysis, GC content and RNA structure prediction to analyze the CRISPR structures of 7 haloarchaeal genomes. We identified the CRISPR structures in 5 halophilic archaea and revealed a conserved palindromic motif in the flanking regions of these CRISPR structures. In addition, we found that the repeat sequences of large CRISPR structures in halophilic archaea were greatly conserved, and two types of predicted RNA secondary structures derived from the repeat sequences were likely determined by the fourth base of the repeat sequence. Our results support the proposal that the leader sequence may function as recognition site by having palindromic structures in flanking regions, and the stem-loop secondary structure formed by repeat sequences may function in mediating the interaction between foreign genetic elements and CAS-encoded proteins.

  4. Analysis of the influence of pasteurization, freezing/thawing, and offer processes on human milk's macronutrient concentrations.

    PubMed

    Vieira, Alan Araujo; Soares, Fernanda Valente Mendes; Pimenta, Hellen Porto; Abranches, Andrea Dunshee; Moreira, Maria Elisabeth Lopes

    2011-08-01

    The macronutrient concentrations of human milk could be influenced by the various processes used in human milk bank. To determine the effect of various process (Holder pasteurization, freezing and thawing and feeding method) on the macronutrient concentration of human milk. The samples of donated fresh human milk were studied before and after each process (Holder pasteurization, freezing and thawing and feeding method) until their delivery to newborn infants. Fifty-seven raw human milk samples were analyzed in the first step (pasteurization) and 228 in the offer step. Repeated measurements of protein, fat and lactose amounts were made in samples of human milk using an Infrared analyzer. The influence of repeated processes on the mean concentration of macronutrients in donor human milk was analyzed by repeated measurements ANOVA, using R statistical package. The most variable macronutrient concentration in the analyzed samples was fat (reduction of 59%). There was a significant reduction of fat and protein mean concentrations following pasteurization (5.5 and 3.9%, respectively). The speed at which the milk was thawed didn't cause a significant variation in the macronutrients concentrations. However, the continuous infusion delivery significantly reduced the fat concentration. When the influence of repeated processes was analyzed, the fat and protein concentrations varied significantly (reduction of 56.6% and 10.1% respectively) (P<0.05). Lactose didn't suffer significant reductions in all steps. The repeated processes that donor human milk is submitted before delivery to newborn infants cause a reduction in the fat and protein concentration. The magnitude of this decrease is higher on the fat concentration and it needs to be considered when this processed milk is used to feed preterm infants. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Optimizing Clinical Trial Enrollment Methods Through "Goal Programming"

    PubMed Central

    Davis, J.M.; Sandgren, A.J.; Manley, A.R.; Daleo, M.A.; Smith, S.S.

    2014-01-01

    Introduction Clinical trials often fail to reach desired goals due to poor recruitment outcomes, including low participant turnout, high recruitment cost, or poor representation of minorities. At present, there is limited literature available to guide recruitment methodology. This study, conducted by researchers at the University of Wisconsin Center for Tobacco Research and Intervention (UW-CTRI), provides an example of how iterative analysis of recruitment data may be used to optimize recruitment outcomes during ongoing recruitment. Study methodology UW-CTRI’s research team provided a description of methods used to recruit smokers in two randomized trials (n = 196 and n = 175). The trials targeted low socioeconomic status (SES) smokers and involved time-intensive smoking cessation interventions. Primary recruitment goals were to meet required sample size and provide representative diversity while working with limited funds and limited time. Recruitment data was analyzed repeatedly throughout each study to optimize recruitment outcomes. Results Estimates of recruitment outcomes based on prior studies on smoking cessation suggested that researchers would be able to recruit 240 low SES smokers within 30 months at a cost of $72,000. With employment of methods described herein, researchers were able to recruit 374 low SES smokers over 30 months at a cost of $36,260. Discussion Each human subjects study presents unique recruitment challenges with time and cost of recruitment dependent on the sample population and study methodology. Nonetheless, researchers may be able to improve recruitment outcomes though iterative analysis of recruitment data and optimization of recruitment methods throughout the recruitment period. PMID:25642125

  6. Efficient quantum repeater with respect to both entanglement-concentration rate and complexity of local operations and classical communication

    NASA Astrophysics Data System (ADS)

    Su, Zhaofeng; Guan, Ji; Li, Lvzhou

    2018-01-01

    Quantum entanglement is an indispensable resource for many significant quantum information processing tasks. However, in practice, it is difficult to distribute quantum entanglement over a long distance, due to the absorption and noise in quantum channels. A solution to this challenge is a quantum repeater, which can extend the distance of entanglement distribution. In this scheme, the time consumption of classical communication and local operations takes an important place with respect to time efficiency. Motivated by this observation, we consider a basic quantum repeater scheme that focuses on not only the optimal rate of entanglement concentration but also the complexity of local operations and classical communication. First, we consider the case where two different two-qubit pure states are initially distributed in the scenario. We construct a protocol with the optimal entanglement-concentration rate and less consumption of local operations and classical communication. We also find a criterion for the projective measurements to achieve the optimal probability of creating a maximally entangled state between the two ends. Second, we consider the case in which two general pure states are prepared and general measurements are allowed. We get an upper bound on the probability for a successful measurement operation to produce a maximally entangled state without any further local operations.

  7. A Rapid Method for Optimizing Running Temperature of Electrophoresis through Repetitive On-Chip CE Operations

    PubMed Central

    Kaneda, Shohei; Ono, Koichi; Fukuba, Tatsuhiro; Nojima, Takahiko; Yamamoto, Takatoki; Fujii, Teruo

    2011-01-01

    In this paper, a rapid and simple method to determine the optimal temperature conditions for denaturant electrophoresis using a temperature-controlled on-chip capillary electrophoresis (CE) device is presented. Since on-chip CE operations including sample loading, injection and separation are carried out just by switching the electric field, we can repeat consecutive run-to-run CE operations on a single on-chip CE device by programming the voltage sequences. By utilizing the high-speed separation and the repeatability of the on-chip CE, a series of electrophoretic operations with different running temperatures can be implemented. Using separations of reaction products of single-stranded DNA (ssDNA) with a peptide nucleic acid (PNA) oligomer, the effectiveness of the presented method to determine the optimal temperature conditions required to discriminate a single-base substitution (SBS) between two different ssDNAs is demonstrated. It is shown that a single run for one temperature condition can be executed within 4 min, and the optimal temperature to discriminate the SBS could be successfully found using the present method. PMID:21845077

  8. High-speed and low-power repeater for VLSI interconnects

    NASA Astrophysics Data System (ADS)

    Karthikeyan, A.; Mallick, P. S.

    2017-10-01

    This paper proposes a repeater for boosting the speed of interconnects with low power dissipation. We have designed and implemented at 45 and 32 nm technology nodes. Delay and power dissipation performances are analyzed for various voltage levels at these technology nodes using Spice simulations. A significant reduction in delay and power dissipation are observed compared to a conventional repeater. The results show that the proposed high-speed low-power repeater has a reduced delay for higher load capacitance. The proposed repeater is also compared with LPTG CMOS repeater, and the results shows that the proposed repeater has reduced delay. The proposed repeater can be suitable for high-speed global interconnects and has the capacity to drive large loads.

  9. Do repeated wildfires change homebuyers' demand for homes in high-risk areas?

    Treesearch

    Julie M. Mueller; John D. Loomis; Armando González-Cabán

    2009-01-01

    Unlike most hedonic studies that analyze the effects of a one-time event, this paper analyzes the effects of forest fires that are several years apart in a small geographical area. We find that repeated forest fires cause house prices to decrease for houses located near the fires. We test and reject the hypothesis that the house price reduction from the first fire is...

  10. Using Animal Instincts to Design Efficient Biomedical Studies via Particle Swarm Optimization.

    PubMed

    Qiu, Jiaheng; Chen, Ray-Bing; Wang, Weichung; Wong, Weng Kee

    2014-10-01

    Particle swarm optimization (PSO) is an increasingly popular metaheuristic algorithm for solving complex optimization problems. Its popularity is due to its repeated successes in finding an optimum or a near optimal solution for problems in many applied disciplines. The algorithm makes no assumption of the function to be optimized and for biomedical experiments like those presented here, PSO typically finds the optimal solutions in a few seconds of CPU time on a garden-variety laptop. We apply PSO to find various types of optimal designs for several problems in the biological sciences and compare PSO performance relative to the differential evolution algorithm, another popular metaheuristic algorithm in the engineering literature.

  11. Indirect ELISA (iELISA) for routine detection of antibodies against Minute Virus of Mice (MVM) in mice colonies.

    PubMed

    Laborde, Juan M; Sguazza, Guillermo H; Fuentealba, Nadia A; Corva, Santiago G; Carbone, Cecilia; Galosi, Cecilia M

    In this study we developed an indirect ELISA to detect antibodies against Minute Virus of Mice (MVM) using an antigen produced from BHK-21 cells infected with a prototype strain of the virus. The optimal antigen concentration and serum dilutions were established. In order to analyze variability in the laboratory, reproducibility and repeatability within and between plates were determined. Then, a panel of 460 sera from conventional facilities and previously classified as positive or negative by the indirect fluorescent antibody assay was analyzed. The cutoff value was determined by a receiver operating characteristic (ROC) curve. The results of the indirect ELISA were compared with those of the indirect fluorescent antibody assay. The ELISA assay showed 100% sensitivity and 99% specificity. ELISA is a useful tool to be developed in standard virology laboratories and can be used for screening animals faster than the traditional indirect fluorescent antibody assay. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Combined shape and topology optimization for minimization of maximal von Mises stress

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

    Lian, Haojie; Christiansen, Asger N.; Tortorelli, Daniel A.

    Here, this work shows that a combined shape and topology optimization method can produce optimal 2D designs with minimal stress subject to a volume constraint. The method represents the surface explicitly and discretizes the domain into a simplicial complex which adapts both structural shape and topology. By performing repeated topology and shape optimizations and adaptive mesh updates, we can minimize the maximum von Mises stress using the p-norm stress measure with p-values as high as 30, provided that the stress is calculated with sufficient accuracy.

  13. Combined shape and topology optimization for minimization of maximal von Mises stress

    DOE PAGES

    Lian, Haojie; Christiansen, Asger N.; Tortorelli, Daniel A.; ...

    2017-01-27

    Here, this work shows that a combined shape and topology optimization method can produce optimal 2D designs with minimal stress subject to a volume constraint. The method represents the surface explicitly and discretizes the domain into a simplicial complex which adapts both structural shape and topology. By performing repeated topology and shape optimizations and adaptive mesh updates, we can minimize the maximum von Mises stress using the p-norm stress measure with p-values as high as 30, provided that the stress is calculated with sufficient accuracy.

  14. Primary analysis of repeat elements of the Asian seabass (Lates calcarifer) transcriptome and genome

    PubMed Central

    Kuznetsova, Inna S.; Thevasagayam, Natascha M.; Sridatta, Prakki S. R.; Komissarov, Aleksey S.; Saju, Jolly M.; Ngoh, Si Y.; Jiang, Junhui; Shen, Xueyan; Orbán, László

    2014-01-01

    As part of our Asian seabass genome project, we are generating an inventory of repeat elements in the genome and transcriptome. The karyotype showed a diploid number of 2n = 24 chromosomes with a variable number of B-chromosomes. The transcriptome and genome of Asian seabass were searched for repetitive elements with experimental and bioinformatics tools. Six different types of repeats constituting 8–14% of the genome were characterized. Repetitive elements were clustered in the pericentromeric heterochromatin of all chromosomes, but some of them were preferentially accumulated in pretelomeric and pericentromeric regions of several chromosomes pairs and have chromosomes specific arrangement. From the dispersed class of fish-specific non-LTR retrotransposon elements Rex1 and MAUI-like repeats were analyzed. They were wide-spread both in the genome and transcriptome, accumulated on the pericentromeric and peritelomeric areas of all chromosomes. Every analyzed repeat was represented in the Asian seabass transcriptome, some showed differential expression between the gonads. The other group of repeats analyzed belongs to the rRNA multigene family. FISH signal for 5S rDNA was located on a single pair of chromosomes, whereas that for 18S rDNA was found on two pairs. A BAC-derived contig containing rDNA was sequenced and assembled into a scaffold containing incomplete fragments of 18S rDNA. Their assembly and chromosomal position revealed that this part of Asian seabass genome is extremely rich in repeats containing evolutionarily conserved and novel sequences. In summary, transcriptome assemblies and cDNA data are suitable for the identification of repetitive DNA from unknown genomes and for comparative investigation of conserved elements between teleosts and other vertebrates. PMID:25120555

  15. Evolutionary conservation of sequence and secondary structures inCRISPR repeats

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

    Kunin, Victor; Sorek, Rotem; Hugenholtz, Philip

    Clustered Regularly Interspaced Palindromic Repeats (CRISPRs) are a novel class of direct repeats, separated by unique spacer sequences of similar length, that are present in {approx}40% of bacterial and all archaeal genomes analyzed to date. More than 40 gene families, called CRISPR-associated sequences (CAS), appear in conjunction with these repeats and are thought to be involved in the propagation and functioning of CRISPRs. It has been proposed that the CRISPR/CAS system samples, maintains a record of, and inactivates invasive DNA that the cell has encountered, and therefore constitutes a prokaryotic analog of an immune system. Here we analyze CRISPR repeatsmore » identified in 195 microbial genomes and show that they can be organized into multiple clusters based on sequence similarity. All individual repeats in any given cluster were inferred to form characteristic RNA secondary structure, ranging from non-existent to pronounced. Stable secondary structures included G:U base pairs and exhibited multiple compensatory base changes in the stem region, indicating evolutionary conservation and functional importance. We also show that the repeat-based classification corresponds to, and expands upon, a previously reported CAS gene-based classification including specific relationships between CRISPR and CAS subtypes.« less

  16. On the improvement of signal repeatability in laser-induced air plasmas

    NASA Astrophysics Data System (ADS)

    Zhang, Shuai; Sheta, Sahar; Hou, Zong-Yu; Wang, Zhe

    2018-04-01

    The relatively low repeatability of laser-induced breakdown spectroscopy (LIBS) severely hinders its wide commercialization. In the present work, we investigate the optimization of LIBS system for repeatability improvement for both signal generation (plasma evolution) and signal collection. Timeintegrated spectra and images were obtained under different laser energies and focal lengths to investigate the optimum configuration for stable plasmas and repeatable signals. Using our experimental setup, the optimum conditions were found to be a laser energy of 250 mJ and a focus length of 100 mm. A stable and homogeneous plasma with the largest hot core area in the optimum condition yielded the most stable LIBS signal. Time-resolved images showed that the rebounding processes through the air plasma evolution caused the relative standard deviation (RSD) to increase with laser energies of > 250 mJ. In addition, the emission collection was improved by using a concave spherical mirror. The line intensities doubled as their RSDs decreased by approximately 25%. When the signal generation and collection were optimized simultaneously, the pulse-to-pulse RSDs were reduced to approximately 3% for O(I), N(I), and H(I) lines, which are better than the RSDs reported for solid samples and showed great potential for LIBS quantitative analysis by gasifying the solid or liquid samples.

  17. A high-precision instrument for analyzing nonlinear dynamic behavior of bearing cage.

    PubMed

    Yang, Z; Chen, H; Yu, T; Li, B

    2016-08-01

    The high-precision ball bearing is fundamental to the performance of complex mechanical systems. As the speed increases, the cage behavior becomes a key factor in influencing the bearing performance, especially life and reliability. This paper develops a high-precision instrument for analyzing nonlinear dynamic behavior of the bearing cage. The trajectory of the rotational center and non-repetitive run-out (NRRO) of the cage are used to evaluate the instability of cage motion. This instrument applied an aerostatic spindle to support and spin test the bearing to decrease the influence of system error. Then, a high-speed camera is used to capture images when the bearing works at high speeds. A 3D trajectory tracking software tema Motion is used to track the spot which marked the cage surface. Finally, by developing the matlab program, a Lissajous' figure was used to evaluate the nonlinear dynamic behavior of the cage with different speeds. The trajectory of rotational center and NRRO of the cage with various speeds are analyzed. The results can be used to predict the initial failure and optimize cage structural parameters. In addition, the repeatability precision of instrument is also validated. In the future, the motorized spindle will be applied to increase testing speed and image processing algorithms will be developed to analyze the trajectory of the cage.

  18. A high-precision instrument for analyzing nonlinear dynamic behavior of bearing cage

    NASA Astrophysics Data System (ADS)

    Yang, Z.; Chen, H.; Yu, T.; Li, B.

    2016-08-01

    The high-precision ball bearing is fundamental to the performance of complex mechanical systems. As the speed increases, the cage behavior becomes a key factor in influencing the bearing performance, especially life and reliability. This paper develops a high-precision instrument for analyzing nonlinear dynamic behavior of the bearing cage. The trajectory of the rotational center and non-repetitive run-out (NRRO) of the cage are used to evaluate the instability of cage motion. This instrument applied an aerostatic spindle to support and spin test the bearing to decrease the influence of system error. Then, a high-speed camera is used to capture images when the bearing works at high speeds. A 3D trajectory tracking software tema Motion is used to track the spot which marked the cage surface. Finally, by developing the matlab program, a Lissajous' figure was used to evaluate the nonlinear dynamic behavior of the cage with different speeds. The trajectory of rotational center and NRRO of the cage with various speeds are analyzed. The results can be used to predict the initial failure and optimize cage structural parameters. In addition, the repeatability precision of instrument is also validated. In the future, the motorized spindle will be applied to increase testing speed and image processing algorithms will be developed to analyze the trajectory of the cage.

  19. A high-precision instrument for analyzing nonlinear dynamic behavior of bearing cage

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

    Yang, Z., E-mail: zhaohui@nwpu.edu.cn; Yu, T.; Chen, H.

    2016-08-15

    The high-precision ball bearing is fundamental to the performance of complex mechanical systems. As the speed increases, the cage behavior becomes a key factor in influencing the bearing performance, especially life and reliability. This paper develops a high-precision instrument for analyzing nonlinear dynamic behavior of the bearing cage. The trajectory of the rotational center and non-repetitive run-out (NRRO) of the cage are used to evaluate the instability of cage motion. This instrument applied an aerostatic spindle to support and spin test the bearing to decrease the influence of system error. Then, a high-speed camera is used to capture images whenmore » the bearing works at high speeds. A 3D trajectory tracking software TEMA Motion is used to track the spot which marked the cage surface. Finally, by developing the MATLAB program, a Lissajous’ figure was used to evaluate the nonlinear dynamic behavior of the cage with different speeds. The trajectory of rotational center and NRRO of the cage with various speeds are analyzed. The results can be used to predict the initial failure and optimize cage structural parameters. In addition, the repeatability precision of instrument is also validated. In the future, the motorized spindle will be applied to increase testing speed and image processing algorithms will be developed to analyze the trajectory of the cage.« less

  20. Evaluating the efficiency of environmental monitoring programs

    USGS Publications Warehouse

    Levine, Carrie R.; Yanai, Ruth D.; Lampman, Gregory G.; Burns, Douglas A.; Driscoll, Charles T.; Lawrence, Gregory B.; Lynch, Jason; Schoch, Nina

    2014-01-01

    Statistical uncertainty analyses can be used to improve the efficiency of environmental monitoring, allowing sampling designs to maximize information gained relative to resources required for data collection and analysis. In this paper, we illustrate four methods of data analysis appropriate to four types of environmental monitoring designs. To analyze a long-term record from a single site, we applied a general linear model to weekly stream chemistry data at Biscuit Brook, NY, to simulate the effects of reducing sampling effort and to evaluate statistical confidence in the detection of change over time. To illustrate a detectable difference analysis, we analyzed a one-time survey of mercury concentrations in loon tissues in lakes in the Adirondack Park, NY, demonstrating the effects of sampling intensity on statistical power and the selection of a resampling interval. To illustrate a bootstrapping method, we analyzed the plot-level sampling intensity of forest inventory at the Hubbard Brook Experimental Forest, NH, to quantify the sampling regime needed to achieve a desired confidence interval. Finally, to analyze time-series data from multiple sites, we assessed the number of lakes and the number of samples per year needed to monitor change over time in Adirondack lake chemistry using a repeated-measures mixed-effects model. Evaluations of time series and synoptic long-term monitoring data can help determine whether sampling should be re-allocated in space or time to optimize the use of financial and human resources.

  1. Experimental definition of a clustered regularly interspaced short palindromic duplicon in Escherichia coli.

    PubMed

    Goren, Moran G; Yosef, Ido; Auster, Oren; Qimron, Udi

    2012-10-12

    We analyzed sequences of newly inserted repeats in an Escherichia coli CRISPR (clustered regularly interspaced short palindromic repeats) array in vivo and showed that a base previously thought to belong to the repeat is actually derived from a protospacer. Based on further experimental results, we propose to use the term "duplicon" for a repeated sequence in a CRISPR array that serves as a template for a new duplicon. Our findings suggest the possibility of redrawing the borders between repeats, spacers, and protospacer adjacent motifs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Free amino acids, biogenic amines, and ammonium profiling in tobacco from different geographical origins using microwave-assisted extraction followed by ultra high performance liquid chromatography.

    PubMed

    Cai, Kai; Xiang, Zhangmin; Li, Hongqin; Zhao, Huina; Lin, Yechun; Pan, Wenjie; Lei, Bo

    2017-12-01

    This work describes a rapid, stable, and accurate method for determining the free amino acids, biogenic amines, and ammonium in tobacco. The target analytes were extracted with microwave-assisted extraction and then derivatized with diethyl ethoxymethylenemalonate, followed by ultra high performance liquid chromatography analysis. The experimental design used to optimize the microwave-assisted extraction conditions showed that the optimal extraction time was 10 min with a temperature of 60°C. The stability of aminoenone derivatives was improved by keeping the pH near 9.0, and there was no obvious degradation during the 80°C heating and room temperature storage. Under optimal conditions, this method showed good linearity (R 2 > 0.999) and sensitivity (limits of detection 0.010-0.081 μg/mL). The extraction recoveries were between 88.4 and 106.5%, while the repeatability and reproducibility ranged from 0.48 to 5.12% and from 1.56 to 6.52%, respectively. The newly developed method was employed to analyze the tobacco from different geographical origins. Principal component analysis showed that four geographical origins of tobacco could be clearly distinguished and that each had their characteristic components. The proposed method also showed great potential for further investigations on nitrogen metabolism in plants. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Selection of specific protein binders for pre-defined targets from an optimized library of artificial helicoidal repeat proteins (alphaRep).

    PubMed

    Guellouz, Asma; Valerio-Lepiniec, Marie; Urvoas, Agathe; Chevrel, Anne; Graille, Marc; Fourati-Kammoun, Zaineb; Desmadril, Michel; van Tilbeurgh, Herman; Minard, Philippe

    2013-01-01

    We previously designed a new family of artificial proteins named αRep based on a subgroup of thermostable helicoidal HEAT-like repeats. We have now assembled a large optimized αRep library. In this library, the side chains at each variable position are not fully randomized but instead encoded by a distribution of codons based on the natural frequency of side chains of the natural repeats family. The library construction is based on a polymerization of micro-genes and therefore results in a distribution of proteins with a variable number of repeats. We improved the library construction process using a "filtration" procedure to retain only fully coding modules that were recombined to recreate sequence diversity. The final library named Lib2.1 contains 1.7×10(9) independent clones. Here, we used phage display to select, from the previously described library or from the new library, new specific αRep proteins binding to four different non-related predefined protein targets. Specific binders were selected in each case. The results show that binders with various sizes are selected including relatively long sequences, with up to 7 repeats. ITC-measured affinities vary with Kd values ranging from micromolar to nanomolar ranges. The formation of complexes is associated with a significant thermal stabilization of the bound target protein. The crystal structures of two complexes between αRep and their cognate targets were solved and show that the new interfaces are established by the variable surfaces of the repeated modules, as well by the variable N-cap residues. These results suggest that αRep library is a new and versatile source of tight and specific binding proteins with favorable biophysical properties.

  4. Synergistic enhancement of cellulase pairs linked by consensus ankyrin repeats: Determination of the roles of spacing, orientation, and enzyme identity.

    PubMed

    Cunha, Eva S; Hatem, Christine L; Barrick, Doug

    2016-08-01

    Biomass deconstruction to small simple sugars is a potential approach to biofuels production; however, the highly recalcitrant nature of biomass limits the economic viability of this approach. Thus, research on efficient biomass degradation is necessary to achieve large-scale production of biofuels. Enhancement of cellulolytic activity by increasing synergism between cellulase enzymes holds promise in achieving high-yield biofuels production. Here we have inserted cellulase pairs from extremophiles into hyperstable α-helical consensus ankyrin repeat domain scaffolds. Such chimeric constructs allowed us to optimize arrays of enzyme pairs against a variety of cellulolytic substrates. We found that endocellulolytic domains CelA (CA) and Cel12A (C12A) act synergistically in the context of ankyrin repeats, with both three and four repeat spacing. The extent of synergy differs for different substrates. Also, having C12A N-terminal to CA provides greater synergy than the reverse construct, especially against filter paper. In contrast, we do not see synergy for these enzymes in tandem with CelK (CK) catalytic domain, a larger exocellulase, demonstrating the importance of enzyme identity in synergistic enhancement. Furthermore, we found endocellulases CelD and CA with three repeat spacing to act synergistically against filter paper. Importantly, connecting CA and C12A with a disordered linker of similar contour length shows no synergistic enhancement, indicating that synergism results from connecting these domains with folded ankyrin repeats. These results show that ankyrin arrays can be used to vary spacing and orientation between enzymes, helping to design and optimize artificial cellulosomes, providing a novel architecture for synergistic enhancement of enzymatic cellulose degradation. Proteins 2016; 84:1043-1054. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Population Fisher information matrix and optimal design of discrete data responses in population pharmacodynamic experiments.

    PubMed

    Ogungbenro, Kayode; Aarons, Leon

    2011-08-01

    In the recent years, interest in the application of experimental design theory to population pharmacokinetic (PK) and pharmacodynamic (PD) experiments has increased. The aim is to improve the efficiency and the precision with which parameters are estimated during data analysis and sometimes to increase the power and reduce the sample size required for hypothesis testing. The population Fisher information matrix (PFIM) has been described for uniresponse and multiresponse population PK experiments for design evaluation and optimisation. Despite these developments and availability of tools for optimal design of population PK and PD experiments much of the effort has been focused on repeated continuous variable measurements with less work being done on repeated discrete type measurements. Discrete data arise mainly in PDs e.g. ordinal, nominal, dichotomous or count measurements. This paper implements expressions for the PFIM for repeated ordinal, dichotomous and count measurements based on analysis by a mixed-effects modelling technique. Three simulation studies were used to investigate the performance of the expressions. Example 1 is based on repeated dichotomous measurements, Example 2 is based on repeated count measurements and Example 3 is based on repeated ordinal measurements. Data simulated in MATLAB were analysed using NONMEM (Laplace method) and the glmmML package in R (Laplace and adaptive Gauss-Hermite quadrature methods). The results obtained for Examples 1 and 2 showed good agreement between the relative standard errors obtained using the PFIM and simulations. The results obtained for Example 3 showed the importance of sampling at the most informative time points. Implementation of these expressions will provide the opportunity for efficient design of population PD experiments that involve discrete type data through design evaluation and optimisation.

  6. Synergistic enhancement of cellulase pairs linked by consensus ankyrin repeats: determination of the roles of spacing, orientation and enzyme identity

    PubMed Central

    Cunha, Eva S.; Hatem, Christine L.; Barrick, Doug

    2017-01-01

    Biomass deconstruction to small simple sugars is a potential approach to biofuels production, however the highly recalcitrant nature of biomass limits the economic viability of this approach. Thus, research on efficient biomass degradation is necessary to achieve large-scale production of biofuels. Enhancement of cellulolytic activity by increasing synergism between cellulase enzymes holds promise in achieving high-yield biofuels production. Here we have inserted cellulase pairs from extremophiles into hyper-stable α-helical consensus ankyrin repeat domain scaffolds. Such chimeric constructs allowed us to optimize arrays of enzyme pairs against a variety of cellulolytic substrates. We found that endocellulolytic domains CelA (CA) and Cel12A (C12A) act synergistically in the context of ankyrin repeats, with both three and four repeat spacing. The extent of synergy differs for different substrates. Also, having C12A N-terminal to CA provides greater synergy than the reverse construct, especially against filter paper. In contrast, we do not see synergy for these enzymes in tandem with CelK (CK) catalytic domain, a larger exocellulase, demonstrating the importance of enzyme identity in synergistic enhancement. Furthermore, we found endocellulases CelD and CA with three repeat spacing to act synergistically against filter paper. Importantly, connecting CA and C12A with a disordered linker of similar contour length, shows no synergistic enhancement, indicating that synergism results from connecting these domains with folded ankyrin repeats. These results show that ankyrin arrays can be used to vary spacing and orientation between enzymes, helping to design and optimize artificial cellulosomes, providing a novel architecture for synergistic enhancement of enzymatic cellulose degradation. PMID:27071357

  7. Selection of Specific Protein Binders for Pre-Defined Targets from an Optimized Library of Artificial Helicoidal Repeat Proteins (alphaRep)

    PubMed Central

    Chevrel, Anne; Graille, Marc; Fourati-Kammoun, Zaineb; Desmadril, Michel; van Tilbeurgh, Herman; Minard, Philippe

    2013-01-01

    We previously designed a new family of artificial proteins named αRep based on a subgroup of thermostable helicoidal HEAT-like repeats. We have now assembled a large optimized αRep library. In this library, the side chains at each variable position are not fully randomized but instead encoded by a distribution of codons based on the natural frequency of side chains of the natural repeats family. The library construction is based on a polymerization of micro-genes and therefore results in a distribution of proteins with a variable number of repeats. We improved the library construction process using a “filtration” procedure to retain only fully coding modules that were recombined to recreate sequence diversity. The final library named Lib2.1 contains 1.7×109 independent clones. Here, we used phage display to select, from the previously described library or from the new library, new specific αRep proteins binding to four different non-related predefined protein targets. Specific binders were selected in each case. The results show that binders with various sizes are selected including relatively long sequences, with up to 7 repeats. ITC-measured affinities vary with Kd values ranging from micromolar to nanomolar ranges. The formation of complexes is associated with a significant thermal stabilization of the bound target protein. The crystal structures of two complexes between αRep and their cognate targets were solved and show that the new interfaces are established by the variable surfaces of the repeated modules, as well by the variable N-cap residues. These results suggest that αRep library is a new and versatile source of tight and specific binding proteins with favorable biophysical properties. PMID:24014183

  8. Uncertainty-based simulation-optimization using Gaussian process emulation: Application to coastal groundwater management

    NASA Astrophysics Data System (ADS)

    Rajabi, Mohammad Mahdi; Ketabchi, Hamed

    2017-12-01

    Combined simulation-optimization (S/O) schemes have long been recognized as a valuable tool in coastal groundwater management (CGM). However, previous applications have mostly relied on deterministic seawater intrusion (SWI) simulations. This is a questionable simplification, knowing that SWI models are inevitably prone to epistemic and aleatory uncertainty, and hence a management strategy obtained through S/O without consideration of uncertainty may result in significantly different real-world outcomes than expected. However, two key issues have hindered the use of uncertainty-based S/O schemes in CGM, which are addressed in this paper. The first issue is how to solve the computational challenges resulting from the need to perform massive numbers of simulations. The second issue is how the management problem is formulated in presence of uncertainty. We propose the use of Gaussian process (GP) emulation as a valuable tool in solving the computational challenges of uncertainty-based S/O in CGM. We apply GP emulation to the case study of Kish Island (located in the Persian Gulf) using an uncertainty-based S/O algorithm which relies on continuous ant colony optimization and Monte Carlo simulation. In doing so, we show that GP emulation can provide an acceptable level of accuracy, with no bias and low statistical dispersion, while tremendously reducing the computational time. Moreover, five new formulations for uncertainty-based S/O are presented based on concepts such as energy distances, prediction intervals and probabilities of SWI occurrence. We analyze the proposed formulations with respect to their resulting optimized solutions, the sensitivity of the solutions to the intended reliability levels, and the variations resulting from repeated optimization runs.

  9. Optimization Of PVDF-TrFE Processing Conditions For The Fabrication Of Organic MEMS Resonators

    PubMed Central

    Ducrot, Pierre-Henri; Dufour, Isabelle; Ayela, Cédric

    2016-01-01

    This paper reports a systematic optimization of processing conditions of PVDF-TrFE piezoelectric thin films, used as integrated transducers in organic MEMS resonators. Indeed, despite data on electromechanical properties of PVDF found in the literature, optimized processing conditions that lead to these properties remain only partially described. In this work, a rigorous optimization of parameters enabling state-of-the-art piezoelectric properties of PVDF-TrFE thin films has been performed via the evaluation of the actuation performance of MEMS resonators. Conditions such as annealing duration, poling field and poling duration have been optimized and repeatability of the process has been demonstrated. PMID:26792224

  10. Optimization Of PVDF-TrFE Processing Conditions For The Fabrication Of Organic MEMS Resonators.

    PubMed

    Ducrot, Pierre-Henri; Dufour, Isabelle; Ayela, Cédric

    2016-01-21

    This paper reports a systematic optimization of processing conditions of PVDF-TrFE piezoelectric thin films, used as integrated transducers in organic MEMS resonators. Indeed, despite data on electromechanical properties of PVDF found in the literature, optimized processing conditions that lead to these properties remain only partially described. In this work, a rigorous optimization of parameters enabling state-of-the-art piezoelectric properties of PVDF-TrFE thin films has been performed via the evaluation of the actuation performance of MEMS resonators. Conditions such as annealing duration, poling field and poling duration have been optimized and repeatability of the process has been demonstrated.

  11. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 with improved proof-reading enhances homology-directed repair.

    PubMed

    Kato-Inui, Tomoko; Takahashi, Gou; Hsu, Szuyin; Miyaoka, Yuichiro

    2018-05-18

    Genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) predominantly induces non-homologous end joining (NHEJ), which generates random insertions or deletions, whereas homology-directed repair (HDR), which generates precise recombination products, is useful for wider applications. However, the factors that determine the ratio of HDR to NHEJ products after CRISPR/Cas9 editing remain unclear, and methods by which the proportion of HDR products can be increased have not yet been fully established. We systematically analyzed the HDR and NHEJ products after genome editing using various modified guide RNAs (gRNAs) and Cas9 variants with an enhanced conformational checkpoint to improve the fidelity at endogenous gene loci in HEK293T cells and HeLa cells. We found that these modified gRNAs and Cas9 variants were able to enhance HDR in both single-nucleotide substitutions and a multi-kb DNA fragment insertion. Our results suggest that the original CRISPR/Cas9 system from the bacterial immune system is not necessarily the best option for the induction of HDR in genome editing and indicate that the modulation of the kinetics of conformational checkpoints of Cas9 can optimize the HDR/NHEJ ratio.

  12. Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.

    PubMed

    Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi W; Chappell, Phillip; Wajsbrot, Dalia B; Nagraj, Praneeta; Abbas, Richat; Palumbo, Donna

    2018-06-01

    To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day; participants were titrated in 10-20 mg/day increments weekly based on efficacy and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. Mean MPH ERCT daily dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1 (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1 [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.

  13. Dynamics of Biomarkers in Relation to Aging and Mortality

    PubMed Central

    Arbeev, Konstantin G.; Ukraintseva, Svetlana V.; Yashin, Anatoliy I.

    2016-01-01

    Contemporary longitudinal studies collect repeated measurements of biomarkers allowing one to analyze their dynamics in relation to mortality, morbidity, or other health-related outcomes. Rich and diverse data collected in such studies provide opportunities to investigate how various socioeconomic, demographic, behavioral and other variables can interact with biological and genetic factors to produce differential rates of aging in individuals. In this paper, we review some recent publications investigating dynamics of biomarkers in relation to mortality, which use single biomarkers as well as cumulative measures combining information from multiple biomarkers. We also discuss the analytical approach, the stochastic process models, which conceptualizes several aging-related mechanisms in the structure of the model and allows evaluating “hidden” characteristics of aging-related changes indirectly from available longitudinal data on biomarkers and follow-up on mortality or onset of diseases taking into account other relevant factors (both genetic and non-genetic). We also discuss an extension of the approach, which considers ranges of “optimal values” of biomarkers rather than a single optimal value as in the original model. We discuss practical applications of the approach to single biomarkers and cumulative measures highlighting that the potential of applications to cumulative measures is still largely underused. PMID:27138087

  14. Improved Test Planning and Analysis Through the Use of Advanced Statistical Methods

    NASA Technical Reports Server (NTRS)

    Green, Lawrence L.; Maxwell, Katherine A.; Glass, David E.; Vaughn, Wallace L.; Barger, Weston; Cook, Mylan

    2016-01-01

    The goal of this work is, through computational simulations, to provide statistically-based evidence to convince the testing community that a distributed testing approach is superior to a clustered testing approach for most situations. For clustered testing, numerous, repeated test points are acquired at a limited number of test conditions. For distributed testing, only one or a few test points are requested at many different conditions. The statistical techniques of Analysis of Variance (ANOVA), Design of Experiments (DOE) and Response Surface Methods (RSM) are applied to enable distributed test planning, data analysis and test augmentation. The D-Optimal class of DOE is used to plan an optimally efficient single- and multi-factor test. The resulting simulated test data are analyzed via ANOVA and a parametric model is constructed using RSM. Finally, ANOVA can be used to plan a second round of testing to augment the existing data set with new data points. The use of these techniques is demonstrated through several illustrative examples. To date, many thousands of comparisons have been performed and the results strongly support the conclusion that the distributed testing approach outperforms the clustered testing approach.

  15. Membrane Introduction Mass Spectrometry Combined with an Orthogonal Partial-Least Squares Calibration Model for Mixture Analysis.

    PubMed

    Li, Min; Zhang, Lu; Yao, Xiaolong; Jiang, Xingyu

    2017-01-01

    The emerging membrane introduction mass spectrometry technique has been successfully used to detect benzene, toluene, ethyl benzene and xylene (BTEX), while overlapped spectra have unfortunately hindered its further application to the analysis of mixtures. Multivariate calibration, an efficient method to analyze mixtures, has been widely applied. In this paper, we compared univariate and multivariate analyses for quantification of the individual components of mixture samples. The results showed that the univariate analysis creates poor models with regression coefficients of 0.912, 0.867, 0.440 and 0.351 for BTEX, respectively. For multivariate analysis, a comparison to the partial-least squares (PLS) model shows that the orthogonal partial-least squares (OPLS) regression exhibits an optimal performance with regression coefficients of 0.995, 0.999, 0.980 and 0.976, favorable calibration parameters (RMSEC and RMSECV) and a favorable validation parameter (RMSEP). Furthermore, the OPLS exhibits a good recovery of 73.86 - 122.20% and relative standard deviation (RSD) of the repeatability of 1.14 - 4.87%. Thus, MIMS coupled with the OPLS regression provides an optimal approach for a quantitative BTEX mixture analysis in monitoring and predicting water pollution.

  16. Optimizing Utilization of Detectors

    DTIC Science & Technology

    2016-03-01

    provide a quantifiable process to determine how much time should be allocated to each task sharing the same asset . This optimized expected time... allocation is calculated by numerical analysis and Monte Carlo simulation. Numerical analysis determines the expectation by involving an integral and...determines the optimum time allocation of the asset by repeatedly running experiments to approximate the expectation of the random variables. This

  17. Analysis of sequence repeats of proteins in the PDB.

    PubMed

    Mary Rajathei, David; Selvaraj, Samuel

    2013-12-01

    Internal repeats in protein sequences play a significant role in the evolution of protein structure and function. Applications of different bioinformatics tools help in the identification and characterization of these repeats. In the present study, we analyzed sequence repeats in a non-redundant set of proteins available in the Protein Data Bank (PDB). We used RADAR for detecting internal repeats in a protein, PDBeFOLD for assessing structural similarity, PDBsum for finding functional involvement and Pfam for domain assignment of the repeats in a protein. Through the analysis of sequence repeats, we found that identity of the sequence repeats falls in the range of 20-40% and, the superimposed structures of the most of the sequence repeats maintain similar overall folding. Analysis sequence repeats at the functional level reveals that most of the sequence repeats are involved in the function of the protein through functionally involved residues in the repeat regions. We also found that sequence repeats in single and two domain proteins often contained conserved sequence motifs for the function of the domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Repeated applications of a transdermal patch: analytical solution and optimal control of the delivery rate.

    PubMed

    Simon, L

    2007-10-01

    The integral transform technique was implemented to solve a mathematical model developed for percutaneous drug absorption. The model included repeated application and removal of a patch from the skin. Fick's second law of diffusion was used to study the transport of a medicinal agent through the vehicle and subsequent penetration into the stratum corneum. Eigenmodes and eigenvalues were computed and introduced into an inversion formula to estimate the delivery rate and the amount of drug in the vehicle and the skin. A dynamic programming algorithm calculated the optimal doses necessary to achieve a desired transdermal flux. The analytical method predicted profiles that were in close agreement with published numerical solutions and provided an automated strategy to perform therapeutic drug monitoring and control.

  19. Maximum likelihood decoding analysis of accumulate-repeat-accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, A.; Divsalar, D.; Yao, K.

    2004-01-01

    In this paper, the performance of the repeat-accumulate codes with (ML) decoding are analyzed and compared to random codes by very tight bounds. Some simple codes are shown that perform very close to Shannon limit with maximum likelihood decoding.

  20. Simultaneous tuning of electric field intensity and structural properties of ZnO: Graphene nanostructures for FOSPR based nicotine sensor.

    PubMed

    Tabassum, Rana; Gupta, Banshi D

    2017-05-15

    We report theoretical and experimental realization of a SPR based fiber optic nicotine sensor having coatings of silver and graphene doped ZnO nanostructure onto the unclad core of the optical fiber. The volume fraction (f) of graphene in ZnO was optimized using simulation of electric field intensity. Four types of graphene doped ZnO nanostructures viz. nanocomposites, nanoflowers, nanotubes and nanofibers were prepared using optimized value of f. The morphology, photoluminescence (PL) spectra and UV-vis spectra of these nanostructures were studied. The peak PL intensity was found to be highest for ZnO: graphene nanofibers. The optimized value of f in ZnO: graphene nanofiber was reconfirmed using UV-vis spectroscopy. The experiments were performed on the fiber optic probe fabricated with Ag/ZnO: graphene layer and optimized parameters for in-situ detection of nicotine. The interaction of nicotine with ZnO: graphene nanostructures alters the dielectric function of ZnO: graphene nanostructure which is manifested in terms of shift in resonance wavelength. From the sensing signal, the performance parameters were measured including sensitivity, limit of detection (LOD), limit of quantification (LOQ), stability, repeatability and selectivity. The real sample prepared using cigarette tobacco leaves and analyzed using the fabricated sensor makes it suitable for practical applications. The achieved values of LOD and LOQ are found to be unrivalled in comparison to the reported ones. The sensor possesses additional advantages such as, immunity to electromagnetic interference, low cost, capability of online monitoring, remote sensing. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Impact of Chaos Functions on Modern Swarm Optimizers.

    PubMed

    Emary, E; Zawbaa, Hossam M

    2016-01-01

    Exploration and exploitation are two essential components for any optimization algorithm. Much exploration leads to oscillation and premature convergence while too much exploitation slows down the optimization algorithm and the optimizer may be stuck in local minima. Therefore, balancing the rates of exploration and exploitation at the optimization lifetime is a challenge. This study evaluates the impact of using chaos-based control of exploration/exploitation rates against using the systematic native control. Three modern algorithms were used in the study namely grey wolf optimizer (GWO), antlion optimizer (ALO) and moth-flame optimizer (MFO) in the domain of machine learning for feature selection. Results on a set of standard machine learning data using a set of assessment indicators prove advance in optimization algorithm performance when using variational repeated periods of declined exploration rates over using systematically decreased exploration rates.

  2. Sequences characterization of microsatellite DNA sequences in Pacific abalone ( Haliotis discus hannai)

    NASA Astrophysics Data System (ADS)

    Li, Qi; Akihiro, Kijima

    2007-01-01

    The microsatellite-enriched library was constructed using magnetic bead hybridization selection method, and the microsatellite DNA sequences were analyzed in Pacific abalone Haliotis discus hannai. Three hundred and fifty white colonies were screened using PCR-based technique, and 84 clones were identified to potentially contain microsatellite repeat motif. The 84 clones were sequenced, and 42 microsatellites and 4 minisatellites with a minimum of five repeats were found (13.1% of white colonies screened). Besides the motif of CA contained in the oligoprobe, we also found other 16 types of microsatellite repeats including a dinucleotide repeat, two tetranucleotide repeats, twelve pentanucleotide repeats and a hexanucleotide repeat. According to Weber (1990), the microsatellite sequences obtained could be categorized structurally into perfect repeats (73.3%), imperfect repeats (13.3%), and compound repeats (13.4%). Among the microsatellite repeats, relatively short arrays (<20 repeats) were most abundant, accounting for 75.0%. The largest length of microsatellites was 48 repeats, and the average number of repeats was 13.4. The data on the composition and length distribution of microsatellites obtained in the present study can be useful for choosing the repeat motifs for microsatellite isolation in other abalone species.

  3. Design of experiments to optimize an in vitro cast to predict human nasal drug deposition.

    PubMed

    Shah, Samir A; Dickens, Colin J; Ward, David J; Banaszek, Anna A; George, Chris; Horodnik, Walter

    2014-02-01

    Previous studies showed nasal spray in vitro tests cannot predict in vivo deposition, pharmacokinetics, or pharmacodynamics. This challenge makes it difficult to assess deposition achieved with new technologies delivering to the therapeutically beneficial posterior nasal cavity. In this study, we determined best parameters for using a regionally divided nasal cast to predict deposition. Our study used a model suspension and a design of experiments to produce repeatable deposition results that mimic nasal deposition patterns of nasal suspensions from the literature. The seven-section (the nozzle locator, nasal vestibule, front turbinate, rear turbinate, olfactory region, nasopharynx, and throat filter) nylon nasal cast was based on computed tomography images of healthy humans. It was coated with a glycerol/Brij-35 solution to mimic mucus. After assembling and orienting, airflow was applied and nasal spray containing a model suspension was sprayed. After disassembling the cast, drug depositing in each section was assayed by HPLC. The success criteria for optimal settings were based on nine in vivo studies in the literature. The design of experiments included exploratory and half factorial screening experiments to identify variables affecting deposition (angles, airflow, and airflow time), optimization experiments, and then repeatability and reproducibility experiments. We found tilt angle and airflow time after actuation affected deposition the most. The optimized settings were flow rate of 16 L/min, postactuation flow time of 12 sec, a tilt angle of 23°, nozzle angles of 0°, and actuation speed of 5 cm/sec. Neither cast nor operator caused significant variation of results. We determined cast parameters to produce results resembling suspension nasal sprays in the literature. The results were repeatable and unaffected by operator or cast. These nasal spray parameters could be used to assess deposition from new devices or formulations. For human deposition studies using radiolabeled formulations, this cast could show that radiolabel deposition represents drug deposition. Our methods could also be used to optimize settings for other casts.

  4. Population-scale whole genome sequencing identifies 271 highly polymorphic short tandem repeats from Japanese population.

    PubMed

    Hirata, Satoshi; Kojima, Kaname; Misawa, Kazuharu; Gervais, Olivier; Kawai, Yosuke; Nagasaki, Masao

    2018-05-01

    Forensic DNA typing is widely used to identify missing persons and plays a central role in forensic profiling. DNA typing usually uses capillary electrophoresis fragment analysis of PCR amplification products to detect the length of short tandem repeat (STR) markers. Here, we analyzed whole genome data from 1,070 Japanese individuals generated using massively parallel short-read sequencing of 162 paired-end bases. We have analyzed 843,473 STR loci with two to six basepair repeat units and cataloged highly polymorphic STR loci in the Japanese population. To evaluate the performance of the cataloged STR loci, we compared 23 STR loci, widely used in forensic DNA typing, with capillary electrophoresis based STR genotyping results in the Japanese population. Seventeen loci had high correlations and high call rates. The other six loci had low call rates or low correlations due to either the limitations of short-read sequencing technology, the bioinformatics tool used, or the complexity of repeat patterns. With these analyses, we have also purified the suitable 218 STR loci with four basepair repeat units and 53 loci with five basepair repeat units both for short read sequencing and PCR based technologies, which would be candidates to the actual forensic DNA typing in Japanese population.

  5. Online solid-phase extraction with high-performance liquid chromatography and mass spectrometry for the determination of five tannins in traditional Chinese medicine injections.

    PubMed

    Sun, Meng; Lin, Yuanyuan; Zhang, Jie; Zheng, Shaohua; Wang, Sicen

    2016-03-01

    A rapid analytical method based on online solid-phase extraction with high-performance liquid chromatography and mass spectrometry has been established and applied to the determination of tannin compounds that may cause adverse effects in traditional Chinese medicine injections. Different solid-phase extraction sorbents have been compared and the elution buffer was optimized. The performance of the method was verified by evaluation of recovery (≥40%), repeatability (RSD ≤ 6%), linearity (r(2) ≥ 0.993), and limit of quantification (≤0.35 μg/mL). Five tannin compounds, gallic acid, cianidanol, gallocatechin gallate, ellagic acid, and penta-O-galloylglucose, were identified with concentrations ranging from 3.1-37.4 μg/mL in the analyzed traditional Chinese medicine injections. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Toward the Standardization of Biochar Analysis: The COST Action TD1107 Interlaboratory Comparison.

    PubMed

    Bachmann, Hans Jörg; Bucheli, Thomas D; Dieguez-Alonso, Alba; Fabbri, Daniele; Knicker, Heike; Schmidt, Hans-Peter; Ulbricht, Axel; Becker, Roland; Buscaroli, Alessandro; Buerge, Diane; Cross, Andrew; Dickinson, Dane; Enders, Akio; Esteves, Valdemar I; Evangelou, Michael W H; Fellet, Guido; Friedrich, Kevin; Gasco Guerrero, Gabriel; Glaser, Bruno; Hanke, Ulrich M; Hanley, Kelly; Hilber, Isabel; Kalderis, Dimitrios; Leifeld, Jens; Masek, Ondrej; Mumme, Jan; Carmona, Marina Paneque; Calvelo Pereira, Roberto; Rees, Frederic; Rombolà, Alessandro G; de la Rosa, José Maria; Sakrabani, Ruben; Sohi, Saran; Soja, Gerhard; Valagussa, Massimo; Verheijen, Frank; Zehetner, Franz

    2016-01-20

    Biochar produced by pyrolysis of organic residues is increasingly used for soil amendment and many other applications. However, analytical methods for its physical and chemical characterization are yet far from being specifically adapted, optimized, and standardized. Therefore, COST Action TD1107 conducted an interlaboratory comparison in which 22 laboratories from 12 countries analyzed three different types of biochar for 38 physical-chemical parameters (macro- and microelements, heavy metals, polycyclic aromatic hydrocarbons, pH, electrical conductivity, and specific surface area) with their preferential methods. The data were evaluated in detail using professional interlaboratory testing software. Whereas intralaboratory repeatability was generally good or at least acceptable, interlaboratory reproducibility was mostly not (20% < mean reproducibility standard deviation < 460%). This paper contributes to better comparability of biochar data published already and provides recommendations to improve and harmonize specific methods for biochar analysis in the future.

  7. Determination of Tryptamines and β-Carbolines in Ayahuasca Beverage Consumed During Brazilian Religious Ceremonies.

    PubMed

    Santos, Mônica Cardoso; Navickiene, Sandro; Gaujac, Alain

    2017-05-01

    Ayahuasca is a potent hallucinogenic beverage prepared from Banisteriopsis caapi in combination with other psychoactive plants. N,N-dimethyltryptamine, tryptamine, harmine, harmaline, harmalol, and tetrahydroharmine were quantified in ayahuasca samples using a simple and low-cost method based on SPE and LC with UV diode-array detection. The experimental variables that affect the SPE method, such as type of solid phase and nature of solvent, were optimized. The method showed good linearity (r > 0.9902) and repeatability (RSD < 0.8%) for alkaloid compounds, with an LOD of 0.12 mg/L. The proposed method was used to analyze 20 samples from an ayahuasca cooking process from a religious group located in the municipality of Fortaleza, state of Ceará, Brazil. The results showed that concentrations of the target compounds ranged from 0.3 to 36.7 g/L for these samples.

  8. Development and characterization of a FIA system for selective assay of L-ascorbic acid in food samples.

    PubMed

    Vig, Attila; Igloi, Attila; Adanyi, Nora; Gyemant, Gyongyi; Csutoras, Csaba; Kiss, Attila

    2010-10-01

    An amperometric detector and an enzymatic reaction were combined for the measurement of L-ascorbic acid. The enzyme cell (containing immobilized ascorbate oxidase) was connected to a flow injection analyzer (FIA) system with a glassy carbon electrode as an amperometric detector. During optimization and measurements two sample injectors were used, one before and one after the enzyme cell, thus eliminating the background interferences. Subtraction of the signal area given in the presence of enzyme from the one given in the absence of enzyme was applied for measuring analyte concentrations and calibration at 400 mV. Analysis capacity of system is 25 samples/hour. The relative standard deviation (RSD) was below 5% (5 times repeated, 400 μmol/L conc.), linearity up to 400 μmol/L, limit of detection (LOD) 5 μmol/L, fitting of calibration curve in 25-400 μmol/L range was R (2) = 0.99.

  9. Dietary Protected Feed Supplement to Increase Milk Production and Quality of Dairy Cows

    NASA Astrophysics Data System (ADS)

    Pramono, A.; Handayanta, E.; Widayati, D. T.; Putro, P. P.; Kustono

    2017-04-01

    The efforts to improve and optimize productivity of dairy cows require sufficient availability of nutrients, especially high energy in the early period of lactation. Increasing energy intake in dairy cows can be conducted by increasing the density of energy. The research aimed to evaluate dietary protected feed supplement on milk production and quality, including: fat, protein, and lactose content of Friesian Holstein dairy cow milk. Protected feed supplement was produced from sardine fish oil, through saponification and microencapsulation protection methods. The experiment consists of two treatments i.e. P0: basal diet (control) and P1: basal diet + 3 % protected feed supplement. Each treatment was repeated 15 times. Data were analyzed by independent samples t-test analysis. Results showed that supplementation of protected sardine fish oil had no effect on lactose content, but increased milk yield production (p<0.01), milk fat content (p<0.05), and protein content (p<0.05).

  10. Fireworks algorithm for mean-VaR/CVaR models

    NASA Astrophysics Data System (ADS)

    Zhang, Tingting; Liu, Zhifeng

    2017-10-01

    Intelligent algorithms have been widely applied to portfolio optimization problems. In this paper, we introduce a novel intelligent algorithm, named fireworks algorithm, to solve the mean-VaR/CVaR model for the first time. The results show that, compared with the classical genetic algorithm, fireworks algorithm not only improves the optimization accuracy and the optimization speed, but also makes the optimal solution more stable. We repeat our experiments at different confidence levels and different degrees of risk aversion, and the results are robust. It suggests that fireworks algorithm has more advantages than genetic algorithm in solving the portfolio optimization problem, and it is feasible and promising to apply it into this field.

  11. Optimal periodic binary codes of lengths 28 to 64

    NASA Technical Reports Server (NTRS)

    Tyler, S.; Keston, R.

    1980-01-01

    Results from computer searches performed to find repeated binary phase coded waveforms with optimal periodic autocorrelation functions are discussed. The best results for lengths 28 to 64 are given. The code features of major concern are where (1) the peak sidelobe in the autocorrelation function is small and (2) the sum of the squares of the sidelobes in the autocorrelation function is small.

  12. Multi-Objective Optimization for Trustworthy Tactical Networks: A Survey and Insights

    DTIC Science & Technology

    2013-06-01

    existing data sources, gathering and maintaining the data needed , and completing and reviewing the collection of information. Send comments regarding...problems: using repeated cooperative games [12], hedonic games [25], and nontransferable utility cooperative games [27]. It should be noted that trust...examined an optimal task allocation problem in a distributed computing system where program modules need to be allocated to different processors to

  13. Coevolutionary dynamics of aspiration and strategy in spatial repeated public goods games

    NASA Astrophysics Data System (ADS)

    Wu, Te; Fu, Feng; Wang, Long

    2018-06-01

    The evolutionary dynamics remain largely unknown for spatial populations where individuals are more likely to interact repeatedly. Under this settings, individuals can make their decisions to cooperate or not based on the decisions previously adopted by others in their neighborhoods. Using repeated public goods game, we construct a spatial model and use a statistical physics approach to study the coevolutionary dynamics of aspiration and strategy. Individuals each have an aspiration towards the groups they are involved. According to the outcome of each group, individuals have assessment of whether their aspirations are satisfied. If satisfied, they cooperate next round. Otherwise, they switch to defecting. Results show threshold phenomenon for harsh collective dilemma: cooperators sticking to high levels of aspiration can prevail over defectors, while cooperators with other levels are invariably wiped out. When the collective dilemma is relaxed, cooperation is greatly facilitated by inducing a high level of diversity of aspiration. Snapshots further show the spatial patterns of how this coevolutionary process leads to the emergence of an optimal solution associated with aspiration level, whose corresponding strategy are most prevalent. This optimal solution lies in one and the highest aspiration level allowed, and depends on the intensity of the social dilemma. By removing the memory effect, our results also confirm that repeated interactions can promote cooperation, but to a limited degree.

  14. Short bowel mucosal morphology, proliferation and inflammation at first and repeat STEP procedures.

    PubMed

    Mutanen, Annika; Barrett, Meredith; Feng, Yongjia; Lohi, Jouko; Rabah, Raja; Teitelbaum, Daniel H; Pakarinen, Mikko P

    2018-04-17

    Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS). Fifteen SBS children, who underwent 13 first and 7 repeat STEP procedures with full thickness small bowel samples at median age 1.5 years (IQR 0.7-3.7) were included. The specimens were analyzed histologically for mucosal morphology, inflammation and muscular thickness. Mucosal proliferation and apoptosis was analyzed with MIB1 and Tunel immunohistochemistry. Median small bowel length increased 42% by initial STEP and 13% by repeat STEP (p=0.05), while enteral caloric intake increased from 6% to 36% (p=0.07) during 14 (12-42) months between the procedures. Abnormal mucosal inflammation was frequently observed both at initial (69%) and additional STEP (86%, p=0.52) surgery. Villus height, crypt depth, enterocyte proliferation and apoptosis as well as muscular thickness were comparable at first and repeat STEP (p>0.05 for all). Patients, who required repeat STEP tended to be younger (p=0.057) with less apoptotic crypt cells (p=0.031) at first STEP. Absence of ileocecal valve associated with increased intraepithelial leukocyte count and reduced crypt cell proliferation index (p<0.05 for both). No adaptive mucosal hyperplasia or muscular alterations occurred between first and repeat STEP. Persistent inflammation and lacking mucosal growth may contribute to continuing bowel dysfunction in SBS children, who require repeat STEP procedure, especially after removal of the ileocecal valve. Level IV, retrospective study. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Single Amino Acid Repeats in the Proteome World: Structural, Functional, and Evolutionary Insights

    PubMed Central

    Kumar, Amitha Sampath; Sowpati, Divya Tej; Mishra, Rakesh K.

    2016-01-01

    Microsatellites or simple sequence repeats (SSR) are abundant, highly diverse stretches of short DNA repeats present in all genomes. Tandem mono/tri/hexanucleotide repeats in the coding regions contribute to single amino acids repeats (SAARs) in the proteome. While SSRs in the coding region always result in amino acid repeats, a majority of SAARs arise due to a combination of various codons representing the same amino acid and not as a consequence of SSR events. Certain amino acids are abundant in repeat regions indicating a positive selection pressure behind the accumulation of SAARs. By analysing 22 proteomes including the human proteome, we explored the functional and structural relationship of amino acid repeats in an evolutionary context. Only ~15% of repeats are present in any known functional domain, while ~74% of repeats are present in the disordered regions, suggesting that SAARs add to the functionality of proteins by providing flexibility, stability and act as linker elements between domains. Comparison of SAAR containing proteins across species reveals that while shorter repeats are conserved among orthologs, proteins with longer repeats, >15 amino acids, are unique to the respective organism. Lysine repeats are well conserved among orthologs with respect to their length and number of occurrences in a protein. Other amino acids such as glutamic acid, proline, serine and alanine repeats are generally conserved among the orthologs with varying repeat lengths. These findings suggest that SAARs have accumulated in the proteome under positive selection pressure and that they provide flexibility for optimal folding of functional/structural domains of proteins. The insights gained from our observations can help in effective designing and engineering of proteins with novel features. PMID:27893794

  16. 40 CFR 1065.303 - Summary of required calibration and verifications

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: Upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers.... For THC FID analyzers: Upon initial installation, after major maintenance, and after FID optimization...

  17. 40 CFR 1065.303 - Summary of required calibration and verifications

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: Upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers.... For THC FID analyzers: Upon initial installation, after major maintenance, and after FID optimization...

  18. Comparison of simple sequence repeats in 19 Archaea.

    PubMed

    Trivedi, S

    2006-12-05

    All organisms that have been studied until now have been found to have differential distribution of simple sequence repeats (SSRs), with more SSRs in intergenic than in coding sequences. SSR distribution was investigated in Archaea genomes where complete chromosome sequences of 19 Archaea were analyzed with the program SPUTNIK to find di- to penta-nucleotide repeats. The number of repeats was determined for the complete chromosome sequences and for the coding and non-coding sequences. Different from what has been found for other groups of organisms, there is an abundance of SSRs in coding regions of the genome of some Archaea. Dinucleotide repeats were rare and CG repeats were found in only two Archaea. In general, trinucleotide repeats are the most abundant SSR motifs; however, pentanucleotide repeats are abundant in some Archaea. Some of the tetranucleotide and pentanucleotide repeat motifs are organism specific. In general, repeats are short and CG-rich repeats are present in Archaea having a CG-rich genome. Among the 19 Archaea, SSR density was not correlated with genome size or with optimum growth temperature. Pentanucleotide density had an inverse correlation with the CG content of the genome.

  19. Psychiatric Hospitalization after Emergency Treatment for Deliberate Self-Harm is Associated with Repeated Deliberate Self-Harm.

    PubMed

    Ichimura, Atshushi; Kato, Koji; Taira, Takayuki; Otsuka, Hiroyuki; Seki, Tomoko; Nakagawa, Yoshihide; Inokuchi, Sadaki

    2018-02-23

    To evaluate whether treatment at a psychiatric hospital reduces the risk of repeating parasuicide. Participants comprised 4,483 parasuicide patients admitted to an emergency department between July 2003 and March 2012. We analyzed the effectiveness of psychiatric hospitalization in preventing repeated parasuicide. We adjusted for background factors using multivariate logistic regression. Effects of psychiatric hospitalization upon the likelihood of repeated parasuicide within one year varied by age (especially those aged <35 years), indicating that hospitalization was a significant risk factor. We must be mindful of the risk of repeated parasuicide following discharge in young patients and to provide them with ongoing outpatient care and multimodal support.

  20. Spin bearing retainer design optimization

    NASA Technical Reports Server (NTRS)

    Boesiger, Edward A.; Warner, Mark H.

    1991-01-01

    The dynamics behavior of spin bearings for momentum wheels (control-moment gyroscope, reaction wheel assembly) is critical to satellite stability and life. Repeated bearing retainer instabilities hasten lubricant deterioration and can lead to premature bearing failure and/or unacceptable vibration. These instabilities are typically distinguished by increases in torque, temperature, audible noise, and vibration induced by increases into the bearing cartridge. Ball retainer design can be optimized to minimize these occurrences. A retainer was designed using a previously successful smaller retainer as an example. Analytical methods were then employed to predict its behavior and optimize its configuration.

  1. Oxidative stress adaptation with acute, chronic, and repeated stress.

    PubMed

    Pickering, Andrew M; Vojtovich, Lesya; Tower, John; A Davies, Kelvin J

    2013-02-01

    Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Experimental designs for a Benign Paroxysmal Positional Vertigo model

    PubMed Central

    2013-01-01

    Background The pathology of the Benign Paroxysmal Positional Vertigo (BPPV) is detected by a clinician through maneuvers consisting of a series of consecutive head turns that trigger the symptoms of vertigo in patient. A statistical model based on a new maneuver has been developed in order to calculate the volume of endolymph displaced after the maneuver. Methods A simplification of the Navier‐Stokes problem from the fluids theory has been used to construct the model. In addition, the same cubic splines that are commonly used in kinematic control of robots were used to obtain an appropriate description of the different maneuvers. Then experimental designs were computed to obtain an optimal estimate of the model. Results D‐optimal and c‐optimal designs of experiments have been calculated. These experiments consist of a series of specific head turns of duration Δt and angle α that should be performed by the clinician on the patient. The experimental designs obtained indicate the duration and angle of the maneuver to be performed as well as the corresponding proportion of replicates. Thus, in the D‐optimal design for 100 experiments, the maneuver consisting of a positive 30° pitch from the upright position, followed by a positive 30° roll, both with a duration of one and a half seconds is repeated 47 times. Then the maneuver with 60° /6° pitch/roll during half a second is repeated 16 times and the maneuver 90° /90° pitch/roll during half a second is repeated 37 times. Other designs with significant differences are computed and compared. Conclusions A biomechanical model was derived to provide a quantitative basis for the detection of BPPV. The robustness study for the D‐optimal design, with respect to the choice of the nominal values of the parameters, shows high efficiencies for small variations and provides a guide to the researcher. Furthermore, c‐optimal designs give valuable assistance to check how efficient the D‐optimal design is for the estimation of each of the parameters. The experimental designs provided in this paper allow the physician to validate the model. The authors of the paper have held consultations with an ENT consultant in order to align the outline more closely to practical scenarios. PMID:23509996

  3. A simple and highly repeatable viral plaque assay for enterovirus 71.

    PubMed

    Yin, Yingxian; Xu, Yi; Ou, Zhiying; Su, Ling; Xia, Huimin

    2015-04-01

    The classic plaque assay is a method for counting infectious viral particles, however its complexity limits its use in a variety of virological experiments. To simplify the operation and to improve the repeatability, we employed an improved plaque assay procedure based on Avicel to make the whole experiment easier and optimize the results on a model of Vero cells infection with Enterovirus 71(EV71). Clear plaques visible to the naked eyes can be formed on a 24-well plate or a 96-well plate without immunostaining. Following further improvement, this plaque assay procedure could be applied to other viruses, being both simple and repeatable. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Cerebral metabolic rate of oxygen (CMRO2 ) mapping with hyperventilation challenge using quantitative susceptibility mapping (QSM).

    PubMed

    Zhang, Jingwei; Zhou, Dong; Nguyen, Thanh D; Spincemaille, Pascal; Gupta, Ajay; Wang, Yi

    2017-05-01

    Our objective was to demonstrate the feasibility of using hyperventilation as an efficient vasoconstrictive challenge and prior knowledge as denoising constraints for cerebral metabolic rate of oxygen (CMRO 2 ) mapping based upon quantitative susceptibility mapping (QSM). Three-dimensional (3D) multi-echo gradient echo and arterial spin labeling imaging were performed to calculate QSM and perfusion maps before and after a hyperventilation challenge in 11 healthy subjects. For comparison, this was repeated using a caffeine challenge. Whole-brain CMRO 2 and oxygen extraction fraction (OEF) maps were computed using constrained optimization. Hyperventilation scans were repeated to measure reproducibility. Regional agreement of CMRO 2 and OEF maps was analyzed within the cortical gray matter (CGM) using t-test and Bland-Altman plots. Hyperventilation challenge eliminates the 30-min waiting time needed for caffeine to exert its vasoconstrictive effects. Mean CMRO 2 (in µmol/100g/min) obtained in CGM using the caffeine and repeated hyperventilation scans were 149 ± 16, 153 ± 19, and 150 ± 20, respectively. This corresponded to an OEF of 33.6 ± 3.4%, 32.3 ± 3.2%, and 34.1 ± 3.8% at baseline state and 39.8 ± 4.8%, 43.6 ± 6.2%, and 42.8 ± 6.8% at challenged state, respectively. Hyperventilation scans produced a good agreement of CMRO 2 and OEF values. Hyperventilation is a feasible, reproducible, and efficient vasoconstrictive challenge for QSM-based quantitative CMRO 2 mapping. Magn Reson Med 77:1762-1773, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  5. Gender, diabetes education, and psychosocial factors are associated with persistent poor glycemic control in patients with type 2 diabetes in the Joint Asia Diabetes Evaluation (JADE) program.

    PubMed

    Yin, Junmei; Yeung, Roseanne; Luk, Andrea; Tutino, Greg; Zhang, Yuying; Kong, Alice; Chung, Harriet; Wong, Rebecca; Ozaki, Risa; Ma, Ronald; Tsang, Chiu-Chi; Tong, Peter; So, Wingyee; Chan, Juliana

    2016-01-01

    Factors associated with persistent poor glycemic control were explored in patients with type 2 diabetes under the Joint Asia Diabetes Evaluation (JADE) program. Chinese adults enrolled in JADE with HbA1c ≥8% at initial comprehensive assessment (CA1) and repeat assessment were analyzed. The improved group was defined as those with a ≥1% absolute reduction in HbA1c, and the unimproved group was those with <1% reduction at the repeat CA (CA2). Of 4458 enrolled patients with HbA1c ≥8% at baseline, 1450 underwent repeat CA. After a median interval of 1.7 years (interquartile range[IQR] 1.1-2.2) between CA1 and CA2, the unimproved group (n = 677) had a mean 0.4% (95% confidence interval [CI] 0.3%, 0.5%) increase in HbA1c compared with a mean 2.8% reduction (95% CI -2.9, -2.6%) in the improved group (n = 773). The unimproved group had a female preponderance with lower education level, and was more likely to be insulin treated. Patients in the improved group received more diabetes education between CAs with improved self-care behaviors, whereas the unimproved group had worsening of health-related quality of life at CA2. Apart from female gender, long disease duration, low educational level, obesity, retinopathy, history of hypoglycemia, and insulin use, lack of education from diabetes nurses between CAs had the strongest association for persistent poor glycemic control. These results highlight the multidimensional nature of glycemic control, and the importance of diabetes education and optimizing diabetes care by considering psychosocial factors. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  6. Improved microgrid arrangement for integrated imaging polarimeters.

    PubMed

    LeMaster, Daniel A; Hirakawa, Keigo

    2014-04-01

    For almost 20 years, microgrid polarimetric imaging systems have been built using a 2×2 repeating pattern of polarization analyzers. In this Letter, we show that superior spatial resolution is achieved over this 2×2 case when the analyzers are arranged in a 2×4 repeating pattern. This unconventional result, in which a more distributed sampling pattern results in finer spatial resolution, is also achieved without affecting the conditioning of the polarimetric data-reduction matrix. Proof is provided theoretically and through Stokes image reconstruction of synthesized data.

  7. Internode length is reduced during myelination and remyelination by neurofilament medium phosphorylation in motor axons.

    PubMed

    Villalón, Eric; Barry, Devin M; Byers, Nathan; Frizzi, Katie; Jones, Maria R; Landayan, Dan S; Dale, Jeffrey M; Downer, Natalie L; Calcutt, Nigel A; Garcia, Michael L

    2018-05-14

    The distance between nodes of Ranvier, referred to as internode length, positively correlates with axon diameter, and is optimized during development to ensure maximal neuronal conduction velocity. Following myelin loss, internode length is reestablished through remyelination. However, remyelination results in short internode lengths and reduced conduction rates. We analyzed the potential role of neurofilament phosphorylation in regulating internode length during remyelination and myelination. Following ethidium bromide induced demyelination, levels of neurofilament medium (NF-M) and heavy (NF-H) phosphorylation were unaffected. Preventing NF-M lysine-serine-proline (KSP) repeat phosphorylation increased internode length by 30% after remyelination. To further analyze the role of NF-M phosphorylation in regulating internode length, gene replacement was used to produce mice in which all KSP serine residues were replaced with glutamate to mimic constitutive phosphorylation. Mimicking constitutive KSP phosphorylation reduced internode length by 16% during myelination and motor nerve conduction velocity by ~27% without altering sensory nerve structure or function. Our results suggest that NF-M KSP phosphorylation is part of a cooperative mechanism between axons and Schwann cells that together determine internode length, and suggest motor and sensory axons utilize different mechanisms to establish internode length. Copyright © 2018. Published by Elsevier Inc.

  8. Piecewise convexity of artificial neural networks.

    PubMed

    Rister, Blaine; Rubin, Daniel L

    2017-10-01

    Although artificial neural networks have shown great promise in applications including computer vision and speech recognition, there remains considerable practical and theoretical difficulty in optimizing their parameters. The seemingly unreasonable success of gradient descent methods in minimizing these non-convex functions remains poorly understood. In this work we offer some theoretical guarantees for networks with piecewise affine activation functions, which have in recent years become the norm. We prove three main results. First, that the network is piecewise convex as a function of the input data. Second, that the network, considered as a function of the parameters in a single layer, all others held constant, is again piecewise convex. Third, that the network as a function of all its parameters is piecewise multi-convex, a generalization of biconvexity. From here we characterize the local minima and stationary points of the training objective, showing that they minimize the objective on certain subsets of the parameter space. We then analyze the performance of two optimization algorithms on multi-convex problems: gradient descent, and a method which repeatedly solves a number of convex sub-problems. We prove necessary convergence conditions for the first algorithm and both necessary and sufficient conditions for the second, after introducing regularization to the objective. Finally, we remark on the remaining difficulty of the global optimization problem. Under the squared error objective, we show that by varying the training data, a single rectifier neuron admits local minima arbitrarily far apart, both in objective value and parameter space. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Design of the VISITOR Tool: A Versatile ImpulSive Interplanetary Trajectory OptimizeR

    NASA Technical Reports Server (NTRS)

    Corpaccioli, Luca; Linskens, Harry; Komar, David R.

    2014-01-01

    The design of trajectories for interplanetary missions represents one of the most complex and important problems to solve during conceptual space mission design. To facilitate conceptual mission sizing activities, it is essential to obtain sufficiently accurate trajectories in a fast and repeatable manner. To this end, the VISITOR tool was developed. This tool modularly augments a patched conic MGA-1DSM model with a mass model, launch window analysis, and the ability to simulate more realistic arrival and departure operations. This was implemented in MATLAB, exploiting the built-in optimization tools and vector analysis routines. The chosen optimization strategy uses a grid search and pattern search, an iterative variable grid method. A genetic algorithm can be selectively used to improve search space pruning, at the cost of losing the repeatability of the results and increased computation time. The tool was validated against seven flown missions: the average total mission (Delta)V offset from the nominal trajectory was 9.1%, which was reduced to 7.3% when using the genetic algorithm at the cost of an increase in computation time by a factor 5.7. It was found that VISITOR was well-suited for the conceptual design of interplanetary trajectories, while also facilitating future improvements due to its modular structure.

  10. RepeatsDB-lite: a web server for unit annotation of tandem repeat proteins.

    PubMed

    Hirsh, Layla; Paladin, Lisanna; Piovesan, Damiano; Tosatto, Silvio C E

    2018-05-09

    RepeatsDB-lite (http://protein.bio.unipd.it/repeatsdb-lite) is a web server for the prediction of repetitive structural elements and units in tandem repeat (TR) proteins. TRs are a widespread but poorly annotated class of non-globular proteins carrying heterogeneous functions. RepeatsDB-lite extends the prediction to all TR types and strongly improves the performance both in terms of computational time and accuracy over previous methods, with precision above 95% for solenoid structures. The algorithm exploits an improved TR unit library derived from the RepeatsDB database to perform an iterative structural search and assignment. The web interface provides tools for analyzing the evolutionary relationships between units and manually refine the prediction by changing unit positions and protein classification. An all-against-all structure-based sequence similarity matrix is calculated and visualized in real-time for every user edit. Reviewed predictions can be submitted to RepeatsDB for review and inclusion.

  11. Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

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

    Torella, JP; Boehm, CR; Lienert, F

    2013-12-28

    In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminatormore » parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates.« less

  12. Enhanced d-lactic acid production by recombinant Saccharomyces cerevisiae following optimization of the global metabolic pathway.

    PubMed

    Yamada, Ryosuke; Wakita, Kazuki; Mitsui, Ryosuke; Ogino, Hiroyasu

    2017-09-01

    Utilization of renewable feedstocks for the production of bio-based chemicals such as d-lactic acid by engineering metabolic pathways in the yeast Saccharomyces cerevisiae has recently become an attractive option. In this study, to realize efficient d-lactic acid production by S. cerevisiae, the expression of 12 glycolysis-related genes and the Leuconostoc mesenteroides d-LDH gene was optimized using a previously developed global metabolic engineering strategy, and repeated batch fermentation was carried out using the resultant strain YPH499/dPdA3-34/DLDH/1-18. Stable d-lactic acid production through 10 repeated batch fermentations was achieved using YPH499/dPdA3-34/DLDH/1-18. The average d-lactic acid production, productivity, and yield with 10 repeated batch fermentations were 60.3 g/L, 2.80 g/L/h, and 0.646, respectively. The present study is the first report of the application of a global metabolic engineering strategy for bio-based chemical production, and it shows the potential for efficient production of such chemicals by global metabolic engineering of the yeast S. cerevisiae. Biotechnol. Bioeng. 2017;114: 2075-2084. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Dynamic positioning configuration and its first-order optimization

    NASA Astrophysics Data System (ADS)

    Xue, Shuqiang; Yang, Yuanxi; Dang, Yamin; Chen, Wu

    2014-02-01

    Traditional geodetic network optimization deals with static and discrete control points. The modern space geodetic network is, on the other hand, composed of moving control points in space (satellites) and on the Earth (ground stations). The network configuration composed of these facilities is essentially dynamic and continuous. Moreover, besides the position parameter which needs to be estimated, other geophysical information or signals can also be extracted from the continuous observations. The dynamic (continuous) configuration of the space network determines whether a particular frequency of signals can be identified by this system. In this paper, we employ the functional analysis and graph theory to study the dynamic configuration of space geodetic networks, and mainly focus on the optimal estimation of the position and clock-offset parameters. The principle of the D-optimization is introduced in the Hilbert space after the concept of the traditional discrete configuration is generalized from the finite space to the infinite space. It shows that the D-optimization developed in the discrete optimization is still valid in the dynamic configuration optimization, and this is attributed to the natural generalization of least squares from the Euclidean space to the Hilbert space. Then, we introduce the principle of D-optimality invariance under the combination operation and rotation operation, and propose some D-optimal simplex dynamic configurations: (1) (Semi) circular configuration in 2-dimensional space; (2) the D-optimal cone configuration and D-optimal helical configuration which is close to the GPS constellation in 3-dimensional space. The initial design of GPS constellation can be approximately treated as a combination of 24 D-optimal helixes by properly adjusting the ascending node of different satellites to realize a so-called Walker constellation. In the case of estimating the receiver clock-offset parameter, we show that the circular configuration, the symmetrical cone configuration and helical curve configuration are still D-optimal. It shows that the given total observation time determines the optimal frequency (repeatability) of moving known points and vice versa, and one way to improve the repeatability is to increase the rotational speed. Under the Newton's law of motion, the frequency of satellite motion determines the orbital altitude. Furthermore, we study three kinds of complex dynamic configurations, one of which is the combination of D-optimal cone configurations and a so-called Walker constellation composed of D-optimal helical configuration, the other is the nested cone configuration composed of n cones, and the last is the nested helical configuration composed of n orbital planes. It shows that an effective way to achieve high coverage is to employ the configuration composed of a certain number of moving known points instead of the simplex configuration (such as D-optimal helical configuration), and one can use the D-optimal simplex solutions or D-optimal complex configurations in any combination to achieve powerful configurations with flexile coverage and flexile repeatability. Alternately, how to optimally generate and assess the discrete configurations sampled from the continuous one is discussed. The proposed configuration optimization framework has taken the well-known regular polygons (such as equilateral triangle and quadrangular) in two-dimensional space and regular polyhedrons (regular tetrahedron, cube, regular octahedron, regular icosahedron, or regular dodecahedron) into account. It shows that the conclusions made by the proposed technique are more general and no longer limited by different sampling schemes. By the conditional equation of D-optimal nested helical configuration, the relevance issues of GNSS constellation optimization are solved and some examples are performed by GPS constellation to verify the validation of the newly proposed optimization technique. The proposed technique is potentially helpful in maintenance and quadratic optimization of single GNSS of which the orbital inclination and the orbital altitude change under the precession, as well as in optimally nesting GNSSs to perform global homogeneous coverage of the Earth.

  14. Structural optimization of structured carbon-based energy-storing composite materials used in space vehicles.

    PubMed

    Yu, Jia; Yu, Zhichao; Tang, Chenlong

    2016-07-04

    The hot work environment of electronic components in the instrument cabin of spacecraft was researched, and a new thermal protection structure, namely graphite carbon foam, which is an impregnated phase-transition material, was adopted to implement the thermal control on the electronic components. We used the optimized parameters obtained from ANSYS to conduct 2D optimization, 3-D modeling and simulation, as well as the strength check. Finally, the optimization results were verified by experiments. The results showed that after optimization, the structured carbon-based energy-storing composite material could reduce the mass and realize the thermal control over electronic components. This phase-transition composite material still possesses excellent temperature control performance after its repeated melting and solidifying.

  15. Effect of post crosslinking haze on the repeatability of Scheimpflug-based and slit-scanning imaging devices

    PubMed Central

    Shetty, Rohit; Agrawal, Aarti; Deshmukh, Rashmi; Kaweri, Luci; Rao, Harsha L; Nagaraja, Harsha; Jayadev, Chaitra

    2017-01-01

    Purpose: The aim of this study was to analyze the effect of postcollagen crosslinking (CXL) haze on the measurement and repeatability of pachymetry and mean keratometry (Km) of four corneal topographers. Materials and Methods: Sixty eyes of sixty patients with progressive keratoconus who had undergone accelerated CXL (ACXL) underwent imaging with a scanning slit imaging device (Orbscan II) and three Scheimpflug imaging devices (Pentacam HR, Sirius, and Galilei). Post-ACXL haze was measured using the densitometry software on the Pentacam HR. Readings of the thinnest corneal thickness (TCT) and Km from three scans of each device were analyzed. Effect of haze on the repeatability of TCT and Km measurements was evaluated using regression models. Repeatability was assessed by coefficient of variation. Results: Corneal densitometry in different zones affected the repeatability of TCT measurement of Orbscan (P < 0.05) significantly but not the repeatability of TCT with Pentacam HR and Sirius (P = 0.03 and 0.05, respectively). Km values were affected by haze when measured with the Pentacam HR (P < 0.05). The repeatability of Km readings for all devices was unaffected by haze. In the anterior 0–2 mm and 2–6 mm zone, TCT (P = 0.43 and 0.45, respectively), Km values (P = 0.4 and 0.6, respectively), repeatability of TCT (P = 0.1 in both zones), and Km (P = 0.5 and 0.1, respectively) with Galilei were found to be the most reliable. Conclusion: Galilei measurements appear to be least affected by post-ACXL haze when compared with other devices. Hence, topography measurements in the presence of haze need to be interpreted with caution. PMID:28513495

  16. Adaptation in human visual cortex as a mechanism for rapid discrimination of aversive stimuli.

    PubMed

    Keil, Andreas; Stolarova, Margarita; Moratti, Stephan; Ray, William J

    2007-06-01

    The ability to react rapidly and efficiently to adverse stimuli is crucial for survival. Neuroscience and behavioral studies have converged to show that visual information associated with aversive content is processed quickly and accurately and is associated with rapid amplification of the neural responses. In particular, unpleasant visual information has repeatedly been shown to evoke increased cortical activity during early visual processing between 60 and 120 ms following the onset of a stimulus. However, the nature of these early responses is not well understood. Using neutral versus unpleasant colored pictures, the current report examines the time course of short-term changes in the human visual cortex when a subject is repeatedly exposed to simple grating stimuli in a classical conditioning paradigm. We analyzed changes in amplitude and synchrony of large-scale oscillatory activity across 2 days of testing, which included baseline measurements, 2 conditioning sessions, and a final extinction session. We found a gradual increase in amplitude and synchrony of very early cortical oscillations in the 20-35 Hz range across conditioning sessions, specifically for conditioned stimuli predicting aversive visual events. This increase for conditioned stimuli affected stimulus-locked cortical oscillations at a latency of around 60-90 ms and disappeared during extinction. Our findings suggest that reorganization of neural connectivity on the level of the visual cortex acts to optimize early perception of specific features indicative of emotional relevance.

  17. Effects of repeated simulated removal activities on feral swine movements and space use

    USGS Publications Warehouse

    Fischer, Justin W.; McMurtry , Dan; Blass, Chad R.; Walter, W. David; Beringer, Jeff; VerCauterren, Kurt C.

    2016-01-01

    Abundance and distribution of feral swine (Sus scrofa) in the USA have increased dramatically during the last 30 years. Effective measures are needed to control and eradicate feral swine populations without displacing animals over wider areas. Our objective was to investigate effects of repeated simulated removal activities on feral swine movements and space use. We analyzed location data from 21 feral swine that we fitted with Global Positioning System harnesses in southern MO, USA. Various removal activities were applied over time to eight feral swine before lethal removal, including trapped-and-released, chased with dogs, chased with hunter, and chased with helicopter. We found that core space-use areas were reduced following the first removal activity, whereas overall space-use areas and diurnal movement distances increased following the second removal activity. Mean geographic centroid shifts did not differ between pre- and post-periods for either the first or second removal activities. Our information on feral swine movements and space use precipitated by human removal activities, such as hunting, trapping, and chasing with dogs, helps fill a knowledge void and will aid wildlife managers. Strategies to optimize management are needed to reduce feral swine populations while preventing enlarged home ranges and displacing individuals, which could lead to increased disease transmission risk and human-feral swine conflict in adjacent areas.

  18. Resource-aware system architecture model for implementation of quantum aided Byzantine agreement on quantum repeater networks

    NASA Astrophysics Data System (ADS)

    Taherkhani, Mohammand Amin; Navi, Keivan; Van Meter, Rodney

    2018-01-01

    Quantum aided Byzantine agreement is an important distributed quantum algorithm with unique features in comparison to classical deterministic and randomized algorithms, requiring only a constant expected number of rounds in addition to giving a higher level of security. In this paper, we analyze details of the high level multi-party algorithm, and propose elements of the design for the quantum architecture and circuits required at each node to run the algorithm on a quantum repeater network (QRN). Our optimization techniques have reduced the quantum circuit depth by 44% and the number of qubits in each node by 20% for a minimum five-node setup compared to the design based on the standard arithmetic circuits. These improvements lead to a quantum system architecture with 160 qubits per node, space-time product (an estimate of the required fidelity) {KQ}≈ 1.3× {10}5 per node and error threshold 1.1× {10}-6 for the total nodes in the network. The evaluation of the designed architecture shows that to execute the algorithm once on the minimum setup, we need to successfully distribute a total of 648 Bell pairs across the network, spread evenly between all pairs of nodes. This framework can be considered a starting point for establishing a road-map for light-weight demonstration of a distributed quantum application on QRNs.

  19. A Simple Artificial Life Model Explains Irrational Behavior in Human Decision-Making

    PubMed Central

    Feher da Silva, Carolina; Baldo, Marcus Vinícius Chrysóstomo

    2012-01-01

    Although praised for their rationality, humans often make poor decisions, even in simple situations. In the repeated binary choice experiment, an individual has to choose repeatedly between the same two alternatives, where a reward is assigned to one of them with fixed probability. The optimal strategy is to perseverate with choosing the alternative with the best expected return. Whereas many species perseverate, humans tend to match the frequencies of their choices to the frequencies of the alternatives, a sub-optimal strategy known as probability matching. Our goal was to find the primary cognitive constraints under which a set of simple evolutionary rules can lead to such contrasting behaviors. We simulated the evolution of artificial populations, wherein the fitness of each animat (artificial animal) depended on its ability to predict the next element of a sequence made up of a repeating binary string of varying size. When the string was short relative to the animats’ neural capacity, they could learn it and correctly predict the next element of the sequence. When it was long, they could not learn it, turning to the next best option: to perseverate. Animats from the last generation then performed the task of predicting the next element of a non-periodical binary sequence. We found that, whereas animats with smaller neural capacity kept perseverating with the best alternative as before, animats with larger neural capacity, which had previously been able to learn the pattern of repeating strings, adopted probability matching, being outperformed by the perseverating animats. Our results demonstrate how the ability to make predictions in an environment endowed with regular patterns may lead to probability matching under less structured conditions. They point to probability matching as a likely by-product of adaptive cognitive strategies that were crucial in human evolution, but may lead to sub-optimal performances in other environments. PMID:22563454

  20. A simple artificial life model explains irrational behavior in human decision-making.

    PubMed

    Feher da Silva, Carolina; Baldo, Marcus Vinícius Chrysóstomo

    2012-01-01

    Although praised for their rationality, humans often make poor decisions, even in simple situations. In the repeated binary choice experiment, an individual has to choose repeatedly between the same two alternatives, where a reward is assigned to one of them with fixed probability. The optimal strategy is to perseverate with choosing the alternative with the best expected return. Whereas many species perseverate, humans tend to match the frequencies of their choices to the frequencies of the alternatives, a sub-optimal strategy known as probability matching. Our goal was to find the primary cognitive constraints under which a set of simple evolutionary rules can lead to such contrasting behaviors. We simulated the evolution of artificial populations, wherein the fitness of each animat (artificial animal) depended on its ability to predict the next element of a sequence made up of a repeating binary string of varying size. When the string was short relative to the animats' neural capacity, they could learn it and correctly predict the next element of the sequence. When it was long, they could not learn it, turning to the next best option: to perseverate. Animats from the last generation then performed the task of predicting the next element of a non-periodical binary sequence. We found that, whereas animats with smaller neural capacity kept perseverating with the best alternative as before, animats with larger neural capacity, which had previously been able to learn the pattern of repeating strings, adopted probability matching, being outperformed by the perseverating animats. Our results demonstrate how the ability to make predictions in an environment endowed with regular patterns may lead to probability matching under less structured conditions. They point to probability matching as a likely by-product of adaptive cognitive strategies that were crucial in human evolution, but may lead to sub-optimal performances in other environments.

  1. Use of C-Arm Cone Beam CT During Hepatic Radioembolization: Protocol Optimization for Extrahepatic Shunting and Parenchymal Enhancement

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

    Hoven, Andor F. van den, E-mail: a.f.vandenhoven@umcutrecht.nl; Prince, Jip F.; Keizer, Bart de

    PurposeTo optimize a C-arm computed tomography (CT) protocol for radioembolization (RE), specifically for extrahepatic shunting and parenchymal enhancement.Materials and MethodsA prospective development study was performed per IDEAL recommendations. A literature-based protocol was applied in patients with unresectable and chemorefractory liver malignancies undergoing an angiography before radioembolization. Contrast and scan settings were adjusted stepwise and repeatedly reviewed in a consensus meeting. Afterwards, two independent raters analyzed all scans. A third rater evaluated the SPECT/CT scans as a reference standard for extrahepatic shunting and lack of target segment perfusion.ResultsFifty scans were obtained in 29 procedures. The first protocol, using a 6 s delaymore » and 10 s scan, showed insufficient parenchymal enhancement. In the second protocol, the delay was determined by timing parenchymal enhancement on DSA power injection (median 8 s, range 4–10 s): enhancement improved, but breathing artifacts increased (from 0 to 27 %). Since the third protocol with a 5 s scan decremented subjective image quality, the second protocol was deemed optimal. Median CNR (range) was 1.7 (0.6–3.2), 2.2 (−1.4–4.0), and 2.1 (−0.3–3.0) for protocol 1, 2, and 3 (p = 0.80). Delineation of perfused segments was possible in 57, 73, and 44 % of scans (p = 0.13). In all C-arm CTs combined, the negative predictive value was 95 % for extrahepatic shunting and 83 % for lack of target segment perfusion.ConclusionAn optimized C-arm CT protocol was developed that can be used to detect extrahepatic shunts and non-perfusion of target segments during RE.« less

  2. Factorial experimental design for the culture of human embryonic stem cells as aggregates in stirred suspension bioreactors reveals the potential for interaction effects between bioprocess parameters.

    PubMed

    Hunt, Megan M; Meng, Guoliang; Rancourt, Derrick E; Gates, Ian D; Kallos, Michael S

    2014-01-01

    Traditional optimization of culture parameters for the large-scale culture of human embryonic stem cells (ESCs) as aggregates is carried out in a stepwise manner whereby the effect of varying each culture parameter is investigated individually. However, as evidenced by the wide range of published protocols and culture performance indicators (growth rates, pluripotency marker expression, etc.), there is a lack of systematic investigation into the true effect of varying culture parameters especially with respect to potential interactions between culture variables. Here we describe the design and execution of a two-parameter, three-level (3(2)) factorial experiment resulting in nine conditions that were run in duplicate 125-mL stirred suspension bioreactors. The two parameters investigated here were inoculation density and agitation rate, which are easily controlled, but currently, poorly characterized. Cell readouts analyzed included fold expansion, maximum density, and exponential growth rate. Our results reveal that the choice of best case culture parameters was dependent on which cell property was chosen as the primary output variable. Subsequent statistical analyses via two-way analysis of variance indicated significant interaction effects between inoculation density and agitation rate specifically in the case of exponential growth rates. Results indicate that stepwise optimization has the potential to miss out on the true optimal case. In addition, choosing an optimum condition for a culture output of interest from the factorial design yielded similar results when repeated with the same cell line indicating reproducibility. We finally validated that human ESCs remain pluripotent in suspension culture as aggregates under our optimal conditions and maintain their differentiation capabilities as well as a stable karyotype and strong expression levels of specific human ESC markers over several passages in suspension bioreactors.

  3. The optimal strategy of percutaneous coronary intervention for ST-elevation myocardial infarction patients with multivessel disease: an updated meta-analysis of 9 randomized controlled trials.

    PubMed

    Fan, Zhong G; Gao, Xiao F; Li, Xiao B; Mao, Wen X; Chen, Li W; Tian, Nai L

    2017-04-01

    The optimal strategy of percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) still remains controversial. This study sought to explore the optimal PCI strategy for those patients. Medline, EMBASE and the Cochrane Controlled Trials Registry were searched for relevant studies. We analyzed the comparison of major adverse cardiac events (MACEs) as the primary end point between the preventive PCI strategy and the culprit only PCI strategy (CV-PCI). The further analysis of two subgroups described as the complete multivessel PCI strategy during primary procedure (CMV-PCI) and the staged PCI strategy (S-PCI) was also performed. Nine randomized trials were identified. The risk of MACEs was reduced significantly regarding to preventive PCI strategy (OR=0.41, 95% CI: 0.31-0.53, P<0.001) compared to CV-PCI strategy. There were lower risks of long-term mortality, reinfarction and repeat revascularization in the preventive PCI group compared to the CV-PCI group (OR=0.41, 95% CI: 0.27-0.62, P<0.001; OR=0.54, 95% CI: 0.32-0.91, P=0.021; OR=0.37, 95% CI: 0.26-0.51, P<0.001). Subgroup analysis showed that staged PCI strategy reduced the incidence of long-term mortality versus CMV-PCI strategy. The preventive PCI is associated with the lower risk of MACEs in STEMI patients with MVD compared to the CV-PCI strategy, and the S-PCI strategy seems to be an optimal choice for these patients rather than the CMV-PCI.

  4. Transvesical Intra-Abdominal Pressure Measurement in Newborn: What Is the Optimal Saline Volume Instillation?

    PubMed

    Defontaine, Anne; Tirel, Olivier; Costet, Nathalie; Beuchée, Alain; Ozanne, Bruno; Gaillot, Théophile; Arnaud, Alexis Pierre; Wodey, Eric

    2016-02-01

    To determine the optimal saline volume bladder instillation to measure intravesical pressure in critically ill newborns weighing less than 4.5 kg, and to establish a reference of intra-abdominal pressure value in this population. Prospective monocentric study. Neonatal ICU and PICU. Newborns, premature or not, weighing less than 4.5 kg who required a urethral catheter. Patients were classified into two groups according to whether they presented a risk factor for intra-abdominal hypertension. Nine intravesical pressure measures per patient were performed after different volume saline instillation. The first one was done without saline instillation and then by increments of 0.5 mL/kg to a maximum of 4 mL/kg. Linear models for repeated measurements of intravesical pressure with unstructured covariance were used to analyze the variation of intravesical pressure measures according to the conditions of measurement (volume instilled). Pairwise comparisons of intravesical pressure adjusted mean values between instillation volumes were done using Tukey tests, corrected for multiple testing to determine an optimal instillation volume. Forty-seven patients with completed measures (nine instillations volumes) were included in the analysis. Mean intravesical pressure values were not significantly different when measured after instillation of 0.5, 1, or 1.5 mL/kg, whereas measures after instillation of 2 mL/kg or more were significantly higher. The median intravesical pressure value in the group without intra-abdominal hypertension risk factor after instillation of 1 mL/kg was 5 mm Hg (2-6 mm Hg). The optimal saline volume bladder instillation to measure intra-abdominal pressure in newborns weighing less than 4.5 kg was 1 mL/kg. Reference intra-abdominal pressure in this population was found to be 5 mm Hg (2-6 mm Hg).

  5. SCA8 Repeat Expansion: Large CTA/CTG Repeat Alleles Are More Common in Ataxic Patients, Including Those with SCA6

    PubMed Central

    Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

    2003-01-01

    We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85–399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as α1A-voltage–dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients. PMID:12545428

  6. SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6.

    PubMed

    Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

    2003-03-01

    We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85-399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as alpha(1A)-voltage-dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients.

  7. Optimal design of structures for earthquake loads by a hybrid RBF-BPSO method

    NASA Astrophysics Data System (ADS)

    Salajegheh, Eysa; Gholizadeh, Saeed; Khatibinia, Mohsen

    2008-03-01

    The optimal seismic design of structures requires that time history analyses (THA) be carried out repeatedly. This makes the optimal design process inefficient, in particular, if an evolutionary algorithm is used. To reduce the overall time required for structural optimization, two artificial intelligence strategies are employed. In the first strategy, radial basis function (RBF) neural networks are used to predict the time history responses of structures in the optimization flow. In the second strategy, a binary particle swarm optimization (BPSO) is used to find the optimum design. Combining the RBF and BPSO, a hybrid RBF-BPSO optimization method is proposed in this paper, which achieves fast optimization with high computational performance. Two examples are presented and compared to determine the optimal weight of structures under earthquake loadings using both exact and approximate analyses. The numerical results demonstrate the computational advantages and effectiveness of the proposed hybrid RBF-BPSO optimization method for the seismic design of structures.

  8. CRISPR/Cas9-mediated knock-in of an optimized TetO repeat for live cell imaging of endogenous loci.

    PubMed

    Tasan, Ipek; Sustackova, Gabriela; Zhang, Liguo; Kim, Jiah; Sivaguru, Mayandi; HamediRad, Mohammad; Wang, Yuchuan; Genova, Justin; Ma, Jian; Belmont, Andrew S; Zhao, Huimin

    2018-06-15

    Nuclear organization has an important role in determining genome function; however, it is not clear how spatiotemporal organization of the genome relates to functionality. To elucidate this relationship, a method for tracking any locus of interest is desirable. Recently clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) or transcription activator-like effectors were adapted for imaging endogenous loci; however, they are mostly limited to visualization of repetitive regions. Here, we report an efficient and scalable method named SHACKTeR (Short Homology and CRISPR/Cas9-mediated Knock-in of a TetO Repeat) for live cell imaging of specific chromosomal regions without the need for a pre-existing repetitive sequence. SHACKTeR requires only two modifications to the genome: CRISPR/Cas9-mediated knock-in of an optimized TetO repeat and its visualization by TetR-EGFP expression. Our simplified knock-in protocol, utilizing short homology arms integrated by polymerase chain reaction, was successful at labeling 10 different loci in HCT116 cells. We also showed the feasibility of knock-in into lamina-associated, heterochromatin regions, demonstrating that these regions prefer non-homologous end joining for knock-in. Using SHACKTeR, we were able to observe DNA replication at a specific locus by long-term live cell imaging. We anticipate the general applicability and scalability of our method will enhance causative analyses between gene function and compartmentalization in a high-throughput manner.

  9. Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats

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

    Rubinsztein, D.C.; Leggo, J.; Whittaker, J.L.

    1996-07-01

    Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 9 trinucleotide lengths suggested that the limits of the normal andmore » disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant. 26 refs., 3 figs., 1 tab.« less

  10. Repeat Chlamydia trachomatis testing among heterosexual STI outpatient clinic visitors in the Netherlands: a longitudinal study.

    PubMed

    Visser, Maartje; van Aar, Fleur; Koedijk, Femke D H; Kampman, Carolina J G; Heijne, Janneke C M

    2017-12-20

    Chlamydia infections are common in both men and women, are often asymptomatic and can cause serious complications. Repeat testing in high-risk groups is therefore indicated. In the Netherlands, guidelines on repeat chlamydia testing differ between testing facilities, and knowledge on repeat testing behaviour is limited. Here, we analyse the current repeat testing behaviour of heterosexual STI clinic visitors, and aim to identify groups for which repeat testing advice could be advantageous. Longitudinal surveillance data from all Dutch STI outpatient clinics were used, which included all STI clinic consultations carried out among heterosexual men and women between June 2014 and December 2015. Repeat testing was defined as returning to the same STI clinic between 35 days and 12 months after initial consultation. We calculated chlamydia positivity at repeat test stratified by initial test result and time between consultations. Logistic regression analyses were used to identify predictors of repeat testing, and predictors of having a chlamydia positive repeat test. In total, 140,486 consultations in 75,487 women and 46,286 men were available for analyses. Overall, 15.4% of women and 11.1% of men returned to the STI clinic within the study period. Highest chlamydia positivity at repeat test was seen 3-5 months after initial positive test. Among both women and men, repeat testing was associated with non-Western ethnicity, having had more than two sex partners in the past 6 months, reporting STI symptoms, having a history of STI, and having a chlamydia positive initial test. Among repeat testers, chlamydia positive repeat test was most strongly associated with younger age, followed by a chlamydia positive initial test. Repeat testing most often resulted in a positive test result among young heterosexuals (<25) and heterosexuals of any age with a chlamydia infection at the initial consultation. Further efforts are needed to determine optimal repeat testing strategies.

  11. 40 CFR 86.523-78 - Oxides of nitrogen analyzer calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... analyzer to optimize performance. (2) Zero the oxides of nitrogen analyzer with zero grade air or zero... samples. Proceed as follows: (1) Adjust analyzer to optimize performance. (2) Zero the oxides of nitrogen analyzer with zero grade air or zero grade nitrogen. (3) Calibrate on each normally used operating range...

  12. A Process Elaboration Formalism for Writing and Analyzing Programs

    DTIC Science & Technology

    1975-10-01

    program is to be proved, a description of its (i) See [MANN 73] for a survey of these debugging tools, di) See [ELSPAS 72] for a complete review of this...öy the instructions which might be found on a shampoo bottle. 1) Wet hair 2) Lather 3) Rinse «) Repeat Statement 4, the source of the problem, *M...tor this simple aigonthm is shown m Figure 52. SHAMPOO WET-HAIR LATHER RINSE REPEAT - WET-HAIR -> LATHER -> RINSE -> REPEAT - (TCRMMAL "WE’T.’NG

  13. Rate-loss analysis of an efficient quantum repeater architecture

    NASA Astrophysics Data System (ADS)

    Guha, Saikat; Krovi, Hari; Fuchs, Christopher A.; Dutton, Zachary; Slater, Joshua A.; Simon, Christoph; Tittel, Wolfgang

    2015-08-01

    We analyze an entanglement-based quantum key distribution (QKD) architecture that uses a linear chain of quantum repeaters employing photon-pair sources, spectral-multiplexing, linear-optic Bell-state measurements, multimode quantum memories, and classical-only error correction. Assuming perfect sources, we find an exact expression for the secret-key rate, and an analytical description of how errors propagate through the repeater chain, as a function of various loss-and-noise parameters of the devices. We show via an explicit analytical calculation, which separately addresses the effects of the principle nonidealities, that this scheme achieves a secret-key rate that surpasses the Takeoka-Guha-Wilde bound—a recently found fundamental limit to the rate-vs-loss scaling achievable by any QKD protocol over a direct optical link—thereby providing one of the first rigorous proofs of the efficacy of a repeater protocol. We explicitly calculate the end-to-end shared noisy quantum state generated by the repeater chain, which could be useful for analyzing the performance of other non-QKD quantum protocols that require establishing long-distance entanglement. We evaluate that shared state's fidelity and the achievable entanglement-distillation rate, as a function of the number of repeater nodes, total range, and various loss-and-noise parameters of the system. We extend our theoretical analysis to encompass sources with nonzero two-pair-emission probability, using an efficient exact numerical evaluation of the quantum state propagation and measurements. We expect our results to spur formal rate-loss analysis of other repeater protocols and also to provide useful abstractions to seed analyses of quantum networks of complex topologies.

  14. Robust Controller for Turbulent and Convective Boundary Layers

    DTIC Science & Technology

    2006-08-01

    filter and an optimal regulator. The Kalman filter equation and the optimal regulator equation corresponding to the state-space equations, (2.20), are...separate steady-state algebraic Riccati equations. The Kalman filter is used here as a state observer rather than as an estimator since no noises are...2001) which will not be repeated here. For robustness, in the design, the Kalman filter input matrix G has been set equal to the control input

  15. [Detection of CRISPR and its relationship to drug resistance in Shigella].

    PubMed

    Wang, Linlin; Wang, Yingfang; Duan, Guangcai; Xue, Zerun; Guo, Xiangjiao; Wang, Pengfei; Xi, Yuanlin; Yang, Haiyan

    2015-04-04

    To detect clustered regularly interspaced short palindromic repeats (CRISPR) in Shigella, and to analyze its relationship to drug resistance. Four pairs of primers were used for the detection of convincing CRISPR structures CRISPR-S2 and CRISPR-S4, questionable CRISPR structures CRISPR-S1 and CRISPR-S3 in 60 Shigella strains. All primers were designed using sequences in CRISPR database. CRISPR Finder was used to analyze CRISPR and susceptibilities of Shigella strains were tested by agar diffusion method. Furthermore, we analyzed the relationship between drug resistance and CRISPR-S4. The positive rate of convincing CRISPR structures was 95%. The four CRISPR loci formed 12 spectral patterns (A-L), all of which contained convincing CRISPR structures except type K. We found one new repeat and 12 new spacers. The multi-drug resistance rate was 53. 33% . We found no significant difference between CRISPR-S4 and drug resistant. However, the repeat sequence of CRISPR-S4 in multi- or TE-resistance strains was mainly R4.1 with AC deletions in the 3' end, and the spacer sequences of CRISPR-S4 in multi-drug resistance strains were mainly Sp5.1, Sp6.1 and Sp7. CRISPR was common in Shigella. Variations df repeat sequences and diversities of spacer sequences might be related to drug resistance in Shigella.

  16. 40 CFR 90.315 - Analyzer initial calibration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specifications in § 90.316(b). (c) Zero setting and calibration. Using purified synthetic air (or nitrogen), set the CO, CO2, NOX. and HC analyzers at zero. Connect the appropriate calibrating gases to the analyzers...) Rechecking of zero setting. Recheck the zero setting and, if necessary, repeat the procedure described in...

  17. 40 CFR 90.315 - Analyzer initial calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... specifications in § 90.316(b). (c) Zero setting and calibration. Using purified synthetic air (or nitrogen), set the CO, CO2, NOX. and HC analyzers at zero. Connect the appropriate calibrating gases to the analyzers...) Rechecking of zero setting. Recheck the zero setting and, if necessary, repeat the procedure described in...

  18. 40 CFR 90.315 - Analyzer initial calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... specifications in § 90.316(b). (c) Zero setting and calibration. Using purified synthetic air (or nitrogen), set the CO, CO2, NOX. and HC analyzers at zero. Connect the appropriate calibrating gases to the analyzers...) Rechecking of zero setting. Recheck the zero setting and, if necessary, repeat the procedure described in...

  19. 40 CFR 90.315 - Analyzer initial calibration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... specifications in § 90.316(b). (c) Zero setting and calibration. Using purified synthetic air (or nitrogen), set the CO, CO2, NOX. and HC analyzers at zero. Connect the appropriate calibrating gases to the analyzers...) Rechecking of zero setting. Recheck the zero setting and, if necessary, repeat the procedure described in...

  20. 40 CFR 90.315 - Analyzer initial calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... specifications in § 90.316(b). (c) Zero setting and calibration. Using purified synthetic air (or nitrogen), set the CO, CO2, NOX. and HC analyzers at zero. Connect the appropriate calibrating gases to the analyzers...) Rechecking of zero setting. Recheck the zero setting and, if necessary, repeat the procedure described in...

  1. An Analysis of Primary School Dropout Patterns in Honduras

    ERIC Educational Resources Information Center

    Sekiya, Takeshi; Ashida, Akemi

    2017-01-01

    This study hypothesized that repeating a grade is one reason why Honduran primary students drop out of school but not the main reason. Using longitudinal data, we analyzed student enrollment patterns up until students left school. The results revealed that many students dropped out suddenly without having previously repeated a grade, although many…

  2. Statistical Methodology for the Analysis of Repeated Duration Data in Behavioral Studies

    ERIC Educational Resources Information Center

    Letué, Frédérique; Martinez, Marie-José; Samson, Adeline; Vilain, Anne; Vilain, Coriandre

    2018-01-01

    Purpose: Repeated duration data are frequently used in behavioral studies. Classical linear or log-linear mixed models are often inadequate to analyze such data, because they usually consist of nonnegative and skew-distributed variables. Therefore, we recommend use of a statistical methodology specific to duration data. Method: We propose a…

  3. Analyzing Multivariate Repeated Measures Designs: A Comparison of Two Approximate Degrees of Freedom Procedures

    ERIC Educational Resources Information Center

    Lix, Lisa M.; Algina, James; Keselman, H. J.

    2003-01-01

    The approximate degrees of freedom Welch-James (WJ) and Brown-Forsythe (BF) procedures for testing within-subjects effects in multivariate groups by trials repeated measures designs were investigated under departures from covariance homogeneity and normality. Empirical Type I error and power rates were obtained for least-squares estimators and…

  4. Counterbalancing and Other Uses of Repeated-Measures Latin-Square Designs: Analyses and Interpretations.

    ERIC Educational Resources Information Center

    Reese, Hayne W.

    1997-01-01

    Recommends that when repeated-measures Latin-square designs are used to counterbalance treatments across a procedural variable or to reduce the number of treatment combinations given to each participant, effects be analyzed statistically, and that in all uses, researchers consider alternative interpretations of the variance associated with the…

  5. Familiarity with Content and Syllogistic Reasoning.

    ERIC Educational Resources Information Center

    Mast, Terrill A.; And Others

    Forty-four education and 44 dental students were administered a 30-item syllogism test containing five syllogic forms six times repeated in three different content forms--technical dental terms, common dental terms, and content-free (letters). Data were analyzed using a two-factor with repeated measures on one factor design. It was found that…

  6. Pulsed coherent population trapping with repeated queries for producing single-peaked high contrast Ramsey interference

    NASA Astrophysics Data System (ADS)

    Warren, Z.; Shahriar, M. S.; Tripathi, R.; Pati, G. S.

    2018-02-01

    A repeated query technique has been demonstrated as a new interrogation method in pulsed coherent population trapping for producing single-peaked Ramsey interference with high contrast. This technique enhances the contrast of the central Ramsey fringe by nearly 1.5 times and significantly suppresses the side fringes by using more query pulses ( >10) in the pulse cycle. Theoretical models have been developed to simulate Ramsey interference and analyze the characteristics of the Ramsey spectrum produced by the repeated query technique. Experiments have also been carried out employing a repeated query technique in a prototype rubidium clock to study its frequency stability performance.

  7. Do gamma-ray burst sources repeat?

    NASA Technical Reports Server (NTRS)

    Meegan, C. A.; Hartmann, D. H.; Brainerd, J. J.; Briggs, M.; Paciesas, W. S.; Pendleton, G.; Kouveliotou, C.; Fishman, G.; Blumenthal, G.; Brock, M.

    1994-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al. 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic ad the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the bursts cannot be excluded.

  8. Comparison between performances of three types of manual wheelchairs often distributed in low-resource settings.

    PubMed

    Rispin, Karen; Wee, Joy

    2015-07-01

    This study was conducted to compare the performance of three types of chairs in a low-resource setting. The larger goal was to provide information which will enable more effective use of limited funds by wheelchair manufacturers and suppliers in low-resource settings. The Motivation Rough Terrain and Whirlwind Rough Rider were compared in six skills tests which participants completed in one wheelchair type and then a day later in the other. A hospital-style folding transport wheelchair was also included in one test. For all skills, participants rated the ease or difficulty on a visual analogue scale. For all tracks, distance traveled and the physiological cost index were recorded. Data were analyzed using repeated measures analysis of variance. The Motivation wheelchair outperformed Whirlwind wheelchair on rough and smooth tracks, and in some metrics on the tight spaces track. Motivation and Whirlwind wheelchairs significantly outperformed the hospital transport wheelchair in all metrics on the rough track skills test. This comparative study provides data that are valuable for manufacturers and for those who provide wheelchairs to users. The comparison with the hospital-style transport chair confirms the cost to users of inappropriate wheelchair provision. Implications for Rehabilitation For those with compromised lower limb function, wheelchairs are essential to enable full participation and improved quality of life. Therefore, provision of wheelchairs which effectively enable mobility in the cultures and environments in which people with disabilities live is crucial. This includes low-resource settings where the need for appropriate seating is especially urgent. A repeated measures study to measure wheelchair performances in everyday skills in the setting where wheelchairs are used gives information on the quality of mobility provided by those wheelchairs. This study highlights differences in the performance of three types of wheelchairs often distributed in low-resource settings. This information can improve mobility for wheelchair users in those settings by enabling wheelchair manufacturers to optimize wheelchair design and providers to optimize the use of limited funds.

  9. Design and development of a wireless sensor network to monitor snow depth in multiple catchments in the American River basin, California: hardware selection and sensor placement techniques

    NASA Astrophysics Data System (ADS)

    Kerkez, B.; Rice, R.; Glaser, S. D.; Bales, R. C.; Saksa, P. C.

    2010-12-01

    A 100-node wireless sensor network (WSN) was designed for the purpose of monitoring snow depth in two watersheds, spanning 3 km2 in the American River basin, in the central Sierra Nevada of California. The network will be deployed as a prototype project that will become a core element of a larger water information system for the Sierra Nevada. The site conditions range from mid-elevation forested areas to sub-alpine terrain with light forest cover. Extreme temperature and humidity fluctuations, along with heavy rain and snowfall events, create particularly challenging conditions for wireless communications. We show how statistics gathered from a previously deployed 60-node WSN, located in the Southern Sierra Critical Zone Observatory, were used to inform design. We adapted robust network hardware, manufactured by Dust Networks for highly demanding industrial monitoring, and added linear amplifiers to the radios to improve transmission distances. We also designed a custom data-logging board to interface the WSN hardware with snow-depth sensors. Due to the large distance between sensing locations, and complexity of terrain, we analyzed network statistics to select the location of repeater nodes, to create a redundant and reliable mesh. This optimized network topology will maximize transmission distances, while ensuring power-efficient network operations throughout harsh winter conditions. At least 30 of the 100 nodes will actively sense snow depth, while the remainder will act as sensor-ready repeaters in the mesh. Data from a previously conducted snow survey was used to create a Gaussian Process model of snow depth; variance estimates produced by this model were used to suggest near-optimal locations for snow-depth sensors to measure the variability across a 1 km2 grid. We compare the locations selected by the sensor placement algorithm to those made through expert opinion, and offer explanations for differences resulting from each approach.

  10. BK/TD models for analyzing in vitro impedance data on cytotoxicity.

    PubMed

    Teng, S; Barcellini-Couget, S; Beaudouin, R; Brochot, C; Desousa, G; Rahmani, R; Pery, A R R

    2015-06-01

    The ban of animal testing has enhanced the development of new in vitro technologies for cosmetics safety assessment. Impedance metrics is one such technology which enables monitoring of cell viability in real time. However, analyzing real time data requires moving from static to dynamic toxicity assessment. In the present study, we built mechanistic biokinetic/toxicodynamic (BK/TD) models to analyze the time course of cell viability in cytotoxicity assay using impedance. These models account for the fate of the tested compounds during the assay. BK/TD models were applied to analyze HepaRG cell viability, after single (48 h) and repeated (4 weeks) exposures to three hepatotoxic compounds (coumarin, isoeugenol and benzophenone-2). The BK/TD models properly fit the data used for their calibration that was obtained for single or repeated exposure. Only for one out of the three compounds, the models calibrated with a single exposure were able to predict repeated exposure data. We therefore recommend the use of long-term exposure in vitro data in order to adequately account for chronic hepatotoxic effects. The models we propose here are capable of being coupled with human biokinetic models in order to relate dose exposure and human hepatotoxicity. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. Ligand-Binding Properties and Conformational Dynamics of Autolysin Repeat Domains in Staphylococcal Cell Wall Recognition

    PubMed Central

    Zoll, Sebastian; Schlag, Martin; Shkumatov, Alexander V.; Rautenberg, Maren; Svergun, Dmitri I.; Götz, Friedrich

    2012-01-01

    The bifunctional major autolysin Atl plays a key role in staphylococcal cell separation. Processing of Atl yields catalytically active amidase (AM) and glucosaminidase (GL) domains that are each fused to repeating units. The two repeats of AM (R1 and R2) target the enzyme to the septum, where it cleaves murein between dividing cells. We have determined the crystal structure of R2, which reveals that each repeat folds into two half-open β-barrel subunits. We further demonstrate that lipoteichoic acid serves as a receptor for the repeats and that this interaction depends on conserved surfaces in each subunit. Small-angle X-ray scattering of the mature amidase reveals the presence of flexible linkers separating the AM, R1, and R2 units. Different levels of flexibility for each linker provide mechanistic insights into the conformational dynamics of the full-length protein and the roles of its components in cell wall association and catalysis. Our analysis supports a model in which the repeats direct the catalytic AM domain to the septum, where it can optimally perform the final step of cell division. PMID:22609916

  12. [Correlation of codon biases and potential secondary structures with mRNA translation efficiency in unicellular organisms].

    PubMed

    Vladimirov, N V; Likhoshvaĭ, V A; Matushkin, Iu G

    2007-01-01

    Gene expression is known to correlate with degree of codon bias in many unicellular organisms. However, such correlation is absent in some organisms. Recently we demonstrated that inverted complementary repeats within coding DNA sequence must be considered for proper estimation of translation efficiency, since they may form secondary structures that obstruct ribosome movement. We have developed a program for estimation of potential coding DNA sequence expression in defined unicellular organism using its genome sequence. The program computes elongation efficiency index. Computation is based on estimation of coding DNA sequence elongation efficiency, taking into account three key factors: codon bias, average number of inverted complementary repeats, and free energy of potential stem-loop structures formed by the repeats. The influence of these factors on translation is numerically estimated. An optimal proportion of these factors is computed for each organism individually. Quantitative translational characteristics of 384 unicellular organisms (351 bacteria, 28 archaea, 5 eukaryota) have been computed using their annotated genomes from NCBI GenBank. Five potential evolutionary strategies of translational optimization have been determined among studied organisms. A considerable difference of preferred translational strategies between Bacteria and Archaea has been revealed. Significant correlations between elongation efficiency index and gene expression levels have been shown for two organisms (S. cerevisiae and H. pylori) using available microarray data. The proposed method allows to estimate numerically the coding DNA sequence translation efficiency and to optimize nucleotide composition of heterologous genes in unicellular organisms. http://www.mgs.bionet.nsc.ru/mgs/programs/eei-calculator/.

  13. Analysis of repeat-mediated deletions in the mitochondrial genome of Saccharomyces cerevisiae.

    PubMed

    Phadnis, Naina; Sia, Rey A; Sia, Elaine A

    2005-12-01

    Mitochondrial DNA deletions and point mutations accumulate in an age-dependent manner in mammals. The mitochondrial genome in aging humans often displays a 4977-bp deletion flanked by short direct repeats. Additionally, direct repeats flank two-thirds of the reported mitochondrial DNA deletions. The mechanism by which these deletions arise is unknown, but direct-repeat-mediated deletions involving polymerase slippage, homologous recombination, and nonhomologous end joining have been proposed. We have developed a genetic reporter to measure the rate at which direct-repeat-mediated deletions arise in the mitochondrial genome of Saccharomyces cerevisiae. Here we analyze the effect of repeat size and heterology between repeats on the rate of deletions. We find that the dependence on homology for repeat-mediated deletions is linear down to 33 bp. Heterology between repeats does not affect the deletion rate substantially. Analysis of recombination products suggests that the deletions are produced by at least two different pathways, one that generates only deletions and one that appears to generate both deletions and reciprocal products of recombination. We discuss how this reporter may be used to identify the proteins in yeast that have an impact on the generation of direct-repeat-mediated deletions.

  14. Analysis of Repeat-Mediated Deletions in the Mitochondrial Genome of Saccharomyces cerevisiae

    PubMed Central

    Phadnis, Naina; Sia, Rey A.; Sia, Elaine A.

    2005-01-01

    Mitochondrial DNA deletions and point mutations accumulate in an age-dependent manner in mammals. The mitochondrial genome in aging humans often displays a 4977-bp deletion flanked by short direct repeats. Additionally, direct repeats flank two-thirds of the reported mitochondrial DNA deletions. The mechanism by which these deletions arise is unknown, but direct-repeat-mediated deletions involving polymerase slippage, homologous recombination, and nonhomologous end joining have been proposed. We have developed a genetic reporter to measure the rate at which direct-repeat-mediated deletions arise in the mitochondrial genome of Saccharomyces cerevisiae. Here we analyze the effect of repeat size and heterology between repeats on the rate of deletions. We find that the dependence on homology for repeat-mediated deletions is linear down to 33 bp. Heterology between repeats does not affect the deletion rate substantially. Analysis of recombination products suggests that the deletions are produced by at least two different pathways, one that generates only deletions and one that appears to generate both deletions and reciprocal products of recombination. We discuss how this reporter may be used to identify the proteins in yeast that have an impact on the generation of direct-repeat-mediated deletions. PMID:16157666

  15. Repeat analysis of intraoral digital imaging performed by undergraduate students using a complementary metal oxide semiconductor sensor: An institutional case study.

    PubMed

    Yusof, Mohd Yusmiaidil Putera Mohd; Rahman, Nur Liyana Abdul; Asri, Amiza Aqiela Ahmad; Othman, Noor Ilyani; Wan Mokhtar, Ilham

    2017-12-01

    This study was performed to quantify the repeat rate of imaging acquisitions based on different clinical examinations, and to assess the prevalence of error types in intraoral bitewing and periapical imaging using a digital complementary metal-oxide-semiconductor (CMOS) intraoral sensor. A total of 8,030 intraoral images were retrospectively collected from 3 groups of undergraduate clinical dental students. The type of examination, stage of the procedure, and reasons for repetition were analysed and recorded. The repeat rate was calculated as the total number of repeated images divided by the total number of examinations. The weighted Cohen's kappa for inter- and intra-observer agreement was used after calibration and prior to image analysis. The overall repeat rate on intraoral periapical images was 34.4%. A total of 1,978 repeated periapical images were from endodontic assessment, which included working length estimation (WLE), trial gutta-percha (tGP), obturation, and removal of gutta-percha (rGP). In the endodontic imaging, the highest repeat rate was from WLE (51.9%) followed by tGP (48.5%), obturation (42.2%), and rGP (35.6%). In bitewing images, the repeat rate was 15.1% and poor angulation was identified as the most common cause of error. A substantial level of intra- and interobserver agreement was achieved. The repeat rates in this study were relatively high, especially for certain clinical procedures, warranting training in optimization techniques and radiation protection. Repeat analysis should be performed from time to time to enhance quality assurance and hence deliver high-quality health services to patients.

  16. Application of Reduced Order Transonic Aerodynamic Influence Coefficient Matrix for Design Optimization

    NASA Technical Reports Server (NTRS)

    Pak, Chan-gi; Li, Wesley W.

    2009-01-01

    Supporting the Aeronautics Research Mission Directorate guidelines, the National Aeronautics and Space Administration [NASA] Dryden Flight Research Center is developing a multidisciplinary design, analysis, and optimization [MDAO] tool. This tool will leverage existing tools and practices, and allow the easy integration and adoption of new state-of-the-art software. Today s modern aircraft designs in transonic speed are a challenging task due to the computation time required for the unsteady aeroelastic analysis using a Computational Fluid Dynamics [CFD] code. Design approaches in this speed regime are mainly based on the manual trial and error. Because of the time required for unsteady CFD computations in time-domain, this will considerably slow down the whole design process. These analyses are usually performed repeatedly to optimize the final design. As a result, there is considerable motivation to be able to perform aeroelastic calculations more quickly and inexpensively. This paper will describe the development of unsteady transonic aeroelastic design methodology for design optimization using reduced modeling method and unsteady aerodynamic approximation. The method requires the unsteady transonic aerodynamics be represented in the frequency or Laplace domain. Dynamically linear assumption is used for creating Aerodynamic Influence Coefficient [AIC] matrices in transonic speed regime. Unsteady CFD computations are needed for the important columns of an AIC matrix which corresponded to the primary modes for the flutter. Order reduction techniques, such as Guyan reduction and improved reduction system, are used to reduce the size of problem transonic flutter can be found by the classic methods, such as Rational function approximation, p-k, p, root-locus etc. Such a methodology could be incorporated into MDAO tool for design optimization at a reasonable computational cost. The proposed technique is verified using the Aerostructures Test Wing 2 actually designed, built, and tested at NASA Dryden Flight Research Center. The results from the full order model and the approximate reduced order model are analyzed and compared.

  17. Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke.

    PubMed

    d'Esterre, Christopher D; Boesen, Mari E; Ahn, Seong Hwan; Pordeli, Pooneh; Najm, Mohamed; Minhas, Priyanka; Davari, Paniz; Fainardi, Enrico; Rubiera, Marta; Khaw, Alexander V; Zini, Andrea; Frayne, Richard; Hill, Michael D; Demchuk, Andrew M; Sajobi, Tolulope T; Forkert, Nils D; Goyal, Mayank; Lee, Ting Y; Menon, Bijoy K

    2015-12-01

    Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min(-1)·100 g(-1) were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=-0.68 and -0.60 for gray and white matter, respectively) parameters. Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion. © 2015 American Heart Association, Inc.

  18. Polymorphic CAG Repeat Numbers in the Androgen Receptor Gene of Female Pattern Hair Loss in a Han Chinese Population.

    PubMed

    Rui, Wenlong; Sheng, Youyu; Hu, Ruiming; Miao, Ying; Han, Yumei; Qi, Sisi; Xu, Feng; Xu, Jinhua; Yang, Qinping

    2016-01-01

    To investigate the association of CAG repeat numbers in the androgen receptor (AR) gene with female pattern hair loss (FPHL) in a Chinese population. A total of 200 Han Chinese patients with FPHL (142 Ludwig II and 58 Ludwig III cases) and 200 healthy controls were enrolled in this study. The polymorphism of CAG repeat numbers was analyzed by the fluorescent amplified fragment length polymorphism technique. The CAG biallelic mean length was 23.73 ± 2.04 repeats in Han Chinese FPHL patients and 23.90 ± 2.13 repeats in healthy controls, without any significant difference between the two groups (p = 0.481). In addition, neither the shorter nor the longer CAG repeat numbers were significantly different between FPHL and control subjects (p = 0.726, p = 0.383). The polymorphism of CAG repeat numbers of the AR gene may not be the genetic marker of FPHL in a Chinese population. © 2016 S. Karger AG, Basel.

  19. Persistent Organic Pollutant Determination in Killer Whale Scat Samples: Optimization of a Gas Chromatography/Mass Spectrometry Method and Application to Field Samples.

    PubMed

    Lundin, Jessica I; Dills, Russell L; Ylitalo, Gina M; Hanson, M Bradley; Emmons, Candice K; Schorr, Gregory S; Ahmad, Jacqui; Hempelmann, Jennifer A; Parsons, Kim M; Wasser, Samuel K

    2016-01-01

    Biologic sample collection in wild cetacean populations is challenging. Most information on toxicant levels is obtained from blubber biopsy samples; however, sample collection is invasive and strictly regulated under permit, thus limiting sample numbers. Methods are needed to monitor toxicant levels that increase temporal and repeat sampling of individuals for population health and recovery models. The objective of this study was to optimize measuring trace levels (parts per billion) of persistent organic pollutants (POPs), namely polychlorinated-biphenyls (PCBs), polybrominated-diphenyl-ethers (PBDEs), dichlorodiphenyltrichloroethanes (DDTs), and hexachlorocyclobenzene, in killer whale scat (fecal) samples. Archival scat samples, initially collected, lyophilized, and extracted with 70 % ethanol for hormone analyses, were used to analyze POP concentrations. The residual pellet was extracted and analyzed using gas chromatography coupled with mass spectrometry. Method detection limits ranged from 11 to 125 ng/g dry weight. The described method is suitable for p,p'-DDE, PCBs-138, 153, 180, and 187, and PBDEs-47 and 100; other POPs were below the limit of detection. We applied this method to 126 scat samples collected from Southern Resident killer whales. Scat samples from 22 adult whales also had known POP concentrations in blubber and demonstrated significant correlations (p < 0.01) between matrices across target analytes. Overall, the scat toxicant measures matched previously reported patterns from blubber samples of decreased levels in reproductive-age females and a decreased p,p'-DDE/∑PCB ratio in J-pod. Measuring toxicants in scat samples provides an unprecedented opportunity to noninvasively evaluate contaminant levels in wild cetacean populations; these data have the prospect to provide meaningful information for vital management decisions.

  20. Ion-pair hollow-fiber liquid-phase microextraction of the quaternary ammonium surfactant dicocodimethylammonium chloride.

    PubMed

    Hultgren, Sofie; Larsson, Niklas; Nilsson, Bo F; Jönsson, Jan Ake

    2009-02-01

    A two-phase hollow-fiber (HF) liquid-phase microextraction (LPME) method was developed for determination of a quaternary ammonium compound surfactant, dicocodimethylammonium chloride, in aqueous samples. The porous HF was fixed on a metal rod support and was impregnated with approximately 6.6 microL of organic extractant, which was immobilized in the HF pores. Surfactant extraction was facilitated by addition of carboxylic acid to the sample forming neutral ion pairs with the quaternary ammonium compound. After extraction, the analyte was transferred from the organic extractant in the fiber pores by dissolving the 1-octanol into 100 microL methanol. The methanol extract was analyzed by liquid chromatography-mass spectrometry. The method was optimized (with optimized parameters in brackets) with regard to type of organic extractant (1-octanol), fiber length (2 cm), choice and concentration of anionic carrier (600 microg L(-1) octanoate), procedure of transfer to methanol (15-min sonication), sample volume (250 mL), extraction time (17 h), pH (10), and ionic strength (50 mM carbonate). Aspects influencing repeatability in LPME of (quaternary ammonium) surfactants are discussed. The enrichment factor achieved in 250-mL carbonate buffer was around 400. Due to matrix effects, the enrichment factors achieved when industrial process water was analyzed were 120 or about 30% of that in carbonate buffer. Detection limits of 0.3 microg L(-1) in carbonate buffer and 0.9 microg L(-1) in industrial process water were obtained. If the studied compound is seen as a model substance representing quaternary dialkylated dimethylated ammonium surfactants in general, the developed method may be applied to other quaternary ammonium surfactants.

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

    Fong, Erika J.; Huang, Chao; Hamilton, Julie

    Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less

  2. ATXN2 trinucleotide repeat length correlates with risk of ALS.

    PubMed

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

    2017-03-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2  = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Microevolution of the Direct Repeat Locus of Mycobacterium tuberculosis in a Strain Prevalent in San Francisco

    PubMed Central

    Aga, Roxanne S.; Fair, Elizabeth; Abernethy, Neil F.; DeRiemer, Kathryn; Paz, E. Antonio; Kawamura, L. Masae; Small, Peter M.; Kato-Maeda, Midori

    2006-01-01

    We describe a microevolutionary event of a prevalent strain of Mycobacterium tuberculosis that caused two outbreaks in San Francisco. During the second outbreak, a direct variable repeat was lost. We discuss the mechanisms of this change and the implications of analyzing multiple genetic loci in this context. PMID:16597893

  4. REPPER—repeats and their periodicities in fibrous proteins

    PubMed Central

    Gruber, Markus; Söding, Johannes; Lupas, Andrei N.

    2005-01-01

    REPPER (REPeats and their PERiodicities) is an integrated server that detects and analyzes regions with short gapless repeats in protein sequences or alignments. It finds periodicities by Fourier Transform (FTwin) and internal similarity analysis (REPwin). FTwin assigns numerical values to amino acids that reflect certain properties, for instance hydrophobicity, and gives information on corresponding periodicities. REPwin uses self-alignments and displays repeats that reveal significant internal similarities. Both programs use a sliding window to ensure that different periodic regions within the same protein are detected independently. FTwin and REPwin are complemented by secondary structure prediction (PSIPRED) and coiled coil prediction (COILS), making the server a versatile analysis tool for sequences of fibrous proteins. REPPER is available at . PMID:15980460

  5. Do gamma-ray burst sources repeat?

    NASA Technical Reports Server (NTRS)

    Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

    1995-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb, 1993; Wang and Lingenfelter, 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al., 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the observed bursts cannot be excluded.

  6. Altimeter Processing Tools for Analyzing Mesoscale Ocean Features

    DTIC Science & Technology

    1990-09-01

    However, since the programs are modular, users can easily use their own orbit and geoid corrections to study basin scale problems. We left programs that...g..repeat c*/c*.a002c > a002cs-m or %g.repeat c???/c???.a002c > a002cs-m The file aOO2cs.m contains the following information in tab delimited ...information in tab delimited columns: The sea surface height residual files are similar to those created by g.repeat. except that fi(z ,t) is the original

  7. Fatigue design of a cellular phone folder using regression model-based multi-objective optimization

    NASA Astrophysics Data System (ADS)

    Kim, Young Gyun; Lee, Jongsoo

    2016-08-01

    In a folding cellular phone, the folding device is repeatedly opened and closed by the user, which eventually results in fatigue damage, particularly to the front of the folder. Hence, it is important to improve the safety and endurance of the folder while also reducing its weight. This article presents an optimal design for the folder front that maximizes its fatigue endurance while minimizing its thickness. Design data for analysis and optimization were obtained experimentally using a test jig. Multi-objective optimization was carried out using a nonlinear regression model. Three regression methods were employed: back-propagation neural networks, logistic regression and support vector machines. The AdaBoost ensemble technique was also used to improve the approximation. Two-objective Pareto-optimal solutions were identified using the non-dominated sorting genetic algorithm (NSGA-II). Finally, a numerically optimized solution was validated against experimental product data, in terms of both fatigue endurance and thickness index.

  8. [Analysis of variance of repeated data measured by water maze with SPSS].

    PubMed

    Qiu, Hong; Jin, Guo-qin; Jin, Ru-feng; Zhao, Wei-kang

    2007-01-01

    To introduce the method of analyzing repeated data measured by water maze with SPSS 11.0, and offer a reference statistical method to clinical and basic medicine researchers who take the design of repeated measures. Using repeated measures and multivariate analysis of variance (ANOVA) process of the general linear model in SPSS and giving comparison among different groups and different measure time pairwise. Firstly, Mauchly's test of sphericity should be used to judge whether there were relations among the repeatedly measured data. If any (P

  9. Deterministic Design Optimization of Structures in OpenMDAO Framework

    NASA Technical Reports Server (NTRS)

    Coroneos, Rula M.; Pai, Shantaram S.

    2012-01-01

    Nonlinear programming algorithms play an important role in structural design optimization. Several such algorithms have been implemented in OpenMDAO framework developed at NASA Glenn Research Center (GRC). OpenMDAO is an open source engineering analysis framework, written in Python, for analyzing and solving Multi-Disciplinary Analysis and Optimization (MDAO) problems. It provides a number of solvers and optimizers, referred to as components and drivers, which users can leverage to build new tools and processes quickly and efficiently. Users may download, use, modify, and distribute the OpenMDAO software at no cost. This paper summarizes the process involved in analyzing and optimizing structural components by utilizing the framework s structural solvers and several gradient based optimizers along with a multi-objective genetic algorithm. For comparison purposes, the same structural components were analyzed and optimized using CometBoards, a NASA GRC developed code. The reliability and efficiency of the OpenMDAO framework was compared and reported in this report.

  10. System, apparatus and methods to implement high-speed network analyzers

    DOEpatents

    Ezick, James; Lethin, Richard; Ros-Giralt, Jordi; Szilagyi, Peter; Wohlford, David E

    2015-11-10

    Systems, apparatus and methods for the implementation of high-speed network analyzers are provided. A set of high-level specifications is used to define the behavior of the network analyzer emitted by a compiler. An optimized inline workflow to process regular expressions is presented without sacrificing the semantic capabilities of the processing engine. An optimized packet dispatcher implements a subset of the functions implemented by the network analyzer, providing a fast and slow path workflow used to accelerate specific processing units. Such dispatcher facility can also be used as a cache of policies, wherein if a policy is found, then packet manipulations associated with the policy can be quickly performed. An optimized method of generating DFA specifications for network signatures is also presented. The method accepts several optimization criteria, such as min-max allocations or optimal allocations based on the probability of occurrence of each signature input bit.

  11. Using design of experiments to optimize derivatization with methyl chloroformate for quantitative analysis of the aqueous phase from hydrothermal liquefaction of biomass.

    PubMed

    Madsen, René Bjerregaard; Jensen, Mads Mørk; Mørup, Anders Juul; Houlberg, Kasper; Christensen, Per Sigaard; Klemmer, Maika; Becker, Jacob; Iversen, Bo Brummerstedt; Glasius, Marianne

    2016-03-01

    Hydrothermal liquefaction is a promising technique for the production of bio-oil. The process produces an oil phase, a gas phase, a solid residue, and an aqueous phase. Gas chromatography coupled with mass spectrometry is used to analyze the complex aqueous phase. Especially small organic acids and nitrogen-containing compounds are of interest. The efficient derivatization reagent methyl chloroformate was used to make analysis of the complex aqueous phase from hydrothermal liquefaction of dried distillers grains with solubles possible. A circumscribed central composite design was used to optimize the responses of both derivatized and nonderivatized analytes, which included small organic acids, pyrazines, phenol, and cyclic ketones. Response surface methodology was used to visualize significant factors and identify optimized derivatization conditions (volumes of methyl chloroformate, NaOH solution, methanol, and pyridine). Twenty-nine analytes of small organic acids, pyrazines, phenol, and cyclic ketones were quantified. An additional three analytes were pseudoquantified with use of standards with similar mass spectra. Calibration curves with high correlation coefficients were obtained, in most cases R (2)  > 0.991. Method validation was evaluated with repeatability, and spike recoveries of all 29 analytes were obtained. The 32 analytes were quantified in samples from the commissioning of a continuous flow reactor and in samples from recirculation experiments involving the aqueous phase. The results indicated when the steady-state condition of the flow reactor was obtained and the effects of recirculation. The validated method will be especially useful for investigations of the effect of small organic acids on the hydrothermal liquefaction process.

  12. Training set optimization and classifier performance in a top-down diabetic retinopathy screening system

    NASA Astrophysics Data System (ADS)

    Wigdahl, J.; Agurto, C.; Murray, V.; Barriga, S.; Soliz, P.

    2013-03-01

    Diabetic retinopathy (DR) affects more than 4.4 million Americans age 40 and over. Automatic screening for DR has shown to be an efficient and cost-effective way to lower the burden on the healthcare system, by triaging diabetic patients and ensuring timely care for those presenting with DR. Several supervised algorithms have been developed to detect pathologies related to DR, but little work has been done in determining the size of the training set that optimizes an algorithm's performance. In this paper we analyze the effect of the training sample size on the performance of a top-down DR screening algorithm for different types of statistical classifiers. Results are based on partial least squares (PLS), support vector machines (SVM), k-nearest neighbor (kNN), and Naïve Bayes classifiers. Our dataset consisted of digital retinal images collected from a total of 745 cases (595 controls, 150 with DR). We varied the number of normal controls in the training set, while keeping the number of DR samples constant, and repeated the procedure 10 times using randomized training sets to avoid bias. Results show increasing performance in terms of area under the ROC curve (AUC) when the number of DR subjects in the training set increased, with similar trends for each of the classifiers. Of these, PLS and k-NN had the highest average AUC. Lower standard deviation and a flattening of the AUC curve gives evidence that there is a limit to the learning ability of the classifiers and an optimal number of cases to train on.

  13. Photopic Negative Response Obtained Using a Handheld Electroretinogram Device: Determining the Optimal Measure and Repeatability

    PubMed Central

    Wu, Zhichao; Hadoux, Xavier; Hui, Flora; Sarossy, Marc G.; Crowston, Jonathan G.

    2016-01-01

    Purpose To determine the measure of the photopic negative response (PhNR) of the full-field electroretinogram (ERG) that exhibits the optimal level of test-retest repeatability, and examine its repeatability under different conditions using a handheld, nonmydriatic ERG system and self-adhering skin electrodes. Methods Multiple ERG recordings (using 200 sweeps each) were performed in both eyes of 20 normal participants at two different sessions to compare its coefficient of repeatability (CoR; where 95% of the test-retest difference is expected to lie) between different PhNR measures and under different testing conditions (within and between examiners, and between sessions). Results The ratio between the PhNR trough to b-wave peak and b-wave peak to a-wave trough amplitude (PhNR/B ratio) exhibited the lowest CoR relative to its effective dynamic range (30 ± 4%) when including three recordings. There were no significant changes in the PhNR/B ratio over seven measurements (4 right and 3 left eyes) at either session (P ≥ 0.100), or significant difference in its CoR between different testing conditions (P = 0.314). Conclusion The PhNR/B ratio was the measure that minimized variability, and its measurements using a novel handheld ERG system with self-adhering skin electrodes and the protocols described in this study were comparable under different testing conditions and over multiple recordings. Translational Relevance The PhNR can be measured for clinical and research purposes using a simple-to-implement technique that is consistent within and between visits, and also between examiners. PMID:27540494

  14. A Sequential Optimization Sampling Method for Metamodels with Radial Basis Functions

    PubMed Central

    Pan, Guang; Ye, Pengcheng; Yang, Zhidong

    2014-01-01

    Metamodels have been widely used in engineering design to facilitate analysis and optimization of complex systems that involve computationally expensive simulation programs. The accuracy of metamodels is strongly affected by the sampling methods. In this paper, a new sequential optimization sampling method is proposed. Based on the new sampling method, metamodels can be constructed repeatedly through the addition of sampling points, namely, extrema points of metamodels and minimum points of density function. Afterwards, the more accurate metamodels would be constructed by the procedure above. The validity and effectiveness of proposed sampling method are examined by studying typical numerical examples. PMID:25133206

  15. The study of the physics of cometary nuclei

    NASA Technical Reports Server (NTRS)

    Whipple, F. L.

    1985-01-01

    The development and utilization of an optimized computer program to analyze orbital stabilization by repeated calculations is presented. The stability of comets in the Opik-Oort Cloud about the Sun against perturbations by the Galactic center involve the same basic type of calculation. The supposed persistence of these bodies in orbits over the life of the solar system, depends upon the stability of bodies of negligible mass in orbits around a body whose mass is small compared to the central mass about which they revolve. The question remains of preferential orientation of extremely eccentric comet orbits, possibly to explain the asymmetry observed among new comet motions. A third application of the computing programs is suited to meteoroids that may exist in orbits about asteroids and that may endanger science spacecraft making flybys too near to asteroids. As in the double-comet case, solar activity and solar gravitational perturbations limit the attendance to an asteroid by small meteroids in their orbits. It is found that the mass distances planned for asteroid fly-bys are adequate.

  16. Developing Lathing Parameters for PBX 9501

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

    Woodrum, Randall Brock

    This thesis presents the work performed on lathing PBX 9501 to gather and analyze cutting force and temperature data during the machining process. This data will be used to decrease federal-regulation-constrained machining time of the high explosive PBX 9501. The effects of machining parameters depth of cut, surface feet per minute, and inches per revolution on cutting force and cutting interface were evaluated. Cutting tools of tip radius 0.005 -inches and 0.05 -inches were tested to determine what effect the tool shape had on the machining process as well. A consistently repeatable relationship of temperature to changing depth of cutmore » and surface feet per minute is found, while only a weak dependence was found to changing inches per revolution. Results also show the relation of cutting force to depth of cut and inches per revolution, while weak dependence on SFM is found. Conclusions suggest rapid, shallow cuts optimize machining time for a billet of PBX 9501, while minimizing temperature increase and cutting force.« less

  17. Enhanced Sensitivity of Wireless Chemical Sensor Based on Love Wave Mode

    NASA Astrophysics Data System (ADS)

    Wang, Wen; Oh, Haekwan; Lee, Keekeun; Yang, Sangsik

    2008-09-01

    A 440 MHz wireless and passive Love-wave-based chemical sensor was developed for CO2 detection. The developed device was composed of a reflective delay line patterned on 41° YX LiNbO3 piezoelectric substrate, a poly(methyl methacrylate) (PMMA) waveguide layer, and Teflon AF 2400 sensitive film. A theoretical model is presented to describe wave propagation in Love wave devices with large piezoelectricity and to allow the design of an optimized structure. In wireless device testing using a network analyzer, infusion of CO2 into the testing chamber induced large phase shifts of the reflection peaks owing to the interaction between the sensing film and the test gas (CO2). Good linearity and repeatability were observed at CO2 concentrations of 0-350 ppm. The obtained sensitivity from the Love wave device was approximately 7.07° ppm-1. The gas response properties of the fabricated Love-wave sensor in terms of linearity and sensitivity were provided, and a comparison to surface acoustic wave devices was also discussed.

  18. The effects of competition on medical service provision.

    PubMed

    Brosig-Koch, Jeannette; Hehenkamp, Burkhard; Kokot, Johanna

    2017-12-01

    We explore how competition between physicians affects medical service provision. Previous research has shown that, without competition, physicians deviate from patient-optimal treatment under payment systems like capitation and fee-for-service. Although competition might reduce these distortions, physicians usually interact with each other repeatedly over time and only a fraction of patients switches providers at all. Both patterns might prevent competition to work in the desired direction. To analyze the behavioral effects of competition, we develop a theoretical benchmark that is then tested in a controlled laboratory experiment. Experimental conditions vary physician payment and patient characteristics. Real patients benefit from provision decisions made in the experiment. Our results reveal that, in line with the theoretical prediction, introducing competition can reduce overprovision and underprovision, respectively. The observed effects depend on patient characteristics and the payment system, though. Tacit collusion is observed and particularly pronounced with fee-for-service payment, but it appears to be less frequent than in related experimental research on price competition. Copyright © 2017 John Wiley & Sons, Ltd.

  19. A predictive control framework for optimal energy extraction of wind farms

    NASA Astrophysics Data System (ADS)

    Vali, M.; van Wingerden, J. W.; Boersma, S.; Petrović, V.; Kühn, M.

    2016-09-01

    This paper proposes an adjoint-based model predictive control for optimal energy extraction of wind farms. It employs the axial induction factor of wind turbines to influence their aerodynamic interactions through the wake. The performance index is defined here as the total power production of the wind farm over a finite prediction horizon. A medium-fidelity wind farm model is utilized to predict the inflow propagation in advance. The adjoint method is employed to solve the formulated optimization problem in a cost effective way and the first part of the optimal solution is implemented over the control horizon. This procedure is repeated at the next controller sample time providing the feedback into the optimization. The effectiveness and some key features of the proposed approach are studied for a two turbine test case through simulations.

  20. Optimality, stochasticity, and variability in motor behavior

    PubMed Central

    Guigon, Emmanuel; Baraduc, Pierre; Desmurget, Michel

    2008-01-01

    Recent theories of motor control have proposed that the nervous system acts as a stochastically optimal controller, i.e. it plans and executes motor behaviors taking into account the nature and statistics of noise. Detrimental effects of noise are converted into a principled way of controlling movements. Attractive aspects of such theories are their ability to explain not only characteristic features of single motor acts, but also statistical properties of repeated actions. Here, we present a critical analysis of stochastic optimality in motor control which reveals several difficulties with this hypothesis. We show that stochastic control may not be necessary to explain the stochastic nature of motor behavior, and we propose an alternative framework, based on the action of a deterministic controller coupled with an optimal state estimator, which relieves drawbacks of stochastic optimality and appropriately explains movement variability. PMID:18202922

  1. Fine-tuning gene networks using simple sequence repeats

    PubMed Central

    Egbert, Robert G.; Klavins, Eric

    2012-01-01

    The parameters in a complex synthetic gene network must be extensively tuned before the network functions as designed. Here, we introduce a simple and general approach to rapidly tune gene networks in Escherichia coli using hypermutable simple sequence repeats embedded in the spacer region of the ribosome binding site. By varying repeat length, we generated expression libraries that incrementally and predictably sample gene expression levels over a 1,000-fold range. We demonstrate the utility of the approach by creating a bistable switch library that programmatically samples the expression space to balance the two states of the switch, and we illustrate the need for tuning by showing that the switch’s behavior is sensitive to host context. Further, we show that mutation rates of the repeats are controllable in vivo for stability or for targeted mutagenesis—suggesting a new approach to optimizing gene networks via directed evolution. This tuning methodology should accelerate the process of engineering functionally complex gene networks. PMID:22927382

  2. Parsimonious Structural Equation Models for Repeated Measures Data, with Application to the Study of Consumer Preferences

    ERIC Educational Resources Information Center

    Elrod, Terry; Haubl, Gerald; Tipps, Steven W.

    2012-01-01

    Recent research reflects a growing awareness of the value of using structural equation models to analyze repeated measures data. However, such data, particularly in the presence of covariates, often lead to models that either fit the data poorly, are exceedingly general and hard to interpret, or are specified in a manner that is highly data…

  3. Repeat analysis of intraoral digital imaging performed by undergraduate students using a complementary metal oxide semiconductor sensor: An institutional case study

    PubMed Central

    Rahman, Nur Liyana Abdul; Asri, Amiza Aqiela Ahmad; Othman, Noor Ilyani; Wan Mokhtar, Ilham

    2017-01-01

    Purpose This study was performed to quantify the repeat rate of imaging acquisitions based on different clinical examinations, and to assess the prevalence of error types in intraoral bitewing and periapical imaging using a digital complementary metal-oxide-semiconductor (CMOS) intraoral sensor. Materials and Methods A total of 8,030 intraoral images were retrospectively collected from 3 groups of undergraduate clinical dental students. The type of examination, stage of the procedure, and reasons for repetition were analysed and recorded. The repeat rate was calculated as the total number of repeated images divided by the total number of examinations. The weighted Cohen's kappa for inter- and intra-observer agreement was used after calibration and prior to image analysis. Results The overall repeat rate on intraoral periapical images was 34.4%. A total of 1,978 repeated periapical images were from endodontic assessment, which included working length estimation (WLE), trial gutta-percha (tGP), obturation, and removal of gutta-percha (rGP). In the endodontic imaging, the highest repeat rate was from WLE (51.9%) followed by tGP (48.5%), obturation (42.2%), and rGP (35.6%). In bitewing images, the repeat rate was 15.1% and poor angulation was identified as the most common cause of error. A substantial level of intra- and interobserver agreement was achieved. Conclusion The repeat rates in this study were relatively high, especially for certain clinical procedures, warranting training in optimization techniques and radiation protection. Repeat analysis should be performed from time to time to enhance quality assurance and hence deliver high-quality health services to patients. PMID:29279822

  4. Effects of different re-warm up activities in football players' performance.

    PubMed

    Abade, Eduardo; Sampaio, Jaime; Gonçalves, Bruno; Baptista, Jorge; Alves, Alberto; Viana, João

    2017-01-01

    Warm up routines are commonly used to optimize football performance and prevent injuries. Yet, official pre-match protocols may require players to passively rest for approximately 10 to 15 minutes between the warm up and the beginning of the match. Therefore, the aim of this study was to explore the effect of different re-warm up activities on the physical performance of football players. Twenty-Two Portuguese elite under-19 football players participated in the study conducted during the competitive season. Different re-warm up protocols were performed 6 minutes after the same standardized warm up in 4 consecutive days in a crossover controlled approach: without, eccentric, plyometric and repeated changes of direction. Vertical jump and Sprint performances were tested immediately after warm up and 12 minutes after warm up. Results showed that repeated changes of direction and plyometrics presented beneficial effects to jump and sprint. Different practical implications may be taken from the eccentric protocol since a vertical jump impairment was observed, suggesting a possibly harmful effect. The absence of re-warm up activities may be detrimental to players' physical performance. However, the inclusion of re-warm up prior to match is a complex issue, since the manipulation of volume, intensity and recovery may positively or negatively affect the subsequent performance. In fact, this exploratory study shows that eccentric exercise may be harmful for physical performance when performed prior a football match. However, plyometric and repeated changes of direction exercises seem to be simple, quick and efficient activities to attenuate losses in vertical jump and sprint capacity after warm up. Coaches should aim to develop individual optimal exercise modes in order to optimize physical performance after re warm activities.

  5. Cross-validation pitfalls when selecting and assessing regression and classification models.

    PubMed

    Krstajic, Damjan; Buturovic, Ljubomir J; Leahy, David E; Thomas, Simon

    2014-03-29

    We address the problem of selecting and assessing classification and regression models using cross-validation. Current state-of-the-art methods can yield models with high variance, rendering them unsuitable for a number of practical applications including QSAR. In this paper we describe and evaluate best practices which improve reliability and increase confidence in selected models. A key operational component of the proposed methods is cloud computing which enables routine use of previously infeasible approaches. We describe in detail an algorithm for repeated grid-search V-fold cross-validation for parameter tuning in classification and regression, and we define a repeated nested cross-validation algorithm for model assessment. As regards variable selection and parameter tuning we define two algorithms (repeated grid-search cross-validation and double cross-validation), and provide arguments for using the repeated grid-search in the general case. We show results of our algorithms on seven QSAR datasets. The variation of the prediction performance, which is the result of choosing different splits of the dataset in V-fold cross-validation, needs to be taken into account when selecting and assessing classification and regression models. We demonstrate the importance of repeating cross-validation when selecting an optimal model, as well as the importance of repeating nested cross-validation when assessing a prediction error.

  6. Molecular view of ligands specificity for CAG repeats in anti-Huntington therapy.

    PubMed

    Bochicchio, Anna; Rossetti, Giulia; Tabarrini, Oriana; Krauβ, Sybille; Carloni, Paolo

    2015-10-13

    Huntington's disease is a fatal and devastating neurodegenerative genetic disorder for which there is currently no cure. It is characterized by Huntingtin protein's mRNA transcripts with 36 or more CAG repeats. Inhibiting the formation of pathological complexes between these expanded transcripts and target proteins may be a valuable strategy against the disease. Yet, the rational design of molecules specifically targeting the expanded CAG repeats is limited by the lack of structural information. Here, we use well-tempered metadynamics-based free energy calculations to investigate pose and affinity of two ligands targeting CAG repeats for which affinities have been previously measured. The first consists of two 4-guanidinophenyl rings linked by an ester group. It is the most potent ligand identified so far, with Kd = 60(30) nM. The second consists of a 4-phenyl dihydroimidazole and 4-1H-indole dihydroimidazole connected by a C-C bond (Kd = 700(80) nM). Our calculations reproduce the experimental affinities and uncover the recognition pattern between ligands' and their RNA target. They also provide a molecular basis for the markedly different affinity of the two ligands for CAG repeats as observed experimentally. These findings may pave the way for a structure-based hit-to-lead optimization to further improve ligand selectivity toward CAG repeat-containing mRNAs.

  7. Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

    PubMed

    Kramer, G M; Liu, Y; de Langen, A J; Jansma, E P; Trigonis, I; Asselin, M-C; Jackson, A; Kenny, L; Aboagye, E O; Hoekstra, O S; Boellaard, R

    2018-06-01

    3'-deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18 F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18 F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five 18 F-FLT repeatability cohorts in solid tumors. 18 F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUV max , SUV mean , SUV peak , proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all 18 F-FLT uptake metrics (R 2  ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUV peak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUV max  ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. In multi-center studies, differences ≥ 25% in 18 F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied.

  8. Fast machine-learning online optimization of ultra-cold-atom experiments.

    PubMed

    Wigley, P B; Everitt, P J; van den Hengel, A; Bastian, J W; Sooriyabandara, M A; McDonald, G D; Hardman, K S; Quinlivan, C D; Manju, P; Kuhn, C C N; Petersen, I R; Luiten, A N; Hope, J J; Robins, N P; Hush, M R

    2016-05-16

    We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates (BEC). BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our 'learner' discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system.

  9. Fast machine-learning online optimization of ultra-cold-atom experiments

    PubMed Central

    Wigley, P. B.; Everitt, P. J.; van den Hengel, A.; Bastian, J. W.; Sooriyabandara, M. A.; McDonald, G. D.; Hardman, K. S.; Quinlivan, C. D.; Manju, P.; Kuhn, C. C. N.; Petersen, I. R.; Luiten, A. N.; Hope, J. J.; Robins, N. P.; Hush, M. R.

    2016-01-01

    We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates (BEC). BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our ‘learner’ discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system. PMID:27180805

  10. Comparison of polynomial approximations and artificial neural nets for response surfaces in engineering optimization

    NASA Technical Reports Server (NTRS)

    Carpenter, William C.

    1991-01-01

    Engineering optimization problems involve minimizing some function subject to constraints. In areas such as aircraft optimization, the constraint equations may be from numerous disciplines such as transfer of information between these disciplines and the optimization algorithm. They are also suited to problems which may require numerous re-optimizations such as in multi-objective function optimization or to problems where the design space contains numerous local minima, thus requiring repeated optimizations from different initial designs. Their use has been limited, however, by the fact that development of response surfaces randomly selected or preselected points in the design space. Thus, they have been thought to be inefficient compared to algorithms to the optimum solution. A development has taken place in the last several years which may effect the desirability of using response surfaces. It may be possible that artificial neural nets are more efficient in developing response surfaces than polynomial approximations which have been used in the past. This development is the concern of the work.

  11. Concurrently examining unrealistic absolute and comparative optimism: Temporal shifts, individual-difference and event-specific correlates, and behavioural outcomes.

    PubMed

    Ruthig, Joelle C; Gamblin, Bradlee W; Jones, Kelly; Vanderzanden, Karen; Kehn, Andre

    2017-02-01

    Researchers have spent considerable effort examining unrealistic absolute optimism and unrealistic comparative optimism, yet there is a lack of research exploring them concurrently. This longitudinal study repeatedly assessed unrealistic absolute and comparative optimism within a performance context over several months to identify the degree to which they shift as a function of proximity to performance and performance feedback, their associations with global individual difference and event-specific factors, and their link to subsequent behavioural outcomes. Results showed similar shifts in unrealistic absolute and comparative optimism based on proximity to performance and performance feedback. Moreover, increases in both types of unrealistic optimism were associated with better subsequent performance beyond the effect of prior performance. However, several differences were found between the two forms of unrealistic optimism in their associations with global individual difference factors and event-specific factors, highlighting the distinctiveness of the two constructs. © 2016 The British Psychological Society.

  12. Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

    PubMed Central

    Tagmouti, Saloua; Slater, Madeline; Benedetti, Andrea; Kik, Sandra V.; Banaei, Niaz; Cattamanchi, Adithya; Metcalfe, John; Dowdy, David; van Zyl Smit, Richard; Dendukuri, Nandini

    2014-01-01

    Rationale: Interferon gamma (IFN-γ) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern. Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols. Methods: We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-γ release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate within-subject SD. Measurements and Main Results: We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-γ response in QuantiFERON under identical conditions was ±0.47 IU/ml (coefficient of variation, 13%) and ±0.26 IU/ml (30%) for individuals with an initial IFN-γ response in the borderline range (0.25–0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (±1.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability. Conclusions: This systematic review shows substantial variability with repeat IFN-γ release assays testing even under identical conditions, suggesting that reversions and conversions around the existing cut-point should be interpreted with caution. PMID:25188809

  13. [Analytical performances of real-time PCR by Abbott RealTime CMV with m2000 for the detection of cytomegalovirus in urine].

    PubMed

    De Monte, Anne; Cannavo, Isabelle; Caramella, Anne; Ollier, Laurence; Giordanengo, Valérie

    2016-01-01

    Congenital cytomegalovirus (CMV) infection is the leading cause of sensoneurinal disability due to infectious congenital disease. The diagnosis of congenital CMV infection is based on the search of CMV in the urine within the first two weeks of life. Viral culture of urine is the gold standard. However, the PCR is highly sensitive and faster. It is becoming an alternative choice. The objective of this study is the validation of real-time PCR by Abbott RealTime CMV with m2000 for the detection of cytomegalovirus in urine. Repeatability, reproducibility, detection limit and inter-sample contamination were evaluated. Urine samples from patients (n=141) were collected and analyzed simultaneously in culture and PCR in order to assess the correlation of these two methods. The sensitivity and specificity of PCR were also calculated. The Abbott RealTime CMV PCR in urine is an automated and sensitive method (detection limit 200 UI/mL). Fidelity is very good (standard deviation of repeatability: 0.08 to 0.15 LogUI/mL and reproducibility 0.18 LogUI/mL). We can note a good correlation between culture and Abbott RealTime CMV PCR (kappa 96%). When considering rapid culture as reference, real-time PCR was highly sensitive (100%) and specific (98.2%). The real-time PCR by Abbott RealTime CMV with m2000 is optimal for CMV detection in urine.

  14. Temperature fluctuations during deep temperature cryopreservation reduce PBMC recovery, viability and T-cell function.

    PubMed

    Germann, Anja; Oh, Young-Joo; Schmidt, Tomm; Schön, Uwe; Zimmermann, Heiko; von Briesen, Hagen

    2013-10-01

    The ability to analyze cryopreserved peripheral blood mononuclear cell (PBMC) from biobanks for antigen-specific immunity is necessary to evaluate response to immune-based therapies. To ensure comparable assay results, collaborative research in multicenter trials needs reliable and reproducible cryopreservation that maintains cell viability and functionality. A standardized cryopreservation procedure is comprised of not only sample collection, preparation and freezing but also low temperature storage in liquid nitrogen without any temperature fluctuations, to avoid cell damage. Therefore, we have developed a storage approach to minimize suboptimal storage conditions in order to maximize cell viability, recovery and T-cell functionality. We compared the influence of repeated temperature fluctuations on cell health from sample storage, sample sorting and removal in comparison to sample storage without temperature rises. We found that cyclical temperature shifts during low temperature storage reduce cell viability, recovery and immune response against specific-antigens. We showed that samples handled under a protective hood system, to avoid or minimize such repeated temperature rises, have comparable cell viability and cell recovery rates to samples stored without any temperature fluctuations. Also T-cell functionality could be considerably increased with the use of the protective hood system compared to sample handling without such a protection system. This data suggests that the impact of temperature fluctuation on cell integrity should be carefully considered in future clinical vaccine trials and consideration should be given to optimal sample storage conditions. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Highly efficient nuclear DNA typing of the World War II skeletal remains using three new autosomal short tandem repeat amplification kits with the extended European Standard Set of loci

    PubMed Central

    Zupanič Pajnič, Irena; Gornjak Pogorelc, Barbara; Balažic, Jože; Zupanc, Tomaž; Štefanič, Borut

    2012-01-01

    Aim To perform an efficiency study of three new amplification kits with the extended European Standard Set (ESS) of loci for autosomal short tandem repeat (STR) typing of skeletal remains excavated from the World War II mass graves in Slovenia. Methods In the beginning of the 2011, we analyzed 102 bones and teeth using the PowerPlex ESX 17 System (Promega), AmpFiSTR NGM PCR Amplification Kit (Applied Biosystems), and Investigator ESSplex Kit (Qiagen). We cleaned the bones and teeth, removed surface contamination, and ground them into a powder using liquid nitrogen. Prior to DNA isolation with Biorobot EZ1 (Qiagen), 0.5 g bone or tooth powder was decalcified. Nuclear DNA of the samples was quantified using real-time polymerase chain reaction. All three kits used the same extract with the amplification conditions recommended by the manufacturers. Results We extracted up to 131 ng DNA/g of powder from the bones and teeth. All three amplification kits showed very similar efficiency, since DNA typing was successful with all amplification kits in 101 out of 102 bones and teeth, which represents a 99% success rate. Conclusion The commercially available ESX 17, ESSplex, and NGM kits are highly reliable for STR typing of World War II skeletal remains with the DNA extraction method optimized in our laboratory. PMID:22351574

  16. Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription

    PubMed Central

    Norouzi, Davood; Katebi, Ataur; Cui, Feng; Zhurkin, Victor B.

    2016-01-01

    The spatial organization of nucleosomes in 30-nm fibers remains unknown in detail. To tackle this problem, we analyzed all stereochemically possible configurations of two-start chromatin fibers with DNA linkers L = 10–70 bp (nucleosome repeat length NRL = 157–217 bp). In our model, the energy of a fiber is a sum of the elastic energy of the linker DNA, steric repulsion, electrostatics, and the H4 tail-acidic patch interaction between two stacked nucleosomes. We found two families of energetically feasible conformations of the fibers—one observed earlier, and the other novel. The fibers from the two families are characterized by different DNA linking numbers—that is, they are topologically different. Remarkably, the optimal geometry of a fiber and its topology depend on the linker length: the fibers with linkers L = 10n and 10n + 5 bp have DNA linking numbers per nucleosome ΔLk ≈ −1.5 and −1.0, respectively. In other words, the level of DNA supercoiling is directly related to the length of the inter-nucleosome linker in the chromatin fiber (and therefore, to NRL). We hypothesize that this topological polymorphism of chromatin fibers may play a role in the process of transcription, which is known to generate different levels of DNA supercoiling upstream and downstream from RNA polymerase. A genome-wide analysis of the NRL distribution in active and silent yeast genes yielded results consistent with this assumption. PMID:28133628

  17. Geodetic Results from Mark 4 VLBI

    NASA Technical Reports Server (NTRS)

    MacMillan, Daniel; Petrov, Leonid; Ma, Chopo

    2002-01-01

    We present geodetic results of a series of 30 VLBI experiments recorded in Mark 4 mode at rates of 128 and 256 Mbps. The formal uncertainties of UT1, polar motion, and nutation offsets derived from these experiments are better than the corresponding uncertainties from NEOS-A experiments by a factor of 1.3-2. Baseline length repeatability for the series of 32 experiments over a period of one year is about 0.9 ppb. For comparison, NEOS-A length repeatability is about 1.4 ppb. We will discuss optimal use of Mark 4 in the design of future observing networks.

  18. Generation and stabilization of Bell states via repeated projective measurements on a driven ancilla qubit

    NASA Astrophysics Data System (ADS)

    Magazzù, L.; Jaramillo, J. D.; Talkner, P.; Hänggi, P.

    2018-06-01

    A protocol is proposed to generate Bell states in two non-directly interacting qubits by means of repeated measurements of the state of a central ancilla connected to both qubits. An optimal measurement rate is found that minimizes the time to stably encode a Bell state in the target qubits, being of advantage in order to reduce detrimental effects from possible interactions with the environment. The quality of the entanglement is assessed in terms of the concurrence and the distance between the qubits state and the target Bell state is quantified by the fidelity.

  19. Repeated self-harm in young people: a review.

    PubMed

    Robinson, Jo

    2017-04-01

    This paper provides a review of the rates of self-harm and repeated self-harm among young people. It describes some of the risk factors associated with these behaviours and summarises some of the barriers to delivering optimal treatment. The review concludes that there is an urgent need for the delivery of respectful and evidence-based practice to all young people who present with self-harm. In addition, improved monitoring of self-harm presentations to hospitals across Australia is required in order that robust data are collected and the impact of practice change can be reliably assessed.

  20. Restoration of Muscle Glycogen and Functional Capacity: Role of Post-Exercise Carbohydrate and Protein Co-Ingestion

    PubMed Central

    Alghannam, Abdullah F.; Betts, James A.

    2018-01-01

    The importance of post-exercise recovery nutrition has been well described in recent years, leading to its incorporation as an integral part of training regimes in both athletes and active individuals. Muscle glycogen depletion during an initial prolonged exercise bout is a main factor in the onset of fatigue and so the replenishment of glycogen stores may be important for recovery of functional capacity. Nevertheless, nutritional considerations for optimal short-term (3–6 h) recovery remain incompletely elucidated, particularly surrounding the precise amount of specific types of nutrients required. Current nutritional guidelines to maximise muscle glycogen availability within limited recovery are provided under the assumption that similar fatigue mechanisms (i.e., muscle glycogen depletion) are involved during a repeated exercise bout. Indeed, recent data support the notion that muscle glycogen availability is a determinant of subsequent endurance capacity following limited recovery. Thus, carbohydrate ingestion can be utilised to influence the restoration of endurance capacity following exhaustive exercise. One strategy with the potential to accelerate muscle glycogen resynthesis and/or functional capacity beyond merely ingesting adequate carbohydrate is the co-ingestion of added protein. While numerous studies have been instigated, a consensus that is related to the influence of carbohydrate-protein ingestion in maximising muscle glycogen during short-term recovery and repeated exercise capacity has not been established. When considered collectively, carbohydrate intake during limited recovery appears to primarily determine muscle glycogen resynthesis and repeated exercise capacity. Thus, when the goal is to optimise repeated exercise capacity following short-term recovery, ingesting carbohydrate at an amount of ≥1.2 g kg body mass−1·h−1 can maximise muscle glycogen repletion. The addition of protein to carbohydrate during post-exercise recovery may be beneficial under circumstances when carbohydrate ingestion is sub-optimal (≤0.8 g kg body mass−1·h−1) for effective restoration of muscle glycogen and repeated exercise capacity. PMID:29473893

  1. Confirming the Stankosky Knowledge Management Framework

    ERIC Educational Resources Information Center

    Ternes, Carl D., Jr.

    2011-01-01

    As a managerial construct, knowledge management (KM) optimizes organizational knowledge assets to achieve sustainable business advantages by connecting people with the intellectual resources needed to operate more effectively. Yet KM may have its greatest impact when used with repeatable, systems engineering-based "frameworks." As such, this study…

  2. Genotyping variability of computationally categorized peach microsatellite markers

    USDA-ARS?s Scientific Manuscript database

    Numerous expressed sequence tag (EST) simple sequence repeat (SSR) primers can be easily mined out. The obstacle to develop them into usable markers is how to optimally select downsized subsets of the primers for genotyping, which accordingly reduces amplification failure and monomorphism often occu...

  3. OPTIMIZATION OF REPEATED BRONCHOALVEOLAR LAVAGE IN RABBITS

    EPA Science Inventory

    Background. Bronchoalveolar lavage (BAL) is a relatively non-invasive technique used to obtain diagnostic samples from the lower airways of companion animals with respira¬tory disease. BAL is also commonly used in laboratory animals to assess pulmo¬nary changes after expos...

  4. Evidence-based post-exercise recovery strategies in basketball.

    PubMed

    Calleja-González, Julio; Terrados, Nicolás; Mielgo-Ayuso, Juan; Delextrat, Anne; Jukic, Igor; Vaquera, Alejandro; Torres, Lorena; Schelling, Xavier; Stojanovic, Marko; Ostojic, Sergej M

    2016-01-01

    Basketball can be described as a moderate-to-long duration exercise including repeated bouts of high-intensity activity interspersed with periods of low to moderate active recovery or passive rest. A match is characterized by repeated explosive activities, such as sprints, jumps, shuffles and rapid changes in direction. In top-level modern basketball, players are frequently required to play consecutive matches with limited time to recover. To ensure adequate recovery after any basketball activity (i.e., match or training), it is necessary to know the type of fatigue induced and, if possible, its underlying mechanisms. Despite limited scientific evidence to support their effectiveness in facilitating optimal recovery, certain recovery strategies are commonly utilized in basketball. It is particularly important to optimize recovery because players spend a much greater proportion of their time recovering than they do in training. Therefore, the main aim of this report is to facilitate useful information that may lead to practical application, based on the scientific evidence and applied knowledge specifically in basketball.

  5. Effect of repeated cycled crystallization on digestibility and molecular structure of glutinous Bora rice starch.

    PubMed

    Borah, Pallab Kumar; Deka, Sankar Chandra; Duary, Raj Kumar

    2017-05-15

    The effects of repeated cycled crystallization on the digestibility and molecular structure of glutinous Bora rice starch were investigated. Temperature cycle 4/45°C; cycle duration 5d; time interval of cycles 24h; and starch to water ratio 1:2 were found to be optimum for SDS (slow digestible starch) product development. The SDS content increased from 18.01±2.11% to 82.81±2.34%. An increase in the resistance to digestion, crystallinity, molecular weight, polydispersity and molecular order was observed in the optimal SDS product. Notably, the FT-IR peak at 947cm -1 and XRD peaks at 2θ≈13° and 20° in the optimal SDS product indicated the formation of V-type complexes even without the presence of co-polymers. Birefringence studies showed a loss of typical Maltese cross in the SDS product and revealed a reorientation of crystalline structures within starch granules, suggestive of imperfect crystallite development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Analysis of tandem repeat units of the promoter of capsanthin/capsorubin synthase (Ccs) gene in pepper fruit.

    PubMed

    Tian, Shi-Lin; Li, Zheng; Li, Li; Shah, S N M; Gong, Zhen-Hui

    2017-07-01

    Capsanthin/capsorubin synthase ( Ccs ) gene is a key gene that regulates the synthesis of capsanthin and the development of red coloration in pepper fruits. There are three tandem repeat units in the promoter region of Ccs , but the potential effects of the number of repetitive units on the transcriptional regulation of Ccs has been unclear. In the present study, expression vectors carrying different numbers of repeat units of the Ccs promoter were constructed, and the transient expression of the β-glucuronidase ( GUS ) gene was used to detect differences in expression levels associated with the promoter fragments. These repeat fragments and the plant expression vector PBI121 containing the 35s CaMV promoter were ligated to form recombinant vectors that were transfected into Agrobacterium tumefaciens GV3101. A fluorescence spectrophotometer was used to analyze the expression associated with the various repeat units. It was concluded that the constructs containing at least one repeat were associated with GUS expression, though they did not differ from one another. This repeating unit likely plays a role in transcription and regulation of Ccs expression.

  7. Evolutionary dynamics of the immunodominant repeats of the Plasmodium vivax malaria-vaccine candidate circumsporozoite protein (CSP)

    PubMed Central

    Patil, Aarti; Orjuela-Sánchez, Pamela; da Silva-Nunes, Mônica; Ferreira, Marcelo U.

    2010-01-01

    The circumsporozoite protein (CSP) of Plasmodium vivax, a major target for malaria vaccine development, has immunodominant B-cell epitopes mapped to central nonapeptide repeat arrays. To determine whether rearrangements of repeat motifs during mitotic DNA replication of parasites create significant CSP diversity under conditions of low effective meiotic recombination rates, we examined csp alleles from sympatric P. vivax isolates systematically sampled from an area of low malaria endemicity in Brazil over a period of 14 months. Nine unique csp types, comprising six different nonapeptide repeats, were observed in 45 isolates analyzed. Identical or nearly identical repeats predominated in most arrays, consistent with their recent expansion. We found strong linkage disequilibrium at sites across the chromosome 8 segment flanking the csp locus, consistent with rare meiotic recombination in this region. We conclude that CSP repeat diversity may not be severely constrained by rare meiotic recombination in areas of low malaria endemicity. New repeat variants may be readily created by nonhomologous recombination even when meiotic recombination is rare, with potential implications for CSP-based vaccine development. PMID:20097310

  8. Repeatability Modeling for Wind-Tunnel Measurements: Results for Three Langley Facilities

    NASA Technical Reports Server (NTRS)

    Hemsch, Michael J.; Houlden, Heather P.

    2014-01-01

    Data from extensive check standard tests of seven measurement processes in three NASA Langley Research Center wind tunnels are statistically analyzed to test a simple model previously presented in 2000 for characterizing short-term, within-test and across-test repeatability. The analysis is intended to support process improvement and development of uncertainty models for the measurements. The analysis suggests that the repeatability can be estimated adequately as a function of only the test section dynamic pressure over a two-orders- of-magnitude dynamic pressure range. As expected for low instrument loading, short-term coefficient repeatability is determined by the resolution of the instrument alone (air off). However, as previously pointed out, for the highest dynamic pressure range the coefficient repeatability appears to be independent of dynamic pressure, thus presenting a lower floor for the standard deviation for all three time frames. The simple repeatability model is shown to be adequate for all of the cases presented and for all three time frames.

  9. 40 CFR 1065.303 - Summary of required calibration and verifications.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...: FID calibrationTHC FID optimization, and THC FID verification Calibrate all FID analyzers: upon initial installation and after major maintenance.Optimize and determine CH4 response for THC FID analyzers: upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers: upon...

  10. 40 CFR 86.521-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... Analyzers used with petroleum fuels and liquefied petroleum gas-fuel shall be optimized using propane. Analyzers used with natural gas-fuel for measurement of hydrocarbons shall be optimized using methane. If a... gas-fuel. Alternate methods yielding equivalent results may be used, if approved in advance by the...

  11. 40 CFR 86.521-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... Analyzers used with petroleum fuels and liquefied petroleum gas-fuel shall be optimized using propane. Analyzers used with natural gas-fuel for measurement of hydrocarbons shall be optimized using methane. If a... gas-fuel. Alternate methods yielding equivalent results may be used, if approved in advance by the...

  12. 40 CFR 86.521-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... Analyzers used with petroleum fuels and liquefied petroleum gas-fuel shall be optimized using propane. Analyzers used with natural gas-fuel for measurement of hydrocarbons shall be optimized using methane. If a... gas-fuel. Alternate methods yielding equivalent results may be used, if approved in advance by the...

  13. Does it really feel the same? Changes in life satisfaction following repeated life events.

    PubMed

    Luhmann, Maike; Eid, Michael

    2009-08-01

    Unemployment, divorce, and marriage are common life events for most people in Western societies. In a longitudinal study, the authors investigated how these life events affect life satisfaction when they occur repeatedly. Data came from the German Socio-Economic Panel, a large-scale representative panel study, and were analyzed using multilevel modeling. Results showed that, in general, life satisfaction decreases with repeated unemployment (sensitization). For repeated divorces, life satisfaction is higher at the second divorce than it had been at the first divorce (adaptation). Finally, life satisfaction is similar at repeated marriages. Neuroticism, extraversion, and gender accounted for interindividual differences in changes in life satisfaction. For instance, the general sensitization pattern associated with repeated unemployment was less pronounced for women. The authors also found main effects of age and the duration of the first event on general differences in life satisfaction. Finally, those with repeated events generally report lower life satisfaction than those with only one occasion of these events, even before the first event actually occurred. Findings show that repeated events can have very different effects on life satisfaction that depend on the nature of the event.

  14. Evaluation of FUS-2000 urine analyzer: analytical properties and particle recognition.

    PubMed

    Beňovská, Miroslava; Wiewiorka, Ondřej; Pinkavová, Jana

    This study evaluates the performance of microscopic part of a hybrid analyzer FUS-2000 (Dirui Industrial Co., Changchun, China), its analytical properties and particle recognition. The evaluation of trueness, repeatability, detection limit, carry-over, linearity range and analytical stability was performed according to Dirui protocol guidelines designed by Dirui Company to guarantee the quality of the instrument. Trueness for low, medium and high-value concentrations was calculated with bias of 15.5, 4.7 and -6.6%, respectively. Detection limit of 5 Ery/μl was confirmed. Coefficient of variation of 11.0, 5.2 and 3.8% was measured for within-run repeatability of low, medium and high concentration. Between-run repeatability for daily quality control had coefficient of variation of 3.0%. Carry-over did not exceed 0.05%. Linearity was confirmed for range of 0-16,000 particles/μl (R 2  = 0.9997). The analytical stability had coefficient of variation of 4.3%. Out of 1258 analyzed urine samples, 362 positive were subjected to light microscopy urine sediment analysis and compared to the analyzer results. Cohen's kappa coefficients were calculated to express the concordance. Squared kappa coefficient was 0.927 (red blood cells), 0.888 (white blood cells), 0.908 (squamous epithelia), 0.634 (transitional epithelia), 0.628 (hyaline casts), 0.843 (granular casts) and 0.623 (bacteria). Single kappa coefficients were 0.885 (yeasts) and 0.756 (crystals), respectively. Aforementioned results show good analytical performance of the analyzer and tight agreement with light microscopy of urine sediment.

  15. Dermatologic infestations.

    PubMed

    Shmidt, Eugenia; Levitt, Jacob

    2012-02-01

    Head lice are transmitted by head to head contact. Optimal therapy includes malathion lotion 0.5% repeated in one week left on for 30 minutes to 8 hours. Spinosad topical suspension 0.9% repeated in one week left on for 10 minutes is another option. Scabies is transmitted mainly by direct contact but also via heavily infested fomites due to crusted scabies. Permethrin 5% cream to the body repeated in four days is often sufficient; however, scalp treatment with malathion lotion 0.5% is helpful in crusted scabies and in infested children. Oral ivermectin 200 mcg/kg is another option, repeated in four days. For scabies more than lice, fomites should be placed in a drier at 60 °C for 10 minutes to kill the arthropods. Treatment of close contacts in both cases will control outbreaks and repeated infestations. Both have been associated with methicillin-resistant Staphylococcus aureus infection. Bed bugs are a common cause for papular urticaria. Identification of the insect in the mattress or bedding confirms the diagnosis. Prevention involves encasing the mattress in a sealed plastic cover and extermination. Delusions of parasitosis is a diagnosis of exclusion that is best treated with an antipsychotic. © 2012 The International Society of Dermatology.

  16. A Comparison of Four Year Health Outcomes following Combat Amputation and Limb Salvage

    DTIC Science & Technology

    2017-01-25

    without amputation (limb salvage, n = 107). Patient medi- cal records were analyzed for four years postinjury. After adjusting for group differences...likelihood of osteoporosis during the first year postinjury. The prevalence of posttraumatic stress disorder increased for all patient groups over four ...between the patient groups over time. Longitudinal results (repeated measures). Repeated measure analyses were conducted for four years postinjury

  17. Self-healing of damage in fibre-reinforced polymer-matrix composites.

    PubMed

    Hayes, S A; Zhang, W; Branthwaite, M; Jones, F R

    2007-04-22

    Self-healing resin systems have been discussed for over a decade and four different technologies had been proposed. However, little work on their application as composite matrices has been published although this was one of the stated aims of the earliest work in the field. This paper reports on the optimization of a solid-state self-healing resin system and its subsequent use as a matrix for high volume fraction glass fibre-reinforced composites. The resin system was optimized using Charpy impact testing and repeated healing, while the efficiency of healing in composites was determined by analysing the growth of delaminations following repeated impacts with or without a healing cycle. To act as a reference, a non-healing resin system was subjected to the same treatments and the results are compared with the healable system. The optimized resin system displays a healing efficiency of 65% after the first healing cycle, dropping to 35 and 30% after the second and third healing cycles, respectively. Correction for any healability due to further curing showed that approximately 50% healing efficiency could be achieved with the bisphenol A-based epoxy resin containing 7.5% of polybisphenol-A-co-epichlorohydrin. The composite, on the other hand, displays a healing efficiency of approximately 30%. It is therefore clear that the solid-state self-healing system is capable of healing transverse cracks and delaminations in a composite, but that more work is needed to optimize matrix healing within a composite and to develop a methodology for assessing recovery in performance.

  18. Fabrication of Thermoplastic Composite Laminates Having Film Interleaves By Automated Fiber Placement

    NASA Technical Reports Server (NTRS)

    Hulcher, A. B.; Tiwari, S. N.; Marchello, J. M.; Johnston, Norman J. (Technical Monitor)

    2001-01-01

    Experiments were carried out at the NASA Langley Research Center automated Fiber placement facility to determine an optimal process for the fabrication of composite materials having polymer film interleaves. A series of experiments was conducted to determine an optimal process for the composite prior to investigation of a process to fabricate laminates with polymer films. The results of the composite tests indicated that a well-consolidated, void-free laminate could be attained. Preliminary interleaf processing trials were then conducted to establish some broad guidelines for film processing. The primary finding of these initial studies was that a two-stage process was necessary in order to process these materials adequately. A screening experiment was then performed to determine the relative influence of the process variables on the quality of the film interface as determined by the wedge peel test method. Parameters that were found to be of minor influence on specimen quality were subsequently held at fixed values enabling a more rapid determination of an optimal process. Optimization studies were then performed by varying the remaining parameters at three film melt processing rates. The resulting peel data were fitted with quadratic response surfaces. Additional specimens were fabricated at levels of high peel strength as predicted by the regression models in an attempt to gage the accuracy of the predicted response and to assess the repeatability of the process. The overall results indicate that quality laminates having film interleaves can be successfully and repeatably fabricated by automated fiber placement.

  19. Determination of N,N-dimethyltryptamine in Mimosa tenuiflora inner barks by matrix solid-phase dispersion procedure and GC-MS.

    PubMed

    Gaujac, Alain; Aquino, Adriano; Navickiene, Sandro; de Andrade, Jailson Bittencourt

    2012-01-15

    N,N-dimethyltryptamine (DMT) is a potent hallucinogen found in beverages consumed in religion rituals and neo-shamanic practices over the world. Two of these religions, Santo Daime and União do Vegetal (UDV), are represented in countries including Australia, the United States and several European nations. In some of this countries there have been legal disputes concerning the legalization of ayahuasca consumption during religious rituals, a beverage rich in DMT. In Brazil, even children and pregnant women are legally authorized to consume ayahuasca in a religious context. A simple and low-cost method based on matrix solid-phase dispersion (MSPD) and gas chromatography with mass spectrometric detection (GC-MS) has been optimized for the determination of N,N-dimethyltryptamine in Mimosa tenuiflora inner bark. The experimental variables that affect the MSPD method, such as the amounts of solid-phase and herbal sample, solvent nature, eluate volume and NaOH concentration were optimized using an experimental design. The method showed good linearity (r = 0.9962) and repeatability (RSD < 7.4%) for DMT compound, with detection limit of 0.12 mg/g. The proposed method was used to analyze 24 samples obtained locally. The results showed that concentrations of the target compound in M. tenuiflora barks, ranged from 1.26 to 9.35 mg/g for these samples. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Multi-objective Decision Based Available Transfer Capability in Deregulated Power System Using Heuristic Approaches

    NASA Astrophysics Data System (ADS)

    Pasam, Gopi Krishna; Manohar, T. Gowri

    2016-09-01

    Determination of available transfer capability (ATC) requires the use of experience, intuition and exact judgment in order to meet several significant aspects in the deregulated environment. Based on these points, this paper proposes two heuristic approaches to compute ATC. The first proposed heuristic algorithm integrates the five methods known as continuation repeated power flow, repeated optimal power flow, radial basis function neural network, back propagation neural network and adaptive neuro fuzzy inference system to obtain ATC. The second proposed heuristic model is used to obtain multiple ATC values. Out of these, a specific ATC value will be selected based on a number of social, economic, deregulated environmental constraints and related to specific applications like optimization, on-line monitoring, and ATC forecasting known as multi-objective decision based optimal ATC. The validity of results obtained through these proposed methods are scrupulously verified on various buses of the IEEE 24-bus reliable test system. The results presented and derived conclusions in this paper are very useful for planning, operation, maintaining of reliable power in any power system and its monitoring in an on-line environment of deregulated power system. In this way, the proposed heuristic methods would contribute the best possible approach to assess multiple objective ATC using integrated methods.

  1. Enhancement of Biohydrogen Production via pH Variation using Molasses as Feedstock in an Attached Growth System

    NASA Astrophysics Data System (ADS)

    Che Zuhar, C. N. S.; Lutpi, N. A.; Idris, N.; Wong, Y. S.; Tengku Izhar, T. N.

    2018-03-01

    In this study, mesophilic biohydrogen production by a mixed culture, obtained from a continuous anaerobic reactor treating molasses effluent from sugarcane bagasse, was improved by using granular activated carbon (GAC) as the carrier material. A series of batch fermentation were performed at 37°C by feeding the anaerobic sludge bacteria with molasses to determine the effect of initial pH in the range of 5.5 to 7.5, and the effect of repeated batch cultivation on biohydrogen production. The enrichment of granular activated carbon (GAC) immobilised cells from the repeated batch cultivation were used as immobilised seed culture to obtain the optimal initial pH. The cumulative hydrogen production results from the optimal pH were fitted into modified Gompertz equation in order to obtained the batch profile of biohydrogen production. The optimal hydrogen production was obtained at an initial pH of 5.5 with the maximum hydrogen production (Hm) was found to be 84.14 ml, and maximum hydrogen production rate (Rm) was 3.63 mL/h with hydrogen concentration of 759 ppm. The results showed that the granular activated carbon was successfully enhanced the biohydrogen production by stabilizing the pH and therefore could be used as a carrier material for fermentative hydrogen production using industrial effluent.

  2. Frozen Scope and Grammatical Optimization

    ERIC Educational Resources Information Center

    Freedman, Michael

    2014-01-01

    The literature on quantifier scope has repeatedly observed that some otherwise expected permutations of scope taking elements are unavailable. Various methods have been proffered explaining these facts. This thesis aims to unify three disparate areas where the scope of operators seems to be frozen: the interaction of universal quantifiers with…

  3. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

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

    Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola, E-mail: ola.hammarsten@clinchem.gu.se

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA andmore » reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.« less

  4. Neural Network and Regression Approximations in High Speed Civil Transport Aircraft Design Optimization

    NASA Technical Reports Server (NTRS)

    Patniak, Surya N.; Guptill, James D.; Hopkins, Dale A.; Lavelle, Thomas M.

    1998-01-01

    Nonlinear mathematical-programming-based design optimization can be an elegant method. However, the calculations required to generate the merit function, constraints, and their gradients, which are frequently required, can make the process computational intensive. The computational burden can be greatly reduced by using approximating analyzers derived from an original analyzer utilizing neural networks and linear regression methods. The experience gained from using both of these approximation methods in the design optimization of a high speed civil transport aircraft is the subject of this paper. The Langley Research Center's Flight Optimization System was selected for the aircraft analysis. This software was exercised to generate a set of training data with which a neural network and a regression method were trained, thereby producing the two approximating analyzers. The derived analyzers were coupled to the Lewis Research Center's CometBoards test bed to provide the optimization capability. With the combined software, both approximation methods were examined for use in aircraft design optimization, and both performed satisfactorily. The CPU time for solution of the problem, which had been measured in hours, was reduced to minutes with the neural network approximation and to seconds with the regression method. Instability encountered in the aircraft analysis software at certain design points was also eliminated. On the other hand, there were costs and difficulties associated with training the approximating analyzers. The CPU time required to generate the input-output pairs and to train the approximating analyzers was seven times that required for solution of the problem.

  5. Mystic: Implementation of the Static Dynamic Optimal Control Algorithm for High-Fidelity, Low-Thrust Trajectory Design

    NASA Technical Reports Server (NTRS)

    Whiffen, Gregory J.

    2006-01-01

    Mystic software is designed to compute, analyze, and visualize optimal high-fidelity, low-thrust trajectories, The software can be used to analyze inter-planetary, planetocentric, and combination trajectories, Mystic also provides utilities to assist in the operation and navigation of low-thrust spacecraft. Mystic will be used to design and navigate the NASA's Dawn Discovery mission to orbit the two largest asteroids, The underlying optimization algorithm used in the Mystic software is called Static/Dynamic Optimal Control (SDC). SDC is a nonlinear optimal control method designed to optimize both 'static variables' (parameters) and dynamic variables (functions of time) simultaneously. SDC is a general nonlinear optimal control algorithm based on Bellman's principal.

  6. Improvement of LysM-Mediated Surface Display of Designed Ankyrin Repeat Proteins (DARPins) in Recombinant and Nonrecombinant Strains of Lactococcus lactis and Lactobacillus Species

    PubMed Central

    Zadravec, Petra; Štrukelj, Borut

    2015-01-01

    Safety and probiotic properties make lactic acid bacteria (LAB) attractive hosts for surface display of heterologous proteins. Protein display on nonrecombinant microorganisms is preferred for therapeutic and food applications due to regulatory requirements. We displayed two designed ankyrin repeat proteins (DARPins), each possessing affinity for the Fc region of human IgG, on the surface of Lactococcus lactis by fusing them to the Usp45 secretion signal and to the peptidoglycan-binding C terminus of AcmA, containing lysine motif (LysM) repeats. Growth medium containing a secreted fusion protein was used to test its heterologous binding to 10 strains of species of the genus Lactobacillus, using flow cytometry, whole-cell enzyme-linked immunosorbent assay (ELISA), and fluorescence microscopy. The fusion proteins bound to the surfaces of all lactobacilli; however, binding to the majority of bacteria was only 2- to 5-fold stronger than that of the control. Lactobacillus salivarius ATCC 11741 demonstrated exceptionally strong binding (32- to 55-fold higher than that of the control) and may therefore be an attractive host for nonrecombinant surface display. Genomic comparison of the species indicated the exopolysaccharides of Lb. salivarius as a possible reason for the difference. Additionally, a 15-fold concentration-dependent increase in nonrecombinant surface display on L. lactis was demonstrated by growing bacteria with sublethal concentrations of the antibiotics chloramphenicol and erythromycin. Nonrecombinant surface display on LAB, based on LysM repeats, was optimized by selecting Lactobacillus salivarius ATCC 11741 as the optimal host and by introducing antibiotics as additives for increasing surface display on L. lactis. Additionally, effective display of DARPins on the surfaces of nonrecombinant LAB has opened up several new therapeutic possibilities. PMID:25576617

  7. Baseline and annual repeat rounds of screening: implications for optimal regimens of screening.

    PubMed

    Henschke, Claudia I; Salvatore, Mary; Cham, Matthew; Powell, Charles A; DiFabrizio, Larry; Flores, Raja; Kaufman, Andrew; Eber, Corey; Yip, Rowena; Yankelevitz, David F

    2018-03-01

    Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan-Meier (K-M) survival rates, separately for baseline and annual rounds. Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long-term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81-89%) for adenocarcinoma, 74% (95% CI 63-85%) for squamous cell, 48% (95% CI 34-62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. • Lung cancer aggressiveness varies considerably by cell type and nodule consistency. • Kaplan-Meier survival rates varied by cell type between 100% and 48%. • The percentages of lung cancers by cell type in screening rounds reflect screening biases. • Rank ordering by cell type survival is consistent with that by lead times. • Empirical evidence provides critical information for the regimen of screening.

  8. Optimization of immunostaining on flat-mounted human corneas.

    PubMed

    Forest, Fabien; Thuret, Gilles; Gain, Philippe; Dumollard, Jean-Marc; Peoc'h, Michel; Perrache, Chantal; He, Zhiguo

    2015-01-01

    In the literature, immunohistochemistry on cross sections is the main technique used to study protein expression in corneal endothelial cells (ECs), even though this method allows visualization of few ECs, without clear subcellular localization, and is subject to the staining artifacts frequently encountered at tissue borders. We previously proposed several protocols, using fixation in 0.5% paraformaldehyde (PFA) or in methanol, allowing immunostaining on flatmounted corneas for proteins of different cell compartments. In the present study, we further refined the technique by systematically assessing the effect of fixative temperature. Last, we used optimized protocols to further demonstrate the considerable advantages of immunostaining on flatmounted intact corneas: detection of rare cells in large fields of thousands of ECs and epithelial cells, and accurate subcellular localization of given proteins. The staining of four ubiquitous proteins, ZO-1, hnRNP L, actin, and histone H3, with clearly different subcellular localizations, was analyzed in ECs of organ-cultured corneas. Whole intact human corneas were fixed for 30 min in 0.5% paraformaldehyde or pure methanol at four temperatures (4 °C for PFA, -20 °C for methanol, and 23, 37, and 50 °C for both). Experiments were performed in duplicate and repeated on three corneas. Standardized pictures were analyzed independently by two experts. Second, optimized immunostaining protocols were applied to fresh corneas for three applications: identification of rare cells that express KI67 in the endothelium of specimens with Fuch's endothelial corneal dystrophy (FECD), the precise localization of neural cell adhesion molecules (NCAMs) in normal ECs and of the cytokeratin pair K3/12 and CD44 in normal epithelial cells, and the identification of cells that express S100b in the normal epithelium. Temperature strongly influenced immunostaining quality. There was no ubiquitous protocol, but nevertheless, room temperature may be recommended as first-line temperature during fixation, instead of the conventional -20 °C for methanol and 4 °C for PFA. Further optimization may be required for certain target proteins. Optimized protocols allowed description of two previously unknown findings: the presence of a few proliferating ECs in FECD specimens, suggesting ineffective compensatory mechanisms against premature EC death, and the localization of NCAMs exclusively in the lateral membranes of ECs, showing hexagonal organization at the apical pole and an irregular shape with increasing complexity toward the basal pole. Optimized protocols were also effective for the epithelium, allowing clear localization of cytokeratin 3/12 and CD44 in superficial and basal epithelial cells, respectively. Finally, S100b allowed identification of clusters of epithelial Langerhans cells near the limbus and more centrally. Fixative temperature is a crucial parameter in optimizing immunostaining on flatmounted intact corneas. Whole-tissue overview and precise subcellular staining are significant advantages over conventional immunohistochemistry (IHC) on cross sections. This technique, initially developed for the corneal endothelium, proved equally suitable for the corneal epithelium and could be used for other superficial mono- and multilayered epithelia.

  9. Active learning: learning a motor skill without a coach.

    PubMed

    Huang, Vincent S; Shadmehr, Reza; Diedrichsen, Jörn

    2008-08-01

    When we learn a new skill (e.g., golf) without a coach, we are "active learners": we have to choose the specific components of the task on which to train (e.g., iron, driver, putter, etc.). What guides our selection of the training sequence? How do choices that people make compare with choices made by machine learning algorithms that attempt to optimize performance? We asked subjects to learn the novel dynamics of a robotic tool while moving it in four directions. They were instructed to choose their practice directions to maximize their performance in subsequent tests. We found that their choices were strongly influenced by motor errors: subjects tended to immediately repeat an action if that action had produced a large error. This strategy was correlated with better performance on test trials. However, even when participants performed perfectly on a movement, they did not avoid repeating that movement. The probability of repeating an action did not drop below chance even when no errors were observed. This behavior led to suboptimal performance. It also violated a strong prediction of current machine learning algorithms, which solve the active learning problem by choosing a training sequence that will maximally reduce the learner's uncertainty about the task. While we show that these algorithms do not provide an adequate description of human behavior, our results suggest ways to improve human motor learning by helping people choose an optimal training sequence.

  10. Y-chromosomal testing of brown bears (Ursus arctos): Validation of a multiplex PCR-approach for nine STRs suitable for fecal and hair samples.

    PubMed

    Aarnes, Siv Grethe; Hagen, Snorre B; Andreassen, Rune; Schregel, Julia; Knappskog, Per M; Hailer, Frank; Stenhouse, Gordon; Janke, Axel; Eiken, Hans Geir

    2015-11-01

    High-resolution Y-chromosomal markers have been applied to humans and other primates to study population genetics, migration, social structures and reproduction. Y-linked markers allow the direct assessment of the genetic structure and gene flow of uniquely male inherited lineages and may also be useful for wildlife conservation and forensics, but have so far been available only for few wild species. Thus, we have developed two multiplex PCR reactions encompassing nine Y-STR markers identified from the brown bear (Ursus arctos) and tested them on hair, fecal and tissue samples. The multiplex PCR approach was optimized and analyzed for species specificity, sensitivity and stutter-peak ratios. The nine Y-STRs also showed specific STR-fragments for male black bears and male polar bears, while none of the nine markers produced any PCR products when using DNA from female bears or males from 12 other mammals. The multiplex PCR approach in two PCR reactions could be amplified with as low as 0.2 ng template input. Precision was high in DNA templates from hairs, fecal scats and tissues, with standard deviations less than 0.14 and median stutter ratios from 0.04 to 0.63. Among the eight di- and one tetra-nucleotide repeat markers, we detected simple repeat structures in seven of the nine markers with 9-25 repeat units. Allelic variation was found for eight of the nine Y-STRs, with 2-9 alleles for each marker and a total of 36 alleles among 453 male brown bears sampled mainly from Northern Europe. We conclude that the multiplex PCR approach with these nine Y-STRs would provide male bear Y-chromosomal specificity and evidence suited for samples from conservation and wildlife forensics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Effect of food on the pharmacokinetics of TAS-102 and its efficacy and safety in patients with advanced solid tumors.

    PubMed

    Yoshino, Takayuki; Kojima, Takashi; Bando, Hideaki; Yamazaki, Tomoko; Naito, Yoichi; Mukai, Hirofumi; Fuse, Nozomu; Goto, Koichi; Ito, Yuko; Doi, Toshihiko; Ohtsu, Atsushi

    2016-05-01

    TAS-102, a novel oral antitumor agent, consists of trifluridine and tipiracil hydrochloride (molar ratio, 1:0.5). We investigated the effects of food on trifluridine and tipiracil hydrochloride. The efficacy and safety of TAS-102 were evaluated in patients with advanced solid tumors. We analyzed drug pharmacokinetics using a randomized, single-dose, two-treatment (fed versus fasting), two-period, two-sequence cross-over design, followed by repeated administration. Patients were given single doses of TAS-102 (35 mg/m(2) ) in the pharmacokinetic phase and received twice-daily doses of TAS-102 in 28-day cycles in the repeated administration phase for evaluating efficacy and safety. Food showed no effect on the area under the curve from 0 to 12 h or 0 h-infinity values of trifluridine following administration of TAS-102 under fasting and fed conditions, whereas those of tipiracil hydrochloride decreased by approximately 40%. Maximum concentrations of both drugs decreased by approximately 40%, indicating that food influenced the absorption and bioavailability of trifluridine and tipiracil hydrochloride, respectively. During the repeated administration, stable disease was observed in nine patients with rectal, small-cell lung, breast, thymic, duodenal, and prostate cancers. Major adverse events were neutropenia, leukopenia, anemia, and nausea. Postprandial administration was optimal for TAS-102 because trifluridine's area under the curve was not changed by food, indicating that its clinical efficacy would not be affected. Additionally, postprandial administration was reasonable because the maximum concentration of trifluridine decreased in neutrophils, which correlated with previous studies. These results suggest that TAS-102 would be an effective treatment for small-cell lung, thymic, and colorectal cancers. This trial is registered with the Japan Pharmaceutical Information Center (no. JapicCTI-111482). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. Optimizing occupational exposure measurement strategies when estimating the log-scale arithmetic mean value--an example from the reinforced plastics industry.

    PubMed

    Lampa, Erik G; Nilsson, Leif; Liljelind, Ingrid E; Bergdahl, Ingvar A

    2006-06-01

    When assessing occupational exposures, repeated measurements are in most cases required. Repeated measurements are more resource intensive than a single measurement, so careful planning of the measurement strategy is necessary to assure that resources are spent wisely. The optimal strategy depends on the objectives of the measurements. Here, two different models of random effects analysis of variance (ANOVA) are proposed for the optimization of measurement strategies by the minimization of the variance of the estimated log-transformed arithmetic mean value of a worker group, i.e. the strategies are optimized for precise estimation of that value. The first model is a one-way random effects ANOVA model. For that model it is shown that the best precision in the estimated mean value is always obtained by including as many workers as possible in the sample while restricting the number of replicates to two or at most three regardless of the size of the variance components. The second model introduces the 'shared temporal variation' which accounts for those random temporal fluctuations of the exposure that the workers have in common. It is shown for that model that the optimal sample allocation depends on the relative sizes of the between-worker component and the shared temporal component, so that if the between-worker component is larger than the shared temporal component more workers should be included in the sample and vice versa. The results are illustrated graphically with an example from the reinforced plastics industry. If there exists a shared temporal variation at a workplace, that variability needs to be accounted for in the sampling design and the more complex model is recommended.

  13. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation.

    PubMed

    Mathew, Sherin T; Bergström, Petra; Hammarsten, Ola

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Reliability-based trajectory optimization using nonintrusive polynomial chaos for Mars entry mission

    NASA Astrophysics Data System (ADS)

    Huang, Yuechen; Li, Haiyang

    2018-06-01

    This paper presents the reliability-based sequential optimization (RBSO) method to settle the trajectory optimization problem with parametric uncertainties in entry dynamics for Mars entry mission. First, the deterministic entry trajectory optimization model is reviewed, and then the reliability-based optimization model is formulated. In addition, the modified sequential optimization method, in which the nonintrusive polynomial chaos expansion (PCE) method and the most probable point (MPP) searching method are employed, is proposed to solve the reliability-based optimization problem efficiently. The nonintrusive PCE method contributes to the transformation between the stochastic optimization (SO) and the deterministic optimization (DO) and to the approximation of trajectory solution efficiently. The MPP method, which is used for assessing the reliability of constraints satisfaction only up to the necessary level, is employed to further improve the computational efficiency. The cycle including SO, reliability assessment and constraints update is repeated in the RBSO until the reliability requirements of constraints satisfaction are satisfied. Finally, the RBSO is compared with the traditional DO and the traditional sequential optimization based on Monte Carlo (MC) simulation in a specific Mars entry mission to demonstrate the effectiveness and the efficiency of the proposed method.

  15. High resolution energy analyzer for broad ion beam characterization

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

    Kanarov, V.; Hayes, A.; Yevtukhov, R.

    2008-09-15

    Characterization of the ion energy distribution function (IEDF) of low energy high current density ion beams by conventional retarding field and deflection type energy analyzers is limited due to finite ion beam emittance and beam space charge spreading inside the analyzer. These deficiencies are, to a large extent, overcome with the recent development of the variable-focusing retarding field energy analyzer (RFEA), which has a cylindrical focusing electrode preceding the planar retarding grid. The principal concept of this analyzer is conversion of a divergent charged particle beam into a quasiparallel beam before analyzing it by the planar retarding field. This allowsmore » analysis of the beam particle total kinetic energy distribution with greatly improved energy resolution. Whereas this concept was first applied to analyze 5-10 keV pulsed electron beams, the present authors have adapted it to analyze the energy distribution of a low energy ({<=}1 KeV) broad ion beam. In this paper we describe the RFEA design, which was modified from the original, mainly as required by the specifics of broad ion beam energy analysis, and the device experimental characterization and modeling results. Among the modifications, an orifice electrode placed in front of the RFEA provides better spatial resolution of the broad ion beam ion optics emission region and reduces the beam plasma density in the vicinity of analyzer entry. An electron repeller grid placed in front of the RFEA collector was found critical for suppressing secondary electrons, both those incoming to the collector and those released from its surface, and improved energy spectrum measurement repeatability and accuracy. The use of finer mesh single- and double-grid retarding structures reduces the retarding grid lens effect and improves the analyzer energy resolution and accuracy of the measured spectrum mean energy. However, additional analyzer component and configuration improvements did not further change the analyzed IEDF shape or mean energy value. This led us to conclude that the optimized analyzer construction provides an energy resolution considerably narrower than the investigated ion beam energy spectrum full width at half maximum, and the derived energy spectrum is an objective and accurate representation of the analyzed broad ion beam energy distribution characteristics. A quantitative study of the focusing voltage and retarding grid field effects based on the experimental data and modeling results have supported this conclusion.« less

  16. The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model.

    PubMed

    Ezzatizadeh, Vahid; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Sandi, Madhavi; Al-Mahdawi, Sahar; Te Riele, Hein; Pook, Mark A

    2012-04-01

    Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability. To explore the potential role of MMR proteins on intergenerational GAA repeat instability in FRDA, we have analyzed the transmission of unstable GAA repeat expansions from FXN transgenic mice which have been crossed with mice that are deficient for Msh2, Msh3, Msh6 or Pms2. We find in all cases that absence of parental MMR protein not only maintains transmission of GAA expansions and contractions, but also increases GAA repeat mutability (expansions and/or contractions) in the offspring. This indicates that Msh2, Msh3, Msh6 and Pms2 proteins are not the cause of intergenerational GAA expansions or contractions, but act in their canonical MMR capacity to protect against GAA repeat instability. We further identified differential modes of action for the four MMR proteins. Thus, Msh2 and Msh3 protect against GAA repeat contractions, while Msh6 protects against both GAA repeat expansions and contractions, and Pms2 protects against GAA repeat expansions and also promotes contractions. Furthermore, we detected enhanced occupancy of Msh2 and Msh3 proteins downstream of the FXN expanded GAA repeat, suggesting a model in which Msh2/3 dimers are recruited to this region to repair mismatches that would otherwise produce intergenerational GAA contractions. These findings reveal substantial differences in the intergenerational dynamics of expanded GAA repeat sequences compared with expanded CAG/CTG repeats, where Msh2 and Msh3 are thought to actively promote repeat expansions. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model

    PubMed Central

    Ezzatizadeh, Vahid; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Sandi, Madhavi; Al-Mahdawi, Sahar; te Riele, Hein; Pook, Mark A.

    2013-01-01

    Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability. To explore the potential role of MMR proteins on intergenerational GAA repeat instability in FRDA, we have analyzed the transmission of unstable GAA repeat expansions from FXN transgenic mice which have been crossed with mice that are deficient for Msh2, Msh3, Msh6 or Pms2. We find in all cases that absence of parental MMR protein not only maintains transmission of GAA expansions and contractions, but also increases GAA repeat mutability (expansions and/or contractions) in the offspring. This indicates that Msh2, Msh3, Msh6 and Pms2 proteins are not the cause of intergenerational GAA expansions or contractions, but act in their canonical MMR capacity to protect against GAA repeat instability. We further identified differential modes of action for the four MMR proteins. Thus, Msh2 and Msh3 protect against GAA repeat contractions, while Msh6 protects against both GAA repeat expansions and contractions, and Pms2 protects against GAA repeat expansions and also promotes contractions. Furthermore, we detected enhanced occupancy of Msh2 and Msh3 proteins downstream of the FXN expanded GAA repeat, suggesting a model in which Msh2/3 dimers are recruited to this region to repair mismatches that would otherwise produce intergenerational GAA contractions. These findings reveal substantial differences in the intergenerational dynamics of expanded GAA repeat sequences compared with expanded CAG/CTG repeats, where Msh2 and Msh3 are thought to actively promote repeat expansions. PMID:22289650

  18. Utility of repeat testing of critical values: a Q-probes analysis of 86 clinical laboratories.

    PubMed

    Lehman, Christopher M; Howanitz, Peter J; Souers, Rhona; Karcher, Donald S

    2014-06-01

    A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result. To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test. Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing. Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care. Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.

  19. Analyzing Randomized Controlled Interventions: Three Notes for Applied Linguists

    ERIC Educational Resources Information Center

    Vanhove, Jan

    2015-01-01

    I discuss three common practices that obfuscate or invalidate the statistical analysis of randomized controlled interventions in applied linguistics. These are (a) checking whether randomization produced groups that are balanced on a number of possibly relevant covariates, (b) using repeated measures ANOVA to analyze pretest-posttest designs, and…

  20. A boundary element approach to optimization of active noise control sources on three-dimensional structures

    NASA Technical Reports Server (NTRS)

    Cunefare, K. A.; Koopmann, G. H.

    1991-01-01

    This paper presents the theoretical development of an approach to active noise control (ANC) applicable to three-dimensional radiators. The active noise control technique, termed ANC Optimization Analysis, is based on minimizing the total radiated power by adding secondary acoustic sources on the primary noise source. ANC Optimization Analysis determines the optimum magnitude and phase at which to drive the secondary control sources in order to achieve the best possible reduction in the total radiated power from the noise source/control source combination. For example, ANC Optimization Analysis predicts a 20 dB reduction in the total power radiated from a sphere of radius at a dimensionless wavenumber ka of 0.125, for a single control source representing 2.5 percent of the total area of the sphere. ANC Optimization Analysis is based on a boundary element formulation of the Helmholtz Integral Equation, and thus, the optimization analysis applies to a single frequency, while multiple frequencies can be treated through repeated analyses.

  1. Ancient DNA in human bone remains from Pompeii archaeological site.

    PubMed

    Cipollaro, M; Di Bernardo, G; Galano, G; Galderisi, U; Guarino, F; Angelini, F; Cascino, A

    1998-06-29

    aDNA extraction and amplification procedures have been optimized for Pompeian human bone remains whose diagenesis has been determined by histological analysis. Single copy genes amplification (X and Y amelogenin loci and Y specific alphoid repeat sequences) have been performed and compared with anthropometric data on sexing.

  2. Efficiency in Second Language Vocabulary Learning

    ERIC Educational Resources Information Center

    Schuetze, Ulf

    2017-01-01

    An ongoing question in second language vocabulary learning is how to optimize the acquisition of words. One approach is the so-called "spaced repetition technique" that uses intervals to repeat words in a given time frame (Balota et al., 2007; Leitner, 1972; Oxford, 1990; Pimsleur, 1967; Roediger & Karpicke, 2010; Schuetze &…

  3. Vaccination in pulses: a strategy for global eradication of measles and polio?

    PubMed

    Nokes, D J; Swinton, J

    1997-01-01

    Recent American successes against poliomyelitis and measles have been attributed to repeated 'pulse' vaccination campaigns. Whilst logistic and economic constraints will be crucial, a deeper epidemiological understanding of the mechanism, strengths and weaknesses of pulse vaccination will optimize the chances of success elsewhere in the world.

  4. Increasing the reliability of the shutdown of 500 - 750-kV overhead lines equipped with shunt reactors in an unsuccessful three-phase automatic repeated closure cycle

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

    Kuz'micheva, K. I.; Merzlyakov, A. S.; Fokin, G. G.

    2013-05-15

    The reasons for circuit-breaker failures during repeated disconnection of 500 - 750 kV overhead lines with shunt reactors in a cycle of unsuccessful three-phase automatic reconnection (TARC) are analyzed. Recommendations are made for increasing the operating reliability of power transmission lines with shunt reactors when there is unsuccessful reconnection.

  5. Mean-Variance portfolio optimization by using non constant mean and volatility based on the negative exponential utility function

    NASA Astrophysics Data System (ADS)

    Soeryana, Endang; Halim, Nurfadhlina Bt Abdul; Sukono, Rusyaman, Endang; Supian, Sudradjat

    2017-03-01

    Investments in stocks investors are also faced with the issue of risk, due to daily price of stock also fluctuate. For minimize the level of risk, investors usually forming an investment portfolio. Establishment of a portfolio consisting of several stocks are intended to get the optimal composition of the investment portfolio. This paper discussed about optimizing investment portfolio of Mean-Variance to stocks by using mean and volatility is not constant based on the Negative Exponential Utility Function. Non constant mean analyzed using models Autoregressive Moving Average (ARMA), while non constant volatility models are analyzed using the Generalized Autoregressive Conditional heteroscedastic (GARCH). Optimization process is performed by using the Lagrangian multiplier technique. As a numerical illustration, the method is used to analyze some stocks in Indonesia. The expected result is to get the proportion of investment in each stock analyzed

  6. Performance seeking control excitation mode

    NASA Technical Reports Server (NTRS)

    Schkolnik, Gerard

    1995-01-01

    Flight testing of the performance seeking control (PSC) excitation mode was successfully completed at NASA Dryden on the F-15 highly integrated digital electronic control (HIDEC) aircraft. Although the excitation mode was not one of the original objectives of the PSC program, it was rapidly prototyped and implemented into the architecture of the PSC algorithm, allowing valuable and timely research data to be gathered. The primary flight test objective was to investigate the feasibility of a future measurement-based performance optimization algorithm. This future algorithm, called AdAPT, which stands for adaptive aircraft performance technology, generates and applies excitation inputs to selected control effectors. Fourier transformations are used to convert measured response and control effector data into frequency domain models which are mapped into state space models using multiterm frequency matching. Formal optimization principles are applied to produce an integrated, performance optimal effector suite. The key technical challenge of the measurement-based approach is the identification of the gradient of the performance index to the selected control effector. This concern was addressed by the excitation mode flight test. The AdAPT feasibility study utilized the PSC excitation mode to apply separate sinusoidal excitation trims to the controls - one aircraft, inlet first ramp (cowl), and one engine, throat area. Aircraft control and response data were recorded using on-board instrumentation and analyzed post-flight. Sensor noise characteristics, axial acceleration performance gradients, and repeatability were determined. Results were compared to pilot comments to assess the ride quality. Flight test results indicate that performance gradients were identified at all flight conditions, sensor noise levels were acceptable at the frequencies of interest, and excitations were generally not sensed by the pilot.

  7. Screen-printed electrode based electrochemical detector coupled with ionic liquid dispersive liquid-liquid microextraction and microvolume back-extraction for determination of mercury in water samples.

    PubMed

    Fernández, Elena; Vidal, Lorena; Martín-Yerga, Daniel; Blanco, María del Carmen; Canals, Antonio; Costa-García, Agustín

    2015-04-01

    A novel approach is presented, whereby gold nanostructured screen-printed carbon electrodes (SPCnAuEs) are combined with in-situ ionic liquid formation dispersive liquid-liquid microextraction (in-situ IL-DLLME) and microvolume back-extraction for the determination of mercury in water samples. In-situ IL-DLLME is based on a simple metathesis reaction between a water-miscible IL and a salt to form a water-immiscible IL into sample solution. Mercury complex with ammonium pyrrolidinedithiocarbamate is extracted from sample solution into the water-immiscible IL formed in-situ. Then, an ultrasound-assisted procedure is employed to back-extract the mercury into 10 µL of a 4 M HCl aqueous solution, which is finally analyzed using SPCnAuEs. Sample preparation methodology was optimized using a multivariate optimization strategy. Under optimized conditions, a linear range between 0.5 and 10 µg L(-1) was obtained with a correlation coefficient of 0.997 for six calibration points. The limit of detection obtained was 0.2 µg L(-1), which is lower than the threshold value established by the Environmental Protection Agency and European Union (i.e., 2 µg L(-1) and 1 µg L(-1), respectively). The repeatability of the proposed method was evaluated at two different spiking levels (3 and 10 µg L(-1)) and a coefficient of variation of 13% was obtained in both cases. The performance of the proposed methodology was evaluated in real-world water samples including tap water, bottled water, river water and industrial wastewater. Relative recoveries between 95% and 108% were obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Spatio-temporal Variations of Characteristic Repeating Earthquake Sequences along the Middle America Trench in Mexico

    NASA Astrophysics Data System (ADS)

    Dominguez, L. A.; Taira, T.; Hjorleifsdottir, V.; Santoyo, M. A.

    2015-12-01

    Repeating earthquake sequences are sets of events that are thought to rupture the same area on the plate interface and thus provide nearly identical waveforms. We systematically analyzed seismic records from 2001 through 2014 to identify repeating earthquakes with highly correlated waveforms occurring along the subduction zone of the Cocos plate. Using the correlation coefficient (cc) and spectral coherency (coh) of the vertical components as selection criteria, we found a set of 214 sequences whose waveforms exceed cc≥95% and coh≥95%. Spatial clustering along the trench shows large variations in repeating earthquakes activity. Particularly, the rupture zone of the M8.1, 1985 earthquake shows an almost absence of characteristic repeating earthquakes, whereas the Guerrero Gap zone and the segment of the trench close to the Guerrero-Oaxaca border shows a significantly larger number of repeating earthquakes sequences. Furthermore, temporal variations associated to stress changes due to major shows episodes of unlocking and healing of the interface. Understanding the different components that control the location and recurrence time of characteristic repeating sequences is a key factor to pinpoint areas where large megathrust earthquakes may nucleate and consequently to improve the seismic hazard assessment.

  9. Clinical oversight and the avoidance of repeat induced abortion.

    PubMed

    Jacovetty, Erica L; Clare, Camille A; Squire, Mary-Beatrice; Kubal, Keshar P; Liou, Sherry; Inchiosa, Mario A

    2018-06-03

    To evaluate the impact of patient counseling, demographics, and contraceptive methods on repeat induced abortion in women attending family planning clinics. A retrospective chart review of repeat induced abortions was performed. The analysis included patients with an initial induced abortion obtained between January 1, 2001, and March 31, 2014, at New York City Health + Hospitals/Metropolitan. The duration of involvement in the family planning program, the use of contraceptive interventions, and 18 patient factors were analyzed for their correlation with the incidence of repeat induced abortions per year of follow-up. A decreased rate of repeat induced abortions was associated with a longer duration of clinical oversight (r 2 =0.449, P<0.001), a higher contraceptive efficacy score (r=0.280, P=0.025), and a larger number of clinic visits for contraception (r=0.333, P=0.007). A continuum of contact with all of the services of a family planning clinic demonstrated a strong efficacy to limit repeat induced abortions. By determining the patient characteristics that most influence repeat induced abortion rates, providers can best choose the most efficacious method of contraception available. © 2018 International Federation of Gynecology and Obstetrics.

  10. Long distance quantum communication with quantum Reed-Solomon codes

    NASA Astrophysics Data System (ADS)

    Muralidharan, Sreraman; Zou, Chang-Ling; Li, Linshu; Jiang, Liang; Jianggroup Team

    We study the construction of quantum Reed Solomon codes from classical Reed Solomon codes and show that they achieve the capacity of quantum erasure channel for multi-level quantum systems. We extend the application of quantum Reed Solomon codes to long distance quantum communication, investigate the local resource overhead needed for the functioning of one-way quantum repeaters with these codes, and numerically identify the parameter regime where these codes perform better than the known quantum polynomial codes and quantum parity codes . Finally, we discuss the implementation of these codes into time-bin photonic states of qubits and qudits respectively, and optimize the performance for one-way quantum repeaters.

  11. Plant genotyping using fluorescently tagged inter-simple sequence repeats (ISSRs): basic principles and methodology.

    PubMed

    Prince, Linda M

    2015-01-01

    Inter-simple sequence repeat PCR (ISSR-PCR) is a fast, inexpensive genotyping technique based on length variation in the regions between microsatellites. The method requires no species-specific prior knowledge of microsatellite location or composition. Very small amounts of DNA are required, making this method ideal for organisms of conservation concern, or where the quantity of DNA is extremely limited due to organism size. ISSR-PCR can be highly reproducible but requires careful attention to detail. Optimization of DNA extraction, fragment amplification, and normalization of fragment peak heights during fluorescent detection are critical steps to minimizing the downstream time spent verifying and scoring the data.

  12. Towards the Integration of Dark- and Photo-Fermentative Waste Treatment. 4. Repeated Batch Sequential Dark- and Photofermentation using Starch as Substrate

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

    Laurinavichene, T. V.; Belokopytov, B. F.; Laurinavichius, K. S.

    In this study we demonstrated the technical feasibility of a prolonged, sequential two-stage integrated process under a repeated batch mode of starch fermentation. In this durable scheme, the photobioreactor with purple bacteria in the second stage was fed directly with dark culture from the first stage without centrifugation, filtration, or sterilization (not demonstrated previously). After preliminary optimization, both the dark- and the photo-stages were performed under repeated batch modes with different process parameters. Continuous H{sub 2} production in this system was observed at a H{sub 2} yield of up to 1.4 and 3.9 mole mole{sup -1} hexose during the dark-more » and photo-stage, respectively (for a total of 5.3 mole mole{sup -1} hexose), and rates of 0.9 and 0.5 L L{sup -1} d{sup -1}, respectively. Prolonged repeated batch H{sub 2} production was maintained for up to 90 days in each stage and was rather stable under non-aseptic conditions. Potential for improvements in these results are discussed.« less

  13. [Optimization of extraction technics of total saponins from Pulsatilla cernua].

    PubMed

    Li, Hai-Yan; Hao, Ning; Xu, Yong-Nan; Piao, Zhong-Yun

    2010-04-01

    The extraction condition of total saponins from Pulsatilla cenua by ultrasonic wave was optimized by single factor and orthogonal experiments. The largest absorbency of saponin was intended to be 470 nm by wavelength scan method with the pulchinenoside B4 as control sample, the linear relationship was observed between the absorbency and the content of saponin in the range of 0 - 0.040 mg/mL. The optimal conditions of extraction was as following: 80% of alcohol concentration, 40 min of ultrasonic time, 1: 20 of solid to liquid ratio, 80 W of ultrasonic power and one time for extraction. Among them, alcohol had the most significant effect on the extraction of total saponins. The content of total saponins in Pulsatilla cernua was 4. 32% under the optimal condition. The method developed here is efficient, stable, accurate and repeatable.

  14. Repeat Syphilis Among Men Who Have Sex With Men in California, 2002–2006: Implications for Syphilis Elimination Efforts

    PubMed Central

    Chew Ng, Rilene A.; Katz, Kenneth A.; Bernstein, Kyle T.; Samuel, Michael C.; Kerndt, Peter R.; Bolan, Gail

    2012-01-01

    Objectives. We examined rates of and risk factors for repeat syphilis infection among men who have sex with men (MSM) in California. Methods. We analyzed 2002 to 2006 California syphilis surveillance system data. Results. During the study period, a mean of 5.9% (range: 4.9%–7.1% per year) of MSM had a repeat primary or secondary (PS) syphilis infection within 2 years of an initial infection. There was no significant increase in the annual proportion of MSM with a repeat syphilis infection (P = .42). In a multivariable model, factors associated with repeat syphilis infection were HIV infection (odds ratio [OR] = 1.65; 95% confidence interval [CI] = 1.14, 2.37), Black race (OR = 1.84; 95% CI = 1.12, 3.04), and 10 or more recent sex partners (OR = 1.99; 95% CI = 1.12, 3.50). Conclusions. Approximately 6% of MSM in California have a repeat PS syphilis infection within 2 years of an initial infection. HIV infection, Black race, and having multiple sex partners are associated with increased odds of repeat infection. Syphilis elimination efforts should include messages about the risk for repeat infection and the importance of follow-up testing. Public health attention to individuals repeatedly infected with syphilis may help reduce local disease burdens. PMID:22095364

  15. Economical Unsteady High-Fidelity Aerodynamics for Structural Optimization with a Flutter Constraint

    NASA Technical Reports Server (NTRS)

    Bartels, Robert E.; Stanford, Bret K.

    2017-01-01

    Structural optimization with a flutter constraint for a vehicle designed to fly in the transonic regime is a particularly difficult task. In this speed range, the flutter boundary is very sensitive to aerodynamic nonlinearities, typically requiring high-fidelity Navier-Stokes simulations. However, the repeated application of unsteady computational fluid dynamics to guide an aeroelastic optimization process is very computationally expensive. This expense has motivated the development of methods that incorporate aspects of the aerodynamic nonlinearity, classical tools of flutter analysis, and more recent methods of optimization. While it is possible to use doublet lattice method aerodynamics, this paper focuses on the use of an unsteady high-fidelity aerodynamic reduced order model combined with successive transformations that allows for an economical way of utilizing high-fidelity aerodynamics in the optimization process. This approach is applied to the common research model wing structural design. As might be expected, the high-fidelity aerodynamics produces a heavier wing than that optimized with doublet lattice aerodynamics. It is found that the optimized lower skin of the wing using high-fidelity aerodynamics differs significantly from that using doublet lattice aerodynamics.

  16. Fast engineering optimization: A novel highly effective control parameterization approach for industrial dynamic processes.

    PubMed

    Liu, Ping; Li, Guodong; Liu, Xinggao

    2015-09-01

    Control vector parameterization (CVP) is an important approach of the engineering optimization for the industrial dynamic processes. However, its major defect, the low optimization efficiency caused by calculating the relevant differential equations in the generated nonlinear programming (NLP) problem repeatedly, limits its wide application in the engineering optimization for the industrial dynamic processes. A novel highly effective control parameterization approach, fast-CVP, is first proposed to improve the optimization efficiency for industrial dynamic processes, where the costate gradient formulae is employed and a fast approximate scheme is presented to solve the differential equations in dynamic process simulation. Three well-known engineering optimization benchmark problems of the industrial dynamic processes are demonstrated as illustration. The research results show that the proposed fast approach achieves a fine performance that at least 90% of the computation time can be saved in contrast to the traditional CVP method, which reveals the effectiveness of the proposed fast engineering optimization approach for the industrial dynamic processes. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  17. Simultaneous optimization of micro-heliostat geometry and field layout using a genetic algorithm

    NASA Astrophysics Data System (ADS)

    Lazardjani, Mani Yousefpour; Kronhardt, Valentina; Dikta, Gerhard; Göttsche, Joachim

    2016-05-01

    A new optimization tool for micro-heliostat (MH) geometry and field layout is presented. The method intends simultaneous performance improvement and cost reduction through iteration of heliostat geometry and field layout parameters. This tool was developed primarily for the optimization of a novel micro-heliostat concept, which was developed at Solar-Institut Jülich (SIJ). However, the underlying approach for the optimization can be used for any heliostat type. During the optimization the performance is calculated using the ray-tracing tool SolCal. The costs of the heliostats are calculated by use of a detailed cost function. A genetic algorithm is used to change heliostat geometry and field layout in an iterative process. Starting from an initial setup, the optimization tool generates several configurations of heliostat geometries and field layouts. For each configuration a cost-performance ratio is calculated. Based on that, the best geometry and field layout can be selected in each optimization step. In order to find the best configuration, this step is repeated until no significant improvement in the results is observed.

  18. Tandem-repeat protein domains across the tree of life.

    PubMed

    Jernigan, Kristin K; Bordenstein, Seth R

    2015-01-01

    Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20-40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species.

  19. Criminal Behavior and Repeat Violent Trauma: A Case-Control Study.

    PubMed

    Nanney, John T; Conrad, Erich J; McCloskey, Michael; Constans, Joseph I

    2015-09-01

    Repeat violent injury is common among young urban men and is increasingly a focus of trauma center-based injury prevention efforts. Though understanding risk factors for repeat violent injury may be critical in designing such interventions, this knowledge is limited. This study aims to determine which criminal behaviors, both before and after the initial trauma, predict repeat violent trauma. Gun, violent, and drug crimes are expected to increase risk of subsequent violent injury among victims of violence. A case-control design examined trauma registry and publicly available criminal data for all male patients aged <40 years presenting for violent trauma between April 2006 and December 2011 (N=1,142) to the sole Level 1 trauma center in a city with high rates of violence. Logistic regression was used to determine criminal behaviors predictive of repeat violent injury. Data were obtained and analyzed between January 2013 and June 2014. Regarding crimes committed before the first injury, only drug crime (OR=5.32) predicted repeat violent trauma. With respect to crimes committed after the initial injury, illegal gun possession (OR=2.70) predicted repeat victimization. Initiating gun (OR=3.53) or drug crime (OR=5.12) was associated with increased risk. Prior drug involvement may identify young male victims of violence as at high risk of repeat violent injury. Gun carrying and initiating drug involvement after the initial injury may increase risk of repeat injury and may be important targets for interventions aimed at preventing repeat violent trauma. Published by Elsevier Inc.

  20. The relationship of social support concept and repeat mammography among Iranian women.

    PubMed

    Farhadifar, Fariba; Taymoori, Parvaneh; Bahrami, Mitra; Zarea, Shamsy

    2015-10-24

    Breast cancer ranks as the first most common cancer among the Iranian women. The regular repeat of mammography with 1-2 year intervals leads to the increased efficiency of early detection of breast cancer. The present study examined the predictors of repeat mammography. It was hypothesized that higher social support is connected with mammography repeat. A cross-sectional study was carried out among 400 women 50 years and older in Sanandaj, Iran. Data was collected by the questionnaire including information on socio demographical variables and measuring social support level. Data was analyzed by SPSS16 software. Multiple logistic regression was used to determine the predictive power of demographic variables and dimensions of social support for repeat mammography. Women aged 50-55 years had three times odds of repeat mammography compared to women aged 56-60 years) OR, 3.02). Married women had greater odds of repeat mammography compared to single women (P < 0.006). The probability of repeat mammography in women with higher social support was 0.93 times greater than the women with lower social support (OR, 0.93; 95 % CI, 0.91-0.95; P < 0.0001). Iranian women are less likely repeat mammography than other Asian women. Identifying the associations between perceived social support and repeat mammography may offer detailed information to allow for future study and guide the development of interventions not only for Iranian women but also for similar cultural that received pay too little attention to date in the breast cancer literature.

  1. 40 CFR 90.321 - NDIR analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... curve. Develop a calibration curve for each range used as follows: (1) Zero the analyzer. (2) Span the... zero response. If it has changed more than 0.5 percent of full scale, repeat the steps given in... the form of the following equation (1) or (2). Include zero as a data point. Compensation for known...

  2. 40 CFR 89.323 - NDIR analyzer calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... curve. Develop a calibration curve for each range used as follows: (1) Zero the analyzer. (2) Span the... zero response. If it has changed more than 0.5 percent of full scale, repeat the steps given in... coefficients. If any range is within 2 percent of being linear a linear calibration may be used. Include zero...

  3. 40 CFR 89.323 - NDIR analyzer calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... curve. Develop a calibration curve for each range used as follows: (1) Zero the analyzer. (2) Span the... zero response. If it has changed more than 0.5 percent of full scale, repeat the steps given in... coefficients. If any range is within 2 percent of being linear a linear calibration may be used. Include zero...

  4. 40 CFR 89.323 - NDIR analyzer calibration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... curve. Develop a calibration curve for each range used as follows: (1) Zero the analyzer. (2) Span the... zero response. If it has changed more than 0.5 percent of full scale, repeat the steps given in... coefficients. If any range is within 2 percent of being linear a linear calibration may be used. Include zero...

  5. 40 CFR 89.323 - NDIR analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... curve. Develop a calibration curve for each range used as follows: (1) Zero the analyzer. (2) Span the... zero response. If it has changed more than 0.5 percent of full scale, repeat the steps given in... coefficients. If any range is within 2 percent of being linear a linear calibration may be used. Include zero...

  6. Micromechanics Fatigue Damage Analysis Modeling for Fabric Reinforced Ceramic Matrix Composites

    NASA Technical Reports Server (NTRS)

    Min, J. B.; Xue, D.; Shi, Y.

    2013-01-01

    A micromechanics analysis modeling method was developed to analyze the damage progression and fatigue failure of fabric reinforced composite structures, especially for the brittle ceramic matrix material composites. A repeating unit cell concept of fabric reinforced composites was used to represent the global composite structure. The thermal and mechanical properties of the repeating unit cell were considered as the same as those of the global composite structure. The three-phase micromechanics, the shear-lag, and the continuum fracture mechanics models were integrated with a statistical model in the repeating unit cell to predict the progressive damages and fatigue life of the composite structures. The global structure failure was defined as the loss of loading capability of the repeating unit cell, which depends on the stiffness reduction due to material slice failures and nonlinear material properties in the repeating unit cell. The present methodology is demonstrated with the analysis results evaluated through the experimental test performed with carbon fiber reinforced silicon carbide matrix plain weave composite specimens.

  7. Crosstalk in concurrent repeated games impedes direct reciprocity and requires stronger levels of forgiveness.

    PubMed

    Reiter, Johannes G; Hilbe, Christian; Rand, David G; Chatterjee, Krishnendu; Nowak, Martin A

    2018-02-07

    Direct reciprocity is a mechanism for cooperation among humans. Many of our daily interactions are repeated. We interact repeatedly with our family, friends, colleagues, members of the local and even global community. In the theory of repeated games, it is a tacit assumption that the various games that a person plays simultaneously have no effect on each other. Here we introduce a general framework that allows us to analyze "crosstalk" between a player's concurrent games. In the presence of crosstalk, the action a person experiences in one game can alter the person's decision in another. We find that crosstalk impedes the maintenance of cooperation and requires stronger levels of forgiveness. The magnitude of the effect depends on the population structure. In more densely connected social groups, crosstalk has a stronger effect. A harsh retaliator, such as Tit-for-Tat, is unable to counteract crosstalk. The crosstalk framework provides a unified interpretation of direct and upstream reciprocity in the context of repeated games.

  8. [Bioinformatics Analysis of Clustered Regularly Interspaced Short Palindromic Repeats in the Genomes of Shigella].

    PubMed

    Wang, Pengfei; Wang, Yingfang; Duan, Guangcai; Xue, Zerun; Wang, Linlin; Guo, Xiangjiao; Yang, Haiyan; Xi, Yuanlin

    2015-04-01

    This study was aimed to explore the features of clustered regularly interspaced short palindromic repeats (CRISPR) structures in Shigella by using bioinformatics. We used bioinformatics methods, including BLAST, alignment and RNA structure prediction, to analyze the CRISPR structures of Shigella genomes. The results showed that the CRISPRs existed in the four groups of Shigella, and the flanking sequences of upstream CRISPRs could be classified into the same group with those of the downstream. We also found some relatively conserved palindromic motifs in the leader sequences. Repeat sequences had the same group with corresponding flanking sequences, and could be classified into two different types by their RNA secondary structures, which contain "stem" and "ring". Some spacers were found to homologize with part sequences of plasmids or phages. The study indicated that there were correlations between repeat sequences and flanking sequences, and the repeats might act as a kind of recognition mechanism to mediate the interaction between foreign genetic elements and Cas proteins.

  9. Inter- and intraobserver repeatability of the Salford Gait Tool: an observation-based clinical gait assessment tool.

    PubMed

    Toro, Brigitte; Nester, Christopher J; Farren, Pauline C

    2007-03-01

    To evaluate the inter- and intraobserver repeatability of the Salford Gait Tool (SF-GT), a new observation-based gait assessment tool for evaluating sagittal plane cerebral palsy (CP) gait. Masked comparative evaluation. University in the United Kingdom. A convenience sample of 23 pediatric physical therapists with varying degrees of clinical experience recruited from the Greater Manchester area. Participants viewed videotapes of the sagittal plane gait of 13 children and used the SF-GT to analyze their 13 different gait styles on 2 occasions. Eleven children had hemiplegic, diplegic, or quadriplegic CP and 2 were neurologically intact. Inter- and intraobserver repeatability of hip, knee, and ankle joint positions at 6 different phases of the gait cycle. The SF-GT demonstrated good interobserver (77%) and intraobserver (75%) repeatability. We have established that the SF-GT is a repeatable clinical assessment tool with which to guide the diagnosis, treatment planning, and evaluation of interventions by pediatric physical therapists of sagittal plane gait deviations in CP.

  10. Research on Scheduling Algorithm for Multi-satellite and Point Target Task on Swinging Mode

    NASA Astrophysics Data System (ADS)

    Wang, M.; Dai, G.; Peng, L.; Song, Z.; Chen, G.

    2012-12-01

    Nowadays, using satellite in space to observe ground is an important and major method to obtain ground information. With the development of the scientific technology in the field of space, many fields such as military and economic and other areas have more and more requirement of space technology because of the benefits of the satellite's widespread, timeliness and unlimited of area and country. And at the same time, because of the wide use of all kinds of satellites, sensors, repeater satellites and ground receiving stations, ground control system are now facing great challenge. Therefore, how to make the best value of satellite resources so as to make full use of them becomes an important problem of ground control system. Satellite scheduling is to distribute the resource to all tasks without conflict to obtain the scheduling result so as to complete as many tasks as possible to meet user's requirement under considering the condition of the requirement of satellites, sensors and ground receiving stations. Considering the size of the task, we can divide tasks into point task and area task. This paper only considers point targets. In this paper, a description of satellite scheduling problem and a chief introduction of the theory of satellite scheduling are firstly made. We also analyze the restriction of resource and task in scheduling satellites. The input and output flow of scheduling process are also chiefly described in the paper. On the basis of these analyses, we put forward a scheduling model named as multi-variable optimization model for multi-satellite and point target task on swinging mode. In the multi-variable optimization model, the scheduling problem is transformed the parametric optimization problem. The parameter we wish to optimize is the swinging angle of every time-window. In the view of the efficiency and accuracy, some important problems relating the satellite scheduling such as the angle relation between satellites and ground targets, positive and negative swinging angle and the computation of time window are analyzed and discussed. And many strategies to improve the efficiency of this model are also put forward. In order to solve the model, we bring forward the conception of activity sequence map. By using the activity sequence map, the activity choice and the start time of the activity can be divided. We also bring forward three neighborhood operators to search the result space. The front movement remaining time and the back movement remaining time are used to analyze the feasibility to generate solution from neighborhood operators. Lastly, the algorithm to solve the problem and model is put forward based genetic algorithm. Population initialization, crossover operator, mutation operator, individual evaluation, collision decrease operator, select operator and collision elimination operator is designed in the paper. Finally, the scheduling result and the simulation for a practical example on 5 satellites and 100 point targets with swinging mode is given, and the scheduling performances are also analyzed while the swinging angle in 0, 5, 10, 15, 25. It can be shown by the result that the model and the algorithm are more effective than those ones without swinging mode.

  11. Optimal approach to quantum communication using dynamic programming.

    PubMed

    Jiang, Liang; Taylor, Jacob M; Khaneja, Navin; Lukin, Mikhail D

    2007-10-30

    Reliable preparation of entanglement between distant systems is an outstanding problem in quantum information science and quantum communication. In practice, this has to be accomplished by noisy channels (such as optical fibers) that generally result in exponential attenuation of quantum signals at large distances. A special class of quantum error correction protocols, quantum repeater protocols, can be used to overcome such losses. In this work, we introduce a method for systematically optimizing existing protocols and developing more efficient protocols. Our approach makes use of a dynamic programming-based searching algorithm, the complexity of which scales only polynomially with the communication distance, letting us efficiently determine near-optimal solutions. We find significant improvements in both the speed and the final-state fidelity for preparing long-distance entangled states.

  12. Optimally Repeatable Kinetic Model Variant for Myocardial Blood Flow Measurements with 82Rb PET.

    PubMed

    Ocneanu, Adrian F; deKemp, Robert A; Renaud, Jennifer M; Adler, Andy; Beanlands, Rob S B; Klein, Ran

    2017-01-01

    Purpose. Myocardial blood flow (MBF) quantification with 82 Rb positron emission tomography (PET) is gaining clinical adoption, but improvements in precision are desired. This study aims to identify analysis variants producing the most repeatable MBF measures. Methods. 12 volunteers underwent same-day test-retest rest and dipyridamole stress imaging with dynamic 82 Rb PET, from which MBF was quantified using 1-tissue-compartment kinetic model variants: (1) blood-pool versus uptake region sampled input function (Blood/Uptake-ROI), (2) dual spillover correction (SOC-On/Off), (3) right blood correction (RBC-On/Off), (4) arterial blood transit delay (Delay-On/Off), and (5) distribution volume (DV) constraint (Global/Regional-DV). Repeatability of MBF, stress/rest myocardial flow reserve (MFR), and stress/rest MBF difference (ΔMBF) was assessed using nonparametric reproducibility coefficients (RPC np = 1.45 × interquartile range). Results. MBF using SOC-On, RVBC-Off, Blood-ROI, Global-DV, and Delay-Off was most repeatable for combined rest and stress: RPC np = 0.21 mL/min/g (15.8%). Corresponding MFR and ΔMBF RPC np were 0.42 (20.2%) and 0.24 mL/min/g (23.5%). MBF repeatability improved with SOC-On at stress ( p < 0.001) and tended to improve with RBC-Off at both rest and stress ( p < 0.08). DV and ROI did not significantly influence repeatability. The Delay-On model was overdetermined and did not reliably converge. Conclusion. MBF and MFR test-retest repeatability were the best with dual spillover correction, left atrium blood input function, and global DV.

  13. What Can We Learn From Point-of-Care Blood Glucose Values Deleted and Repeated by Nurses?

    PubMed

    Corl, Dawn; Yin, Tom; Ulibarri, May; Lien, Heather; Tylee, Tracy; Chao, Jing; Wisse, Brent E

    2018-03-01

    Hospitals rely on point-of-care (POC) blood glucose (BG) values to guide important decisions related to insulin administration and glycemic control. Evaluation of POC BG in hospitalized patients is associated with measurement and operator errors. Based on a previous quality improvement (QI) project we introduced an option for operators to delete and repeat POC BG values suspected as erroneous. The current project evaluated our experience with deleted POC BG values over a 2-year period. A retrospective QI project included all patients hospitalized at two regional academic medical centers in the Pacific Northwest during 2014 and 2015. Laboratory Medicine POC BG data were reviewed to evaluate all inpatient episodes of deleted and repeated POC BG. Inpatient operators choose to delete and repeat only 0.8% of all POC BG tests. Hypoglycemic and extreme hyperglycemic BG values are more likely to be deleted and repeated. Of initial values <40 mg/dL, 58% of deleted values (18% of all values) are errors. Of values >400 mg/dL, 40% of deleted values (5% of all values) are errors. Not all repeated POC BG values are first deleted. Optimal use of the option to delete and repeat POC BG values <40 mg/dL could decrease reported rates of severe hypoglycemia by as much as 40%. This project demonstrates that operators are frequently able to identify POC BG values that are measurement/operator errors. Eliminating these errors significantly reduces documented rates of severe hypoglycemia and hyperglycemia, and has the potential to improve patient safety.

  14. Effects of blur and repeated testing on sensitivity estimates with frequency doubling perimetry.

    PubMed

    Artes, Paul H; Nicolela, Marcelo T; McCormick, Terry A; LeBlanc, Raymond P; Chauhan, Balwantray C

    2003-02-01

    To investigate the effect of blur and repeated testing on sensitivity with frequency doubling technology (FDT) perimetry. One eye of 12 patients with glaucoma (mean deviation [MD] mean, -2.5 dB, range +0.5 to -4.3 dB) and 11 normal control subjects underwent six consecutive tests with the FDT N30 threshold program in each of two sessions. In session 1, blur was induced by trial lenses (-6.00, -3.00, 0.00, +3.00, and +6.00 D, in random order). In session 2, only the effects of repeated testing were evaluated. The MD and pattern standard deviation (PSD) indices were evaluated as functions of blur and of test order. By correcting the data of session 1 for the reduction of sensitivity with repeated testing (session 2), the effect of blur on FDT sensitivities was established, and its clinical consequences evaluated on total- and pattern-deviation probability maps. FDT sensitivities decreased with blur (by <0.5 dB/D) and with repeated testing (by approximately 2 dB between the first and sixth tests). Blur and repeated testing independently led to larger numbers of locations with significant total and pattern deviation. Sensitivity reductions were similar in normal control subjects and patients with glaucoma, at central and peripheral test locations and at locations with high and low sensitivities. However, patients with glaucoma showed larger deterioration in the total-deviation-probability maps. To optimize the performance of the device, refractive errors should be corrected and immediate retesting avoided. Further research is needed to establish the cause of sensitivity loss with repeated FDT testing.

  15. Effects of environmental exposure on cryogenic thermal insulation materials

    NASA Technical Reports Server (NTRS)

    Parmley, R. T.; Smith, F. J.; Glassford, A. P.; Coleman, J.; Stevenson, D. R.

    1973-01-01

    Investigation was made to optimize selection of insulation materials for reusable space vehicles which will be repeatedly operated over periods of up to ten years. Results of study are summarized in two reports. Volume I describes tests and significant findings. In Volume II, extensive test data obtained are organized in handbook form.

  16. Optimal Rating Procedures and Methodology for NAEP Open- Ended Items. Working Paper Series.

    ERIC Educational Resources Information Center

    Patz, Richard J.; Wilson, Mark; Hoskens, Machteld

    The National Assessment of Educational Progress (NAEP) collects data in the form of repeated, discrete measures (test items) with hierarchical structure for both measures and subjects, that is complex by any standard. This complexity has been managed through a "divide and conquer" approach of isolating and evaluating sources of…

  17. Influence of Fallible Item Parameters on Test Information During Adaptive Testing.

    ERIC Educational Resources Information Center

    Wetzel, C. Douglas; McBride, James R.

    Computer simulation was used to assess the effects of item parameter estimation errors on different item selection strategies used in adaptive and conventional testing. To determine whether these effects reduced the advantages of certain optimal item selection strategies, simulations were repeated in the presence and absence of item parameter…

  18. The ABCs of Challenging Behavior: Understanding Basic Concepts

    ERIC Educational Resources Information Center

    Meadan, Hedda; Ayvazo, Shiri; Ostrosky, Michaelene M.

    2016-01-01

    Many young children engage in challenging behaviors that could have short- and long-term negative effects for both the children and their families. Challenging behaviors refer to "any repeated pattern of behavior, or perception of behavior, that interferes with or is at risk of interfering with optimal learning or engagement in prosocial…

  19. Combined Exact-Repeat and Geodetic Mission Altimetry for High-Resolution Empirical Tide Mapping

    NASA Astrophysics Data System (ADS)

    Zaron, E. D.

    2014-12-01

    The configuration of present and historical exact-repeat mission (ERM) altimeter ground tracks determines the maximum resolution of empirical tidal maps obtained with ERM data. Although the mode-1 baroclinic tide is resolvable at mid-latitudes in the open ocean, the ability to detect baroclinic and barotropic tides near islands and complex coastlines is limited, in part, by ERM track density. In order to obtain higher resolution maps, the possibility of combining ERM and geodetic mission (GM) altimetry is considered, using a combination of spatial thin-plate splines and temporal harmonic analysis. Given the present spatial and temporal distribution of GM missions, it is found that GM data can contribute to resolving tidal features smaller than 75 km, provided the signal amplitude is greater than about 1 cm. Uncertainties in the mean sea surface and environmental corrections are significant components of the GM error budget, and methods to optimize data selection and along-track filtering are still being optimized. Application to two regions, Monterey Bay and Luzon Strait, finds evidence for complex tidal fields in agreement with independent observations and modeling studies.

  20. Interpersonal Values and Academic Performance Related to Delinquent Behaviors

    PubMed Central

    Molero Jurado, María Del Mar; Pérez Fuentes, María Del Carmen; Luque De La Rosa, Antonio; Martos Martínez, África; Barragán Martín, Ana Belén; Simón Márquez, María del Mar

    2016-01-01

    The present study analyzes the relation between delinquent behaviors, interpersonal values, and academic performance. It also analyzes the possible protective function of interpersonal values against delinquent behaviors. The Interpersonal Values Questionnaire (IVQ) was used to assess interpersonal values, and the Antisocial-Delinquent Behaviors Questionnaire (A-D) was employed to assess antisocial behaviors. The sample was made up of 885 students of Compulsory Secondary Education, aged from 14 to 17 years. The results show that individuals who fail a subject as well as those who repeat a course present higher means in delinquent behaviors. Repeaters present higher means in the values of recognition and leadership, and non-repeaters in the value stimulation, whereas students who do not fail obtain higher scores in the value benevolence. Students with high levels of recognition, independence, and leadership, as well as students with low levels of conformity and benevolence display significantly higher levels of delinquent behaviors. Lastly, the probability of presenting a high level of delinquent behaviors is greater in individuals with: high independence, high leadership, high recognition, low benevolence, and low conformity. PMID:27799914

  1. Single-Walled Carbon Nanotubes (SWCNTs), as a Novel Sorbent for Determination of Mercury in Air

    PubMed Central

    Golbabaei, Farideh; Ebrahimi, Ali; Shirkhanloo, Hamid; Koohpaei, Alireza; Faghihi-Zarandi, Ali

    2016-01-01

    Background: Based on the noticeable toxicity and numerous application of mercury in industries, removal of mercury vapor through sorbent is an important environmental challenge. Purpose of the Study: Due to their highly porous and hollow structure, large specific surface area, light mass density and strong interaction, Single-Walled Carbon Nanotubes (SWCNTs) sorbent were selected for this investigation. Methods: In this study, instrumental conditions, method procedure and different effective parameters such as adsorption efficiency, desorption capacity, time, temperature and repeatability as well as retention time of adsorbed mercury were studied and optimized. Also, mercury vapor was determined by cold vapor atomic absorption spectrometry (CV-AAS). Obtained data were analyzed by Independent T- test, Multivariate linear regression and one way–ANOVA finally. Results: For 80 mg nanotubes, working range of SWCNT were achieved 0.02-0.7 μg with linear range (R2=0.994). Our data revealed that maximum absorption capacity was 0.5 μg g-1 as well as limit of detection (LOD) for studied sorbent was 0.006 μg. Also, optimum time and temperature were reported, 10 min and 250 °C respectively. Retention time of mercury on CNTs for three weeks was over 90%. Results of repeated trials indicated that the CNTs had long life, so that after 30 cycles of experiments, efficiency was determined without performance loss. Conclusion: Results showed that carbon nanotubes have high potential for efficient extraction of mercury from air and can be used for occupational and environmental purposes. The study of adsorption properties of CNTs is recommended. PMID:26925918

  2. FTIR and FT-Raman spectra and DFT vibrational analysis of phosphorus-containing dendrons

    NASA Astrophysics Data System (ADS)

    Furer, V. L.; Vandyukova, I. I.; Vandyukov, A. E.; Majoral, J. P.; Caminade, A. M.; Kovalenko, V. I.

    2008-12-01

    FTIR and FT-Raman spectra of four generations of phosphorus-containing dendrons with terminal aldehyde or P sbnd Cl groups have been recorded and analyzed. Their spectral patterns are determined by the ratio T/ R ( T, the number of terminal groups; R, the number of repeated units). Bands assigned to the core, repeated units and terminal groups were separated by the difference spectroscopy method. The optimized geometry, frequencies and intensity of IR bands of G1v generation dendron with terminal aldehyde groups were obtained by the density functional theory (DFT). It was found that the internal skeleton of molecules exists in a single stable conformation with planar sbnd O- C6H4- CHdbnd N- N( CH3)- P( dbnd S)< fragments, but terminal groups may adopt the t, g, g- and t,- g, g-rotational isomers. The t,- g, g-conformer is 0.74 kcal/mol less stable compared to the t, g, g-conformer. The bond length and bond angles obtained by DFT show the best agreement with experimental data. Relying on DFT calculations a complete assignment of vibrations is proposed for different parts of the studied dendrons. The calculated frequencies and intensity of IR bands of the t, g, g- and t,- g, g-conformers of G1v are found to be in reasonable agreement with the experimental results. The most reactive site in dendron is the core function and vinyl group is preferred for nucleophilic attack. In dendrimer the most reactive are the terminal groups.

  3. Survival benefit of repeat liver transplantation in the United States: a serial MELD analysis by hepatitis C status and donor risk index.

    PubMed

    Biggins, S W; Gralla, J; Dodge, J L; Bambha, K M; Tong, S; Barón, A E; Inadomi, J; Terrault, N; Rosen, H R

    2014-11-01

    Survival benefit (SB) for first liver transplantation (LT) is favorable at Model for End-Stage Liver Disease (MELD)≥15. Herein, we identify the MELD threshold for SB from repeat liver transplantation (ReLT) by recipient hepatitis C virus (HCV) status and donor risk index (DRI). We analyzed lab MELD scores in new United Network for Organ Sharing registrants for ReLT from March 2002 to January 2010. Risk of ReLT graft failure≤1 year versus waitlist mortality was calculated using Cox regression, adjusting for recipient characteristics. Of 3057 ReLT candidates, 54% had HCV and 606 died while listed. There were 1985 ReLT recipients, 52% had HCV and 567 ReLT graft failures by 1 year. Unadjusted waitlist mortality and post-ReLT graft failure rates were 416 (95% confidence interval [CI] 384-450) and 375 (95% CI 345-407) per 1000 patient-years, respectively. Waitlist mortality was higher with increasing waitlist MELD (p<0.001). The MELD for SB from ReLT overall was 21 (21 in non-HCV and 24 in HCV patients). MELD for SB varied by DRI in HCV patients (MELD 21, 24 and 27 for low, medium and high DRI, respectively) but did not vary for non-HCV patients. Compared to first LT, ReLT requires a higher MELD threshold to achieve an SB resulting in a narrower therapeutic window to optimize the utility of scarce liver grafts. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Polymeric ionic liquid based on magnetic materials fabricated through layer-by-layer assembly as adsorbents for extraction of pesticides.

    PubMed

    He, Lijun; Cui, Wenhang; Wang, Yali; Zhao, Wenjie; Xiang, Guoqiang; Jiang, Xiuming; Mao, Pu; He, Juan; Zhang, Shusheng

    2017-11-03

    In this study, layer-by-layer assembly of polyelectrolyte multilayer films on magnetic silica provided a convenient and controllable way to prepare polymeric ionic liquid-based magnetic adsorbents. The resulting particles were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and magnetic measurements. The data showed that the magnetic particles had more homogeneous spherical shapes with higher saturation magnetization when compared to those obtained by free radical polymerization method. This facilitated the convenient collection of magnetic particles, with higher extraction repeatability. The extraction performance of the multilayer polymeric ionic liquid-based adsorbents was evaluated by magnetic solid-phase extraction of four pesticides including quinalphos, fenthion, phoxim, and chlorpropham. The data suggested that the extraction efficiency depended on the number of layers in the film. The parameters affecting the extraction efficiency were optimized, and good linearity ranging from 2 to 250μgL -1 was obtained with correlation coefficients of 0.9994-0.9998. Moreover, the proposed method presented low limit of detection (0.5μgL -1 , S/N=3) and limit of quantification (1.5μgL -1 , S/N=10), and good repeatability expressed by the relative standard deviation (2.0%-4.6%, n=5). The extraction recoveries of four pesticides were found to range from 58.9% to 85.8%. The reliability of the proposed method was demonstrated by analyzing environmental water samples, and the results revealed satisfactory spiked recovery, relative standard deviation, and selectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Different fatigue-resistant leg muscles and EMG response during whole-body vibration.

    PubMed

    Simsek, Deniz

    2017-12-01

    The purpose of this study was to determine the effects of static whole-body vibration (WBV) on the Electromyograhic (EMG) responses of leg muscles, which are fatigue-resistant in different manner. The study population was divided into two groups according to the values obtained by the Fatigue Index [Group I: Less Fatigue Resistant (LFR), n=11; Group II: More Fatigue Resistant (MFR), n=11]. The repeated electromyographic (EMG) activities of four leg muscles were analyzed the following determinants: (1) frequency (30 Hz, 35 Hz and 40 Hz); (2) stance position (static squat position); (3) amplitude (2 mm and 4 mm) and (4) knee flexion angle (120°), (5) vertical vibration platform. Vibration data were analyzed using Minitab 16 (Minitab Ltd, State College, PA, USA). The significance level was set at p<.05. The study results showed that static WBV stimuli given at different frequencies and amplitudes resulted in a significant increase (p<.05) in compared, the LFR group showed significantly (1) higher rates of quadriceps femoris and hamstring muscle fatigue (p<.05), (2) higher levels of knee extensor and flexor torque (p<.05) and (3) higher percentage increases in EMG activation at higher frequencies (max at 40 Hz) and amplitudes (4 mm) (p<.05). The present study can be used for the optimal prescription of vibration exercise and can serve to guide the development of training programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Frequency specificity in intercellular communication. Influence of patterns of periodic signaling on target cell responsiveness.

    PubMed Central

    Li, Y; Goldbeter, A

    1989-01-01

    Cells often communicate by means of periodic signals, as exemplified by a large number of hormones and by the aggregation of Dictyostelium discoideum amebas in response to periodic pulses of cyclic AMP. Periodic signaling allows bypassing the phenomenon of desensitization brought about by constant stimuli. To gain further insight into the efficiency of pulsatile signaling, we analyze the effect of periodic stimulation on the dynamic behavior of a receptor system capable of desensitization toward its ligand. We first show that the receptor system adapts to square-wave stimuli, i.e., the response eventually reaches a steady, periodic pattern after a transient phase. By analyzing the dependence of the response on the characteristics of the square-wave stimulation, we show that there exist a waveform and a period of that signal that result in maximum responsiveness of the target system. Similar results are obtained when the signal takes the more realistic form of a periodically repeated stimulation followed by exponential decay of the ligand. The results are discussed with respect to the role of pulsatile secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and of periodic signaling by cyclic AMP pulses in Dictyostelium. The analysis accounts for the existence, in both cases, of an optimal frequency and waveform of the periodic stimulus that correspond to maximum target cell responsiveness. PMID:2930817

  7. Characterization of retroviral infectivity and superinfection resistance during retrovirus-mediated transduction of mammalian cells.

    PubMed

    Liao, J; Wei, Q; Fan, J; Zou, Y; Song, D; Liu, J; Liu, F; Ma, C; Hu, X; Li, L; Yu, Y; Qu, X; Chen, L; Yu, X; Zhang, Z; Zhao, C; Zeng, Z; Zhang, R; Yan, S; Wu, T; Wu, X; Shu, Y; Lei, J; Li, Y; Zhang, W; Wang, J; Reid, R R; Lee, M J; Huang, W; Wolf, J M; He, T-C; Wang, J

    2017-06-01

    Retroviral vectors including lentiviral vectors are commonly used tools to stably express transgenes or RNA molecules in mammalian cells. Their utilities are roughly divided into two categories, stable overexpression of transgenes and RNA molecules, which requires maximal transduction efficiency, or functional selection with retrovirus (RV)-based libraries, which takes advantage of retroviral superinfection resistance. However, the dynamic features of RV-mediated transduction are not well characterized. Here, we engineered two murine stem cell virus-based retroviral vectors expressing dual fluorescence proteins and antibiotic markers, and analyzed virion production efficiency and virion stability, dynamic infectivity and superinfection resistance in different cell types, and strategies to improve transduction efficiency. We found that the highest virion production occurred between 60 and 72 h after transfection. The stability of the collected virion supernatant decreased by >60% after 3 days in storage. We found that RV infectivity varied drastically in the tested human cancer lines, while low transduction efficiency was partially overcome with increased virus titer, prolonged infection duration and/or repeated infections. Furthermore, we demonstrated that RV receptors PIT1 and PIT2 were lowly expressed in the analyzed cells, and that PIT1 and/or PIT2 overexpression significantly improved transduction efficiency in certain cell lines. Thus, our findings provide resourceful information for the optimal conditions of retroviral-mediated gene delivery.

  8. Semiautomated determination of neonicotinoids and characteristic metabolite in urine samples using TurboFlow™ coupled to ultra high performance liquid chromatography coupled to Orbitrap analyzer.

    PubMed

    López-García, Marina; Romero-González, Roberto; Lacasaña, Marina; Garrido Frenich, Antonia

    2017-11-30

    A semiautomated method based on ultra-high performance liquid chromatography (UHPLC) coupled to Orbitrap high resolution mass spectrometry has been developed for the determination of neonicotinoids (imidacloprid, acetamiprid, clothianidin, dinotefuran, nitenpyram, thiacloprid and thiamethoxam) and the metabolite acetamiprid-n-desmethyl in urine samples. Two automated methods were tested (solid-phase extraction "SPE" and turbulent flow chromatography "TurboFlow™"), obtaining the best results when TurboFlow™ was applied. The total analysis time for the developed method was 14min. The optimized method was validated, obtaining suitable results for all validation parameters. Recoveries ranged from 78% to 116% meanwhile repeatability and reproducibility were evaluated obtaining values lower than 10% and 20% respectively (except for dinotefuran and nitenpyram at 0.2μgL -1 ). The limit of quantification (LOQ) for all compounds was established at 0.2μgL -1 . The proposed analytical methodology was applied to analyze the target compounds in thirty six urine samples from pregnant women living in agricultural areas of Almería (Spain). Imidacloprid, acetamiprid and acetamiprid-n-desmethyl were detected in some of the samples at concentrations ranging from 0.23 to 1.57μgL -1 . Furthermore, dinotefuran was identified in two samples at trace levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Mapping Optimal Charge Density and Length of ROMP-Based PTDMs for siRNA Internalization.

    PubMed

    Caffrey, Leah M; deRonde, Brittany M; Minter, Lisa M; Tew, Gregory N

    2016-10-10

    A fundamental understanding of how polymer structure impacts internalization and delivery of biologically relevant cargoes, particularly small interfering ribonucleic acid (siRNA), is of critical importance to the successful design of improved delivery reagents. Herein we report the use of ring-opening metathesis polymerization (ROMP) methods to synthesize two series of guanidinium-rich protein transduction domain mimics (PTDMs): one based on an imide scaffold that contains one guanidinium moiety per repeat unit, and another based on a diester scaffold that contains two guanidinium moieties per repeat unit. By varying both the degree of polymerization and, in effect, the relative number of cationic charges in each PTDM, the performances of the two ROMP backbones for siRNA internalization were evaluated and compared. Internalization of fluorescently labeled siRNA into Jurkat T cells demonstrated that fluorescein isothiocyanate (FITC)-siRNA internalization had a charge content dependence, with PTDMs containing approximately 40 to 60 cationic charges facilitating the most internalization. Despite this charge content dependence, the imide scaffold yielded much lower viabilities in Jurkat T cells than the corresponding diester PTDMs with similar numbers of cationic charges, suggesting that the diester scaffold is preferred for siRNA internalization and delivery applications. These developments will not only improve our understanding of the structural factors necessary for optimal siRNA internalization, but will also guide the future development of optimized PTDMs for siRNA internalization and delivery.

  10. A microfluidic platform for precision small-volume sample processing and its use to size separate biological particles with an acoustic microdevice [Precision size separation of biological particles in small-volume samples by an acoustic microfluidic system

    DOE PAGES

    Fong, Erika J.; Huang, Chao; Hamilton, Julie; ...

    2015-11-23

    Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less

  11. Noise tolerant illumination optimization applied to display devices

    NASA Astrophysics Data System (ADS)

    Cassarly, William J.; Irving, Bruce

    2005-02-01

    Display devices have historically been designed through an iterative process using numerous hardware prototypes. This process is effective but the number of iterations is limited by the time and cost to make the prototypes. In recent years, virtual prototyping using illumination software modeling tools has replaced many of the hardware prototypes. Typically, the designer specifies the design parameters, builds the software model, predicts the performance using a Monte Carlo simulation, and uses the performance results to repeat this process until an acceptable design is obtained. What is highly desired, and now possible, is to use illumination optimization to automate the design process. Illumination optimization provides the ability to explore a wider range of design options while also providing improved performance. Since Monte Carlo simulations are often used to calculate the system performance but those predictions have statistical uncertainty, the use of noise tolerant optimization algorithms is important. The use of noise tolerant illumination optimization is demonstrated by considering display device designs that extract light using 2D paint patterns as well as 3D textured surfaces. A hybrid optimization approach that combines a mesh feedback optimization with a classical optimizer is demonstrated. Displays with LED sources and cold cathode fluorescent lamps are considered.

  12. A Kinematic Calibration Process for Flight Robotic Arms

    NASA Technical Reports Server (NTRS)

    Collins, Curtis L.; Robinson, Matthew L.

    2013-01-01

    The Mars Science Laboratory (MSL) robotic arm is ten times more massive than any Mars robotic arm before it, yet with similar accuracy and repeatability positioning requirements. In order to assess and validate these requirements, a higher-fidelity model and calibration processes were needed. Kinematic calibration of robotic arms is a common and necessary process to ensure good positioning performance. Most methodologies assume a rigid arm, high-accuracy data collection, and some kind of optimization of kinematic parameters. A new detailed kinematic and deflection model of the MSL robotic arm was formulated in the design phase and used to update the initial positioning and orientation accuracy and repeatability requirements. This model included a higher-fidelity link stiffness matrix representation, as well as a link level thermal expansion model. In addition, it included an actuator backlash model. Analytical results highlighted the sensitivity of the arm accuracy to its joint initialization methodology. Because of this, a new technique for initializing the arm joint encoders through hardstop calibration was developed. This involved selecting arm configurations to use in Earth-based hardstop calibration that had corresponding configurations on Mars with the same joint torque to ensure repeatability in the different gravity environment. The process used to collect calibration data for the arm included the use of multiple weight stand-in turrets with enough metrology targets to reconstruct the full six-degree-of-freedom location of the rover and tool frames. The follow-on data processing of the metrology data utilized a standard differential formulation and linear parameter optimization technique.

  13. Convergent evolution of mechanically optimal locomotion in aquatic invertebrates and vertebrates.

    PubMed

    Bale, Rahul; Neveln, Izaak D; Bhalla, Amneet Pal Singh; MacIver, Malcolm A; Patankar, Neelesh A

    2015-04-01

    Examples of animals evolving similar traits despite the absence of that trait in the last common ancestor, such as the wing and camera-type lens eye in vertebrates and invertebrates, are called cases of convergent evolution. Instances of convergent evolution of locomotory patterns that quantitatively agree with the mechanically optimal solution are very rare. Here, we show that, with respect to a very diverse group of aquatic animals, a mechanically optimal method of swimming with elongated fins has evolved independently at least eight times in both vertebrate and invertebrate swimmers across three different phyla. Specifically, if we take the length of an undulation along an animal's fin during swimming and divide it by the mean amplitude of undulations along the fin length, the result is consistently around twenty. We call this value the optimal specific wavelength (OSW). We show that the OSW maximizes the force generated by the body, which also maximizes swimming speed. We hypothesize a mechanical basis for this optimality and suggest reasons for its repeated emergence through evolution.

  14. Development of optimization model for sputtering process parameter based on gravitational search algorithm

    NASA Astrophysics Data System (ADS)

    Norlina, M. S.; Diyana, M. S. Nor; Mazidah, P.; Rusop, M.

    2016-07-01

    In the RF magnetron sputtering process, the desirable layer properties are largely influenced by the process parameters and conditions. If the quality of the thin film has not reached up to its intended level, the experiments have to be repeated until the desirable quality has been met. This research is proposing Gravitational Search Algorithm (GSA) as the optimization model to reduce the time and cost to be spent in the thin film fabrication. The optimization model's engine has been developed using Java. The model is developed based on GSA concept, which is inspired by the Newtonian laws of gravity and motion. In this research, the model is expected to optimize four deposition parameters which are RF power, deposition time, oxygen flow rate and substrate temperature. The results have turned out to be promising and it could be concluded that the performance of the model is satisfying in this parameter optimization problem. Future work could compare GSA with other nature based algorithms and test them with various set of data.

  15. People adopt optimal policies in simple decision-making, after practice and guidance.

    PubMed

    Evans, Nathan J; Brown, Scott D

    2017-04-01

    Organisms making repeated simple decisions are faced with a tradeoff between urgent and cautious strategies. While animals can adopt a statistically optimal policy for this tradeoff, findings about human decision-makers have been mixed. Some studies have shown that people can optimize this "speed-accuracy tradeoff", while others have identified a systematic bias towards excessive caution. These issues have driven theoretical development and spurred debate about the nature of human decision-making. We investigated a potential resolution to the debate, based on two factors that routinely differ between human and animal studies of decision-making: the effects of practice, and of longer-term feedback. Our study replicated the finding that most people, by default, are overly cautious. When given both practice and detailed feedback, people moved rapidly towards the optimal policy, with many participants reaching optimality with less than 1 h of practice. Our findings have theoretical implications for cognitive and neural models of simple decision-making, as well as methodological implications.

  16. Emotional Intelligence and Emotions Associated with Optimal and Dysfunctional Athletic Performance

    PubMed Central

    Lane, Andrew M.; Devonport, Tracey J.; Soos, Istvan; Karsai, Istvan; Leibinger, Eva; Hamar, Pal

    2010-01-01

    This study investigated relationships between self-report measures of emotional intelligence and memories of pre-competitive emotions before optimal and dysfunctional athletic performance. Participant-athletes (n = 284) completed a self-report measure of emotional intelligence and two measures of pre-competitive emotions; a) emotions experienced before an optimal performance, and b) emotions experienced before a dysfunctional performance. Consistent with theoretical predictions, repeated MANOVA results demonstrated pleasant emotions associated with optimal performance and unpleasant emotions associated with dysfunctional performance. Emotional intelligence correlated with pleasant emotions in both performances with individuals reporting low scores on the self-report emotional intelligence scale appearing to experience intense unpleasant emotions before dysfunctional performance. We suggest that future research should investigate relationships between emotional intelligence and emotion-regulation strategies used by athletes. Key points Athletes reporting high scores of self-report emotional intelligence tend to experience pleasant emotions. Optimal performance is associated with pleasant emotions and dysfunctional performance is associated with unpleasant emotions. Emotional intelligence might help athletes recognize which emotional states help performance. PMID:24149631

  17. Emotional intelligence and emotions associated with optimal and dysfunctional athletic performance.

    PubMed

    Lane, Andrew M; Devonport, Tracey J; Soos, Istvan; Karsai, Istvan; Leibinger, Eva; Hamar, Pal

    2010-01-01

    This study investigated relationships between self-report measures of emotional intelligence and memories of pre-competitive emotions before optimal and dysfunctional athletic performance. Participant-athletes (n = 284) completed a self-report measure of emotional intelligence and two measures of pre-competitive emotions; a) emotions experienced before an optimal performance, and b) emotions experienced before a dysfunctional performance. Consistent with theoretical predictions, repeated MANOVA results demonstrated pleasant emotions associated with optimal performance and unpleasant emotions associated with dysfunctional performance. Emotional intelligence correlated with pleasant emotions in both performances with individuals reporting low scores on the self-report emotional intelligence scale appearing to experience intense unpleasant emotions before dysfunctional performance. We suggest that future research should investigate relationships between emotional intelligence and emotion-regulation strategies used by athletes. Key pointsAthletes reporting high scores of self-report emotional intelligence tend to experience pleasant emotions.Optimal performance is associated with pleasant emotions and dysfunctional performance is associated with unpleasant emotions.Emotional intelligence might help athletes recognize which emotional states help performance.

  18. Sensitivity of measurement-based purification processes to inner interactions

    NASA Astrophysics Data System (ADS)

    Militello, Benedetto; Napoli, Anna

    2018-02-01

    The sensitivity of a repeated measurement-based purification scheme to additional undesired couplings is analyzed, focusing on the very simple and archetypical system consisting of two two-level systems interacting with a repeatedly measured one. Several regimes are considered and in the strong coupling limit (i.e., when the coupling constant of the undesired interaction is very large) the occurrence of a quantum Zeno effect is proven to dramatically jeopardize the efficiency of the purification process.

  19. Environmental enrichment reverses memory impairment induced by toluene in mice.

    PubMed

    Montes, Sergio; Solís-Guillén, Rocío Del Carmen; García-Jácome, David; Páez-Martínez, Nayeli

    2017-05-01

    Toluene is the main component of a variety of inhalants that are used for intoxication purposes. Alterations in memory have been reported in inhalant users; however, it is unclear whether these impairments could be reversed, and the mechanisms involved in the putative recovery. Therefore, the main purpose of this study was to model the deleterious effects of toluene on memory in mice and to evaluate the effect of environmental enrichment on that response. In the second part of the study, the concentrations of glutamate and GABA, following chronic toluene exposure and after environmental enrichment treatment, were evaluated. Adolescent mice were exposed to either a single or repeated schedule of toluene administration and their responses to object recognition were analyzed. An independent group of mice was repeatedly exposed to toluene and then housed either under environmental enrichment or standard conditions for four weeks. At the end of the housing period, the rodents' performance in object recognition test, as well as the concentrations of neurotransmitters, were analyzed. The results showed that toluene caused memory impairment in mice that received a single or repeated solvent exposure. Remarkably, environmental enrichment could reverse memory deficits induced by repeated administration of toluene. Cessation of toluene exposure in mice in standard housing did not produce that response. The glutamate and GABA tissue contents were not involved in the effects of toluene or environmental enrichment of memory. Copyright © 2017. Published by Elsevier Inc.

  20. Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity.

    PubMed

    Hunter, Jessica Ezzell; Epstein, Michael P; Tinker, Stuart W; Charen, Krista H; Sherman, Stephanie L

    2008-09-01

    The fragile X mental retardation gene (FMR1) contains a CGG repeat sequence in its 5' untranslated region that can become unstable and expand in length from generation to generation. Alleles with expanded repeats in the range of approximately 55-199, termed premutation alleles, are associated with an increased risk for fragile-X-associated primary ovarian insufficiency (FXPOI). However, not all women who carry the premutation develop FXPOI. To determine if additional genes could explain variability in onset and severity, we used a random-effects Cox proportional hazards model to analyze age at menopause on 680 women from 225 families who have a history of fragile X syndrome and 321 women from 219 families from the general population. We tested for the presence of a residual additive genetic effect after adjustment for FMR1 repeat length, race, smoking, body mass index, and method of ascertainment. Results showed significant familial aggregation of age at menopause with an estimated additive genetic variance of 0.55-0.96 depending on the parameterization of FMR1 repeat size and definition of age at menopause (P-values ranging between 0.0002 and 0.0027). This is the first study to analyze familial aggregation of FXPOI. This result is important for proper counseling of women who carry FMR1 premutation alleles and for guidance of future studies to identify additional genes that influence ovarian insufficiency. (c) 2008 Wiley-Liss, Inc.

  1. Noninvasive assessment of the facilitation of the nociceptive withdrawal reflex by repeated electrical stimulations in conscious dogs.

    PubMed

    Bergadano, Alessandra; Andersen, Ole K; Arendt-Nielsen, Lars; Spadavecchia, Claudia

    2007-08-01

    To investigate the facilitation of the nociceptive withdrawal reflex (NWR) by repeated electrical stimuli and the associated behavioral response scores in conscious, nonmedicated dogs as a measure of temporal summation and analyze the influence of stimulus intensity and frequency on temporal summation responses. 8 adult Beagles. Surface electromyographic responses evoked by transcutaneous constant-current electrical stimulation of ulnaris and digital plantar nerves were recorded from the deltoideus, cleidobrachialis, biceps femoris, and cranial tibial muscles. A repeated stimulus was given at 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, and 1.1 x I(t) (the individual NWR threshold intensity) at 2, 5, and 20 Hz. Threshold intensity and relative amplitude and latency of the reflex were analyzed for each stimulus configuration. Behavioral reactions were subjectively scored. Repeated sub-I(t) stimuli summated and facilitated the NWR. To elicit temporal summation, significantly lower intensities were needed for the hind limb, compared with the forelimb. Stimulus frequency did not influence temporal summation, whereas increasing intensity resulted in significantly stronger electromyographic responses and nociception (determined via behavioral response scoring) among the dogs. In dogs, it is possible to elicit nociceptive temporal summation that correlates with behavioral reactions. These data suggest that this experimental technique can be used to evaluate nociceptive system excitability and efficacy of analgesics in canids.

  2. Osimertinib for the treatment of non-small cell lung cancer.

    PubMed

    Sun, Jong-Mu; Lee, Se-Hoon; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung-Ju

    2017-02-01

    The T790 M mutation of the epidermal growth factor receptor (EGFR) gene is the most common mechanism underlying resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR TKI, shows robust clinical efficacy in patients with T790 M-mutated lung cancer. Areas covered: We analyzed and reviewed clinical data for which patients who experienced acquired resistance to first- or second-generation EGFR TKIs. In addition, we briefly reviewed the potential role of osimertinib as a first-line therapy. Expert opinion: Osimertinib was recently licensed for use in NSCLC patients with acquired resistance to other EGFR TKIs due to a T790 M mutation. However, unresolved issues surrounding the optimal application of osimertinib remain, specifically the development of a plasma-based mutation test to overcome the difficulty of repeat biopsy, the efficacy of osimertinib for brain or leptomeningeal metastases, the development of resistance to osimertinib, and the use of osimertinib therapy as a first-line treatment. Many ongoing studies are currently exploring these issues.

  3. Humidity Sensor Based on PEDOT:PSS and Zinc Stannate Nano-composite

    NASA Astrophysics Data System (ADS)

    Aziz, Shahid; Chang, Dong Eui; Doh, Yang Hoi; Kang, Chul Ung; Choi, Kyung Hyun

    2015-10-01

    A composite of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) and zinc stannate (ZnSnO3) has been introduced for impedance-based humidity sensing, owing to its high sensitivity, good stability, very fast response (˜0.2 s) and recovery time (˜0.2 s), small hysteresis, repeatability, low-cost fabrication and wide range of sensitivity. Both materials were mixed in three different weight percentage ratios, to optimize the performance of the sensors. Best response was observed for 5 wt.% PEDOT:PSS and 5 wt.% ZnSnO3. The impedance of the sensor was dropped immensely from 1.5 MΩ to 50 kΩ by changing relative humidity from 0% to 90%. The reason for this improvement in sensitivity was analyzed by virtue of sensing mechanisms and different characterizations (three dimensional (3D) nano-profiler, optical microscope, and fourier transform infra-red (FTIR) spectroscopy) revealing the surface morphology and chemical structure of the film. Due to its response and ability to sense human breath and skin humidity, it is suitable for environmental, artificial skin and food industry applications.

  4. Reusable electrochemical cell for rapid separation of [18F]fluoride from [18O]water for flow-through synthesis of 18F-labeled tracers

    PubMed Central

    Sadeghi, Saman; Liang, Vincent; Cheung, Shilin; Woo, Suh; Wu, Curtis; Ly, Jimmy; Deng, Yuliang; Eddings, Mark; van Dam, R. Michael

    2015-01-01

    A brass-platinum electrochemical micro flow cell was developed to extract [18F]fluoride from an aqueous solution and release it into an organic based solution, suitable for subsequent radio-synthesis, in a fast and reliable manner. This cell does not suffer electrode erosion and is thus reusable while operating faster by enabling increased voltages. By optimizing temperature, trapping and release potentials, flow rates, and electrode materials, an overall [18F]fluoride trapping and release efficiency of 84±5% (n=7) was achieved. X-ray photoelectron spectroscopy (XPS) was used to analyze electrode surfaces of various metal-metal systems and the findings were correlated with the performance of the electrochemical cell. To demonstrate the reactivity of the released [18F]fluoride, the cell was coupled to a flow-through reactor and automated synthesis of [18F]FDG with a repeatable decay-corrected yield of 56±4% (n=4) was completed in <15 min. A multi-human dose of 5.92 GBq [18F]FDG was also demonstrated. PMID:23474380

  5. Analytical method for the simultaneous determination of polyfunctional amines used as monomers in the manufacture of food packaging materials.

    PubMed

    Paseiro-Cerrato, R; de Quirós, A Rodríguez-Bernaldo; Sendón, Raquel; Bustos, Juana; Ruíz, E; Cruz, J M; Paseiro-Losada, P

    2011-10-07

    This paper describes the development of a multi-analyte method for the determination of polyfunctional amines commonly used as monomers in the manufacture of food contact materials. Amines were analyzed by high-performance-liquid chromatography with diode-array detection (HPLC-DAD) after derivatization with dansyl chloride. The chromatographic analysis and the derivatization conditions were optimized. The proposed method was validated in terms of linearity, limits of detection and repeatabilities. The method showed an excellent sensitivity (LOD≤0.05 μg/mL) and appropriate repeatabilites (RSD (n=7)≤5%)). LC-MS/MS was used as a confirmatory technique. The stability of the amines in five food simulants (distilled water, 3% acetic acid, 10% ethanol, 50% ethanol and olive oil) under the most common testing conditions (10 days at 40 °C) was also studied. Results showed that amines had an acceptable stability in aqueous simulants but in the olive oil a loss of 100% was observed for all analytes. Copyright © 2011. Published by Elsevier B.V.

  6. Ionic liquid-based air-assisted liquid-liquid microextraction followed by high performance liquid chromatography for the determination of five fungicides in juice samples.

    PubMed

    You, Xiangwei; Chen, Xiaochu; Liu, Fengmao; Hou, Fan; Li, Yiqiang

    2018-01-15

    A novel and simple ionic liquid-based air-assisted liquid-liquid microextraction technique combined with high performance liquid chromatography was developed to analyze five fungicides in juice samples. In this method, ionic liquid was used instead of a volatile organic solvent as the extraction solvent. The emulsion was formed by pulling in and pushing out the mixture of aqueous sample solution and extraction solvent repeatedly using a 10mL glass syringe. No organic dispersive solvent was required. Under the optimized conditions, the limits of detection (LODs) were 0.4-1.8μgL -1 at a signal-to-noise ratio of 3. The limits of quantification (LOQs) set as the lowest spiking levels with acceptable recovery in juices were 10μgL -1 , except for fludioxonil whose LOQ was 20μgL -1 . The proposed method was applied to determine the target fungicides in juice samples, and acceptable recoveries ranging from 74.9% to 115.4% were achieved. Copyright © 2017. Published by Elsevier Ltd.

  7. Boosted Multivariate Trees for Longitudinal Data

    PubMed Central

    Pande, Amol; Li, Liang; Rajeswaran, Jeevanantham; Ehrlinger, John; Kogalur, Udaya B.; Blackstone, Eugene H.; Ishwaran, Hemant

    2017-01-01

    Machine learning methods provide a powerful approach for analyzing longitudinal data in which repeated measurements are observed for a subject over time. We boost multivariate trees to fit a novel flexible semi-nonparametric marginal model for longitudinal data. In this model, features are assumed to be nonparametric, while feature-time interactions are modeled semi-nonparametrically utilizing P-splines with estimated smoothing parameter. In order to avoid overfitting, we describe a relatively simple in sample cross-validation method which can be used to estimate the optimal boosting iteration and which has the surprising added benefit of stabilizing certain parameter estimates. Our new multivariate tree boosting method is shown to be highly flexible, robust to covariance misspecification and unbalanced designs, and resistant to overfitting in high dimensions. Feature selection can be used to identify important features and feature-time interactions. An application to longitudinal data of forced 1-second lung expiratory volume (FEV1) for lung transplant patients identifies an important feature-time interaction and illustrates the ease with which our method can find complex relationships in longitudinal data. PMID:29249866

  8. Microwave assisted direct saponification for the simultaneous determination of cholesterol and cholesterol oxides in shrimp.

    PubMed

    Souza, Hugo A L; Mariutti, Lilian R B; Bragagnolo, Neura

    2017-05-01

    A novel microwave-assisted direct saponification method for the simultaneous determination of cholesterol and cholesterol oxides in shrimp was developed and validated. Optimal saponification conditions, determined by means of an experimental design, were achieved using 500mg of sample and 20mL of 1mol/L KOH ethanol solution for 16min at 45°C at maximum power at 200W and magnetic stirring at 120rpm. Higher extraction of cholesterol oxides in a reduced saponification time (∼75 times) was achieved in comparison with the direct cold saponification method. The new method showed low detection (≤0.57μg/mL) and quantification (≤1.73μg/mL) limits, good repeatability (≤10.50% intraday and ≤8.56% interday) and low artifact formation (evaluated by using a deuterated cholesterol-D6 standard). Raw, salted and dried-salted shrimps were successfully analyzed by the validated method. The content of cholesterol oxides increased after salting and decreased after drying. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics.

    PubMed

    Anderson, Diana; Najafzadeh, Mojgan; Gopalan, Rajendran; Ghaderi, Nader; Scally, Andrew J; Britland, Stephen T; Jacobs, Badie K; Reynolds, P Dominic; Davies, Justin; Wright, Andrew L; Al-Ghazal, Shariff; Sharpe, David; Denyer, Morgan C

    2014-10-01

    Lymphocyte responses from 208 individuals: 20 with melanoma, 34 with colon cancer, and 4 with lung cancer (58), 18 with suspected melanoma, 28 with polyposis, and 10 with COPD (56), and 94 healthy volunteers were examined. The natural logarithm of the Olive tail moment (OTM) was plotted for exposure to UVA through 5 different agar depths (100 cell measurements/depth) and analyzed using a repeated measures regression model. Responses of patients with cancer plateaued after treatment with different UVA intensities, but returned toward control values for healthy volunteers. For precancerous conditions and suspected cancers, intermediate responses occurred. ROC analysis of mean log OTMs, for cancers plus precancerous/suspect conditions vs. controls, cancer vs. precancerous/suspect conditions plus controls, and cancer vs. controls, gave areas under the curve of 0.87, 0.89, and 0.93, respectively (P<0.001). Optimization allowed test sensitivity or specificity to approach 100% with acceptable complementary measures. This modified comet assay could represent a stand-alone test or an adjunct to other investigative procedures for detecting cancer. © FASEB.

  10. Technical note: A method for isolating glycogen granules from ruminal protozoa for further characterization.

    PubMed

    Hall, Mary Beth

    2016-03-01

    Evaluation of physical, chemical, and enzymatic hydrolysis characteristics of protozoal glycogen is best performed on a pure substrate to avoid interference from other cell components. A method for isolating protozoal glycogen granules without use of detergents or other potentially contaminating chemicals was developed. Rumen inoculum was incubated anerobically in vitro with glucose. Glycogen-laden protozoa produced in the fermentation, primarily isotrichids, were allowed to sediment in a separatory funnel and were dispensed. The protozoa were processed through repeated centrifugations and sonication to isolate glycogen granules largely free of feed and cellular debris. The final water-insoluble lyophilized product analyzed as 98.3% α-glucan with very rare starch granules and 1.9% protein. Observed losses of glycogen granules during the clean-up process indicate that this procedure should not be used for quantitative assessment of protozoal glycogen from fermentations. Further optimization of this procedure to enhance the amount of glycogen obtained per fermentation may be possible. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles.

    PubMed

    Tichy, Elisia D; Sidibe, David K; Tierney, Matthew T; Stec, Michael J; Sharifi-Sanjani, Maryam; Hosalkar, Harish; Mubarak, Scott; Johnson, F Brad; Sacco, Alessandra; Mourkioti, Foteini

    2017-10-10

    Muscle stem cells (MuSCs) contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or humans. Our analysis showed no differences in telomere length between young and aged MuSCs from uninjured wild-type mice, but MuSCs isolated from young dystrophic mice exhibited significantly shortened telomeres. In corroboration, we demonstrated that telomere attrition is present in human dystrophic MuSCs, which underscores its importance in diseased regenerative failure. The robust technique described herein provides analysis at a single-cell resolution and may be utilized for other cell types, especially rare populations of cells. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. An Accelerated Analytical Process for the Development of STR Profiles for Casework Samples.

    PubMed

    Laurin, Nancy; Frégeau, Chantal J

    2015-07-01

    Significant efforts are being devoted to the development of methods enabling rapid generation of short tandem repeat (STR) profiles in order to reduce turnaround times for the delivery of human identification results from biological evidence. Some of the proposed solutions are still costly and low throughput. This study describes the optimization of an analytical process enabling the generation of complete STR profiles (single-source or mixed profiles) for human identification in approximately 5 h. This accelerated process uses currently available reagents and standard laboratory equipment. It includes a 30-min lysis step, a 27-min DNA extraction using the Promega Maxwell(®) 16 System, DNA quantification in <1 h using the Qiagen Investigator(®) Quantiplex HYres kit, fast amplification (<26 min) of the loci included in AmpFℓSTR(®) Identifiler(®), and analysis of the profiles on the 3500-series Genetic Analyzer. This combination of fast individual steps produces high-quality profiling results and offers a cost-effective alternative approach to rapid DNA analysis. © 2015 American Academy of Forensic Sciences.

  13. Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

    PubMed Central

    Zhang, Rongxiao; Gladstone, David J.; Williams, Benjamin B.; Glaser, Adam K.; Pogue, Brian W.; Jarvis, Lesley A.

    2016-01-01

    Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R2 = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R2 = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. Conclusions: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments. PMID:26843259

  14. Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

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

    Andreozzi, Jacqueline M., E-mail: Jacqueline.M.Andreozzi.th@dartmouth.edu, E-mail: Lesley.A.Jarvis@hitchcock.org; Glaser, Adam K.; Zhang, Rongxiao

    2016-02-15

    Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, compositemore » images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R{sup 2} = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R{sup 2} = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. Conclusions: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments.« less

  15. Genetic variation and evolutionary stability of the FMR1 CGG repeat in six closed human populations

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

    Eichler, E.E.; Nelson, D.L.

    1996-07-12

    In an attempt to understand the allelic diversity and mutability of the human FMR1 CGG repeat, we have analyzed the AGG substructure of this locus within six genetically-closed populations (Mbuti pygmy, Baka pygmy, R. surui, Karitiana, Mayan, and Hutterite). Most alleles (61/92 or 66%) possessed two AGG interspersions occurring with a periodicity of one AGG every nine or ten CGG repeats, indicating that this pattern is highly conserved in all human populations. Significant differences in allele distribution were observed among the populations for rare variants possessing fewer or more AGG interruptions than the canonical FMR1 CGG repeat sequence. Comparisons ofmore » expected heterozygosity of the FMR1 CGG repeat locus with 30 other microsatellite loci, demonstrated remarkably similar levels of polymorphism within each population, suggesting that most FMR1 CGG repeat alleles mutate at rates indistinguishable from other microsatellite loci. A single allele (1 out of 92) was identified with a large uninterrupted tract of pure repeats (42 pure CGG triplets). Retrospective pedigree analysis indicated that this allele had been transmitted unstably. Although such alleles mutate rapidly and likely represent evolving premutations, our analysis suggests that in spite of the estimated frequency of their occurrence, these unstable alleles do not significantly alter the expected heterozygosity of the FMR1 CGG repeat in the human population. 45 refs., 1 fig., 2 tabs.« less

  16. Revisiting the TALE repeat.

    PubMed

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  17. MutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia

    PubMed Central

    Ezzatizadeh, Vahid; Sandi, Chiranjeevi; Sandi, Madhavi; Anjomani-Virmouni, Sara; Al-Mahdawi, Sahar; Pook, Mark A.

    2014-01-01

    Background Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. PMID:24971578

  18. A survey of FRAXE allele sizes in three populations

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

    Zhong, N.; Ju, W.; Curley, D.

    1996-08-09

    FRAXE is a fragile site located at Xq27-8, which contains polymorphic triplet GCC repeats associated with a CpG island. Similar to FRAXA, expansion of the GCC repeats results in an abnormal methylation of the CpG island and is associated with a mild mental retardation syndrome (FRAXE-MR). We surveyed the GCC repeat alleles of FRAXE from 3 populations. A total of 665 X chromosomes including 416 from a New York Euro-American sample (259 normal and 157 with FRAXA mutations), 157 from a Chinese sample (144 normal and 13 FRAXA), and 92 from a Finnish sample (56 normal and 36 FRAXA) weremore » analyzed by polymerase chain reaction. Twenty-seven alleles, ranging from 4 to 39 GCC repeats, were observed. The modal repeat number was 16 in the New York and Finnish samples and accounted for 24% of all the chromosomes tested (162/665). The modal repeat number in the Chinese sample was 18. A founder effect for FRAXA was suggested among the Finnish FRAXA samples in that 75% had the FRAXE 16 repeat allele versus only 30% of controls. Sequencing of the FRAXE region showed no imperfections within the GCC repeat region, such as those commonly seen in FRAXA. The smaller size and limited range of repeats and the lack of imperfections suggests the molecular mechanisms underlying FRAXE triplet mutations may be different from those underlying FRAXA. 27 refs., 4 figs., 1 tab.« less

  19. Variable-Number Tandem Repeats That Are Useful in Genotyping Isolates of Salmonella enterica subsp. enterica Serovars Typhimurium and Newport▿

    PubMed Central

    Witonski, D. ; Stefanova, R.; Ranganathan, A.; Schutze, G. E.; Eisenach, K. D.; Cave, M. D.

    2006-01-01

    The genome of Salmonella enterica subsp. enterica serovar Typhimurium strain LT2 was analyzed for direct repeats, and 54 sequences containing variable-number tandem repeat loci were identified. Ten primer pairs that anneal upstream and downstream of each selected locus were designed and used to amplify PCR targets in isolates of S. enterica serovars Typhimurium and Newport. Four of the 10 loci did not show polymorphism in the length of products. Six loci were selected for analysis. Isolates of S. enterica serovars Typhimurium and Newport that were related to specific outbreaks and showed identical pulsed-field gel electrophoresis patterns were indistinguishable by the length of the six variable-number tandem repeats. Isolates that differed in their pulsed-field gel electrophoresis patterns showed polymorphism in variable-number tandem repeat profiles. Length of the products was confirmed by DNA sequence analysis. Only 2 of the 10 loci contained exact integers of the direct repeat. Eight loci contained partial copies. The partial copies were maintained at the ends of the variable-number tandem repeat loci in all isolates. In spite of having partial copies that were maintained in all isolates, the number of direct repeats at a locus was polymorphic. Six variable-number tandem repeat loci were useful in distinguishing isolates of S. enterica serovars Typhimurium and Newport that had different pulsed-field gel electrophoresis patterns and in identifying outbreak-associated cases that shared a common pulsed-field gel pattern. PMID:16943354

  20. Tandem-repeat protein domains across the tree of life

    PubMed Central

    Jernigan, Kristin K.

    2015-01-01

    Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20–40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species. PMID:25653910

  1. Mixed Effects Modeling of Morris Water Maze Data: Advantages and Cautionary Notes

    ERIC Educational Resources Information Center

    Young, Michael E.; Clark, M. H.; Goffus, Andrea; Hoane, Michael R.

    2009-01-01

    Morris water maze data are most commonly analyzed using repeated measures analysis of variance in which daily test sessions are analyzed as an unordered categorical variable. This approach, however, may lack power, relies heavily on post hoc tests of daily performance that can complicate interpretation, and does not target the nonlinear trends…

  2. Bambus 2: scaffolding metagenomes.

    PubMed

    Koren, Sergey; Treangen, Todd J; Pop, Mihai

    2011-11-01

    Sequencing projects increasingly target samples from non-clonal sources. In particular, metagenomics has enabled scientists to begin to characterize the structure of microbial communities. The software tools developed for assembling and analyzing sequencing data for clonal organisms are, however, unable to adequately process data derived from non-clonal sources. We present a new scaffolder, Bambus 2, to address some of the challenges encountered when analyzing metagenomes. Our approach relies on a combination of a novel method for detecting genomic repeats and algorithms that analyze assembly graphs to identify biologically meaningful genomic variants. We compare our software to current assemblers using simulated and real data. We demonstrate that the repeat detection algorithms have higher sensitivity than current approaches without sacrificing specificity. In metagenomic datasets, the scaffolder avoids false joins between distantly related organisms while obtaining long-range contiguity. Bambus 2 represents a first step toward automated metagenomic assembly. Bambus 2 is open source and available from http://amos.sf.net. mpop@umiacs.umd.edu. Supplementary data are available at Bioinformatics online.

  3. Bambus 2: scaffolding metagenomes

    PubMed Central

    Koren, Sergey; Treangen, Todd J.; Pop, Mihai

    2011-01-01

    Motivation: Sequencing projects increasingly target samples from non-clonal sources. In particular, metagenomics has enabled scientists to begin to characterize the structure of microbial communities. The software tools developed for assembling and analyzing sequencing data for clonal organisms are, however, unable to adequately process data derived from non-clonal sources. Results: We present a new scaffolder, Bambus 2, to address some of the challenges encountered when analyzing metagenomes. Our approach relies on a combination of a novel method for detecting genomic repeats and algorithms that analyze assembly graphs to identify biologically meaningful genomic variants. We compare our software to current assemblers using simulated and real data. We demonstrate that the repeat detection algorithms have higher sensitivity than current approaches without sacrificing specificity. In metagenomic datasets, the scaffolder avoids false joins between distantly related organisms while obtaining long-range contiguity. Bambus 2 represents a first step toward automated metagenomic assembly. Availability: Bambus 2 is open source and available from http://amos.sf.net. Contact: mpop@umiacs.umd.edu Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:21926123

  4. Flame Spread and Damaged Properties of RCD Cases by Tracking

    NASA Astrophysics Data System (ADS)

    Choi, Chung-Seog; Kim, Hyang-Kon; Shong, Kil-Mok; Kim, Dong-Woo

    In this paper, the flame spread and damaged properties of residual current protective devices (RCDs) by tracking were analyzed. Pictures of tracking process were taken by High Speed Imaging System (HSIS), and fire progression was observed by timeframe. During the tracking process of RCD, it seemed to explode just once in appearance, but in the results of HSIS analysis, a small fire broke out and disappeared repeatedly 35 times and a flash of light repeated 15 times. Finally, an explosion with a flash of light occurred and lots of particles were scattered. Electric muffle furnace was used for heat treatment of RCD cases. The surface characteristics of specimens due to heat treatment and tracking deterioration were taken by Scanning Electron Microscope (SEM). Chemical and thermal properties of these deteriorated specimens were analyzed by Fourier Transform Infrared Spectrometer (FT-IR) and Differential Thermal Analyzer (DTA). The carbonization characteristics showed different chemical properties due to energy sources, and the results could be applicable to judge the accident causes.

  5. Surface characterization protocol for precision aspheric optics

    NASA Astrophysics Data System (ADS)

    Sarepaka, RamaGopal V.; Sakthibalan, Siva; Doodala, Somaiah; Panwar, Rakesh S.; Kotaria, Rajendra

    2017-10-01

    In Advanced Optical Instrumentation, Aspherics provide an effective performance alternative. The aspheric fabrication and surface metrology, followed by aspheric design are complementary iterative processes for Precision Aspheric development. As in fabrication, a holistic approach of aspheric surface characterization is adopted to evaluate actual surface error and to aim at the deliverance of aspheric optics with desired surface quality. Precision optical surfaces are characterized by profilometry or by interferometry. Aspheric profiles are characterized by contact profilometers, through linear surface scans to analyze their Form, Figure and Finish errors. One must ensure that, the surface characterization procedure does not add to the resident profile errors (generated during the aspheric surface fabrication). This presentation examines the errors introduced post-surface generation and during profilometry of aspheric profiles. This effort is to identify sources of errors and is to optimize the metrology process. The sources of error during profilometry may be due to: profilometer settings, work-piece placement on the profilometer stage, selection of zenith/nadir points of aspheric profiles, metrology protocols, clear aperture - diameter analysis, computational limitations of the profiler and the software issues etc. At OPTICA, a PGI 1200 FTS contact profilometer (Taylor-Hobson make) is used for this study. Precision Optics of various profiles are studied, with due attention to possible sources of errors during characterization, with multi-directional scan approach for uniformity and repeatability of error estimation. This study provides an insight of aspheric surface characterization and helps in optimal aspheric surface production methodology.

  6. Conceptual Design Oriented Wing Structural Analysis and Optimization

    NASA Technical Reports Server (NTRS)

    Lau, May Yuen

    1996-01-01

    Airplane optimization has always been the goal of airplane designers. In the conceptual design phase, a designer's goal could be tradeoffs between maximum structural integrity, minimum aerodynamic drag, or maximum stability and control, many times achieved separately. Bringing all of these factors into an iterative preliminary design procedure was time consuming, tedious, and not always accurate. For example, the final weight estimate would often be based upon statistical data from past airplanes. The new design would be classified based on gross characteristics, such as number of engines, wingspan, etc., to see which airplanes of the past most closely resembled the new design. This procedure works well for conventional airplane designs, but not very well for new innovative designs. With the computing power of today, new methods are emerging for the conceptual design phase of airplanes. Using finite element methods, computational fluid dynamics, and other computer techniques, designers can make very accurate disciplinary-analyses of an airplane design. These tools are computationally intensive, and when used repeatedly, they consume a great deal of computing time. In order to reduce the time required to analyze a design and still bring together all of the disciplines (such as structures, aerodynamics, and controls) into the analysis, simplified design computer analyses are linked together into one computer program. These design codes are very efficient for conceptual design. The work in this thesis is focused on a finite element based conceptual design oriented structural synthesis capability (CDOSS) tailored to be linked into ACSYNT.

  7. A case study in nonconformance and performance trend analysis

    NASA Technical Reports Server (NTRS)

    Maloy, Joseph E.; Newton, Coy P.

    1990-01-01

    As part of NASA's effort to develop an agency-wide approach to trend analysis, a pilot nonconformance and performance trending analysis study was conducted on the Space Shuttle auxiliary power unit (APU). The purpose of the study was to (1) demonstrate that nonconformance analysis can be used to identify repeating failures of a specific item (and the associated failure modes and causes) and (2) determine whether performance parameters could be analyzed and monitored to provide an indication of component or system degradation prior to failure. The nonconformance analysis of the APU did identify repeating component failures, which possibly could be reduced if key performance parameters were monitored and analyzed. The performance-trending analysis verified that the characteristics of hardware parameters can be effective in detecting degradation of hardware performance prior to failure.

  8. Iterative optimization method for design of quantitative magnetization transfer imaging experiments.

    PubMed

    Levesque, Ives R; Sled, John G; Pike, G Bruce

    2011-09-01

    Quantitative magnetization transfer imaging (QMTI) using spoiled gradient echo sequences with pulsed off-resonance saturation can be a time-consuming technique. A method is presented for selection of an optimum experimental design for quantitative magnetization transfer imaging based on the iterative reduction of a discrete sampling of the Z-spectrum. The applicability of the technique is demonstrated for human brain white matter imaging at 1.5 T and 3 T, and optimal designs are produced to target specific model parameters. The optimal number of measurements and the signal-to-noise ratio required for stable parameter estimation are also investigated. In vivo imaging results demonstrate that this optimal design approach substantially improves parameter map quality. The iterative method presented here provides an advantage over free form optimal design methods, in that pragmatic design constraints are readily incorporated. In particular, the presented method avoids clustering and repeated measures in the final experimental design, an attractive feature for the purpose of magnetization transfer model validation. The iterative optimal design technique is general and can be applied to any method of quantitative magnetization transfer imaging. Copyright © 2011 Wiley-Liss, Inc.

  9. 40 CFR 1065.303 - Summary of required calibration and verifications.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... initial installation and after major maintenance. THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers: upon initial installation, within 185 days before...

  10. 40 CFR 1065.303 - Summary of required calibration and verifications.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... initial installation and after major maintenance. THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers: upon initial installation, within 185 days before...

  11. [Mutation Analysis of 19 STR Loci in 20 723 Cases of Paternity Testing].

    PubMed

    Bi, J; Chang, J J; Li, M X; Yu, C Y

    2017-06-01

    To observe and analyze the confirmed cases of paternity testing, and to explore the mutation rules of STR loci. The mutant STR loci were screened from 20 723 confirmed cases of paternity testing by Goldeneye 20A system.The mutation rates, and the sources, fragment length, steps and increased or decreased repeat sequences of mutant alleles were counted for the analysis of the characteristics of mutation-related factors. A total of 548 mutations were found on 19 STR loci, and 557 mutation events were observed. The loci mutation rate was 0.07‰-2.23‰. The ratio of paternal to maternal mutant events was 3.06:1. One step mutation was the main mutation, and the number of the increased repeat sequences was almost the same as the decreased repeat sequences. The repeat sequences were more likely to decrease in two steps mutation and above. Mutation mainly occurred in the medium allele, and the number of the increased repeat sequences was almost the same as the decreased repeat sequences. In long allele mutations, the decreased repeat sequences were significantly more than the increased repeat sequences. The number of the increased repeat sequences was almost the same as the decreased repeat sequences in paternal mutation, while the decreased repeat sequences were more than the increased in maternal mutation. There are significant differences in the mutation rate of each locus. When one or two loci do not conform to the genetic law, other detection system should be added, and PI value should be calculated combined with the information of the mutate STR loci in order to further clarify the identification opinions. Copyright© by the Editorial Department of Journal of Forensic Medicine

  12. Few millimeter precision for baselines in the California Permanent GPS Geodetic Array

    NASA Technical Reports Server (NTRS)

    Lindqwister, Ulf J.; Zumberge, James F.; Webb, Frank H.; Blewitt, Geoffrey

    1991-01-01

    Geodetic measurements with Rogue GPS receivers from sites in the California Permanent GPS geodetic Array (PGGA) have been analyzed using the GIPSY orbit-determination and baseline-estimation software. Based on an unbiased selection of 23 daily measurements spanning 8 months, the LF contributions to the long-term repeatabilities of baseline measurements are approximately 5, 3, and 8 mm for the east, north, and vertical components. Short-term contributions to the long-term repeatabilities were evaluated by examining data from the week of October 21, 1990, which showed the lowest short-term scatter. For this week, daily repeatabilities of 2-3 mm in the horizontal and 4 mm in the vertical have been achieved for the 172-km JPL-Pinyon baseline, consistent with carrier phase date noise of about 6 mm. High quality (less than about 5 mm) repeatabilities have been achieved for all components of the other baselines as well.

  13. Impact of Repeated Questioning on Interviewers: Learning From a Forensic Interview Training Project.

    PubMed

    Duron, Jacquelynn F; Cheung, Monit

    2016-01-01

    Forensic interviewers have a difficult job with high risk for career burnout and secondary trauma. Few studies have addressed how new forensic interviewers or trainees experience repeated questioning and multiple interviews. This study simulated the process of training new forensic interviewers through the creation of two interview videos in which social work graduate students participated as actors portraying the roles of interviewer and child. These films served as instructional aids preparing graduate social work students for professional child welfare roles while promoting research-based approaches to interviewing children about sexual abuse allegations. Qualitative data from two cohorts of student actors were collected to analyze interviewers' perspectives on repeated questioning and interviews in child sexual abuse cases. Two themes were extracted from the subjects' experiences: "It is emotionally taxing" and "Navigating the interviewer role is unexpectedly complex." Exposure to repeated questions and multiple interviews affected the performance and confidence of the interviewers.

  14. Identification and characterization of tandem repeats in exon III of dopamine receptor D4 (DRD4) genes from different mammalian species.

    PubMed

    Larsen, Svend Arild; Mogensen, Line; Dietz, Rune; Baagøe, Hans Jørgen; Andersen, Mogens; Werge, Thomas; Rasmussen, Henrik Berg

    2005-12-01

    In this study we have identified and characterized dopamine receptor D4 (DRD4) exon III tandem repeats in 33 public available nucleotide sequences from different mammalian species. We found that the tandem repeat in canids could be described in a novel and simple way, namely, as a structure composed of 15- and 12- bp modules. Tandem repeats composed of 18-bp modules were found in sequences from the horse, zebra, onager, and donkey, Asiatic bear, polar bear, common raccoon, dolphin, harbor porpoise, and domestic cat. Several of these sequences have been analyzed previously without a tandem repeat being found. In the domestic cow and gray seal we identified tandem repeats composed of 36-bp modules, each consisting of two closely related 18-bp basic units. A tandem repeat consisting of 9-bp modules was identified in sequences from mink and ferret. In the European otter we detected an 18-bp tandem repeat, while a tandem repeat consisting of 27-bp modules was identified in a sequence from European badger. Both these tandem repeats were composed of 9-bp basic units, which were closely related with the 9-bp repeat modules identified in the mink and ferret. Tandem repeats could not be identified in sequences from rodents. All tandem repeats possessed a high GC content with a strong bias for C. On phylogenetic analysis of the tandem repeats evolutionary related species were clustered into the same groups. The degree of conservation of the tandem repeats varied significantly between species. The deduced amino acid sequences of most of the tandem repeats exhibited a high propensity for disorder. This was also the case with an amino acid sequence of the human DRD4 exon III tandem repeat, which was included in the study for comparative purposes. We identified proline-containing motifs for SH3 and WW domain binding proteins, potential phosphorylation sites, PDZ domain binding motifs, and FHA domain binding motifs in the amino acid sequences of the tandem repeats. The numbers of potential functional sites varied pronouncedly between species. Our observations provide a platform for future studies of the architecture and evolution of the DRD4 exon III tandem repeat, and they suggest that differences in the structure of this tandem repeat contribute to specialization and generation of diversity in receptor function.

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

    Hart, William; Laird, Carl; Siirola, John

    Pyomo provides a rich software environment for formulating and analyzing optimization applications. Pyomo supports the algebraic specification of complex sets of objectives and constraints, which enables optimization solvers to exploit problem structure to efficiently perform optimization.

  16. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum.

    PubMed

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    Growing awareness of cerebellar involvement in addiction is based on the cerebellum's intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction.

  17. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    PubMed Central

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction. PMID:24634647

  18. Strategies for Helping Parents of Young Children Address Challenging Behaviors in the Home

    ERIC Educational Resources Information Center

    Chai, Zhen; Lieberman-Betz, Rebecca

    2016-01-01

    Challenging behavior can be defined as any repeated pattern of behavior, or perception of behavior, that interferes with or is at risk of interfering with optimal learning or engagement in prosocial interactions with peers and adults. It is generally accepted in young children that challenging behaviors serve some sort of communicative purpose--to…

  19. MAKER-P: a tool-kit for the creation, management, and quality control of plant genome annotations

    USDA-ARS?s Scientific Manuscript database

    We have optimized and extended the widely used annotation-engine MAKER for use on plant genomes. We have benchmarked the resulting software, MAKER-P, using the A. thaliana genome and the TAIR10 gene models. Here we demonstrate the ability of the MAKER-P toolkit to generate de novo repeat databases, ...

  20. Application of Polarimetric-Interferometric Phase Coherence Optimization (PIPCO) Procedure to SIR-C/X-SAR Tien-Shan Tracks 122.20(94 Oct. 08)/154.20(94 Oct. 09) Repeat-Orbit C/L-Band Pol-D-InSAR Imag

    NASA Technical Reports Server (NTRS)

    Boerner, W. M.; Mott, H.; Verdi, J.; Darizhapov, D.; Dorjiev, B.; Tsybjito, T.; Korsunov, V.; Tatchkov, G.; Bashkuyev, Y.; Cloude, S.; hide

    1998-01-01

    During the past decade, Radar Polarimetry has established itself as a mature science and advanced technology in high resolution POL-SAR imaging, image target characterization and selective image feature extraction.

  1. Design Process for High Speed Civil Transport Aircraft Improved by Neural Network and Regression Methods

    NASA Technical Reports Server (NTRS)

    Hopkins, Dale A.

    1998-01-01

    A key challenge in designing the new High Speed Civil Transport (HSCT) aircraft is determining a good match between the airframe and engine. Multidisciplinary design optimization can be used to solve the problem by adjusting parameters of both the engine and the airframe. Earlier, an example problem was presented of an HSCT aircraft with four mixed-flow turbofan engines and a baseline mission to carry 305 passengers 5000 nautical miles at a cruise speed of Mach 2.4. The problem was solved by coupling NASA Lewis Research Center's design optimization testbed (COMETBOARDS) with NASA Langley Research Center's Flight Optimization System (FLOPS). The computing time expended in solving the problem was substantial, and the instability of the FLOPS analyzer at certain design points caused difficulties. In an attempt to alleviate both of these limitations, we explored the use of two approximation concepts in the design optimization process. The two concepts, which are based on neural network and linear regression approximation, provide the reanalysis capability and design sensitivity analysis information required for the optimization process. The HSCT aircraft optimization problem was solved by using three alternate approaches; that is, the original FLOPS analyzer and two approximate (derived) analyzers. The approximate analyzers were calibrated and used in three different ranges of the design variables; narrow (interpolated), standard, and wide (extrapolated).

  2. Individuality in nutritional preferences: a multi-level approach in field crickets.

    PubMed

    Han, Chang S; Jäger, Heidi Y; Dingemanse, Niels J

    2016-06-30

    Selection may favour individuals of the same population to differ consistently in nutritional preference, for example, because optimal diets covary with morphology or personality. We provided Southern field crickets (Gryllus bimaculatus) with two synthetic food sources (carbohydrates and proteins) and quantified repeatedly how much of each macronutrient was consumed by each individual. We then quantified (i) whether individuals were repeatable in carbohydrate and protein intake rate, (ii) whether an individual's average daily intake of carbohydrates was correlated with its average daily intake of protein, and (iii) whether short-term changes in intake of carbohydrates coincided with changes in intake of protein within individuals. Intake rates were individually repeatable for both macronutrients. However, individuals differed in their relative daily intake of carbohydrates versus proteins (i.e., 'nutritional preference'). By contrast, total consumption varied plastically as a function of body weight within individuals. Body weight-but not personality (i.e., aggression, exploration behaviour)-positively predicted nutritional preference at the individual level as large crickets repeatedly consumed a higher carbohydrate to protein ratio compared to small ones. Our finding of level-specific associations between the consumption of distinct nutritional components demonstrates the merit of applying multivariate and multi-level viewpoints to the study of nutritional preference.

  3. Assessing Diversity of DNA Structure-Related Sequence Features in Prokaryotic Genomes

    PubMed Central

    Huang, Yongjie; Mrázek, Jan

    2014-01-01

    Prokaryotic genomes are diverse in terms of their nucleotide and oligonucleotide composition as well as presence of various sequence features that can affect physical properties of the DNA molecule. We present a survey of local sequence patterns which have a potential to promote non-canonical DNA conformations (i.e. different from standard B-DNA double helix) and interpret the results in terms of relationships with organisms' habitats, phylogenetic classifications, and other characteristics. Our present work differs from earlier similar surveys not only by investigating a wider range of sequence patterns in a large number of genomes but also by using a more realistic null model to assess significant deviations. Our results show that simple sequence repeats and Z-DNA-promoting patterns are generally suppressed in prokaryotic genomes, whereas palindromes and inverted repeats are over-represented. Representation of patterns that promote Z-DNA and intrinsic DNA curvature increases with increasing optimal growth temperature (OGT), and decreases with increasing oxygen requirement. Additionally, representations of close direct repeats, palindromes and inverted repeats exhibit clear negative trends with increasing OGT. The observed relationships with environmental characteristics, particularly OGT, suggest possible evolutionary scenarios of structural adaptation of DNA to particular environmental niches. PMID:24408877

  4. Opportunities to Foster Efficient Communication in Labor and Delivery Using Simulation.

    PubMed

    Daniels, Kay; Hamilton, Colleen; Crowe, Susan; Lipman, Steven S; Halamek, Louis P; Lee, Henry C

    2017-01-01

    Introduction  Communication errors are an important contributing factor in adverse outcomes in labor and delivery (L&D) units. The objective of this study was to identify common lapses in verbal communication using simulated obstetrical scenarios and propose alternative formats for communication. Methods  Health care professionals in L&D participated in three simulated clinical scenarios. Scenarios were recorded and reviewed to identify questions repeated within and across scenarios. Questions that were repeated more than once due to ineffective communication were identified. The frequency with which the questions were asked across simulations was identified. Results  Questions were commonly repeated both within and across 27 simulated scenarios. The median number of questions asked was 27 per simulated scenario. Commonly repeated questions focused on three general topics: (1) historical data/information (i.e., estimated gestational age), (2) maternal clinical status (i.e., estimated blood loss), and (3) personnel (i.e., "Has anesthesiologist been called?"). Conclusion  Inefficient verbal communication exists in the process of transferring information during obstetric emergencies. These findings can inform improved training and development of information displays to improve teamwork and communication. A visual display that can report static historical information and specific dynamic clinical data may facilitate optimal human performance.

  5. Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9.

    PubMed

    Prykhozhij, Sergey V; Fuller, Charlotte; Steele, Shelby L; Veinotte, Chansey J; Razaghi, Babak; Robitaille, Johane M; McMaster, Christopher R; Shlien, Adam; Malkin, David; Berman, Jason N

    2018-06-14

    We have optimized point mutation knock-ins into zebrafish genomic sites using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 reagents and single-stranded oligodeoxynucleotides. The efficiency of knock-ins was assessed by a novel application of allele-specific polymerase chain reaction and confirmed by high-throughput sequencing. Anti-sense asymmetric oligo design was found to be the most successful optimization strategy. However, cut site proximity to the mutation and phosphorothioate oligo modifications also greatly improved knock-in efficiency. A previously unrecognized risk of off-target trans knock-ins was identified that we obviated through the development of a workflow for correct knock-in detection. Together these strategies greatly facilitate the study of human genetic diseases in zebrafish, with additional applicability to enhance CRISPR-based approaches in other animal model systems.

  6. Influence of a heptad repeat stutter on the pH-dependent conformational behavior of the central coiled-coil from influenza hemagglutinin HA2.

    PubMed

    Higgins, Chelsea D; Malashkevich, Vladimir N; Almo, Steven C; Lai, Jonathan R

    2014-09-01

    The coiled-coil is one of the most common protein structural motifs. Amino acid sequences of regions that participate in coiled-coils contain a heptad repeat in which every third then forth residue is occupied by a hydrophobic residue. Here we examine the consequences of a "stutter," a deviation of the idealized heptad repeat that is found in the central coiled-coil of influenza hemagluttinin HA2. Characterization of a peptide containing the native stutter-containing HA2 sequence, as well as several variants in which the stutter was engineered out to restore an idealized heptad repeat pattern, revealed that the stutter is important for allowing coiled-coil formation in the WT HA2 at both neutral and low pH (7.1 and 4.5). By contrast, all variants that contained idealized heptad repeats exhibited marked pH-dependent coiled-coil formation with structures forming much more stably at low pH. A crystal structure of one variant containing an idealized heptad repeat, and comparison to the WT HA2 structure, suggest that the stutter distorts the optimal interhelical core packing arrangement, resulting in unwinding of the coiled-coil superhelix. Interactions between acidic side chains, in particular E69 and E74 (present in all peptides studied), are suggested to play a role in mediating these pH-dependent conformational effects. This conclusion is partially supported by studies on HA2 variant peptides in which these positions were altered to aspartic acid. These results provide new insight into the structural role of the heptad repeat stutter in HA2. © 2014 Wiley Periodicals, Inc.

  7. Discovery of Escherichia coli CRISPR sequences in an undergraduate laboratory.

    PubMed

    Militello, Kevin T; Lazatin, Justine C

    2017-05-01

    Clustered regularly interspaced short palindromic repeats (CRISPRs) represent a novel type of adaptive immune system found in eubacteria and archaebacteria. CRISPRs have recently generated a lot of attention due to their unique ability to catalog foreign nucleic acids, their ability to destroy foreign nucleic acids in a mechanism that shares some similarity to RNA interference, and the ability to utilize reconstituted CRISPR systems for genome editing in numerous organisms. In order to introduce CRISPR biology into an undergraduate upper-level laboratory, a five-week set of exercises was designed to allow students to examine the CRISPR status of uncharacterized Escherichia coli strains and to allow the discovery of new repeats and spacers. Students started the project by isolating genomic DNA from E. coli and amplifying the iap CRISPR locus using the polymerase chain reaction (PCR). The PCR products were analyzed by Sanger DNA sequencing, and the sequences were examined for the presence of CRISPR repeat sequences. The regions between the repeats, the spacers, were extracted and analyzed with BLASTN searches. Overall, CRISPR loci were sequenced from several previously uncharacterized E. coli strains and one E. coli K-12 strain. Sanger DNA sequencing resulted in the discovery of 36 spacer sequences and their corresponding surrounding repeat sequences. Five of the spacers were homologous to foreign (non-E. coli) DNA. Assessment of the laboratory indicates that improvements were made in the ability of students to answer questions relating to the structure and function of CRISPRs. Future directions of the laboratory are presented and discussed. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):262-269, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

  8. Exceptionally long 5' UTR short tandem repeats specifically linked to primates.

    PubMed

    Namdar-Aligoodarzi, P; Mohammadparast, S; Zaker-Kandjani, B; Talebi Kakroodi, S; Jafari Vesiehsari, M; Ohadi, M

    2015-09-10

    We have previously reported genome-scale short tandem repeats (STRs) in the core promoter interval (i.e. -120 to +1 to the transcription start site) of protein-coding genes that have evolved identically in primates vs. non-primates. Those STRs may function as evolutionary switch codes for primate speciation. In the current study, we used the Ensembl database to analyze the 5' untranslated region (5' UTR) between +1 and +60 of the transcription start site of the entire human protein-coding genes annotated in the GeneCards database, in order to identify "exceptionally long" STRs (≥5-repeats), which may be of selective/adaptive advantage. The importance of this critical interval is its function as core promoter, and its effect on transcription and translation. In order to minimize ascertainment bias, we analyzed the evolutionary status of the human 5' UTR STRs of ≥5-repeats in several species encompassing six major orders and superorders across mammals, including primates, rodents, Scandentia, Laurasiatheria, Afrotheria, and Xenarthra. We introduce primate-specific STRs, and STRs which have expanded from mouse to primates. Identical co-occurrence of the identified STRs of rare average frequency between 0.006 and 0.0001 in primates supports a role for those motifs in processes that diverged primates from other mammals, such as neuronal differentiation (e.g. APOD and FGF4), and craniofacial development (e.g. FILIP1L). A number of the identified STRs of ≥5-repeats may be human-specific (e.g. ZMYM3 and DAZAP1). Future work is warranted to examine the importance of the listed genes in primate/human evolution, development, and disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models

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

    Teng, S.; Tebby, C.

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro – in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-timemore » cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. - Highlights: • We could predict cell response over repeated exposure to mixtures of cosmetics. • Compounds acted independently on the cells. • Metabolic interactions impacted exposure concentrations to the compounds.« less

  10. Single-Laboratory Validation for the Determination of Flavonoids in Hawthorn Leaves and Finished Products by LC-UV.

    PubMed

    Mudge, Elizabeth M; Liu, Ying; Lund, Jensen A; Brown, Paula N

    2016-11-01

    Suitably validated analytical methods that can be used to quantify medicinally active phytochemicals in natural health products are required by regulators, manufacturers, and consumers. Hawthorn ( Crataegus ) is a botanical ingredient in natural health products used for the treatment of cardiovascular disorders. A method for the quantitation of vitexin-2″- O - rhamnoside, vitexin, isovitexin, rutin, and hyperoside in hawthorn leaf and flower raw materials and finished products was optimized and validated according to AOAC International guidelines. A two-level partial factorial study was used to guide the optimization of the sample preparation. The optimal conditions were found to be a 60-minute extraction using 50 : 48 : 2 methanol : water : acetic acid followed by a 25-minute separation using a reversed-phased liquid chromatography column with ultraviolet absorbance detection. The single-laboratory validation study evaluated method selectivity, accuracy, repeatability, linearity, limit of quantitation, and limit of detection. Individual flavonoid content ranged from 0.05 mg/g to 17.5 mg/g in solid dosage forms and raw materials. Repeatability ranged from 0.7 to 11.7 % relative standard deviation corresponding to HorRat ranges from 0.2 to 1.6. Calibration curves for each flavonoid were linear within the analytical ranges with correlation coefficients greater than 99.9 %. Herein is the first report of a validated method that is fit for the purpose of quantifying five major phytochemical marker compounds in both raw materials and finished products made from North American ( Crataegus douglasii ) and European ( Crataegus monogyna and Crataegus laevigata) hawthorn species. The method includes optimized extraction of samples without a prolonged drying process and reduced liquid chromatography separation time. Georg Thieme Verlag KG Stuttgart · New York.

  11. Optimization of the HS-SPME-GC-IT/MS method using a central composite design for volatile carbonyl compounds determination in beers.

    PubMed

    Moreira, Nathalie; Meireles, Sónia; Brandão, Tiago; de Pinho, Paula Guedes

    2013-12-15

    An automated headspace solid-phase microextraction (HS-SPME) combined with gas chromatography and ion trap mass spectrometry detection (GC-IT/MS) was developed in order to quantify a large number of carbonyl compounds in beers. Carbonyl compounds were previously derivatized with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA). Volatile carbonyl compounds associated with staling beer aroma includes alkanals, alkenals, alkadienals, dicarbonyl compounds, Strecker aldehydes, ketones and furans. The HS-SPME was performed using a polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber. The procedures were optimized for HS-SPME pre-incubation temperature and time, extraction temperature and time, and PFBHA addition. A central composite design was used in the optimization of extraction conditions and PFBHA addition. The volatile compounds showed optimal extraction incubating 5 ml of beer with 700 mg l(-1) of PFBHA for 7 min and extracted for more 20 min at 45 °C. The method was validated with regard to the linearity, repeatability, inter and intra-day precision and accuracy. The method achieved detection limits ranging from 0.003 to 0.510 µg l(-1), except for furans (1.54-3.44 µg l(-1)). The quantification limits varied from 0.010 to 1.55 µg l(-1), except for 2-furfural (4.68 µg l(-1)), 5-methyl-2-furfural (5.82 µg l(-1)) and 5-hyfroxymethylfurfural (10.4 µg l(-1)). Repeatability values of all compounds were lower than 17%. The method accuracy was satisfactory with recoveries ranging from 88% to 114%. The validated method showed to be suitable for a fast and reliable determination of main carbonyl compounds in beers. © 2013 Published by Elsevier B.V.

  12. Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

    NASA Astrophysics Data System (ADS)

    Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

    2018-04-01

    Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

  13. Economic analysis of secondary and enhanced oil recovery techniques in Wyoming

    NASA Astrophysics Data System (ADS)

    Kara, Erdal

    This dissertation primarily aims to theoretically analyze a firm's optimization of enhanced oil recovery (EOR) and carbon dioxide sequestration under different social policies and empirically analyze the firm's optimization of enhanced oil recovery. The final part of the dissertation empirically analyzes how geological factors and water injection management influence oil recovery. The first chapter builds a theoretical model to analyze economic optimization of EOR and geological carbon sequestration under different social policies. Specifically, it analyzes how social policies on sequestration influence the extent of oil operations, optimal oil production and CO2 sequestration. The theoretical results show that the socially optimal policy is a subsidy on the net CO2 sequestration, assuming negative net emissions from EOR. Such a policy is expected to increase a firm's total carbon dioxide sequestration. The second chapter statistically estimates the theoretical oil production model and its different versions. Empirical results are not robust over different estimation techniques and not in line with the theoretical production model. The last part of the second chapter utilizes a simplified version of theoretical model and concludes that EOR via CO2 injection improves oil recovery. The final chapter analyzes how a contemporary oil recovery technology (water flooding of oil reservoirs) and various reservoir-specific geological factors influence oil recovery in Wyoming. The results show that there is a positive concave relationship between cumulative water injection and cumulative oil recovery and also show that certain geological factors affect the oil recovery. Moreover, the curvature of the concave functional relationship between cumulative water injection and oil recovery is reservoir-specific due to heterogeneities among different reservoirs.

  14. R&D 100, 2016: Pyomo 4.0 – Python Optimization Modeling Objects

    ScienceCinema

    Hart, William; Laird, Carl; Siirola, John

    2018-06-13

    Pyomo provides a rich software environment for formulating and analyzing optimization applications. Pyomo supports the algebraic specification of complex sets of objectives and constraints, which enables optimization solvers to exploit problem structure to efficiently perform optimization.

  15. Aggregating quantum repeaters for the quantum internet

    NASA Astrophysics Data System (ADS)

    Azuma, Koji; Kato, Go

    2017-09-01

    The quantum internet holds promise for accomplishing quantum teleportation and unconditionally secure communication freely between arbitrary clients all over the globe, as well as the simulation of quantum many-body systems. For such a quantum internet protocol, a general fundamental upper bound on the obtainable entanglement or secret key has been derived [K. Azuma, A. Mizutani, and H.-K. Lo, Nat. Commun. 7, 13523 (2016), 10.1038/ncomms13523]. Here we consider its converse problem. In particular, we present a universal protocol constructible from any given quantum network, which is based on running quantum repeater schemes in parallel over the network. For arbitrary lossy optical channel networks, our protocol has no scaling gap with the upper bound, even based on existing quantum repeater schemes. In an asymptotic limit, our protocol works as an optimal entanglement or secret-key distribution over any quantum network composed of practical channels such as erasure channels, dephasing channels, bosonic quantum amplifier channels, and lossy optical channels.

  16. Spatial context learning survives interference from working memory load

    PubMed Central

    Vickery, Timothy J.; Sussman, Rachel S.; Jiang, Yuhong V.

    2010-01-01

    The human visual system is constantly confronted with an overwhelming amount of information, only a subset of which can be processed in complete detail. Attention and implicit learning are two important mechanisms that optimize vision. This study addresses the relationship between these two mechanisms. Specifically we ask: Is implicit learning of spatial context affected by the amount of working memory load devoted to an irrelevant task? We tested observers in visual search tasks where search displays occasionally repeated. Observers became faster searching repeated displays than unrepeated ones, showing contextual cueing. We found that the size of contextual cueing was unaffected by whether observers learned repeated displays under unitary attention or when their attention was divided using working memory manipulations. These results held when working memory was loaded by colors, dot patterns, individual dot locations, or multiple potential targets. We conclude that spatial context learning is robust to interference from manipulations that limit the availability of attention and working memory. PMID:20853996

  17. O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals.

    PubMed

    Sawaguchi, Shogo; Varshney, Shweta; Ogawa, Mitsutaka; Sakaidani, Yuta; Yagi, Hirokazu; Takeshita, Kyosuke; Murohara, Toyoaki; Kato, Koichi; Sundaram, Subha; Stanley, Pamela; Okajima, Tetsuya

    2017-04-11

    The glycosyltransferase EOGT transfers O-GlcNAc to a consensus site in epidermal growth factor-like (EGF) repeats of a limited number of secreted and membrane proteins, including Notch receptors. In EOGT-deficient cells, the binding of DLL1 and DLL4, but not JAG1, canonical Notch ligands was reduced, and ligand-induced Notch signaling was impaired. Mutagenesis of O-GlcNAc sites on NOTCH1 also resulted in decreased binding of DLL4. EOGT functions were investigated in retinal angiogenesis that depends on Notch signaling. Global or endothelial cell-specific deletion of Eogt resulted in defective retinal angiogenesis, with a mild phenotype similar to that caused by reduced Notch signaling in retina. Combined deficiency of different Notch1 mutant alleles exacerbated the abnormalities in Eogt -/- retina, and Notch target gene expression was decreased in Eogt -/- endothelial cells. Thus, O-GlcNAc on EGF repeats of Notch receptors mediates ligand-induced Notch signaling required in endothelial cells for optimal vascular development.

  18. Photometric Repeatability of Scanned Imagery: UVIS

    NASA Astrophysics Data System (ADS)

    Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia

    2017-08-01

    We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

  19. Repeat cranial tomography in patients with mild head injury and stable neurological examination ---- a perspective from a developing country.

    PubMed

    Nasir, Sadaf; Hussain, Manzar

    2011-01-01

    To determine the frequency of altered findings on repeat cranial tomography (CT) in patients with mild head injury along with stable neurological examination at tertiary care hospital. Cross-sectional study was done in the Department of Radiology, Liaquat National Hospital, Karachi from January 2008 to September 2010. All patients with mild head injury in terms of Glasgow Coma Scale (GCS) who underwent repeat scan without clinical or neurological deterioration in the emergency department of a tertiary care centre were included. The collected data were accordingly entered and analyzed by the principal investigator using Statistical Package for Social Sciences (SPSS) version 16.0. In all 275 patients, only 17 (6%) of the patients were found worseing on repeat CT, 120 (43.63%) scans improved, 138 (50.18%) unchanged and 17 (6.18%) worsened. None of these patients showed signs of clinical deterioration. Our results suggest that for patients with mild head injury and stable neurological examination, only 6% of them show deterioration on repeat CT, especially when patients'GCS is below 13.

  20. Sampling characteristics of satellite orbits

    NASA Technical Reports Server (NTRS)

    Wunsch, Carl

    1989-01-01

    The irregular space-time sampling of any finite region by an orbiting satellite raises difficult questions as to which frequencies and wavenumbers can be determined and which will alias into others. Conventional sampling theorems must be extended to account for both irregular data distributions and observational noise - the sampling irregularity making the system much more susceptible to noise than in regularly sampled cases. The problem is formulated here in terms of least-squares and applied to spacecraft in 10-day and 17-day repeating orbits. The 'diamond-pattern' laid down spatially in such repeating orbits means that either repeat period adequately samples the spatial variables, but the slow overall temporal coverage in the 17-day pattern leads to much greater uncertainty than in the shorter repeat cycle. The result is not definitive and it is not concluded that a 10-day orbit repeat is the most appropriate one. A major conclusion, however, is that different orbital choices have potentially quite different sampling characteristics which need to be analyzed in terms of the spectral characteristics of the moving sea surface.

  1. Nonlinear optimal filter technique for analyzing energy depositions in TES sensors driven into saturation

    DOE PAGES

    Shank, B.; Yen, J. J.; Cabrera, B.; ...

    2014-11-04

    We present a detailed thermal and electrical model of superconducting transition edge sensors (TESs) connected to quasiparticle (qp) traps, such as the W TESs connected to Al qp traps used for CDMS (Cryogenic Dark Matter Search) Ge and Si detectors. We show that this improved model, together with a straightforward time-domain optimal filter, can be used to analyze pulses well into the nonlinear saturation region and reconstruct absorbed energies with optimal energy resolution.

  2. Spatial cluster detection for repeatedly measured outcomes while accounting for residential history.

    PubMed

    Cook, Andrea J; Gold, Diane R; Li, Yi

    2009-10-01

    Spatial cluster detection has become an important methodology in quantifying the effect of hazardous exposures. Previous methods have focused on cross-sectional outcomes that are binary or continuous. There are virtually no spatial cluster detection methods proposed for longitudinal outcomes. This paper proposes a new spatial cluster detection method for repeated outcomes using cumulative geographic residuals. A major advantage of this method is its ability to readily incorporate information on study participants relocation, which most cluster detection statistics cannot. Application of these methods will be illustrated by the Home Allergens and Asthma prospective cohort study analyzing the relationship between environmental exposures and repeated measured outcome, occurrence of wheeze in the last 6 months, while taking into account mobile locations.

  3. A Subsonic Aircraft Design Optimization With Neural Network and Regression Approximators

    NASA Technical Reports Server (NTRS)

    Patnaik, Surya N.; Coroneos, Rula M.; Guptill, James D.; Hopkins, Dale A.; Haller, William J.

    2004-01-01

    The Flight-Optimization-System (FLOPS) code encountered difficulty in analyzing a subsonic aircraft. The limitation made the design optimization problematic. The deficiencies have been alleviated through use of neural network and regression approximations. The insight gained from using the approximators is discussed in this paper. The FLOPS code is reviewed. Analysis models are developed and validated for each approximator. The regression method appears to hug the data points, while the neural network approximation follows a mean path. For an analysis cycle, the approximate model required milliseconds of central processing unit (CPU) time versus seconds by the FLOPS code. Performance of the approximators was satisfactory for aircraft analysis. A design optimization capability has been created by coupling the derived analyzers to the optimization test bed CometBoards. The approximators were efficient reanalysis tools in the aircraft design optimization. Instability encountered in the FLOPS analyzer was eliminated. The convergence characteristics were improved for the design optimization. The CPU time required to calculate the optimum solution, measured in hours with the FLOPS code was reduced to minutes with the neural network approximation and to seconds with the regression method. Generation of the approximators required the manipulation of a very large quantity of data. Design sensitivity with respect to the bounds of aircraft constraints is easily generated.

  4. The Impact of Repeated Freeze-Thaw Cycles on the Quality of Biomolecules in Four Different Tissues.

    PubMed

    Ji, Xiaoli; Wang, Min; Li, Lingling; Chen, Fang; Zhang, Yanyang; Li, Qian; Zhou, Junmei

    2017-10-01

    High-quality biosamples are valuable resources for biomedical research. However, some tissues are stored without being sectioned into small aliquots and have to undergo repeated freeze-thaw cycles throughout prolonged experimentation. Little is known regarding the effects of repeated freeze-thaw cycles on the quality of biomolecules in tissues. The aim of this study was to evaluate the impact of repeated freeze-thaw (at room temperature or on ice) cycles on biomolecules and gene expression in four different types of tissues. Each fresh tissue was sectioned into seven aliquots and snap-frozen before undergoing repeated freeze-thaw cycles at room temperature or on ice. Biomolecules were extracted and analyzed. Both relative and absolute quantification were used to detect the changes in gene expression. The results indicated that the impact of repeated freeze-thaw cycles on RNA integrity varied by tissue type. Gene expression, including the housekeeping gene, was affected in RNA-degraded samples according to absolute quantification rather than relative quantification. Furthermore, our results suggest that thawing on ice could protect RNA integrity compared with thawing at room temperature. No obvious degradation of protein or DNA was observed with repeated freeze-thaw cycles either at room temperature or on ice. This research provides ample evidence for the necessity of sectioning fresh tissues into small aliquots before snap-freezing, thus avoiding degradation of RNA and alteration of gene expression resulting from repeated freeze-thaw cycles. For frozen tissue samples that were already in storage and had to be used repeatedly during their lifecycle, thawing on ice or sectioned at ultralow temperature is recommended.

  5. Analyses of carnivore microsatellites and their intimate association with tRNA-derived SINEs.

    PubMed

    López-Giráldez, Francesc; Andrés, Olga; Domingo-Roura, Xavier; Bosch, Montserrat

    2006-10-23

    The popularity of microsatellites has greatly increased in the last decade on account of their many applications. However, little is currently understood about the factors that influence their genesis and distribution among and within species genomes. In this work, we analyzed carnivore microsatellite clones from GenBank to study their association with interspersed repeats and elucidate the role of the latter in microsatellite genesis and distribution. We constructed a comprehensive carnivore microsatellite database comprising 1236 clones from GenBank. Thirty-three species of 11 out of 12 carnivore families were represented, although two distantly related species, the domestic dog and cat, were clearly overrepresented. Of these clones, 330 contained tRNALys-derived SINEs and 357 contained other interspersed repeats. Our rough estimates of tRNA SINE copies per haploid genome were much higher than published ones. Our results also revealed a distinct juxtaposition of AG and A-rich repeats and tRNALys-derived SINEs suggesting their coevolution. Both microsatellites arose repeatedly in two regions of the interspersed repeat. Moreover, microsatellites associated with tRNALys-derived SINEs showed the highest complexity and less potential instability. Our results suggest that tRNALys-derived SINEs are a significant source for microsatellite generation in carnivores, especially for AG and A-rich repeat motifs. These observations indicate two modes of microsatellite generation: the expansion and variation of pre-existing tandem repeats and the conversion of sequences with high cryptic simplicity into a repeat array; mechanisms which are not specific to tRNALys-derived SINEs. Microsatellite and interspersed repeat coevolution could also explain different distribution of repeat types among and within species genomes.Finally, due to their higher complexity and lower potential informative content of microsatellites associated with tRNALys-derived SINEs, we recommend avoiding their use as genetic markers.

  6. Optimal control and optimal trajectories of regional macroeconomic dynamics based on the Pontryagin maximum principle

    NASA Astrophysics Data System (ADS)

    Bulgakov, V. K.; Strigunov, V. V.

    2009-05-01

    The Pontryagin maximum principle is used to prove a theorem concerning optimal control in regional macroeconomics. A boundary value problem for optimal trajectories of the state and adjoint variables is formulated, and optimal curves are analyzed. An algorithm is proposed for solving the boundary value problem of optimal control. The performance of the algorithm is demonstrated by computing an optimal control and the corresponding optimal trajectories.

  7. Optimal Scaling of Interaction Effects in Generalized Linear Models

    ERIC Educational Resources Information Center

    van Rosmalen, Joost; Koning, Alex J.; Groenen, Patrick J. F.

    2009-01-01

    Multiplicative interaction models, such as Goodman's (1981) RC(M) association models, can be a useful tool for analyzing the content of interaction effects. However, most models for interaction effects are suitable only for data sets with two or three predictor variables. Here, we discuss an optimal scaling model for analyzing the content of…

  8. Russian Loanword Adaptation in Persian; Optimal Approach

    ERIC Educational Resources Information Center

    Kambuziya, Aliye Kord Zafaranlu; Hashemi, Eftekhar Sadat

    2011-01-01

    In this paper we analyzed some of the phonological rules of Russian loanword adaptation in Persian, on the view of Optimal Theory (OT) (Prince & Smolensky, 1993/2004). It is the first study of phonological process on Russian loanwords adaptation in Persian. By gathering about 50 current Russian loanwords, we selected some of them to analyze. We…

  9. NMR-Based Metabolomic Study on Isatis tinctoria: Comparison of Different Accessions, Harvesting Dates, and the Effect of Repeated Harvesting.

    PubMed

    Guldbrandsen, Niels; Kostidis, Sarantos; Schäfer, Hartmut; De Mieri, Maria; Spraul, Manfred; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Hamburger, Matthias

    2015-05-22

    Isatis tinctoria is an ancient dye and medicinal plant with potent anti-inflammatory and antiallergic properties. Metabolic differences were investigated by NMR spectroscopy of accessions from different origins that were grown under identical conditions on experimental plots. For these accessions, metabolite profiles at different harvesting dates were analyzed, and single and repeatedly harvested plants were compared. Leaf samples were shock-frozen in liquid N2 immediately after being harvested, freeze-dried, and cryomilled prior to extraction. Extracts were prepared by pressurized liquid extraction with ethyl acetate and 70% aqueous methanol. NMR spectra were analyzed using a combination of different methods of multivariate data analysis such as principal component analysis (PCA), canonical analysis (CA), and k-nearest neighbor concept (k-NN). Accessions and harvesting dates were well separated in the PCA/CA/k-NN analysis in both extracts. Pairwise statistical total correlation spectroscopy (STOCSY) revealed unsaturated fatty acids, porphyrins, carbohydrates, indole derivatives, isoprenoids, phenylpropanoids, and minor aromatic compounds as the cause of these differences. In addition, the metabolite profile was affected by the repeated harvest regime, causing a decrease of 1,5-anhydroglucitol, sucrose, unsaturated fatty acids, porphyrins, isoprenoids, and a flavonoid.

  10. Analyzing Web pages visual scanpaths: between and within tasks variability.

    PubMed

    Drusch, Gautier; Bastien, J M Christian

    2012-01-01

    In this paper, we propose a new method for comparing scanpaths in a bottom-up approach, and a test of the scanpath theory. To do so, we conducted a laboratory experiment in which 113 participants were invited to accomplish a set of tasks on two different websites. For each site, they had to perform two tasks that had to be repeated ounce. The data were analyzed using a procedure similar to the one used by Duchowski et al. [8]. The first step was to automatically identify, then label, AOIs with the mean-shift clustering procedure [19]. Then, scanpaths were compared two by two with a modified version of the string-edit method, which take into account the order of AOIs visualizations [2]. Our results show that scanpaths variability between tasks but within participants seems to be lower than the variability within task for a given participant. In other words participants seem to be more coherent when they perform different tasks, than when they repeat the same tasks. In addition, participants view more of the same AOI when they perform a different task on the same Web page than when they repeated the same task. These results are quite different from what predicts the scanpath theory.

  11. Intra-Platform Repeatability and Inter-Platform Comparability of MicroRNA Microarray Technology

    PubMed Central

    Sato, Fumiaki; Tsuchiya, Soken; Terasawa, Kazuya; Tsujimoto, Gozoh

    2009-01-01

    Over the last decade, DNA microarray technology has provided a great contribution to the life sciences. The MicroArray Quality Control (MAQC) project demonstrated the way to analyze the expression microarray. Recently, microarray technology has been utilized to analyze a comprehensive microRNA expression profiling. Currently, several platforms of microRNA microarray chips are commercially available. Thus, we compared repeatability and comparability of five different microRNA microarray platforms (Agilent, Ambion, Exiqon, Invitrogen and Toray) using 309 microRNAs probes, and the Taqman microRNA system using 142 microRNA probes. This study demonstrated that microRNA microarray has high intra-platform repeatability and comparability to quantitative RT-PCR of microRNA. Among the five platforms, Agilent and Toray array showed relatively better performances than the others. However, the current lineup of commercially available microRNA microarray systems fails to show good inter-platform concordance, probably because of lack of an adequate normalization method and severe divergence in stringency of detection call criteria between different platforms. This study provided the basic information about the performance and the problems specific to the current microRNA microarray systems. PMID:19436744

  12. Repeatability study of replicate crash tests: A signal analysis approach.

    PubMed

    Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

    2017-10-03

    To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test protocols.

  13. Multilocus variable-number tandem repeat analysis distinguishes outbreak and sporadic Escherichia coli O157:H7 isolates.

    PubMed

    Noller, Anna C; McEllistrem, M Catherine; Pacheco, Antonio G F; Boxrud, David J; Harrison, Lee H

    2003-12-01

    Escherichia coli O157:H7 is a major cause of food-borne illness in the United States. Outbreak detection involves traditional epidemiological methods and routine molecular subtyping by pulsed-field gel electrophoresis (PFGE). PFGE is labor-intensive, and the results are difficult to analyze and not easily transferable between laboratories. Multilocus variable-number tandem repeat (VNTR) analysis (MLVA) is a fast, portable method that analyzes multiple VNTR loci, which are areas of the bacterial genome that evolve quickly. Eighty isolates, including 21 isolates from five epidemiologically well-characterized outbreaks from Pennsylvania and Minnesota, were analyzed by PFGE and MLVA. Strains in PFGE clusters were defined as strains that differed by less than or equal to one band by using XbaI and the confirmatory enzyme SpeI. MLVA was performed by comparing the number of tandem repeats at seven loci. From 6 to 30 alleles were found at the seven loci, resulting in 64 MLVA types among the 80 isolates. MLVA correctly identified the isolates from all five outbreaks if only a single-locus variant was allowed. MLVA differentiated strains with unique PFGE types. Additionally, MLVA discriminated strains within PFGE-defined clusters that were not known to be part of an outbreak. In addition to being a simple and validated method for E. coli O157:H7 outbreak detection, MLVA appears to have a sensitivity equal to that of PFGE and a specificity superior to that of PFGE.

  14. The need to control for regression to the mean in social psychology studies.

    PubMed

    Yu, Rongjun; Chen, Li

    2014-01-01

    It is common in repeated measurements for extreme values at the first measurement to approach the mean at the subsequent measurement, a phenomenon called regression to the mean (RTM). If RTM is not fully controlled, it will lead to erroneous conclusions. The wide use of repeated measurements in social psychology creates a risk that an RTM effect will influence results. However, insufficient attention is paid to RTM in most social psychological research. Notable cases include studies on the phenomena of social conformity and unrealistic optimism (Klucharev et al., 2009, 2011; Sharot et al., 2011, 2012b; Campbell-Meiklejohn et al., 2012; Kim et al., 2012; Garrett and Sharot, 2014). In Study 1, 13 university students rated and re-rated the facial attractiveness of a series of female faces as a test of the social conformity effect (Klucharev et al., 2009). In Study 2, 15 university students estimated and re-estimated their risk of experiencing a series of adverse life events as a test of the unrealistic optimism effect (Sharot et al., 2011). Although these studies used methodologies similar to those used in earlier research, the social conformity and unrealistic optimism effects were no longer evident after controlling for RTM. Based on these findings we suggest several ways to control for the RTM effect in social psychology studies, such as adding the initial rating as a covariate in regression analysis, selecting a subset of stimuli for which the participant' initial ratings were matched across experimental conditions, and using a control group.

  15. Interpersonal violence and the prediction of short-term risk of repeat suicide attempt

    PubMed Central

    Haglund, Axel; Lindh, Åsa U.; Lysell, Henrik; Renberg, Ellinor Salander; Jokinen, Jussi; Waern, Margda; Runeson, Bo

    2016-01-01

    In this multi-center cohort study, suicide attempters presenting to hospital (N = 355, 63% women) were interviewed using the Karolinska Interpersonal Violence Scale (KIVS) and followed-up by medical record review. Main outcome was non-fatal or fatal repeat suicide attempt within six months. Also, repeat attempt using a violent method was used as an additional outcome in separate analyses. Data were analyzed for the total group and for men and women separately. Repeat attempts were observed within six months in 78 persons (22%) and 21 (6%) of these used a violent method. KIVS total score of 6 or more was associated with repeat suicide attempt within six months (OR = 1.81, CI 1.08–3.02) and predicted new attempts with a sensitivity of 62% and a specificity of 53%. A three-fold increase in odds ratio was observed for repeat attempt using a violent method (OR = 3.40, CI 1.22–9.49). An association between exposure to violence in adulthood and violent reattempt was seen in women (OR = 1.38, CI 1.06–1.82). The overall conclusions are that information about interpersonal violence may help predict short-term risk for repeat suicide attempt, and that structured assessment of interpersonal violence may be of value in risk assessment after attempted suicide. PMID:27841333

  16. Repeat infection with Neisseria gonorrhoeae among active duty U.S. Army personnel: a population-based case-series study

    PubMed Central

    Wurapa, Eyako K; Sateren, Warren B; Morris, Sara M; Hollingsworth, Bruce P; Sanchez, Jose L

    2016-01-01

    Little information is known on the rate of repeat gonorrhea infection among U.S. military personnel. We analyzed all gonorrhea cases reported to the Defense Medical Surveillance System during 2006–2012 to determine the rate of repeat infection. During the seven-year study period, 17,602 active duty U.S. Army personnel with a first incident gonorrhea infection were reported. Among the 4987 women with a first gonorrhea infection, 14.4% had at least one repeat infection. Among the 12,615 men with a first gonorrhea infection, 13.7% had at least one repeat infection. Overall, the rate of repeat gonorrhea infection was 44.5 and 48.9 per 1000 person-years for women and men, respectively. Service members aged 17–19 years (hazard ratio [HR] for women = 1.51; HR for men = 1.71), African-American personnel (HR for women = 1.26; HR for men = 2.17), junior enlisted personnel (HR for women = 2.64; HR for men = 1.37), and those with one year or less of service (HR for women = 1.23; HR for men = 1.37) were at higher risk of repeat infection. The findings from this study highlight the need to develop targeted prevention initiatives including education, counseling, and retesting to prevent gonorrhea reinfections among U.S. Army personnel. PMID:27885067

  17. Repeat infection with Neisseria gonorrhoeae among active duty U.S. Army personnel: a population-based case-series study.

    PubMed

    Bautista, Christian T; Wurapa, Eyako K; Sateren, Warren B; Morris, Sara M; Hollingsworth, Bruce P; Sanchez, Jose L

    2017-09-01

    Little information is known on the rate of repeat gonorrhea infection among U.S. military personnel. We analyzed all gonorrhea cases reported to the Defense Medical Surveillance System during 2006-2012 to determine the rate of repeat infection. During the seven-year study period, 17,602 active duty U.S. Army personnel with a first incident gonorrhea infection were reported. Among the 4987 women with a first gonorrhea infection, 14.4% had at least one repeat infection. Among the 12,615 men with a first gonorrhea infection, 13.7% had at least one repeat infection. Overall, the rate of repeat gonorrhea infection was 44.5 and 48.9 per 1000 person-years for women and men, respectively. Service members aged 17-19 years (hazard ratio [HR] for women = 1.51; HR for men = 1.71), African-American personnel (HR for women = 1.26; HR for men = 2.17), junior enlisted personnel (HR for women = 2.64; HR for men = 1.37), and those with one year or less of service (HR for women = 1.23; HR for men = 1.37) were at higher risk of repeat infection. The findings from this study highlight the need to develop targeted prevention initiatives including education, counseling, and retesting to prevent gonorrhea reinfections among U.S. Army personnel.

  18. Deconvolution of continuous paleomagnetic data from pass-through magnetometer: A new algorithm to restore geomagnetic and environmental information based on realistic optimization

    NASA Astrophysics Data System (ADS)

    Oda, Hirokuni; Xuan, Chuang

    2014-10-01

    development of pass-through superconducting rock magnetometers (SRM) has greatly promoted collection of paleomagnetic data from continuous long-core samples. The output of pass-through measurement is smoothed and distorted due to convolution of magnetization with the magnetometer sensor response. Although several studies could restore high-resolution paleomagnetic signal through deconvolution of pass-through measurement, difficulties in accurately measuring the magnetometer sensor response have hindered the application of deconvolution. We acquired reliable sensor response of an SRM at the Oregon State University based on repeated measurements of a precisely fabricated magnetic point source. In addition, we present an improved deconvolution algorithm based on Akaike's Bayesian Information Criterion (ABIC) minimization, incorporating new parameters to account for errors in sample measurement position and length. The new algorithm was tested using synthetic data constructed by convolving "true" paleomagnetic signal containing an "excursion" with the sensor response. Realistic noise was added to the synthetic measurement using Monte Carlo method based on measurement noise distribution acquired from 200 repeated measurements of a u-channel sample. Deconvolution of 1000 synthetic measurements with realistic noise closely resembles the "true" magnetization, and successfully restored fine-scale magnetization variations including the "excursion." Our analyses show that inaccuracy in sample measurement position and length significantly affects deconvolution estimation, and can be resolved using the new deconvolution algorithm. Optimized deconvolution of 20 repeated measurements of a u-channel sample yielded highly consistent deconvolution results and estimates of error in sample measurement position and length, demonstrating the reliability of the new deconvolution algorithm for real pass-through measurements.

  19. Visualization and quantitative analysis of extrachromosomal telomere-repeat DNA in individual human cells by Halo-FISH

    PubMed Central

    Komosa, Martin; Root, Heather; Meyn, M. Stephen

    2015-01-01

    Current methods for characterizing extrachromosomal nuclear DNA in mammalian cells do not permit single-cell analysis, are often semi-quantitative and frequently biased toward the detection of circular species. To overcome these limitations, we developed Halo-FISH to visualize and quantitatively analyze extrachromosomal DNA in single cells. We demonstrate Halo-FISH by using it to analyze extrachromosomal telomere-repeat (ECTR) in human cells that use the Alternative Lengthening of Telomeres (ALT) pathway(s) to maintain telomere lengths. We find that GM847 and VA13 ALT cells average ∼80 detectable G/C-strand ECTR DNA molecules/nucleus, while U2OS ALT cells average ∼18 molecules/nucleus. In comparison, human primary and telomerase-positive cells contain <5 ECTR DNA molecules/nucleus. ECTR DNA in ALT cells exhibit striking cell-to-cell variations in number (<20 to >300), range widely in length (<1 to >200 kb) and are composed of primarily G- or C-strand telomere-repeat DNA. Halo-FISH enables, for the first time, the simultaneous analysis of ECTR DNA and chromosomal telomeres in a single cell. We find that ECTR DNA comprises ∼15% of telomere-repeat DNA in GM847 and VA13 cells, but <4% in U2OS cells. In addition to its use in ALT cell analysis, Halo-FISH can facilitate the study of a wide variety of extrachromosomal DNA in mammalian cells. PMID:25662602

  20. Mining and validation of pyrosequenced simple sequence repeats (SSRs) from American cranberry (Vaccinium macrocarpon Ait.).

    PubMed

    Zhu, H; Senalik, D; McCown, B H; Zeldin, E L; Speers, J; Hyman, J; Bassil, N; Hummer, K; Simon, P W; Zalapa, J E

    2012-01-01

    The American cranberry (Vaccinium macrocarpon Ait.) is a major commercial fruit crop in North America, but limited genetic resources have been developed for the species. Furthermore, the paucity of codominant DNA markers has hampered the advance of genetic research in cranberry and the Ericaceae family in general. Therefore, we used Roche 454 sequencing technology to perform low-coverage whole genome shotgun sequencing of the cranberry cultivar 'HyRed'. After de novo assembly, the obtained sequence covered 266.3 Mb of the estimated 540-590 Mb in cranberry genome. A total of 107,244 SSR loci were detected with an overall density across the genome of 403 SSR/Mb. The AG repeat was the most frequent motif in cranberry accounting for 35% of all SSRs and together with AAG and AAAT accounted for 46% of all loci discovered. To validate the SSR loci, we designed 96 primer-pairs using contig sequence data containing perfect SSR repeats, and studied the genetic diversity of 25 cranberry genotypes. We identified 48 polymorphic SSR loci with 2-15 alleles per locus for a total of 323 alleles in the 25 cranberry genotypes. Genetic clustering by principal coordinates and genetic structure analyzes confirmed the heterogeneous nature of cranberries. The parentage composition of several hybrid cultivars was evident from the structure analyzes. Whole genome shotgun 454 sequencing was a cost-effective and efficient way to identify numerous SSR repeats in the cranberry sequence for marker development.

  1. Repeatability data and agreement of keratometry with the VERION system compared to the IOLMaster.

    PubMed

    Nemeth, Gabor; Szalai, Eszter; Hassan, Ziad; Lipecz, Agnes; Berta, Andras; Modis, Laszlo

    2015-05-01

    To analyze the repeatability of keratometric and white-to-white (WTW) distance measurements with the VERION Measurement Module (Alcon Laboratories, Inc., Fort Worth, TX) and to compare the measured data to the results of the IOLMaster (Carl Zeiss Meditec, Jena, Germany). Three images were captured with the VERION and the flattest and steepest keratometric data, the astigmatism axis, and the WTW distance were recorded. Subsequently, the axial length, the keratometric data with axis, and the WTW distance were measured with an IOLMaster. The repeatability data of the keratometric value of the VERION System, converted to cross cylinder J0 and J45 vector components, were analyzed. The agreement data for keratometry obtained by the VERION System and the differences regarding keratometric data and WTW distance compared to IOLMaster were calculated. The measurements were conducted in 50 eyes of 50 healthy volunteers (median age: 50.32 years, range: 19.34 to 85.3 years). The flattest and the steepest keratometric data, the diopter of astigmatism, the J0 and J45 vector components, and WTW distance did not differ significantly between devices (P > .05). Intraclass correlation coefficients (range: 0.863 to 0.994) and Cronbach's alpha values (range: 0.950 to 0.998) were high for all parameters measured by the VERION System. The VERION System has high repeatability and agreement with the IOLMaster, making it suitable as an alternative tool in clinical practice. Copyright 2015, SLACK Incorporated.

  2. Optimization of CO2 Storage in Saline Aquifers Using Water-Alternating Gas (WAG) Scheme - Case Study for Utsira Formation

    NASA Astrophysics Data System (ADS)

    Agarwal, R. K.; Zhang, Z.; Zhu, C.

    2013-12-01

    For optimization of CO2 storage and reduced CO2 plume migration in saline aquifers, a genetic algorithm (GA) based optimizer has been developed which is combined with the DOE multi-phase flow and heat transfer numerical simulation code TOUGH2. Designated as GA-TOUGH2, this combined solver/optimizer has been verified by performing optimization studies on a number of model problems and comparing the results with brute-force optimization which requires a large number of simulations. Using GA-TOUGH2, an innovative reservoir engineering technique known as water-alternating-gas (WAG) injection has been investigated to determine the optimal WAG operation for enhanced CO2 storage capacity. The topmost layer (layer # 9) of Utsira formation at Sleipner Project, Norway is considered as a case study. A cylindrical domain, which possesses identical characteristics of the detailed 3D Utsira Layer #9 model except for the absence of 3D topography, was used. Topographical details are known to be important in determining the CO2 migration at Sleipner, and are considered in our companion model for history match of the CO2 plume migration at Sleipner. However, simplification on topography here, without compromising accuracy, is necessary to analyze the effectiveness of WAG operation on CO2 migration without incurring excessive computational cost. Selected WAG operation then can be simulated with full topography details later. We consider a cylindrical domain with thickness of 35 m with horizontal flat caprock. All hydrogeological properties are retained from the detailed 3D Utsira Layer #9 model, the most important being the horizontal-to-vertical permeability ratio of 10. Constant Gas Injection (CGI) operation with nine-year average CO2 injection rate of 2.7 kg/s is considered as the baseline case for comparison. The 30-day, 15-day, and 5-day WAG cycle durations are considered for the WAG optimization design. Our computations show that for the simplified Utsira Layer #9 model, the WAG operation with 5-day cycle leads to most noticeable reduction in plume migration. For 5-day WAG cycle, the values of design variables corresponding to optimal WAG operation are found as optimal CO2 injection ICO2,optimal = 11.56 kg/s, and optimal water injection Iwater,optimal = 7.62 kg/s. The durations of CO2 and water injection in one WAG cycle are 11 and 19 days, respectively. Identical WAG cycles are repeated 20 times to complete a two-year operation. Significant reduction (22%) in CO2 migration is achieved compared to CGI operation after only two years of WAG operation. In addition, CO2 dissolution is also significantly enhanced from about 9% to 22% of the total injected CO2 . The results obtained from this and other optimization studies suggest that over 50% reduction of in situ CO2 footprint, greatly enhanced CO2 dissolution, and significantly improved well injectivity can be achieved by employing GA-TOUGH2. The optimization code has also been employed to determine the optimal well placement in a multi-well injection operation. GA-TOUGH2 appears to hold great promise for studying a host of other optimization problems related to Carbon Storage.

  3. Optimal Power Allocation for CC-HARQ-based Cognitive Radio with Statistical CSI in Nakagami Slow Fading Channels

    NASA Astrophysics Data System (ADS)

    Xu, Ding; Li, Qun

    2017-01-01

    This paper addresses the power allocation problem for cognitive radio (CR) based on hybrid-automatic-repeat-request (HARQ) with chase combining (CC) in Nakagamimslow fading channels. We assume that, instead of the perfect instantaneous channel state information (CSI), only the statistical CSI is available at the secondary user (SU) transmitter. The aim is to minimize the SU outage probability under the primary user (PU) interference outage constraint. Using the Lagrange multiplier method, an iterative and recursive algorithm is derived to obtain the optimal power allocation for each transmission round. Extensive numerical results are presented to illustrate the performance of the proposed algorithm.

  4. Immobilization of cross-linked tannase enzyme on multiwalled carbon nanotubes and its catalytic behavior.

    PubMed

    Ong, Chong-Boon; Annuar, Mohamad S M

    2018-02-07

    Immobilization of cross-linked tannase on pristine multiwalled carbon nanotubes (MWCNT) was successfully performed. Cross-linking of tannase molecules was made through glutaraldehyde. The immobilized tannase exhibited significantly improved pH, thermal, and recycling stability. The optimal pH for both free and immobilized tannase was observed at pH 5.0 with optimal operating temperature at 30°C. Moreover, immobilized enzyme retained greater biocatalytic activities upon 10 repeated uses compared to free enzyme in solution. Immobilization of tannase was accomplished by strong hydrophobic interaction most likely between hydrophobic amino acid moieties of the glutaraldehyde-cross-linked tannase to the MWCNT.

  5. Thermometric enzyme linked immunosorbent assay in continuous flow system: optimization and evaluation using human serum albumin as a model system.

    PubMed

    Borrebaeck, C; Börjeson, J; Mattiasson, B

    1978-06-15

    Thermometric enzyme-linked immunosorbent assay (TELISA) is described. After the procedure of optimization, human serum albumin was assayed using anti-human serum albumin bound to Sepharose CL 4-B in the enzyme thermistor unit and catalase as label on the free antigen. The model system was used for assays down to 10(-13)M and the preparation of immobilized antibodies was used repeatedly up to 100 times. Comparative studies of the TELISA technique with bromocresol green, immunoturbidimetric and rocket immunoelectrophoretic methods were carried out and showed that TELISA could be used as an alternative method.

  6. A Case Study on the Application of a Structured Experimental Method for Optimal Parameter Design of a Complex Control System

    NASA Technical Reports Server (NTRS)

    Torres-Pomales, Wilfredo

    2015-01-01

    This report documents a case study on the application of Reliability Engineering techniques to achieve an optimal balance between performance and robustness by tuning the functional parameters of a complex non-linear control system. For complex systems with intricate and non-linear patterns of interaction between system components, analytical derivation of a mathematical model of system performance and robustness in terms of functional parameters may not be feasible or cost-effective. The demonstrated approach is simple, structured, effective, repeatable, and cost and time efficient. This general approach is suitable for a wide range of systems.

  7. Advanced Targeting Cost Function Design for Evolutionary Optimization of Control of Logistic Equation

    NASA Astrophysics Data System (ADS)

    Senkerik, Roman; Zelinka, Ivan; Davendra, Donald; Oplatkova, Zuzana

    2010-06-01

    This research deals with the optimization of the control of chaos by means of evolutionary algorithms. This work is aimed on an explanation of how to use evolutionary algorithms (EAs) and how to properly define the advanced targeting cost function (CF) securing very fast and precise stabilization of desired state for any initial conditions. As a model of deterministic chaotic system, the one dimensional Logistic equation was used. The evolutionary algorithm Self-Organizing Migrating Algorithm (SOMA) was used in four versions. For each version, repeated simulations were conducted to outline the effectiveness and robustness of used method and targeting CF.

  8. Two Simple and Efficient Algorithms to Compute the SP-Score Objective Function of a Multiple Sequence Alignment.

    PubMed

    Ranwez, Vincent

    2016-01-01

    Multiple sequence alignment (MSA) is a crucial step in many molecular analyses and many MSA tools have been developed. Most of them use a greedy approach to construct a first alignment that is then refined by optimizing the sum of pair score (SP-score). The SP-score estimation is thus a bottleneck for most MSA tools since it is repeatedly required and is time consuming. Given an alignment of n sequences and L sites, I introduce here optimized solutions reaching O(nL) time complexity for affine gap cost, instead of O(n2L), which are easy to implement.

  9. Tracing Staphylococcus aureus in small and medium-sized food-processing factories on the basis of molecular sub-species typing.

    PubMed

    Koreňová, Janka; Rešková, Zuzana; Véghová, Adriana; Kuchta, Tomáš

    2015-01-01

    Contamination by Staphylococcus aureus of the production environment of three small or medium-sized food-processing factories in Slovakia was investigated on the basis of sub-species molecular identification by multiple locus variable number of tandem repeats analysis (MLVA). On the basis of MLVA profiling, bacterial isolates were assigned to 31 groups. Data from repeated samplings over a period of 3 years facilitated to draw spatial and temporal maps of the contamination routes for individual factories, as well as identification of potential persistent strains. Information obtained by MLVA typing allowed to identify sources and routes of contamination and, subsequently, will allow to optimize the technical and sanitation measures to ensure hygiene.

  10. Limitations in transmitter-receiver distances for terrestrial microwave transmissions

    NASA Astrophysics Data System (ADS)

    Njau, E. C.

    1990-12-01

    Directional microwave repeater systems are still in significant use for radio-telephone communications as well as terrestrial TV transmissions. In these systems, the optimally maximum distance D(sub 0) between one transmitter and the next repeater-receiver partly depends on meteorological conditions since the refractive index n for microwaves is considerably influenced by these conditions. We show that, under dry atmospheric conditions, certain zonally travelling heat/temperature waves which are normally in the weather/climate system significantly vary n and hence inevitably impose specific conditions on the evaluation of D(sub 0). Finally we use some Tanzanian meteorological records to arrive at an expression for D(sub 0) that is suitable for regions whose meteorological conditions are comparable to those in Tanzania.

  11. Research on a new fiber-optic axial pressure sensor of transformer winding based on fiber Bragg grating

    NASA Astrophysics Data System (ADS)

    Liu, Yuan; Li, Lianqing; Zhao, Lin; Wang, Jiqiang; Liu, Tongyu

    2017-12-01

    Based on the principle of the fiber Bragg grating, a new type of fiber-optic pressure sensor for axial force measurement of transformer winding is designed, which is designed with the structure of bending plate beam, the optimization of the packaging process, and material of the sensor. Through the calibration experiment to calibrate the sensor, the field test results of the Taikai transformer factory show that the sensitivity of the sensor is 0.133 pm/kPa and the repeatability error is 2.7% FS. The data of the fiber-optic pressure sensor in different positions maintain consistent and repeatable, which can meet the requirement of the real-time monitoring of the axial force of transformer winding.

  12. Discovery of DF-461, a Potent Squalene Synthase Inhibitor

    PubMed Central

    2013-01-01

    We report the development of a new trifluoromethyltriazolobenzoxazepine series of squalene synthase inhibitors. Structure–activity studies and pharmacokinetics optimization on this series led to the identification of compound 23 (DF-461), which exhibited potent squalene synthase inhibitory activity, high hepatic selectivity, excellent rat hepatic cholesterol synthesis inhibitory activity, and plasma lipid lowering efficacy in nonrodent repeated dose studies. PMID:24900587

  13. Firefly

    DTIC Science & Technology

    2012-05-29

    Hunter College has completed work on baseline measurements of relaxation times for pentacene at various temperatures in order to determine optimal...temperatures for measuring relaxation rate as a function of doping. We have also repeated these measurements on pentacene samples at 2 different...P3HT using a time-lag method. 2 Technical Accomplishments This Period Relaxation Measurements on Pentacene . As described initially in the 1Q

  14. Risk preferences in strategic wildfire decision making: A choice experiment with U.S. wildfire managers

    Treesearch

    Matthew J. Wibbenmeyer; Michael S. Hand; David E. Calkin; Tyron J. Venn; Matthew P. Thompson

    2013-01-01

    Federal policy has embraced risk management as an appropriate paradigm for wildfire management. Economic theory suggests that over repeated wildfire events, potential economic costs and risks of ecological damage are optimally balanced when management decisions are free from biases, risk aversion, and risk seeking. Of primary concern in this article is how managers...

  15. Bagasse hydrolyzates from Agave tequilana as substrates for succinic acid production by Actinobacillus succinogenes in batch and repeated batch reactor.

    PubMed

    Corona-González, Rosa Isela; Varela-Almanza, Karla María; Arriola-Guevara, Enrique; Martínez-Gómez, Álvaro de Jesús; Pelayo-Ortiz, Carlos; Toriz, Guillermo

    2016-04-01

    The aim of this work was to obtain fermentable sugars by enzymatic or acid hydrolyses of Agave tequilana Weber bagasse in order to produce succinic acid with Actinobacillus succinogenes. Hydrolyses were carried out with mineral acids (sulfuric and hydrochloric acids) or a commercial cellulolytic enzyme, and were optimized statistically by a response surface methodology, having as factors the concentration of acid/enzyme and time of hydrolysis. The concentration of sugars obtained at optimal conditions for each hydrolysis were 21.7, 22.4y 19.8g/L for H2SO4, HCl and the enzymatic preparation respectively. Concerning succinic acid production, the enzymatic hydrolyzates resulted in the highest yield (0.446g/g) and productivity (0.57g/Lh) using A. succinogenes in a batch reactor system. Repeated batch fermentation with immobilized A. succinogenes in agar and with the enzymatic hydrolyzates resulted in a maximum concentration of succinic acid of 33.6g/L from 87.2g/L monosaccharides after 5 cycles in 40h, obtaining a productivity of 1.32g/Lh. Copyright © 2016. Published by Elsevier Ltd.

  16. Intelligent Computation for Optimal Fabrication Condition of a Protein Chip with Ni-Co Alloy-Coated Surface.

    PubMed

    Chang, Yaw-Jen; Chang, Cheng-Hao

    2016-06-01

    Based on the principle of immobilized metal affinity chromatography (IMAC), it has been found that a Ni-Co alloy-coated protein chip is able to immobilize functional proteins with a His-tag attached. In this study, an intelligent computational approach was developed to promote the performance and repeatability of a Ni-Co alloy-coated protein chip. This approach was launched out of L18 experiments. Based on the experimental data, the fabrication process model of a Ni-Co protein chip was established by using an artificial neural network, and then an optimal fabrication condition was obtained using the Taguchi genetic algorithm. The result was validated experimentally and compared with a nitrocellulose chip. Consequentially, experimental outcomes revealed that the Ni-Co alloy-coated chip, fabricated using the proposed approach, had the best performance and repeatability compared with the Ni-Co chips of an L18 orthogonal array design and the nitrocellulose chip. Moreover, the low fluorescent background of the chip surface gives a more precise fluorescent detection. Based on a small quantity of experiments, this proposed intelligent computation approach can significantly reduce the experimental cost and improve the product's quality. © 2015 Society for Laboratory Automation and Screening.

  17. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

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

    Karatas, Hacer; Li, Yangbing; Liu, Liu

    We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis formore » their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.« less

  18. Planar solid-phase microextraction-ion mobility spectrometry: a diethoxydiphenylsilane-based coating for the detection of explosives and explosive taggants.

    PubMed

    Mattarozzi, M; Bianchi, F; Bisceglie, F; Careri, M; Mangia, A; Mori, G; Gregori, A

    2011-03-01

    A novel diethoxydiphenylsilane-based coating for planar solid-phase microextraction was developed using sol-gel technology and used for ion mobility spectrometric detection of the explosives 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and of the explosive taggant ethylene glycol dinitrate. The trap was characterized in terms of coating thickness, morphology, inter-batch repeatability, and extraction efficiency. An average thickness of 143 ± 13 μm with a uniform distribution of the coating was obtained. Good performances of the developed procedure in terms of both intra-batch and inter-batch repeatability with relative standard deviations <7% were obtained. Experimental design and desirability function were used to find the optimal conditions for simultaneous headspace extraction of the investigated compounds: the optimal values were found in correspondence of a time and a temperature of extraction of 45 min and 40 °C, respectively. Detection and quantitation limits in low nanogram levels were achieved proving the superior extraction capability of the developed coating, obtaining ion mobility spectrometric responses at least two times higher than those achieved using commercial teflon and paper traps.

  19. Combining measurements to estimate properties and characterization extent of complex biochemical mixtures; applications to Heparan Sulfate

    PubMed Central

    Pradines, Joël R.; Beccati, Daniela; Lech, Miroslaw; Ozug, Jennifer; Farutin, Victor; Huang, Yongqing; Gunay, Nur Sibel; Capila, Ishan

    2016-01-01

    Complex mixtures of molecular species, such as glycoproteins and glycosaminoglycans, have important biological and therapeutic functions. Characterization of these mixtures with analytical chemistry measurements is an important step when developing generic drugs such as biosimilars. Recent developments have focused on analytical methods and statistical approaches to test similarity between mixtures. The question of how much uncertainty on mixture composition is reduced by combining several measurements still remains mostly unexplored. Mathematical frameworks to combine measurements, estimate mixture properties, and quantify remaining uncertainty, i.e. a characterization extent, are introduced here. Constrained optimization and mathematical modeling are applied to a set of twenty-three experimental measurements on heparan sulfate, a mixture of linear chains of disaccharides having different levels of sulfation. While this mixture has potentially over two million molecular species, mathematical modeling and the small set of measurements establish the existence of nonhomogeneity of sulfate level along chains and the presence of abundant sulfate repeats. Constrained optimization yields not only estimations of sulfate repeats and sulfate level at each position in the chains but also bounds on these levels, thereby estimating the extent of characterization of the sulfation pattern which is achieved by the set of measurements. PMID:27112127

  20. Combining measurements to estimate properties and characterization extent of complex biochemical mixtures; applications to Heparan Sulfate.

    PubMed

    Pradines, Joël R; Beccati, Daniela; Lech, Miroslaw; Ozug, Jennifer; Farutin, Victor; Huang, Yongqing; Gunay, Nur Sibel; Capila, Ishan

    2016-04-26

    Complex mixtures of molecular species, such as glycoproteins and glycosaminoglycans, have important biological and therapeutic functions. Characterization of these mixtures with analytical chemistry measurements is an important step when developing generic drugs such as biosimilars. Recent developments have focused on analytical methods and statistical approaches to test similarity between mixtures. The question of how much uncertainty on mixture composition is reduced by combining several measurements still remains mostly unexplored. Mathematical frameworks to combine measurements, estimate mixture properties, and quantify remaining uncertainty, i.e. a characterization extent, are introduced here. Constrained optimization and mathematical modeling are applied to a set of twenty-three experimental measurements on heparan sulfate, a mixture of linear chains of disaccharides having different levels of sulfation. While this mixture has potentially over two million molecular species, mathematical modeling and the small set of measurements establish the existence of nonhomogeneity of sulfate level along chains and the presence of abundant sulfate repeats. Constrained optimization yields not only estimations of sulfate repeats and sulfate level at each position in the chains but also bounds on these levels, thereby estimating the extent of characterization of the sulfation pattern which is achieved by the set of measurements.

  1. Combining measurements to estimate properties and characterization extent of complex biochemical mixtures; applications to Heparan Sulfate

    NASA Astrophysics Data System (ADS)

    Pradines, Joël R.; Beccati, Daniela; Lech, Miroslaw; Ozug, Jennifer; Farutin, Victor; Huang, Yongqing; Gunay, Nur Sibel; Capila, Ishan

    2016-04-01

    Complex mixtures of molecular species, such as glycoproteins and glycosaminoglycans, have important biological and therapeutic functions. Characterization of these mixtures with analytical chemistry measurements is an important step when developing generic drugs such as biosimilars. Recent developments have focused on analytical methods and statistical approaches to test similarity between mixtures. The question of how much uncertainty on mixture composition is reduced by combining several measurements still remains mostly unexplored. Mathematical frameworks to combine measurements, estimate mixture properties, and quantify remaining uncertainty, i.e. a characterization extent, are introduced here. Constrained optimization and mathematical modeling are applied to a set of twenty-three experimental measurements on heparan sulfate, a mixture of linear chains of disaccharides having different levels of sulfation. While this mixture has potentially over two million molecular species, mathematical modeling and the small set of measurements establish the existence of nonhomogeneity of sulfate level along chains and the presence of abundant sulfate repeats. Constrained optimization yields not only estimations of sulfate repeats and sulfate level at each position in the chains but also bounds on these levels, thereby estimating the extent of characterization of the sulfation pattern which is achieved by the set of measurements.

  2. Simultaneous determination of multiclass preservatives including isothiazolinones and benzophenone-type UV filters in household and personal care products by micellar electrokinetic chromatography.

    PubMed

    Lopez-Gazpio, Josu; Garcia-Arrona, Rosa; Millán, Esmeralda

    2015-04-01

    In this work, a simple and reliable micellar electrokinetic chromatography method for the separation and quantification of 14 preservatives, including isothiazolinones, and two benzophenone-type UV filters in household, cosmetic and personal care products was developed. The selected priority compounds are widely used as ingredients in many personal care products, and are included in the European Regulation concerning cosmetic products. The electrophoretic separation parameters were optimized by means of a modified chromatographic response function in combination with an experimental design, namely a central composite design. After optimization of experimental conditions, the BGE selected for the separation of the targets consisted of 60 mM SDS, 18 mM sodium tetraborate, pH 9.4 and 10% v/v methanol. The MEKC method was checked in terms of linearity, LODs and quantification, repeatability, intermediate precision, and accuracy, providing appropriate values (i.e. R(2) ≥ 0.992, repeatability RSD values ˂9%, and accuracy 90-115%). Applicability of the validated method was successfully assessed by quantifying preservatives and UV filters in commercial consumer products. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Massively parallel sequencing of 17 commonly used forensic autosomal STRs and amelogenin with small amplicons.

    PubMed

    Kim, Eun Hye; Lee, Hwan Young; Yang, In Seok; Jung, Sang-Eun; Yang, Woo Ick; Shin, Kyoung-Jin

    2016-05-01

    The next-generation sequencing (NGS) method has been utilized to analyze short tandem repeat (STR) markers, which are routinely used for human identification purposes in the forensic field. Some researchers have demonstrated the successful application of the NGS system to STR typing, suggesting that NGS technology may be an alternative or additional method to overcome limitations of capillary electrophoresis (CE)-based STR profiling. However, there has been no available multiplex PCR system that is optimized for NGS analysis of forensic STR markers. Thus, we constructed a multiplex PCR system for the NGS analysis of 18 markers (13CODIS STRs, D2S1338, D19S433, Penta D, Penta E and amelogenin) by designing amplicons in the size range of 77-210 base pairs. Then, PCR products were generated from two single-sources, mixed samples and artificially degraded DNA samples using a multiplex PCR system, and were prepared for sequencing on the MiSeq system through construction of a subsequent barcoded library. By performing NGS and analyzing the data, we confirmed that the resultant STR genotypes were consistent with those of CE-based typing. Moreover, sequence variations were detected in targeted STR regions. Through the use of small-sized amplicons, the developed multiplex PCR system enables researchers to obtain successful STR profiles even from artificially degraded DNA as well as STR loci which are analyzed with large-sized amplicons in the CE-based commercial kits. In addition, successful profiles can be obtained from mixtures up to a 1:19 ratio. Consequently, the developed multiplex PCR system, which produces small size amplicons, can be successfully applied to STR NGS analysis of forensic casework samples such as mixtures and degraded DNA samples. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Multiplex screening for RB1 germline mutations in 106 patients with hereditary retinoblastoma

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

    Lohmann, D.R.; Brandt, B.; Passarge, E.

    1994-09-01

    The identification of germline mutations in the retinoblastoma susceptibility gene (RB1) is important for genetic counseling in hereditary retinoblastoma. Due to the complex genomic organization of this gene and the heterogeneity of mutations, efficient screening procedures are important for rapid mutation detection. We have developed methods based on simultaneous analysis of multiple regions of this gene in an ABI automated DNA fragment analyzer to examine 106 patients with hereditary retinoblastoma in which no alteration was identified by Southern blot hybridization. Primers for the amplification of all 27 exons of the RB1 gene as well as the promoter and poly(A) signalmore » sequences were labelled with distinct fluorescent dyes (FAM, HEX, TAMRA) to enable simultaneous electrophoretic analysis of PCR products with similar mobility. PCR fragments distinguishable by size or color were co-amplified by multiplex PCR and analyzed for length by GENESCAN analysis. Using this approach, small deletions ranging from 1 bp to 22 bp were identified in 24 patients (23%). Short sequence repeats or polypyrimidine runs were present in the vicinity of most of these deletions. In 4 patients (4%), insertions from 1 bp to 4 bp were found. The majority of length mutations resulted in a truncated gene product due to frameshift and premature termination. No mutation was identified in exons 25 to 27 possibly indicating that the encoded protein domains have minor functional importance. In order to screen for base substitutions that are not detectable by fragment length analysis, we adapted heteroduplex analysis for the use in the DNA fragment analyzer. During the optimization of this method we detected 10 single base substitutions most of which generated stop codons. Intriguingly, two identical missense mutations were identified in two unrelated families with a low-penetrance phenotype.« less

  5. Measurement and characterization of RF nonuniformity over the heart at 3T using body coil transmission.

    PubMed

    Sung, Kyunghyun; Nayak, Krishna S

    2008-03-01

    To measure and characterize variations in the transmitted radio frequency (RF) (B1+) field in cardiac magnetic resonance imaging (MRI) at 3 Tesla. Knowledge of the B1+ field is necessary for the calibration of pulse sequences, image-based quantitation, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) optimization. A variation of the saturated double-angle method for cardiac B1+ mapping is described. A total of eight healthy volunteers and two cardiac patients were scanned using six parallel short-axis slices spanning the left ventricle (LV). B1+ profiles were analyzed to determine the amount of variation and dominant patterns of variation across the LV. A total of five to 10 measurements were obtained in each volunteer to determine an upper bound of measurement repeatability. The amount of flip angle variation was found to be 23% to 48% over the LV in mid-short-axis slices and 32% to 63% over the entire LV volume. The standard deviation (SD) of multiple flip angle measurements was <1.4 degrees over the LV in all subjects, indicating excellent repeatability of the proposed measurement method. The pattern of in-plane flip angle variation was found to be primarily unidirectional across the LV, with a residual variation of < or =3% in all subjects. The in-plane B1+ variation over the LV at 3T with body-coil transmission is on the order of 32% to 63% and is predominantly unidirectional in short-axis slices. Reproducible B1+ measurements over the whole heart can be obtained in a single breathhold of 16 heartbeats.

  6. Measurement of glomerular filtration rate in the conscious rat.

    PubMed

    Pestel, Sabine; Krzykalla, Volker; Weckesser, Gerhard

    2007-01-01

    Glomerular filtration rate (GFR) is an important parameter for studying drug-induced impairments on renal function in rats. The GFR is calculated from the concentration of creatinine and blood urea nitrogen (BUN) in serum and in urine, respectively. Following current protocols serum and urine samples must be taken from the same animal. Thus, in order to determine time-dependent effects it is necessary to use for each time point one separated group of animals. We developed a statistical test which allows analyzing the GFR from two different groups of animals: one used for repeated serum and the other one used for repeated urine analysis. Serum and urine samples were taken from two different sets of rats which were otherwise treated identically, i.e. drug doses, routes of administration (per os or per inhalation) and tap water loading. For each dose group GFR mean, standard deviation and statistical analysis to identify differences between the dose groups were determined. After determination of the optimal time points for measurements, the effect on GFR of the three reference compounds, furosemide, hydrochlorothiazide and formoterol, was calculated. The results showed that the diuretic drugs furosemide and hydrochlorothiazide decreased the GFR and the antidiuretic drug formoterol increased the GFR, as counter regulation on urine loss or urine retention, respectively. A mathematical model and the corresponding algorithm were developed, which can be used to calculate the GFR, and to test for differences between groups from two separated sets of rats, one used for urine, and the other one for serum analysis. This new method has the potential to reduce the number of animals needed and to improve the quality of data generated from various groups of animals in renal function studies.

  7. Characterization of the differentially methylated region of the Impact gene that exhibits Glires-specific imprinting.

    PubMed

    Okamura, Kohji; Wintle, Richard F; Scherer, Stephen W

    2008-01-01

    Imprinted genes are exclusively expressed from one of the two parental alleles in a parent-of-origin-specific manner. In mammals, nearly 100 genes are documented to be imprinted. To understand the mechanism behind this gene regulation and to identify novel imprinted genes, common features of DNA sequences have been analyzed; however, the general features required for genomic imprinting have not yet been identified, possibly due to variability in underlying molecular mechanisms from locus to locus. We performed a thorough comparative genomic analysis of a single locus, Impact, which is imprinted only in Glires (rodents and lagomorphs). The fact that Glires and primates diverged from each other as recent as 70 million years ago makes comparisons between imprinted and non-imprinted orthologues relatively reliable. In species from the Glires clade, Impact bears a differentially methylated region, whereby the maternal allele is hypermethylated. Analysis of this region demonstrated that imprinting was not associated with the presence of direct tandem repeats nor with CpG dinucleotide density. In contrast, a CpG periodicity of 8 bp was observed in this region in species of the Glires clade compared to those of carnivores, artiodactyls, and primates. We show that tandem repeats are dispensable, establishment of the differentially methylated region does not rely on G+C content and CpG density, and the CpG periodicity of 8 bp is meaningful to the imprinting. This interval has recently been reported to be optimal for de novo methylation by the Dnmt3a-Dnmt3L complex, suggesting its importance in the establishment of imprinting in Impact and other genes.

  8. Predictors of Long-Term Outcomes of Percutaneous Mitral Valvuloplasty in Patients with Rheumatic Mitral Stenosis.

    PubMed

    Kim, Darae; Chung, Hyemoon; Nam, Jong Ho; Park, Dong Hyuk; Shim, Chi Young; Kim, Jung Sun; Chang, Hyuk Jae; Hong, Geu Ru; Ha, Jong Won

    2018-03-01

    We determined factors associated with long-term outcomes of patients who underwent successful percutaneous mitral balloon valvuloplasty (PMV). Between August 1980 and May 2013, 1187 patients underwent PMV at Severance Hospital, Seoul, Korea. A total of 742 patients who underwent regular clinic visits for more than 10 years were retrospectively analyzed. The endpoints consisted of repeated PMV, mitral valve (MV) surgery, and cardiovascular-related death. The optimal result, defined as a post-PMV mitral valve area (MVA) >1.5 cm² and mitral regurgitation ≤Grade II, was obtained in 631 (85%) patients. Over a mean follow up duration of 214±50 months, 54 (7.3%) patients underwent repeat PMV, 4 (0.5%) underwent trido-PMV, and 248 (33.4%) underwent MV surgery. A total of 33 patients (4.4%) had stroke, and 35 (4.7%) patients died from cardiovascular-related reasons. In a multivariate analysis, echocardiographic score [p=0.003, hazard ratio=1.56, 95% confidence interval (CI): 1.01-2.41] and post-MVA cut-off (p<0.001, relative risk=0.39, 95% CI: 0.37-0.69) were the only significant predictors of long-term clinical outcomes after adjusting for confounding variables. A post-MVA cut-off value of 1.76 cm² showed satisfactory predictive power for poor long-term clinical outcomes. In this long-term follow up study (up to 20 years), an echocardiographic score >8 and post-MVA ≤1.76 cm² were independent predictors of poor long-term clinical outcomes after PMV, including MV reintervention, stroke, and cardiovascular-related death. © Copyright: Yonsei University College of Medicine 2018

  9. Perpetual extraction of work from a nonequilibrium dynamical system under Markovian feedback control

    NASA Astrophysics Data System (ADS)

    Kosugi, Taichi

    2013-09-01

    By treating both control parameters and dynamical variables as probabilistic variables, we develop a succinct theory of perpetual extraction of work from a generic classical nonequilibrium system subject to a heat bath via repeated measurements under a Markovian feedback control. It is demonstrated that a problem for perpetual extraction of work in a nonequilibrium system is reduced to a problem of Markov chain in the higher-dimensional phase space. We derive a version of the detailed fluctuation theorem, which was originally derived for classical nonequilibrium systems by Horowitz and Vaikuntanathan [Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.82.061120 82, 061120 (2010)], in a form suitable for the analyses of perpetual extraction of work. Since our theory is formulated for generic dynamics of probability distribution function in phase space, its application to a physical system is straightforward. As simple applications of the theory, two exactly solvable models are analyzed. The one is a nonequilibrium two-state system and the other is a particle confined to a one-dimensional harmonic potential in thermal equilibrium. For the former example, it is demonstrated that the observer on the transitory steps to the stationary state can lose energy and that work larger than that achieved in the stationary state can be extracted. For the latter example, it is demonstrated that the optimal protocol for the extraction of work via repeated measurements can differ from that via a single measurement. The validity of our version of the detailed fluctuation theorem, which determines the upper bound of the expected work in the stationary state, is also confirmed for both examples. These observations provide useful insights into exploration for realistic modeling of a machine that extracts work from its environment.

  10. Overview of Nonoperative Blunt Splenic Injury Management with Associated Splenic Artery Pseudoaneurysm.

    PubMed

    Morrison, Chet A; Gross, Brian W; Kauffman, Matthew; Rittenhouse, Katelyn J; Rogers, Frederick B

    2017-06-01

    The delayed development of splenic artery pseudoaneurysm (SAP) can complicate the nonoperative management of splenic injuries. We sought to determine the utility of repeat imaging in diagnosing SAP in patients managed nonoperatively without angioembolization. We hypothesized that a significant rate of SAPs would be found in this population on repeat imaging. Patients undergoing nonoperative splenic injury management from January 2011 to June 2015 were queried from the trauma registry. Rates of repeat imaging, angioembolization, readmission, and SAP development were analyzed. Further, subanalyses investigating the incidence of SAP in patients managed nonoperatively without angioembolization were conducted. A total of 133 patients met inclusion criteria. Repeat imaging rate was 40 per cent, angioembolization rate was 26 per cent, and readmission rate was 6 per cent. Within the study population, nine SAPs were found (8/9 in patients with splenic injury grade ≥III). Of these nine SAPs, three (33%) were identified on initial scans and embolized, whereas six (67%) were found on repeat imaging in patients not initially receiving angioembolization. Splenic injuries are typically managed nonoperatively without serious complications. Our results suggest patients with splenic injuries grade ≥III managed nonoperatively without angioembolization should have repeat imaging within 48 hours to rule out the possibility of SAP.

  11. A novel tandem repeat sequence located on human chromosome 4p: isolation and characterization.

    PubMed

    Kogi, M; Fukushige, S; Lefevre, C; Hadano, S; Ikeda, J E

    1997-06-01

    In an effort to analyze the genomic region of the distal half of human chromosome 4p, to where Huntington disease and other diseases have been mapped, we have isolated the cosmid clone (CRS447) that was likely to contain a region with specific repeat sequences. Clone CRS447 was subjected to detailed analysis, including chromosome mapping, restriction mapping, and DNA sequencing. Chromosome mapping by both a human-CHO hybrid cell panel and FISH revealed that CRS447 was predominantly located in the 4p15.1-15.3 region. CRS447 was shown to consist of tandem repeats of 4.7-kb units present on chromosome 4p. A single EcoRI unit was subcloned (pRS447), and the complete sequence was determined as 4752 nucleotides. When pRS447 was used as a probe, the number of copies of this repeat per haploid genome was estimated to be 50-70. Sequence analysis revealed that it contained two internal CA repeats and one putative ORF. Database search established that this sequence was unreported. However, two homologous STS markers were found in the database. We concluded that CRS447/pRS447 is a novel tandem repeat sequence that is mainly specific to human chromosome 4p.

  12. The use of a fully integrated electronic medical record to minimize cumulative lifetime radiation exposure from CT scanning to detect urinary tract calculi.

    PubMed

    Kohler, Steven W; Chen, Richard; Kagan, Alex; Helvey, Dustin W; Buccigrossi, David

    2013-06-01

    In order to determine the effects of implementation of an electronic medical record on rates of repeat computed tomography (CT) scanning in the emergency department (ED) setting, we analyzed the utilization of CT of the kidneys, ureters, and bladder (CT KUB) for the detection of urinary tract calculi for periods before and after the implementation of a hospital-wide electronic medical record system. Rates of repeat CT scanning within a 6-month period of previous scan were determined pre- and post-implementation and compared. Prior to implementation, there was a 6-month repeat rate of 6.2 % compared with the post-implementation period, which was associated with a 6-month repeat rate of 4.1 %. Statistical analysis using a two-sample, one-tailed t test for difference of means was associated with a p value of 0.00007. This indicates that the implementation of the electronic medical record system was associated with a 34 % decrease in 6-month repeat CT KUB scans. We conclude that the use of an electronic medical record can be associated with a decrease in utilization of unnecessary repeat CT imaging, leading to decreased cumulative lifetime risk for cancer in these patients and more efficient utilization of ED and radiologic resources.

  13. Systemic exposure to benzoic acid and hippuric acid following topical application of clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel in Japanese patients with acne vulgaris.

    PubMed

    Ino, Hiroko; Takahashi, Naoki; Saenz, Alessandra Alio; Wakamatsu, Akira; Hashimoto, Hirofumi; Nakahara, Norie; Hasegawa, Setsuo

    2015-01-01

    Clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel (CLDM/BPO3%) is a topical product for the treatment of acne vulgaris. In this study, plasma and urine concentrations of benzoic acid (BA) and hippuric acid (HA) were analyzed to estimate the pharmacokinetics (PK) of BPO after application of CLDM/BPO3% twice-daily for 7 days in Japanese patients with acne vulgaris. Seven-day repeated application of CLDM/BPO3% appears to be safe in this patient population. Concentrations of plasma and urine BA were below the limit of quantification before and after repeated application in most of the 12 adult male patients. Mean difference in Cmax and AUC0-last for plasma HA indicated increased exposures after repeated application, but with wide 90% confidence intervals. Mean Ae0-12 for urine HA was similar before and after repeated application. Repeated application of CLDM/BPO3% is thus unlikely to result in accumulation of BA and HA. The study suggests negligible systemic exposure to BPO metabolites from CLDM/BPO3% after 7-day repeated application in male patients with acne vulgaris. © 2014, The American College of Clinical Pharmacology.

  14. Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage in Streptococcus thermophilus

    PubMed Central

    Wei, Yunzhou; Chesne, Megan T.; Terns, Rebecca M.; Terns, Michael P.

    2015-01-01

    CRISPR-Cas systems are RNA-based immune systems that protect prokaryotes from invaders such as phages and plasmids. In adaptation, the initial phase of the immune response, short foreign DNA fragments are captured and integrated into host CRISPR loci to provide heritable defense against encountered foreign nucleic acids. Each CRISPR contains a ∼100–500 bp leader element that typically includes a transcription promoter, followed by an array of captured ∼35 bp sequences (spacers) sandwiched between copies of an identical ∼35 bp direct repeat sequence. New spacers are added immediately downstream of the leader. Here, we have analyzed adaptation to phage infection in Streptococcus thermophilus at the CRISPR1 locus to identify cis-acting elements essential for the process. We show that the leader and a single repeat of the CRISPR locus are sufficient for adaptation in this system. Moreover, we identified a leader sequence element capable of stimulating adaptation at a dormant repeat. We found that sequences within 10 bp of the site of integration, in both the leader and repeat of the CRISPR, are required for the process. Our results indicate that information at the CRISPR leader-repeat junction is critical for adaptation in this Type II-A system and likely other CRISPR-Cas systems. PMID:25589547

  15. Real time optimal guidance of low-thrust spacecraft: an application of nonlinear model predictive control.

    PubMed

    Arrieta-Camacho, Juan José; Biegler, Lorenz T

    2005-12-01

    Real time optimal guidance is considered for a class of low thrust spacecraft. In particular, nonlinear model predictive control (NMPC) is utilized for computing the optimal control actions required to transfer a spacecraft from a low Earth orbit to a mission orbit. The NMPC methodology presented is able to cope with unmodeled disturbances. The dynamics of the transfer are modeled using a set of modified equinoctial elements because they do not exhibit singularities for zero inclination and zero eccentricity. The idea behind NMPC is the repeated solution of optimal control problems; at each time step, a new control action is computed. The optimal control problem is solved using a direct method-fully discretizing the equations of motion. The large scale nonlinear program resulting from the discretization procedure is solved using IPOPT--a primal-dual interior point algorithm. Stability and robustness characteristics of the NMPC algorithm are reviewed. A numerical example is presented that encourages further development of the proposed methodology: the transfer from low-Earth orbit to a molniya orbit.

  16. Convergent Evolution of Mechanically Optimal Locomotion in Aquatic Invertebrates and Vertebrates

    PubMed Central

    Bale, Rahul; Neveln, Izaak D.; Bhalla, Amneet Pal Singh

    2015-01-01

    Examples of animals evolving similar traits despite the absence of that trait in the last common ancestor, such as the wing and camera-type lens eye in vertebrates and invertebrates, are called cases of convergent evolution. Instances of convergent evolution of locomotory patterns that quantitatively agree with the mechanically optimal solution are very rare. Here, we show that, with respect to a very diverse group of aquatic animals, a mechanically optimal method of swimming with elongated fins has evolved independently at least eight times in both vertebrate and invertebrate swimmers across three different phyla. Specifically, if we take the length of an undulation along an animal’s fin during swimming and divide it by the mean amplitude of undulations along the fin length, the result is consistently around twenty. We call this value the optimal specific wavelength (OSW). We show that the OSW maximizes the force generated by the body, which also maximizes swimming speed. We hypothesize a mechanical basis for this optimality and suggest reasons for its repeated emergence through evolution. PMID:25919026

  17. Rapid discrimination and determination of antibiotics drugs in plastic syringes using near infrared spectroscopy with chemometric analysis: Application to amoxicillin and penicillin.

    PubMed

    Lê, Laetitia Minh Mai; Eveleigh, Luc; Hasnaoui, Ikram; Prognon, Patrice; Baillet-Guffroy, Arlette; Caudron, Eric

    2017-05-10

    The aim of this study was to investigate near infrared spectroscopy (NIRS) combined to chemometric analysis to discriminate and quantify three antibiotics by direct measurement in plastic syringes.Solutions of benzylpenicillin (PENI), amoxicillin (AMOX) and amoxicillin/clavulanic acid (AMOX/CLAV) were analyzed at therapeutic concentrations in glass vials and plastic syringes with NIR spectrometer by direct measurement. Chemometric analysis using partial least squares regression and discriminative analysis was conducted to develop qualitative and quantitative calibration models. Discrimination of the three antibiotics was optimal for concentrated solutions with 100% of accuracy. For quantitative analysis, the three antibiotics furnished a linear response (R²>0.9994) for concentrations ranging from 0.05 to 0.2 g/mL for AMOX, 0.1 to 1.0 MUI/mL for PENI and 0.005 to 0.05 g/mL for AMOX/CLAV with excellent repeatability (maximum 1.3%) and intermediate precision (maximum of 3.2%). Based on proposed models, 94.4% of analyzed AMOX syringes, 80.0% of AMOX/CLAV syringes and 85.7% of PENI syringes were compliant with a relative error including the limit of ± 15%.NIRS as rapid, non-invasive and non-destructive analytical method represents a potentially powerful tool to further develop for securing the drug administration circuit of healthcare institutions to ensure that patients receive the correct product at the right dose. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Optimal strategy analysis based on robust predictive control for inventory system with random demand

    NASA Astrophysics Data System (ADS)

    Saputra, Aditya; Widowati, Sutrisno

    2017-12-01

    In this paper, the optimal strategy for a single product single supplier inventory system with random demand is analyzed by using robust predictive control with additive random parameter. We formulate the dynamical system of this system as a linear state space with additive random parameter. To determine and analyze the optimal strategy for the given inventory system, we use robust predictive control approach which gives the optimal strategy i.e. the optimal product volume that should be purchased from the supplier for each time period so that the expected cost is minimal. A numerical simulation is performed with some generated random inventory data. We simulate in MATLAB software where the inventory level must be controlled as close as possible to a set point decided by us. From the results, robust predictive control model provides the optimal strategy i.e. the optimal product volume that should be purchased and the inventory level was followed the given set point.

  19. Numerical integration and optimization of motions for multibody dynamic systems

    NASA Astrophysics Data System (ADS)

    Aguilar Mayans, Joan

    This thesis considers the optimization and simulation of motions involving rigid body systems. It does so in three distinct parts, with the following topics: optimization and analysis of human high-diving motions, efficient numerical integration of rigid body dynamics with contacts, and motion optimization of a two-link robot arm using Finite-Time Lyapunov Analysis. The first part introduces the concept of eigenpostures, which we use to simulate and analyze human high-diving motions. Eigenpostures are used in two different ways: first, to reduce the complexity of the optimal control problem that we solve to obtain such motions, and second, to generate an eigenposture space to which we map existing real world motions to better analyze them. The benefits of using eigenpostures are showcased through different examples. The second part reviews an extensive list of integration algorithms used for the integration of rigid body dynamics. We analyze the accuracy and stability of the different integrators in the three-dimensional space and the rotation space SO(3). Integrators with an accuracy higher than first order perform more efficiently than integrators with first order accuracy, even in the presence of contacts. The third part uses Finite-time Lyapunov Analysis to optimize motions for a two-link robot arm. Finite-Time Lyapunov Analysis diagnoses the presence of time-scale separation in the dynamics of the optimized motion and provides the information and methodology for obtaining an accurate approximation to the optimal solution, avoiding the complications that timescale separation causes for alternative solution methods.

  20. A novel surrogate-based approach for optimal design of electromagnetic-based circuits

    NASA Astrophysics Data System (ADS)

    Hassan, Abdel-Karim S. O.; Mohamed, Ahmed S. A.; Rabie, Azza A.; Etman, Ahmed S.

    2016-02-01

    A new geometric design centring approach for optimal design of central processing unit-intensive electromagnetic (EM)-based circuits is introduced. The approach uses norms related to the probability distribution of the circuit parameters to find distances from a point to the feasible region boundaries by solving nonlinear optimization problems. Based on these normed distances, the design centring problem is formulated as a max-min optimization problem. A convergent iterative boundary search technique is exploited to find the normed distances. To alleviate the computation cost associated with the EM-based circuits design cycle, space-mapping (SM) surrogates are used to create a sequence of iteratively updated feasible region approximations. In each SM feasible region approximation, the centring process using normed distances is implemented, leading to a better centre point. The process is repeated until a final design centre is attained. Practical examples are given to show the effectiveness of the new design centring method for EM-based circuits.

  1. Optimization of parameters of special asynchronous electric drives

    NASA Astrophysics Data System (ADS)

    Karandey, V. Yu; Popov, B. K.; Popova, O. B.; Afanasyev, V. L.

    2018-03-01

    The article considers the solution of the problem of parameters optimization of special asynchronous electric drives. The solution of the problem will allow one to project and create special asynchronous electric drives for various industries. The created types of electric drives will have optimum mass-dimensional and power parameters. It will allow one to realize and fulfill the set characteristics of management of technological processes with optimum level of expenses of electric energy, time of completing the process or other set parameters. The received decision allows one not only to solve a certain optimizing problem, but also to construct dependences between the optimized parameters of special asynchronous electric drives, for example, with the change of power, current in a winding of the stator or rotor, induction in a gap or steel of magnetic conductors and other parameters. On the constructed dependences, it is possible to choose necessary optimum values of parameters of special asynchronous electric drives and their components without carrying out repeated calculations.

  2. M13-Tailed Simple Sequence Repeat (SSR) Markers in Studies of Genetic Diversity and Population Structure of Common Oat Germplasm.

    PubMed

    Onyśk, Agnieszka; Boczkowska, Maja

    2017-01-01

    Simple Sequence Repeat (SSR) markers are one of the most frequently used molecular markers in studies of crop diversity and population structure. This is due to their uniform distribution in the genome, the high polymorphism, reproducibility, and codominant character. Additional advantages are the possibility of automatic analysis and simple interpretation of the results. The M13 tagged PCR reaction significantly reduces the costs of analysis by the automatic genetic analyzers. Here, we also disclose a short protocol of SSR data analysis.

  3. Repeatability analysis on LPFGs written by a CO2 laser

    NASA Astrophysics Data System (ADS)

    Nespereira, Marta; Castro Alves, D.; Coelho, João. M. P.; Monteiro, Fernando; Abreu, Manuel; Rebordão, J. M.

    2014-08-01

    The physical mechanisms involved in the writing process of long period fiber gratings (LPFG) using mid-infrared radiation emitted by CO2 lasers limit the obtained characteristics, in particular the minimum period that can be achieved. In order to evaluate the performances of a new methodology developed by us, we analyzed its capability to produce gratings with different periods (from 600 μm down to 300 μm). We also present a repeatability study on the obtained LPFG characteristics (mainly the resonant wavelength and grating length) for several values of the repetition period.

  4. A nationwide, population-based, long-term follow-up study of repeated self-harm in Taiwan

    PubMed Central

    2012-01-01

    Background Previous follow-up studies of repeated self-harm show that the cumulative risk of repeated self-harm within one year is 5.7%–15%, with females at greatest risk. However, relatively few studies have focused on the Far East. The objective of this study was to calculate the cumulative risk of repeated self-harm over different lengths of follow-up time (3 months, 6 months, and 1–8 years), to determine factors influencing repeated self-harm and to explore the interaction between gender and self-harm methods. Methods We used self-harm patient who hospitalized due to first-time self-harm between 2000 and 2007 from 1,230 hospitals in Taiwan. Hospitalization for repeated self-harm among members of this cohort was tracked after 3 months, 6 months, and 1–8 years. Tracking continued until December 31, 2008. We analyzed the cumulative risk and risk factors of repeated self-harm by using negative binomial regression. Results Of the 39,875 individual study samples, 3,388 individuals (8.50%) were found to have repeatedly self-harmed. The cumulative risk of repeated self-harm within three months was 7.19% and within one year was 8%. Within 8 years, it was 8.70%. Females were more likely to repeatedly self-harm than males (RR = 1.21, 95% CI = 1.15–1.76). The main method of self-harm was solid or liquid substances (RR = 1.88, 95% CI = 1.23–2.04) or cutting or piercing (RR = 1.36, 95% CI = 1.02–1.82), and in patients with psychiatric disorders were more likely to self-harm (RR = 1.61, 95% CI = 1.48–1.75). Conclusions The key time for intervention for repeated self-harm is within three months. Appropriate prevention programs should be developed based on gender differences. PMID:22950416

  5. DNA-directed mutations. Leading and lagging strand specificity

    NASA Technical Reports Server (NTRS)

    Sinden, R. R.; Hashem, V. I.; Rosche, W. A.

    1999-01-01

    The fidelity of replication has evolved to reproduce B-form DNA accurately, while allowing a low frequency of mutation. The fidelity of replication can be compromised, however, by defined order sequence DNA (dosDNA) that can adopt unusual or non B-DNA conformations. These alternative DNA conformations, including hairpins, cruciforms, triplex DNAs, and slipped-strand structures, may affect enzyme-template interactions that potentially lead to mutations. To analyze the effect of dosDNA elements on spontaneous mutagenesis, various mutational inserts containing inverted repeats or direct repeats were cloned in a plasmid containing a unidirectional origin of replication and a selectable marker for the mutation. This system allows for analysis of mutational events that are specific for the leading or lagging strands during DNA replication in Escherichia coli. Deletions between direct repeats, involving misalignment stabilized by DNA secondary structure, occurred preferentially on the lagging strand. Intermolecular strand switch events, correcting quasipalindromes to perfect inverted repeats, occurred preferentially during replication of the leading strand.

  6. Therapeutic outcomes of transsphenoidal surgery in pediatric patients with craniopharyngiomas: a single-center study.

    PubMed

    Yamada, Shozo; Fukuhara, Noriaki; Yamaguchi-Okada, Mitsuo; Nishioka, Hiroshi; Takeshita, Akira; Takeuchi, Yasuhiro; Inoshita, Naoko; Ito, Junko

    2018-03-30

    OBJECTIVE The aim of this study was to analyze the outcomes of transsphenoidal surgery (TSS) in a single-center clinical series of pediatric craniopharyngioma patients treated with gross-total resection (GTR). METHODS The authors retrospectively reviewed the surgical outcomes for 65 consecutive patients with childhood craniopharyngiomas (28 girls and 37 boys, mean age 9.6 years) treated with TSS (45 primary and 20 repeat surgeries) between 1990 and 2015. Tumors were classified as subdiaphragmatic or supradiaphragmatic. Demographic and clinical characteristics, including extent of resection, complications, incidence of recurrence, pre- and postoperative visual disturbance, pituitary function, and incidence of diabetes insipidus (DI), as well as new-onset obesity, were analyzed and compared between the primary surgery and repeat surgery groups. RESULTS Of the 45 patients in the primary surgery group, 26 (58%) had subdiaphragmatic tumors and 19 had supradiaphragmatic tumors. Of the 20 patients in the repeat surgery group, 9 (45%) had subdiaphragmatic tumors and 11 had supradiaphragmatic tumors. The only statistically significant difference between the 2 surgical groups was in tumor size; tumors were larger (mean maximum diameter 30 mm) in the primary surgery group than in the repeat surgery group (25 mm) (p = 0.008). GTR was accomplished in 59 (91%) of the 65 cases; the GTR rate was higher in the primary surgery group than in the repeat surgery group (98% vs 75%, p = 0.009). Among the patients who underwent GTR, 12% experienced tumor recurrence, with a median follow-up of 7.8 years, and recurrence tended to occur less frequently in primary than in repeat surgery patients (7% vs 27%, p = 0.06). Of the 45 primary surgery patients, 80% had deteriorated pituitary function and 83% developed DI, whereas 100% of the repeat surgery patients developed these conditions. Among patients with preoperative visual disturbance, vision improved in 62% but worsened in 11%. Visual improvement was more frequent in primary than in repeat surgery patients (71% vs 47%, p < 0.001), whereas visual deterioration was less frequent following primary surgery than repeat surgery (4% vs 24%, p = 0.04). Among the 57 patients without preoperative obesity, new-onset postoperative obesity was found in 9% of primary surgery patients and 21% of repeat surgery patients (p = 0.34) despite aggressive resection, suggesting that hypothalamic dysfunction was rarely associated with GTR by TSS in this series. However, obesity was found in 25% of the repeat surgery patients preoperatively due to prior transcranial surgery. Although there were no perioperative deaths, there were complications in 12 cases (18%) (6 cases of CSF leaks, 3 cases of meningitis, 2 cases of transient memory disturbance, and 1 case of hydrocephalus). Postoperative CSF leakage appeared to be more common in repeat than in primary surgery patients (20% vs 4.4%, p = 0.2). CONCLUSIONS The results of TSS for pediatric craniopharyngioma in this case series suggest that GTR should be the goal for the first surgical attempt. GTR should be achievable without serious complications, although most patients require postoperative hormonal replacement. When GTR is not possible or tumor recurrence occurs after GTR, radiosurgery is recommended to prevent tumor regrowth or progression.

  7. DRD4 dopamine receptor allelic diversity in various primate species

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

    Adamson, M.; Higley, D.; O`Brien, S.

    The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypesmore » in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.« less

  8. Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals.

    PubMed

    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Hsu, Ling-I; Lien, Li-Ming; Wang, Chih-Hao; Hsieh, Yi-Chen; Wang, Yuan-Hung; Hsueh, Yu-Mei; Lee, Te-Chang; Cheng, Wen-Fang; Chen, Chien-Jen

    2011-12-01

    Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (<27 repeats) or L (≥ 27 repeats) alleles. Multivariate analyses were used to estimate the effect size after accounting for CV covariates. Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles. HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Is Adaptive Treatment Planning Required for Stereotactic Radiotherapy of Stage I Non-Small-Cell Lung Cancer?

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

    Haasbeek, Cornelis J.A.; Lagerwaard, Frank J.; Cuijpers, Johan P.

    2007-04-01

    Purpose: Changes in position or size of target volumes have been observed during radiotherapy for lung cancer. The need for adaptive treatment planning during stereotactic radiotherapy of Stage I tumors was retrospectively analyzed using repeat four-dimensional computed tomography (4DCT) scans. Methods and Materials: A planning study was performed for 60 tumors in 59 patients using 4DCT scans repeated after two or more treatment fractions. Planning target volumes (PTV) encompassed all tumor mobility, and dose distributions from the initial plan were projected onto PTVs derived from the repeat 4DCT. A dosimetric and volumetric analysis was performed. Results: The repeat 4DCT scansmore » were performed at a mean of 6.6 days (range, 2-12 days) after the first fraction of stereotactic radiotherapy. In 25% of cases the repeat PTV was larger, but the difference exceeded 1 mL in 5 patients only. The mean 3D displacement between the center of mass of both PTVs was 2.0 mm. The initial 80% prescription isodose ensured a mean coverage of 98% of repeat PTVs, and this isodose fully encompassed the repeat internal target volumes in all but 1 tumor. 'Inadequate' coverage in the latter was caused by a new area of atelectasis adjacent to the tumor on the repeat 4DCT. Conclusions: Limited 'time trends' were observed in PTVs generated by repeated uncoached 4DCT scans, and the dosimetric consequences proved to be minimal. Treatment based only on the initial PTV would not have resulted in major tumor underdosage, indicating that adaptive treatment planning is of limited value for fractionated stereotactic radiotherapy.« less

  10. Correlation between fibroin amino acid sequence and physical silk properties.

    PubMed

    Fedic, Robert; Zurovec, Michal; Sehnal, Frantisek

    2003-09-12

    The fiber properties of lepidopteran silk depend on the amino acid repeats that interact during H-fibroin polymerization. The aim of our research was to relate repeat composition to insect biology and fiber strength. Representative regions of the H-fibroin genes were sequenced and analyzed in three pyralid species: wax moth (Galleria mellonella), European flour moth (Ephestia kuehniella), and Indian meal moth (Plodia interpunctella). The amino acid repeats are species-specific, evidently a diversification of an ancestral region of 43 residues, and include three types of regularly dispersed motifs: modifications of GSSAASAA sequence, stretches of tripeptides GXZ where X and Z represent bulky residues, and sequences similar to PVIVIEE. No concatenations of GX dipeptide or alanine, which are typical for Bombyx silkworms and Antheraea silk moths, respectively, were found. Despite different repeat structure, the silks of G. mellonella and E. kuehniella exhibit similar tensile strength as the Bombyx and Antheraea silks. We suggest that in these latter two species, variations in the repeat length obstruct repeat alignment, but sufficiently long stretches of iterated residues get superposed to interact. In the pyralid H-fibroins, interactions of the widely separated and diverse motifs depend on the precision of repeat matching; silk is strong in G. mellonella and E. kuehniella, with 2-3 types of long homogeneous repeats, and nearly 10 times weaker in P. interpunctella, with seven types of shorter erratic repeats. The high proportion of large amino acids in the H-fibroin of pyralids has probably evolved in connection with the spinning habit of caterpillars that live in protective silk tubes and spin continuously, enlarging the tubes on one end and partly devouring the other one. The silk serves as a depot of energetically rich and essential amino acids that may be scarce in the diet.

  11. Development of Pineapple Microsatellite Markers and Germplasm Genetic Diversity Analysis

    PubMed Central

    Tong, Helin; Chen, You; Wang, Jingyi; Chen, Yeyuan; Sun, Guangming; He, Junhu; Wu, Yaoting

    2013-01-01

    Two methods were used to develop pineapple microsatellite markers. Genomic library-based SSR development: using selectively amplified microsatellite assay, 86 sequences were generated from pineapple genomic library. 91 (96.8%) of the 94 Simple Sequence Repeat (SSR) loci were dinucleotide repeats (39 AC/GT repeats and 52 GA/TC repeats, accounting for 42.9% and 57.1%, resp.), and the other three were mononucleotide repeats. Thirty-six pairs of SSR primers were designed; 24 of them generated clear bands of expected sizes, and 13 of them showed polymorphism. EST-based SSR development: 5659 pineapple EST sequences obtained from NCBI were analyzed; among 1397 nonredundant EST sequences, 843 were found containing 1110 SSR loci (217 of them contained more than one SSR locus). Frequency of SSRs in pineapple EST sequences is 1SSR/3.73 kb, and 44 types were found. Mononucleotide, dinucleotide, and trinucleotide repeats dominate, accounting for 95.6% in total. AG/CT and AGC/GCT were the dominant type of dinucleotide and trinucleotide repeats, accounting for 83.5% and 24.1%, respectively. Thirty pairs of primers were designed for each of randomly selected 30 sequences; 26 of them generated clear and reproducible bands, and 22 of them showed polymorphism. Eighteen pairs of primers obtained by the one or the other of the two methods above that showed polymorphism were selected to carry out germplasm genetic diversity analysis for 48 breeds of pineapple; similarity coefficients of these breeds were between 0.59 and 1.00, and they can be divided into four groups accordingly. Amplification products of five SSR markers were extracted and sequenced, corresponding repeat loci were found and locus mutations are mainly in copy number of repeats and base mutations in the flanking region. PMID:24024187

  12. Improving the satellite communication efficiency of the accumulative acknowledgement strategies

    NASA Astrophysics Data System (ADS)

    Duarte, Otto Carlos M. B.; de Lima, Heliomar Medeiros

    The performances of two finite buffer error recovery strategies are analyzed. In both strategies the retransmission request decision between selective repeat and continuous retransmission is based on an imminent buffer overflow condition. These are accumulative acknowledgment schemes, but in the second strategy the selective-repeat control frame is uniquely an individual negative acknowledgment. The two strategies take advantage of the availability of a greater buffer capacity, making the most of the selective repeat, postponing the sending of a continuous retransmission request. Numerical results show a better performance very close to the ideal, but it does not integrally conform to the high-level data link control (HDLC) procedures. It is shown that these strategies are well suited for high-speed data transfer in the high-error-rate satellite environment.

  13. System and method of detecting cavitation in pumps

    DOEpatents

    Lu, Bin; Sharma, Santosh Kumar; Yan, Ting; Dimino, Steven A.

    2017-10-03

    A system and method for detecting cavitation in pumps for fixed and variable supply frequency applications is disclosed. The system includes a controller having a processor programmed to repeatedly receive real-time operating current data from a motor driving a pump, generate a current frequency spectrum from the current data, and analyze current data within a pair of signature frequency bands of the current frequency spectrum. The processor is further programmed to repeatedly determine fault signatures as a function of the current data within the pair of signature frequency bands, repeatedly determine fault indices based on the fault signatures and a dynamic reference signature, compare the fault indices to a reference index, and identify a cavitation condition in a pump based on a comparison between the reference index and a current fault index.

  14. Systematic ultrasound-guided saturation and template biopsy of the prostate: indications and advantages of extended sampling.

    PubMed

    Isbarn, Hendrik; Briganti, Alberto; De Visschere, Pieter J L; Fütterer, Jurgen J; Ghadjar, Pirus; Giannarini, Gianluca; Ost, Piet; Ploussard, Guillaume; Sooriakumaran, Prasanna; Surcel, Christian I; van Oort, Inge M; Yossepowitch, Ofer; van den Bergh, Roderick C N

    2015-04-01

    Prostate biopsy (PB) is the gold standard for the diagnosis of prostate cancer (PCa). However, the optimal number of biopsy cores remains debatable. We sought to compare contemporary standard (10-12 cores) vs. saturation (=18 cores) schemes on initial as well as repeat PB. A non-systematic review of the literature was performed from 2000 through 2013. Studies of highest evidence (randomized controlled trials, prospective non-randomized studies, and retrospective reports of high quality) comparing standard vs saturation schemes on initial and repeat PB were evaluated. Outcome measures were overall PCa detection rate, detection rate of insignificant PCa, and procedure-associated morbidity. On initial PB, there is growing evidence that a saturation scheme is associated with a higher PCa detection rate compared to a standard one in men with lower PSA levels (<10 ng/ml), larger prostates (>40 cc), or lower PSA density values (<0.25 ng/ml/cc). However, these cut-offs are not uniform and differ among studies. Detection rates of insignificant PCa do not differ in a significant fashion between standard and saturation biopsies. On repeat PB, PCa detection rate is likewise higher with saturation protocols. Estimates of insignificant PCa vary widely due to differing definitions of insignificant disease. However, the rates of insignificant PCa appear to be comparable for the schemes in patients with only one prior negative biopsy, while saturation biopsy seems to detect more cases of insignificant PCa compared to standard biopsy in men with two or more prior negative biopsies. Very extensive sampling is associated with a high rate of acute urinary retention, whereas other severe adverse events, such as sepsis, appear not to occur more frequently with saturation schemes. Current evidence suggests that saturation schemes are associated with a higher PCa detection rate compared to standard ones on initial PB in men with lower PSA levels or larger prostates, and on repeat PB. Since most data are derived from retrospective studies, other endpoints such as detection rate of insignificant disease - especially on repeat PB - show broad variations throughout the literature and must, thus, be interpreted with caution. Future prospective controlled trials should be conducted to compare extended templates with newer techniques, such as image-guided sampling, in order to optimize PCa diagnostic strategy.

  15. Complex structure of knob DNA on maize chromosome 9. Retrotransposon invasion into heterochromatin.

    PubMed Central

    Ananiev, E V; Phillips, R L; Rines, H W

    1998-01-01

    The recovery of maize (Zea mays L.) chromosome addition lines of oat (Avena sativa L.) from oat x maize crosses enables us to analyze the structure and composition of specific regions, such as knobs, of individual maize chromosomes. A DNA hybridization blot panel of eight individual maize chromosome addition lines revealed that 180-bp repeats found in knobs are present in each of these maize chromosomes, but the copy number varies from approximately 100 to 25, 000. Cosmid clones with knob DNA segments were isolated from a genomic library of an oat-maize chromosome 9 addition line with the help of the 180-bp knob-associated repeated DNA sequence used as a probe. Cloned knob DNA segments revealed a complex organization in which blocks of tandemly arranged 180-bp repeating units are interrupted by insertions of other repeated DNA sequences, mostly represented by individual full size copies of retrotransposable elements. There is an obvious preference for the integration of retrotransposable elements into certain sites (hot spots) of the 180-bp repeat. Sequence microheterogeneity including point mutations and duplications was found in copies of 180-bp repeats. The 180-bp repeats within an array all had the same polarity. Restriction maps constructed for 23 cloned knob DNA fragments revealed the positions of polymorphic sites and sites of integration of insertion elements. Discovery of the interspersion of retrotransposable elements among blocks of tandem repeats in maize and some other organisms suggests that this pattern may be basic to heterochromatin organization for eukaryotes. PMID:9691055

  16. Space geodetic observations of repeating slow slip events beneath the Bonin Islands

    NASA Astrophysics Data System (ADS)

    Arisa, Deasy; Heki, Kosuke

    2017-09-01

    The Pacific Plate subducts beneath the Philippine Sea Plate along the Izu-Bonin Trench. We investigated crustal movements at the Bonin Islands, using Global Navigation Satellite System and geodetic Very Long Baseline Interferometry data to reveal how the two plates converge in this subduction zone. These islands are located ∼100 km from the trench, just at the middle between the volcanic arc and the trench, making these islands suitable for detecting signatures of episodic deformation such as slow slip events (SSEs). During 2007-2016, we found five SSEs repeating quasi-periodically with similar displacement patterns. In estimating their fault parameters, we assumed that the fault lies on the prescribed plate boundary, and optimized the size, shape and position of the fault and dislocation vectors. Average fault slip was ∼5 cm, and the average moment magnitude was ∼6.9. We also found one SSE occurred in 2008 updip of the repeating SSE in response to an M6 class interplate earthquake. In spite of the frequent occurrence of SSEs, there is no evidence for long-term strain accumulation in the Bonin Islands that may lead to future megathrust earthquakes. Plate convergence in Mariana-type subduction zones may occur, to a large extent, episodically as repeating SSEs.

  17. En face Doppler total retinal blood flow measurement with 70 kHz spectral optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Tan, Ou; Liu, Gangjun; Liang, Liu; Gao, Simon S.; Pechauer, Alex D.; Jia, Yali; Huang, David

    2015-06-01

    An automated algorithm was developed for total retinal blood flow (TRBF) using 70-kHz spectral optical coherence tomography (OCT). The OCT was calibrated for the transformation from Doppler shift to speed based on a flow phantom. The TRBF scan pattern contained five repeated volume scans (2×2 mm) obtained in 3 s and centered on central retinal vessels in the optic disc. The TRBF was calculated using an en face Doppler technique. For each retinal vein, blood flow was measured at an optimal plane where the calculated flow was maximized. The TRBF was calculated by summing flow in all veins. The algorithm tracked vascular branching so that either root or branch veins are summed, but never both. The TRBF in five repeated volumes were averaged to reduce variation due to cardiac cycle pulsation. Finally, the TRBF was corrected for eye length variation. Twelve healthy eyes and 12 glaucomatous eyes were enrolled to test the algorithm. The TRBF was 45.4±6.7 μl/min for healthy control and 34.7±7.6 μl/min for glaucomatous participants (p-value=0.01). The intravisit repeatability was 8.6% for healthy controls and 8.4% for glaucoma participants. The proposed automated method provided repeatable TRBF measurement.

  18. MO-AB-BRA-08: Rapid Treatment Field Uniformity Optimization for Total Skin Electron Beam Therapy Using Cherenkov Imaging

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

    Andreozzi, J; Zhang, R; Glaser, A

    Purpose: To evaluate treatment field heterogeneity resulting from gantry angle choice in total skin electron beam therapy (TSEBT) following a modified Stanford dual-field technique, and determine a relationship between source to surface distance (SSD) and optimized gantry angle spread. Methods: Cherenkov imaging was used to image 62 treatment fields on a sheet of 1.2m x 2.2m x 1.2cm polyethylene following standard TSEBT setup at our institution (6 MeV, 888 MU/min, no spoiler, SSD=441cm), where gantry angles spanned from 239.5° to 300.5° at 1° increments. Average Cherenkov intensity and coefficient of variation in the region of interest were compared for themore » set of composite Cherenkov images created by summing all unique combinations of angle pairs to simulate dual-field treatment. The angle pair which produced the lowest coefficient of variation was further studied using an ionization chamber. The experiment was repeated at SSD=300cm, and SSD=370.5cm. Cherenkov imaging was also implemented during TSEBT of three patients. Results: The most uniform treatment region from a symmetric angle spread was achieved using gantry angles +/−17.5° about the horizontal axis at SSD=441cm, +/−18.5° at SSD=370.5cm, and +/−19.5° at SSD=300cm. Ionization chamber measurements comparing the original treatment spread (+/−14.5°) and the optimized angle pair (+/−17.5°) at SSD=441cm showed no significant deviation (r=0.999) in percent depth dose curves, and chamber measurements from nine locations within the field showed an improvement in dose uniformity from 24.41% to 9.75%. Ionization chamber measurements correlated strongly (r=0.981) with Cherenkov intensity measured concurrently on the flat Plastic Water phantom. Patient images and TLD results also showed modest uniformity improvements. Conclusion: A decreasing linear relationship between optimal angle spread and SSD was observed. Cherenkov imaging offers a new method of rapidly analyzing and optimizing TSEBT setup geometry by providing a 2D image of the treatment plane as a sum of the two fields. This study has been funded by NIH grants R21EB17559 and R01CA109558 as well as Norris Cotton Cancer Center Pilot funding.« less

  19. Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs.

    PubMed

    Yoon, Nara; Vander Velde, Robert; Marusyk, Andriy; Scott, Jacob G

    2018-05-07

    Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, [Formula: see text] and [Formula: see text], each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for [Formula: see text] and [Formula: see text], we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point, T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e., [Formula: see text]-long for DrugA and [Formula: see text]-long for DrugB with [Formula: see text] and [Formula: see text]). We prove that the optimal duration of the initial stage, in which the first drug is administered, T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, [Formula: see text], and the effect of each drug. We determine a critical ratio, which we term [Formula: see text], at which the two drugs are equally effective. As the first stage of the optimal strategy is applied, [Formula: see text] changes monotonically to [Formula: see text] and then, during the second stage, remains at [Formula: see text] thereafter. Beyond our analytic results, we explored an individual-based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.

  20. Dendritic spine dynamics leading to spine elimination after repeated inductions of LTD

    PubMed Central

    Hasegawa, Sho; Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2015-01-01

    Memory is fixed solidly by repetition. However, the cellular mechanism underlying this repetition-dependent memory consolidation/reconsolidation remains unclear. In our previous study using stable slice cultures of the rodent hippocampus, we found long-lasting synaptic enhancement/suppression coupled with synapse formation/elimination after repeated inductions of chemical LTP/LTD, respectively. We proposed these phenomena as useful model systems for analyzing repetition-dependent memory consolidation. Recently, we analyzed the dynamics of dendritic spines during development of the enhancement, and found that the spines increased in number following characteristic stochastic processes. The current study investigates spine dynamics during the development of the suppression. We found that the rate of spine retraction increased immediately leaving that of spine generation unaltered. Spine elimination occurred independent of the pre-existing spine density on the dendritic segment. In terms of elimination, mushroom-type spines were not necessarily more stable than stubby-type and thin-type spines. PMID:25573377

  1. Increased instrument intelligence--can it reduce laboratory error?

    PubMed

    Jekelis, Albert W

    2005-01-01

    Recent literature has focused on the reduction of laboratory errors and the potential impact on patient management. This study assessed the intelligent, automated preanalytical process-control abilities in newer generation analyzers as compared with older analyzers and the impact on error reduction. Three generations of immuno-chemistry analyzers were challenged with pooled human serum samples for a 3-week period. One of the three analyzers had an intelligent process of fluidics checks, including bubble detection. Bubbles can cause erroneous results due to incomplete sample aspiration. This variable was chosen because it is the most easily controlled sample defect that can be introduced. Traditionally, lab technicians have had to visually inspect each sample for the presence of bubbles. This is time consuming and introduces the possibility of human error. Instruments with bubble detection may be able to eliminate the human factor and reduce errors associated with the presence of bubbles. Specific samples were vortexed daily to introduce a visible quantity of bubbles, then immediately placed in the daily run. Errors were defined as a reported result greater than three standard deviations below the mean and associated with incomplete sample aspiration of the analyte of the individual analyzer Three standard deviations represented the target limits of proficiency testing. The results of the assays were examined for accuracy and precision. Efficiency, measured as process throughput, was also measured to associate a cost factor and potential impact of the error detection on the overall process. The analyzer performance stratified according to their level of internal process control The older analyzers without bubble detection reported 23 erred results. The newest analyzer with bubble detection reported one specimen incorrectly. The precision and accuracy of the nonvortexed specimens were excellent and acceptable for all three analyzers. No errors were found in the nonvortexed specimens. There were no significant differences in overall process time for any of the analyzers when tests were arranged in an optimal configuration. The analyzer with advanced fluidic intelligence demostrated the greatest ability to appropriately deal with an incomplete aspiration by not processing and reporting a result for the sample. This study suggests that preanalytical process-control capabilities could reduce errors. By association, it implies that similar intelligent process controls could favorably impact the error rate and, in the case of this instrument, do it without negatively impacting process throughput. Other improvements may be realized as a result of having an intelligent error-detection process including further reduction in misreported results, fewer repeats, less operator intervention, and less reagent waste.

  2. Capillary electrophoresis for aluminum ion speciation: Optimized separation conditions for complex polycation mixtures.

    PubMed

    Ouadah, Nesrine; Moire, Claudine; Brothier, Fabien; Kuntz, Jean-François; Deschaume, Olivier; Bartic, Carmen; Cottet, Hervé

    2018-06-01

    Aluminum chlorohydrates (ACH) are used in numerous applications and commercial products on a global scale including water treatment, catalysis or antiperspirants. They are complex mixtures of water soluble aluminum polycations of different degrees of polymerization, that are difficult to separate and quantify due to their susceptibility to depolymerize in solution when placed out of equilibrium, which is inherent to any separation process. We recently achieved the first capillary electrophoresis separation and characterization of ACH oligomers using 4-morpholineethanesulfonic acid (MES) as background electrolyte counter-ion. MES stabilizes the separated ACH oligomers during the electrophoretic process leading to highly repeatable and fast separations. In this work, the separation of ACH oligomers was further studied and perfected by varying the ionic strength, MES concentration and pH of the background electrolyte. Complex electrophoretic behavior is reported for the separation of Al 13 , Al 30 and Na + ions according to these experimental parameters. The transformation of the electropherograms in effective mobility scale and the use of the slope-plot approach are used to better understand the observed changes in selectivity/resolution. Optimal conditions (700 mM MES at 25 mM ionic strength containing 0.1 mM didodecyldimethylammonium bromide for dynamic capillary coating, pH 4.8) obtained for the separation of ACH oligomers are used for the baseline separation of samples difficult to analyze with other methods, including different molecular, aggregated and colloidal forms of aluminum from the Al 13 , Al 30 and Na + mixture, validating the rationale of the approach. Copyright © 2018. Published by Elsevier B.V.

  3. CT fluoroscopy guided transpleural cutting needle biopsy of small (≤2.5 cm) subpleural pulmonary nodules.

    PubMed

    Prosch, Helmut; Oschatz, Elisabeth; Eisenhuber, Edith; Wohlschlager, Helmut; Mostbeck, Gerhard H

    2011-01-01

    Small subpleural pulmonary lesions are difficult to biopsy. While the direct, short needle path has been reported to have a lower rate of pneumothorax, the indirect path provides a higher diagnostic yield. Therefore, we tried to optimize the needle pathway and minimize the iatrogenic pneumothorax risk by evaluating a CT fluoroscopy guided direct approach to biopsy subpleural lesions. Between 01/2005 and 01/2007, CT fluoroscopy guided core biopsies were performed in 24 patients. Using our technique, the tip of the guide needle remains outside the visceral pleura (17 G coaxial guide needle, 18 G Biopsy-gun, 15 or 22 mm needle path). The position of the lesion relative to the needle tip can be optimized using CT fluoroscopy by adjusting the breathing position of the patient. The Biopty gun is fired with the needle tip still outside the pleural space. Cytological smears are analyzed by a cytopathologist on-site, and biopsies are repeated as indicated with the coaxial needle still outside the pleura. Median nodule size was 1.6 cm (0.7-2.3 cm). A definitive diagnosis was obtained in 22 patients by histology and/or cytology. In one patient, only necrotic material could be obtained. In another patient, the intervention had to be aborted as the dyspnoic patient could not follow breathing instructions. An asymptomatic pneumothorax was present in seven patients; chest tube placement was not required. The presented biopsy approach has a high diagnostic yield and is especially advantageous for biopsies of small subpleural lesions in the lower lobes. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  4. Unappreciated epidemiology: the churn effect in a regional HIV care programme.

    PubMed

    Gill, M J; Krentz, H B

    2009-08-01

    High levels of geographic mobility in and out of HIV care centres (i.e. the churn effect) can disrupt the continuity of patient care, misalign prevention services, impact local prevalence data perturbing optimal allocation of resources, and contribute to logical challenges in repeated transfer of health records. We report on the clinical, demographic, and administrative impact of high population turnover within HIV populations.

  5. Comparative Analysis of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) of Streptococcus thermophilus St-I and its Bacteriophage-Insensitive Mutants (BIM) Derivatives.

    PubMed

    Li, Wan; Bian, Xin; Evivie, Smith Etareri; Huo, Gui-Cheng

    2016-09-01

    The CRISPR-Cas (CRISPR together with CRISPR-associated proteins) modules are the adaptive immune system, acting as an adaptive and heritable immune system in bacteria and archaea. CRISPR-based immunity acts by integrating short virus sequences in the cell's CRISPR locus, allowing the cell to remember, recognize, and clear infections. In this study, the homology of CRISPRs sequence in BIMs (bacteriophage-insensitive mutants) of Streptococcus thermophilus St-I were analyzed. Secondary structures of the repeats and the PAMs (protospacer-associated motif) of each CRISPR locus were also predicted. Results showed that CRISPR1 has 27 repeat-spacer units, 5 of them had duplicates; CRISPR2 has one repeat-spacer unit; CRISPR3 has 28 repeat-spacer units. Only BIM1 had a new spacer acquisition in CRISPR3, while BIM2 and BIM3 had no new spacers' insertion, thus indicating that while most CRISPR1 were more active than CRISPR3, new spacer acquisition occurred just in CRSPR3 in some situations. These findings will help establish the foundation for the study of CRSPR-Cas systems in lactic acid bacteria.

  6. Optimal Hydrophobicity in Ring-Opening Metathesis Polymerization-Based Protein Mimics Required for siRNA Internalization.

    PubMed

    deRonde, Brittany M; Posey, Nicholas D; Otter, Ronja; Caffrey, Leah M; Minter, Lisa M; Tew, Gregory N

    2016-06-13

    Exploring the role of polymer structure for the internalization of biologically relevant cargo, specifically siRNA, is of critical importance to the development of improved delivery reagents. Herein, we report guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold containing tunable hydrophobic moieties that promote siRNA internalization. Structure-activity relationships using Jurkat T cells and HeLa cells were explored to determine how the length of the hydrophobic block and the hydrophobic side chain compositions of these PTDMs impacted siRNA internalization. To explore the hydrophobic block length, two different series of diblock copolymers were synthesized: one series with symmetric block lengths and one with asymmetric block lengths. At similar cationic block lengths, asymmetric and symmetric PTDMs promoted siRNA internalization in the same percentages of the cell population regardless of the hydrophobic block length; however, with 20 repeat units of cationic charge, the asymmetric block length had greater siRNA internalization, highlighting the nontrivial relationships between hydrophobicity and overall cationic charge. To further probe how the hydrophobic side chains impacted siRNA internalization, an additional series of asymmetric PTDMs was synthesized that featured a fixed hydrophobic block length of five repeat units that contained either dimethyl (dMe), methyl phenyl (MePh), or diphenyl (dPh) side chains and varied cationic block lengths. This series was further expanded to incorporate hydrophobic blocks consisting of diethyl (dEt), diisobutyl (diBu), and dicyclohexyl (dCy) based repeat units to better define the hydrophobic window for which our PTDMs had optimal activity. High-performance liquid chromatography retention times quantified the relative hydrophobicities of the noncationic building blocks. PTDMs containing the MePh, diBu, and dPh hydrophobic blocks were shown to have superior siRNA internalization capabilities compared to their more and less hydrophobic counterparts, demonstrating a critical window of relative hydrophobicity for optimal internalization. This better understanding of how hydrophobicity impacts PTDM-induced internalization efficiencies will help guide the development of future delivery reagents.

  7. Design Considerations for a Dedicated Gravity Recovery Satellite Mission Consisting of Two Pairs of Satellites

    NASA Technical Reports Server (NTRS)

    Wiese, D. N.; Nerem, R. S.; Lemoine, F. G.

    2011-01-01

    Future satellite missions dedicated to measuring time-variable gravity will need to address the concern of temporal aliasing errors; i.e., errors due to high-frequency mass variations. These errors have been shown to be a limiting error source for future missions with improved sensors. One method of reducing them is to fly multiple satellite pairs, thus increasing the sampling frequency of the mission. While one could imagine a system architecture consisting of dozens of satellite pairs, this paper explores the more economically feasible option of optimizing the orbits of two pairs of satellites. While the search space for this problem is infinite by nature, steps have been made to reduce it via proper assumptions regarding some parameters and a large number of numerical simulations exploring appropriate ranges for other parameters. A search space originally consisting of 15 variables is reduced to two variables with the utmost impact on mission performance: the repeat period of both pairs of satellites (shown to be near-optimal when they are equal to each other), as well as the inclination of one of the satellite pairs (the other pair is assumed to be in a polar orbit). To arrive at this conclusion, we assume circular orbits, repeat groundtracks for both pairs of satellites, a 100-km inter-satellite separation distance, and a minimum allowable operational satellite altitude of 290 km based on a projected 10-year mission lifetime. Given the scientific objectives of determining time-variable hydrology, ice mass variations, and ocean bottom pressure signals with higher spatial resolution, we find that an optimal architecture consists of a polar pair of satellites coupled with a pair inclined at 72deg, both in 13-day repeating orbits. This architecture provides a 67% reduction in error over one pair of satellites, in addition to reducing the longitudinal striping to such a level that minimal post-processing is required, permitting a substantial increase in the spatial resolution of the gravity field products. It should be emphasized that given different sets of scientific objectives for the mission, or a different minimum allowable satellite altitude, different architectures might be selected.

  8. A mechano-acoustic indentor system for in vivo measurement of nonlinear elastic properties of soft tissue.

    PubMed

    Koo, Terry K; Cohen, Jeffrey H; Zheng, Yongping

    2011-11-01

    Soft tissue exhibits nonlinear stress-strain behavior under compression. Characterizing its nonlinear elasticity may aid detection, diagnosis, and treatment of soft tissue abnormality. The purposes of this study were to develop a rate-controlled Mechano-Acoustic Indentor System and a corresponding finite element optimization method to extract nonlinear elastic parameters of soft tissue and evaluate its test-retest reliability. An indentor system using a linear actuator to drive a force-sensitive probe with a tip-mounted ultrasound transducer was developed. Twenty independent sites at the upper lateral quadrant of the buttock from 11 asymptomatic subjects (7 men and 4 women from a chiropractic college) were indented at 6% per second for 3 sessions, each consisting of 5 trials. Tissue thickness, force at 25% deformation, and area under the load-deformation curve from 0% to 25% deformation were calculated. Optimized hyperelastic parameters of the soft tissue were calculated with a finite element model using a first-order Ogden material model. Load-deformation response on a standardized block was then simulated, and the corresponding area and force parameters were calculated. Between-trials repeatability and test-retest reliability of each parameter were evaluated using coefficients of variation and intraclass correlation coefficients, respectively. Load-deformation responses were highly reproducible under repeated measurements. Coefficients of variation of tissue thickness, area under the load-deformation curve from 0% to 25% deformation, and force at 25% deformation averaged 0.51%, 2.31%, and 2.23%, respectively. Intraclass correlation coefficients ranged between 0.959 and 0.999, indicating excellent test-retest reliability. The automated Mechano-Acoustic Indentor System and its corresponding optimization technique offers a viable technology to make in vivo measurement of the nonlinear elastic properties of soft tissue. This technology showed excellent between-trials repeatability and test-retest reliability with potential to quantify the effects of a wide variety of manual therapy techniques on the soft tissue elastic properties. Copyright © 2011 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  9. Optimization design of wireless charging system for autonomous robots based on magnetic resonance coupling

    NASA Astrophysics Data System (ADS)

    Wang, Junhua; Hu, Meilin; Cai, Changsong; Lin, Zhongzheng; Li, Liang; Fang, Zhijian

    2018-05-01

    Wireless charging is the key technology to realize real autonomy of mobile robots. As the core part of wireless power transfer system, coupling mechanism including coupling coils and compensation topology is analyzed and optimized through simulations, to achieve stable and practical wireless charging suitable for ordinary robots. Multi-layer coil structure, especially double-layer coil is explored and selected to greatly enhance coupling performance, while shape of ferrite shielding goes through distributed optimization to guarantee coil fault tolerance and cost effectiveness. On the basis of optimized coils, primary compensation topology is analyzed to adopt composite LCL compensation, to stabilize operations of the primary side under variations of mutual inductance. Experimental results show the optimized system does make sense for wireless charging application for robots based on magnetic resonance coupling, to realize long-term autonomy of robots.

  10. Structural Performance’s Optimally Analysing and Implementing Based on ANSYS Technology

    NASA Astrophysics Data System (ADS)

    Han, Na; Wang, Xuquan; Yue, Haifang; Sun, Jiandong; Wu, Yongchun

    2017-06-01

    Computer-aided Engineering (CAE) is a hotspot both in academic field and in modern engineering practice. Analysis System(ANSYS) simulation software for its excellent performance become outstanding one in CAE family, it is committed to the innovation of engineering simulation to help users to shorten the design process, improve product innovation and performance. Aimed to explore a structural performance’s optimally analyzing model for engineering enterprises, this paper introduced CAE and its development, analyzed the necessity for structural optimal analysis as well as the framework of structural optimal analysis on ANSYS Technology, used ANSYS to implement a reinforced concrete slab structural performance’s optimal analysis, which was display the chart of displacement vector and the chart of stress intensity. Finally, this paper compared ANSYS software simulation results with the measured results,expounded that ANSYS is indispensable engineering calculation tools.

  11. Evaluating data worth for ground-water management under uncertainty

    USGS Publications Warehouse

    Wagner, B.J.

    1999-01-01

    A decision framework is presented for assessing the value of ground-water sampling within the context of ground-water management under uncertainty. The framework couples two optimization models-a chance-constrained ground-water management model and an integer-programing sampling network design model-to identify optimal pumping and sampling strategies. The methodology consists of four steps: (1) The optimal ground-water management strategy for the present level of model uncertainty is determined using the chance-constrained management model; (2) for a specified data collection budget, the monitoring network design model identifies, prior to data collection, the sampling strategy that will minimize model uncertainty; (3) the optimal ground-water management strategy is recalculated on the basis of the projected model uncertainty after sampling; and (4) the worth of the monitoring strategy is assessed by comparing the value of the sample information-i.e., the projected reduction in management costs-with the cost of data collection. Steps 2-4 are repeated for a series of data collection budgets, producing a suite of management/monitoring alternatives, from which the best alternative can be selected. A hypothetical example demonstrates the methodology's ability to identify the ground-water sampling strategy with greatest net economic benefit for ground-water management.A decision framework is presented for assessing the value of ground-water sampling within the context of ground-water management under uncertainty. The framework couples two optimization models - a chance-constrained ground-water management model and an integer-programming sampling network design model - to identify optimal pumping and sampling strategies. The methodology consists of four steps: (1) The optimal ground-water management strategy for the present level of model uncertainty is determined using the chance-constrained management model; (2) for a specified data collection budget, the monitoring network design model identifies, prior to data collection, the sampling strategy that will minimize model uncertainty; (3) the optimal ground-water management strategy is recalculated on the basis of the projected model uncertainty after sampling; and (4) the worth of the monitoring strategy is assessed by comparing the value of the sample information - i.e., the projected reduction in management costs - with the cost of data collection. Steps 2-4 are repeated for a series of data collection budgets, producing a suite of management/monitoring alternatives, from which the best alternative can be selected. A hypothetical example demonstrates the methodology's ability to identify the ground-water sampling strategy with greatest net economic benefit for ground-water management.

  12. Comparative Chromosome Map and Heterochromatin Features of the Gray Whale Karyotype (Cetacea).

    PubMed

    Kulemzina, Anastasia I; Proskuryakova, Anastasia A; Beklemisheva, Violetta R; Lemskaya, Natalia A; Perelman, Polina L; Graphodatsky, Alexander S

    2016-01-01

    Cetacean karyotypes possess exceptionally stable diploid numbers and highly conserved chromosomes. To date, only toothed whales (Odontoceti) have been analyzed by comparative chromosome painting. Here, we studied the karyotype of a representative of baleen whales, the gray whale (Eschrichtius robustus, Mysticeti), by Zoo-FISH with dromedary camel and human chromosome-specific probes. We confirmed a high degree of karyotype conservation and found an identical order of syntenic segments in both branches of cetaceans. Yet, whale chromosomes harbor variable heterochromatic regions constituting up to a third of the genome due to the presence of several types of repeats. To investigate the cause of this variability, several classes of repeated DNA sequences were mapped onto chromosomes of whale species from both Mysticeti and Odontoceti. We uncovered extensive intrapopulation variability in the size of heterochromatic blocks present in homologous chromosomes among 3 individuals of the gray whale by 2-step differential chromosome staining. We show that some of the heteromorphisms observed in the gray whale karyotype are due to distinct amplification of a complex of common cetacean repeat and heavy satellite repeat on homologous autosomes. Furthermore, we demonstrate localization of the telomeric repeat in the heterochromatin of both gray and pilot whale (Globicephala melas, Odontoceti). Heterochromatic blocks in the pilot whale represent a composite of telomeric and common repeats, while heavy satellite repeat is lacking in the toothed whale consistent with previous studies. © 2016 S. Karger AG, Basel.

  13. Context-Dependent Sensitivity to Mutations Disrupting the Structural Integrity of Individual EGF Repeats in the Mouse Notch Ligand DLL1

    PubMed Central

    Schuster-Gossler, Karin; Cordes, Ralf; Müller, Julia; Geffers, Insa; Delany-Heiken, Patricia; Taft, Manuel; Preller, Matthias; Gossler, Achim

    2016-01-01

    The highly conserved Notch-signaling pathway mediates cell-to-cell communication and is pivotal for multiple developmental processes and tissue homeostasis in adult organisms. Notch receptors and their ligands are transmembrane proteins with multiple epidermal-growth-factor-like (EGF) repeats in their extracellular domains. In vitro the EGF repeats of mammalian ligands that are essential for Notch activation have been defined. However, in vivo the significance of the structural integrity of each EGF repeat in the ligand ectodomain for ligand function is still unclear. Here, we analyzed the mouse Notch ligand DLL1. We expressed DLL1 proteins with mutations disrupting disulfide bridges in each individual EGF repeat from single-copy transgenes in the HPRT locus of embryonic stem cells. In Notch transactivation assays all mutations impinged on DLL1 function and affected both NOTCH1 and NOTCH2 receptors similarly. An allelic series in mice that carried the same point mutations in endogenous Dll1, generated using a mini-gene strategy, showed that early developmental processes depending on DLL1-mediated NOTCH activation were differently sensitive to mutation of individual EGF repeats in DLL1. Notably, some mutations affected only somite patterning and resulted in vertebral column defects resembling spondylocostal dysostosis. In conclusion, the structural integrity of each individual EGF repeat in the extracellular domain of DLL1 is necessary for full DLL1 activity, and certain mutations in Dll1 might contribute to spondylocostal dysostosis in humans. PMID:26801181

  14. SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

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

    Chen, Y; Souri, S; Gill, G

    Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose tomore » its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.« less

  15. Determination of fluoroquinolones in fish tissues, biological fluids, and environmental waters by liquid chromatography tandem mass spectrometry.

    PubMed

    Ziarrusta, Haizea; Val, Nahia; Dominguez, Haizea; Mijangos, Leire; Prieto, Ailette; Usobiaga, Aresatz; Etxebarria, Nestor; Zuloaga, Olatz; Olivares, Maitane

    2017-11-01

    This work describes the optimization, validation, and application in real samples of accurate and precise analytical methods to determine ten fluoroquinolones (FQs) (norfloxacin, enoxacin, pefloxacin, ofloxacin, levofloxacin, ciprofloxacin, danofloxacin, lomefloxacin, enrofloxacin, and sparfloxacin) in different environmental matrices, such as water (estuarine, seawater, and wastewater treatment plant effluent), fish tissues (muscle and liver), and fish biofluids (plasma and bile). The analysis step performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was fully optimized to improve the separation and detection steps. The extraction of analytes from fish tissues was accomplished using focused ultrasound solid-liquid extraction using methanol/acetic acid (95:5 v/v) as extractant. The preconcentration and clean-up steps were optimized in terms of extraction efficiency and cleanliness and the best strategy for each matrix was selected: (i) Oasis HLB for seawater and muscle, (ii) liquid-liquid extraction combined with Oasis HLB for the lipid-rich liver, (iii) the combination of Evolute-WAX and Oasis HLB for estuarine water and wastewater treatment plant effluent, and (iv) molecular imprinted polymers for biofluids. The methods afforded satisfactory apparent recoveries (80-126%) and repeatability (RSD < 15%), except for sparfloxacin, which showed a lack of correction with the available isotopically labeled surrogates ([ 2 H 8 ]-ciprofloxacin and [ 2 H 5 ]-enrofloxacin). Ciprofloxacin, norfloxacin, and ofloxacin were detected in both water and fish liver samples from the Biscay Coast at concentrations up to 278 ng/L and 4 ng/g, respectively. To the best of our knowledge, this work is one of the few analyzing up to ten FQs and in so many fish tissues and biofluids. Graphical abstract Determination of fluoroquinolones in different environmental matrices, such as water (estuarine, seawater, and wastewater treatment plant effluent), fish tissues (muscle and liver), and fish biofluids (plasma and bile).

  16. Models of supply function equilibrium with applications to the electricity industry

    NASA Astrophysics Data System (ADS)

    Aromi, J. Daniel

    Electricity market design requires tools that result in a better understanding of incentives of generators and consumers. Chapter 1 and 2 provide tools and applications of these tools to analyze incentive problems in electricity markets. In chapter 1, models of supply function equilibrium (SFE) with asymmetric bidders are studied. I prove the existence and uniqueness of equilibrium in an asymmetric SFE model. In addition, I propose a simple algorithm to calculate numerically the unique equilibrium. As an application, a model of investment decisions is considered that uses the asymmetric SFE as an input. In this model, firms can invest in different technologies, each characterized by distinct variable and fixed costs. In chapter 2, option contracts are introduced to a supply function equilibrium (SFE) model. The uniqueness of the equilibrium in the spot market is established. Comparative statics results on the effect of option contracts on the equilibrium price are presented. A multi-stage game where option contracts are traded before the spot market stage is considered. When contracts are optimally procured by a central authority, the selected profile of option contracts is such that the spot market price equals marginal cost for any load level resulting in a significant reduction in cost. If load serving entities (LSEs) are price takers, in equilibrium, there is no trade of option contracts. Even when LSEs have market power, the central authority's solution cannot be implemented in equilibrium. In chapter 3, we consider a game in which a buyer must repeatedly procure an input from a set of firms. In our model, the buyer is able to sign long term contracts that establish the likelihood with which the next period contract is awarded to an entrant or the incumbent. We find that the buyer finds it optimal to favor the incumbent, this generates more intense competition between suppliers. In a two period model we are able to completely characterize the optimal mechanism.

  17. Optimization of sequence alignment for simple sequence repeat regions.

    PubMed

    Jighly, Abdulqader; Hamwieh, Aladdin; Ogbonnaya, Francis C

    2011-07-20

    Microsatellites, or simple sequence repeats (SSRs), are tandemly repeated DNA sequences, including tandem copies of specific sequences no longer than six bases, that are distributed in the genome. SSR has been used as a molecular marker because it is easy to detect and is used in a range of applications, including genetic diversity, genome mapping, and marker assisted selection. It is also very mutable because of slipping in the DNA polymerase during DNA replication. This unique mutation increases the insertion/deletion (INDELs) mutation frequency to a high ratio - more than other types of molecular markers such as single nucleotide polymorphism (SNPs).SNPs are more frequent than INDELs. Therefore, all designed algorithms for sequence alignment fit the vast majority of the genomic sequence without considering microsatellite regions, as unique sequences that require special consideration. The old algorithm is limited in its application because there are many overlaps between different repeat units which result in false evolutionary relationships. To overcome the limitation of the aligning algorithm when dealing with SSR loci, a new algorithm was developed using PERL script with a Tk graphical interface. This program is based on aligning sequences after determining the repeated units first, and the last SSR nucleotides positions. This results in a shifting process according to the inserted repeated unit type.When studying the phylogenic relations before and after applying the new algorithm, many differences in the trees were obtained by increasing the SSR length and complexity. However, less distance between different linage had been observed after applying the new algorithm. The new algorithm produces better estimates for aligning SSR loci because it reflects more reliable evolutionary relations between different linages. It reduces overlapping during SSR alignment, which results in a more realistic phylogenic relationship.

  18. Behavioural thermoregulation is highly repeatable and unaffected by digestive status in Agama atra.

    PubMed

    van Berkel, Jenna; Clusella-Trullas, Susana

    2018-05-03

    The precision and the extent of behavioral thermoregulation are likely to provide fitness benefits to ectotherms. Yet the factors driving variation in selected or preferred body temperature (T set ) and its usefulness as a proxy for optimal physiological temperature (T opt ) are still debated. Although T set is often conserved among closely related species, substantial variation at the individual, population, and species level has also been reported but repeatability (sensu the intra-class correlation coefficient, ICC) of T set is generally low. One factor that influences T set is feeding status, with fed reptiles typically showing higher T set , a process thought to aid meal digestion. Here using experiments simulating realistic ranges of feeding and fasting regimes in Agama atra, a heliothermic lizard from southern Africa, we test if T set and its repeatability under these two states significantly differ. Daily T set ranged from 33.7 to 38.4° C, with a mean (± SE) of 36.7 ± 0.1° C for fed and 36.6 ± 0.1° C for unfed individuals. Comparisons of repeatability showed that females tend to be more consistent in the selection of body temperature than males, but not significantly so regardless of feeding status. We report some of the highest repeatability estimates of T set to date (full range: 0.229 - 0.642), and that the weak positive effects of feeding status on T set detected here do not hinder obtaining relatively high repeatability estimates. In conclusion, one of the major prerequisites for natural selection, consistent among-individual variation, is present, making the adaptive significance of T set considerably more plausible. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Improved PCR-Based Detection of Soil Transmitted Helminth Infections Using a Next-Generation Sequencing Approach to Assay Design.

    PubMed

    Pilotte, Nils; Papaiakovou, Marina; Grant, Jessica R; Bierwert, Lou Ann; Llewellyn, Stacey; McCarthy, James S; Williams, Steven A

    2016-03-01

    The soil transmitted helminths are a group of parasitic worms responsible for extensive morbidity in many of the world's most economically depressed locations. With growing emphasis on disease mapping and eradication, the availability of accurate and cost-effective diagnostic measures is of paramount importance to global control and elimination efforts. While real-time PCR-based molecular detection assays have shown great promise, to date, these assays have utilized sub-optimal targets. By performing next-generation sequencing-based repeat analyses, we have identified high copy-number, non-coding DNA sequences from a series of soil transmitted pathogens. We have used these repetitive DNA elements as targets in the development of novel, multi-parallel, PCR-based diagnostic assays. Utilizing next-generation sequencing and the Galaxy-based RepeatExplorer web server, we performed repeat DNA analysis on five species of soil transmitted helminths (Necator americanus, Ancylostoma duodenale, Trichuris trichiura, Ascaris lumbricoides, and Strongyloides stercoralis). Employing high copy-number, non-coding repeat DNA sequences as targets, novel real-time PCR assays were designed, and assays were tested against established molecular detection methods. Each assay provided consistent detection of genomic DNA at quantities of 2 fg or less, demonstrated species-specificity, and showed an improved limit of detection over the existing, proven PCR-based assay. The utilization of next-generation sequencing-based repeat DNA analysis methodologies for the identification of molecular diagnostic targets has the ability to improve assay species-specificity and limits of detection. By exploiting such high copy-number repeat sequences, the assays described here will facilitate soil transmitted helminth diagnostic efforts. We recommend similar analyses when designing PCR-based diagnostic tests for the detection of other eukaryotic pathogens.

  20. Surveillance of risk profiles among new and repeat blood donors with transfusion-transmissible infections from 1995 through 2003 in the Netherlands.

    PubMed

    Van der Bij, Akke K; Coutinho, Roel A; Van der Poel, Cees L

    2006-10-01

    To evaluate the effectiveness of blood donor selection, this study reports risk profiles of donors with transfusion-transmissible infections as obtained by ongoing surveillance, 1995 through 2003, in the Netherlands. A surveillance program was installed to monitor risk profiles among new and repeat donors infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), or human T-lymphotropic virus (HTLV), or positive for the presence of syphilis antibodies. At posttest counseling, a physician interviewed donors to clarify possible sources of infection. A total of 167 repeat donors and 404 new donors were interviewed: 33 with HIV, 123 with HCV, 279 with HBV, 21 with HTLV, and 112 with syphilis antibodies. Most HBV, HCV, and HTLV infections were among new donors (80, 85, and 67%), whereas most HIV infections were among repeat donors (79%). Nearly 25 percent of the donors did not report factors at screening that would have deferred them from donating blood. At posttest interviews, new donors with HCV often reported injecting drug use (19%). Repeat donors with HIV often reported male-to-male sex (8/26, 31%). A significant level of deferrable behavioral risks was found among donors with confirmed transfusion-transmissible infections that persist despite current donor selection. Reporting such behavior at initial donor selection would have eliminated a substantial part of the infections found. This study argues against relaxing the existing donor deferral of persons practicing male-to-male sex, given their significant proportion of HIV infections among repeat donors. Systematic surveillance of risk factors among infected blood donors provides ongoing information about the effectivity of donor selection and is recommended to evaluate and optimize blood policies.

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