Combined immunotherapy of breast cancer with EGF and VEGF vaccines from DNA shuffling in a mouse model.

PubMed

Jin, Dong; Yu, Xin; Chen, Bing; Li, Zhitao; Ding, Jia; Zhao, Xiuyun; Qi, Gaofu

2017-06-01

Development of EGF and VEGF vaccines with high antigenicity for combined immunotherapy of EGF-EGFR signaling-dependent epithelial tumors such as breast cancer. EGF genes from mouse, human and chicken were randomly assembled to chimeric genes by DNA shuffling, then a chimeric EGF was selected out by PCR, SDS-PAGE and immunization for combined immunotherapy of breast cancer with a previously constructed chimeric VEGF vaccine from shuffling. Combined vaccination with chimeric EGF and VEGF from shuffling could induce high titer of antibodies against EGF and VEGF to inhibit tumor growth and angiogenesis, and improve the survival rate of mice with breast cancer. Combined vaccination with EGF and VEGF from shuffling showed better immunotherapy on EGF-EGFR signaling-dependent epithelial tumors such as breast cancer than the single-agent EGF vaccination.

Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages

PubMed Central

del Sol, Antonio; Araúzo-Bravo, Marcos J; Amoros, Dolors; Nussinov, Ruth

2007-01-01

Background Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. Results We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Gαs subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization. Conclusion Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages. PMID:17531094

Computational and experimental analysis of DNA shuffling

PubMed Central

Maheshri, Narendra; Schaffer, David V.

2003-01-01

We describe a computational model of DNA shuffling based on the thermodynamics and kinetics of this process. The model independently tracks a representative ensemble of DNA molecules and records their states at every stage of a shuffling reaction. These data can subsequently be analyzed to yield information on any relevant metric, including reassembly efficiency, crossover number, type and distribution, and DNA sequence length distributions. The predictive ability of the model was validated by comparison to three independent sets of experimental data, and analysis of the simulation results led to several unique insights into the DNA shuffling process. We examine a tradeoff between crossover frequency and reassembly efficiency and illustrate the effects of experimental parameters on this relationship. Furthermore, we discuss conditions that promote the formation of useless “junk” DNA sequences or multimeric sequences containing multiple copies of the reassembled product. This model will therefore aid in the design of optimal shuffling reaction conditions. PMID:12626764

An assessment of 'shuffle algorithm' collision mechanics for particle simulations

NASA Technical Reports Server (NTRS)

Feiereisen, William J.; Boyd, Iain D.

1991-01-01

Among the algorithms for collision mechanics used at present, the 'shuffle algorithm' of Baganoff (McDonald and Baganoff, 1988; Baganoff and McDonald, 1990) not only allows efficient vectorization, but also discretizes the possible outcomes of a collision. To assess the applicability of the shuffle algorithm, a simulation was performed of flows in monoatomic gases and the calculated characteristics of shock waves was compared with those obtained using a commonly employed isotropic scattering law. It is shown that, in general, the shuffle algorithm adequately represents the collision mechanics in cases when the goal of calculations are mean profiles of density and temperature.

Wavelet-based image compression using shuffling and bit plane correlation

NASA Astrophysics Data System (ADS)

Kim, Seungjong; Jeong, Jechang

2000-12-01

In this paper, we propose a wavelet-based image compression method using shuffling and bit plane correlation. The proposed method improves coding performance in two steps: (1) removing the sign bit plane by shuffling process on quantized coefficients, (2) choosing the arithmetic coding context according to maximum correlation direction. The experimental results are comparable or superior for some images with low correlation, to existing coders.

Prospecting Metagenomic Enzyme Subfamily Genes for DNA Family Shuffling by a Novel PCR-based Approach*

PubMed Central

Wang, Qiuyan; Wu, Huili; Wang, Anming; Du, Pengfei; Pei, Xiaolin; Li, Haifeng; Yin, Xiaopu; Huang, Lifeng; Xiong, Xiaolong

2010-01-01

DNA family shuffling is a powerful method for enzyme engineering, which utilizes recombination of naturally occurring functional diversity to accelerate laboratory-directed evolution. However, the use of this technique has been hindered by the scarcity of family genes with the required level of sequence identity in the genome database. We describe here a strategy for collecting metagenomic homologous genes for DNA shuffling from environmental samples by truncated metagenomic gene-specific PCR (TMGS-PCR). Using identified metagenomic gene-specific primers, twenty-three 921-bp truncated lipase gene fragments, which shared 64–99% identity with each other and formed a distinct subfamily of lipases, were retrieved from 60 metagenomic samples. These lipase genes were shuffled, and selected active clones were characterized. The chimeric clones show extensive functional and genetic diversity, as demonstrated by functional characterization and sequence analysis. Our results indicate that homologous sequences of genes captured by TMGS-PCR can be used as suitable genetic material for DNA family shuffling with broad applications in enzyme engineering. PMID:20962349

Development of novel vaccines using DNA shuffling and screening strategies.

PubMed

Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

2004-02-01

DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

Efficient preparation of shuffled DNA libraries through recombination (Gateway) cloning.

PubMed

Lehtonen, Soili I; Taskinen, Barbara; Ojala, Elina; Kukkurainen, Sampo; Rahikainen, Rolle; Riihimäki, Tiina A; Laitinen, Olli H; Kulomaa, Markku S; Hytönen, Vesa P

2015-01-01

Efficient and robust subcloning is essential for the construction of high-diversity DNA libraries in the field of directed evolution. We have developed a more efficient method for the subcloning of DNA-shuffled libraries by employing recombination cloning (Gateway). The Gateway cloning procedure was performed directly after the gene reassembly reaction, without additional purification and amplification steps, thus simplifying the conventional DNA shuffling protocols. Recombination-based cloning, directly from the heterologous reassembly reaction, conserved the high quality of the library and reduced the time required for the library construction. The described method is generally compatible for the construction of DNA-shuffled gene libraries. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Statistical mechanics of two-dimensional shuffled foams: prediction of the correlation between geometry and topology.

PubMed

Durand, Marc; Käfer, Jos; Quilliet, Catherine; Cox, Simon; Talebi, Shirin Ataei; Graner, François

2011-10-14

We propose an analytical model for the statistical mechanics of shuffled two-dimensional foams with moderate bubble size polydispersity. It predicts without any adjustable parameters the correlations between the number of sides n of the bubbles (topology) and their areas A (geometry) observed in experiments and numerical simulations of shuffled foams. Detailed statistics show that in shuffled cellular patterns n correlates better with √A (as claimed by Desch and Feltham) than with A (as claimed by Lewis and widely assumed in the literature). At the level of the whole foam, standard deviations Δn and ΔA are in proportion. Possible applications include correlations of the detailed distributions of n and A, three-dimensional foams, and biological tissues.

Direct Ethanol Production from Lignocellulosic Sugars and Sugarcane Bagasse by a Recombinant Trichoderma reesei Strain HJ48

PubMed Central

Huang, Jun; Chen, Dong; Wei, Yutuo; Wang, Qingyan; Li, Zhenchong; Chen, Ying; Huang, Ribo

2014-01-01

Trichoderma reesei can be considered as a candidate for consolidated bioprocessing (CBP) microorganism. However, its ethanol yield needs to be improved significantly. Here the ethanol production of T. reesei CICC 40360 was improved by genome shuffling while simultaneously enhancing the ethanol resistance. The initial mutant population was generated by nitrosoguanidine treatment of the spores, and an improved population producing more than fivefold ethanol than wild type was obtained by genome shuffling. The results show that the shuffled strain HJ48 can efficiently convert lignocellulosic sugars to ethanol under aerobic conditions. Furthermore, it was able to produce ethanol directly from sugarcane bagasse, demonstrating that the shuffled strain HJ48 is a suitable microorganism for consolidated bioprocessing. PMID:24995362

Direct ethanol production from lignocellulosic sugars and sugarcane bagasse by a recombinant Trichoderma reesei strain HJ48.

PubMed

Huang, Jun; Chen, Dong; Wei, Yutuo; Wang, Qingyan; Li, Zhenchong; Chen, Ying; Huang, Ribo

2014-01-01

Trichoderma reesei can be considered as a candidate for consolidated bioprocessing (CBP) microorganism. However, its ethanol yield needs to be improved significantly. Here the ethanol production of T. reesei CICC 40360 was improved by genome shuffling while simultaneously enhancing the ethanol resistance. The initial mutant population was generated by nitrosoguanidine treatment of the spores, and an improved population producing more than fivefold ethanol than wild type was obtained by genome shuffling. The results show that the shuffled strain HJ48 can efficiently convert lignocellulosic sugars to ethanol under aerobic conditions. Furthermore, it was able to produce ethanol directly from sugarcane bagasse, demonstrating that the shuffled strain HJ48 is a suitable microorganism for consolidated bioprocessing.

T2 shuffling: Sharp, multicontrast, volumetric fast spin-echo imaging.

PubMed

Tamir, Jonathan I; Uecker, Martin; Chen, Weitian; Lai, Peng; Alley, Marcus T; Vasanawala, Shreyas S; Lustig, Michael

2017-01-01

A new acquisition and reconstruction method called T 2 Shuffling is presented for volumetric fast spin-echo (three-dimensional [3D] FSE) imaging. T 2 Shuffling reduces blurring and recovers many images at multiple T 2 contrasts from a single acquisition at clinically feasible scan times (6-7 min). The parallel imaging forward model is modified to account for temporal signal relaxation during the echo train. Scan efficiency is improved by acquiring data during the transient signal decay and by increasing echo train lengths without loss in signal-to-noise ratio (SNR). By (1) randomly shuffling the phase encode view ordering, (2) constraining the temporal signal evolution to a low-dimensional subspace, and (3) promoting spatio-temporal correlations through locally low rank regularization, a time series of virtual echo time images is recovered from a single scan. A convex formulation is presented that is robust to partial voluming and radiofrequency field inhomogeneity. Retrospective undersampling and in vivo scans confirm the increase in sharpness afforded by T 2 Shuffling. Multiple image contrasts are recovered and used to highlight pathology in pediatric patients. A proof-of-principle method is integrated into a clinical musculoskeletal imaging workflow. The proposed T 2 Shuffling method improves the diagnostic utility of 3D FSE by reducing blurring and producing multiple image contrasts from a single scan. Magn Reson Med 77:180-195, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Shuffling cross-validation-bee algorithm as a new descriptor selection method for retention studies of pesticides in biopartitioning micellar chromatography.

PubMed

Zarei, Kobra; Atabati, Morteza; Ahmadi, Monire

2017-05-04

Bee algorithm (BA) is an optimization algorithm inspired by the natural foraging behaviour of honey bees to find the optimal solution which can be proposed to feature selection. In this paper, shuffling cross-validation-BA (CV-BA) was applied to select the best descriptors that could describe the retention factor (log k) in the biopartitioning micellar chromatography (BMC) of 79 heterogeneous pesticides. Six descriptors were obtained using BA and then the selected descriptors were applied for model development using multiple linear regression (MLR). The descriptor selection was also performed using stepwise, genetic algorithm and simulated annealing methods and MLR was applied to model development and then the results were compared with those obtained from shuffling CV-BA. The results showed that shuffling CV-BA can be applied as a powerful descriptor selection method. Support vector machine (SVM) was also applied for model development using six selected descriptors by BA. The obtained statistical results using SVM were better than those obtained using MLR, as the root mean square error (RMSE) and correlation coefficient (R) for whole data set (training and test), using shuffling CV-BA-MLR, were obtained as 0.1863 and 0.9426, respectively, while these amounts for the shuffling CV-BA-SVM method were obtained as 0.0704 and 0.9922, respectively.

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa21[C][W][OA

PubMed Central

Slootweg, Erik J.; Spiridon, Laurentiu N.; Roosien, Jan; Butterbach, Patrick; Pomp, Rikus; Westerhof, Lotte; Wilbers, Ruud; Bakker, Erin; Bakker, Jaap; Petrescu, Andrei-José; Smant, Geert; Goverse, Aska

2013-01-01

Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins. PMID:23660837

Roots of angiosperm formins: The evolutionary history of plant FH2 domain-containing proteins

PubMed Central

2008-01-01

Background Shuffling of modular protein domains is an important source of evolutionary innovation. Formins are a family of actin-organizing proteins that share a conserved FH2 domain but their overall domain architecture differs dramatically between opisthokonts (metazoans and fungi) and plants. We performed a phylogenomic analysis of formins in most eukaryotic kingdoms, aiming to reconstruct an evolutionary scenario that may have produced the current diversity of domain combinations with focus on the origin of the angiosperm formin architectures. Results The Rho GTPase-binding domain (GBD/FH3) reported from opisthokont and Dictyostelium formins was found in all lineages except plants, suggesting its ancestral character. Instead, mosses and vascular plants possess the two formin classes known from angiosperms: membrane-anchored Class I formins and Class II formins carrying a PTEN-like domain. PTEN-related domains were found also in stramenopile formins, where they have been probably acquired independently rather than by horizontal transfer, following a burst of domain rearrangements in the chromalveolate lineage. A novel RhoGAP-related domain was identified in some algal, moss and lycophyte (but not angiosperm) formins that define a specific branch (Class III) of the formin family. Conclusion We propose a scenario where formins underwent multiple domain rearrangements in several eukaryotic lineages, especially plants and chromalveolates. In plants this replaced GBD/FH3 by a probably inactive RhoGAP-like domain, preserving a formin-mediated association between (membrane-anchored) Rho GTPases and the actin cytoskeleton. Subsequent amplification of formin genes, possibly coincident with the expansion of plants to dry land, was followed by acquisition of alternative membrane attachment mechanisms present in extant Class I and Class II formins, allowing later loss of the RhoGAP-like domain-containing formins in angiosperms. PMID:18430232

Structural determinants at the interface of the ARC2 and leucine-rich repeat domains control the activation of the plant immune receptors Rx1 and Gpa2.

PubMed

Slootweg, Erik J; Spiridon, Laurentiu N; Roosien, Jan; Butterbach, Patrick; Pomp, Rikus; Westerhof, Lotte; Wilbers, Ruud; Bakker, Erin; Bakker, Jaap; Petrescu, Andrei-José; Smant, Geert; Goverse, Aska

2013-07-01

Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins.

Genome shuffling of Saccharomyces cerevisiae for enhanced glutathione yield and relative gene expression analysis using fluorescent quantitation reverse transcription polymerase chain reaction.

PubMed

Yin, Hua; Ma, Yanlin; Deng, Yang; Xu, Zhenbo; Liu, Junyan; Zhao, Junfeng; Dong, Jianjun; Yu, Junhong; Chang, Zongming

2016-08-01

Genome shuffling is an efficient and promising approach for the rapid improvement of microbial phenotypes. In this study, genome shuffling was applied to enhance the yield of glutathione produced by Saccharomyces cerevisiae YS86. Six isolates with subtle improvements in glutathione yield were obtained from populations generated by ultraviolet (UV) irradiation and nitrosoguanidine (NTG) mutagenesis. These yeast strains were then subjected to recursive pool-wise protoplast fusion. A strain library that was likely to yield positive colonies was created by fusing the lethal protoplasts obtained from both UV irradiation and heat treatments. After two rounds of genome shuffling, a high-yield recombinant YSF2-19 strain that exhibited 3.2- and 3.3-fold increases in glutathione production in shake flask and fermenter respectively was obtained. Comparative analysis of synthetase gene expression was conducted between the initial and shuffled strains using FQ (fluorescent quantitation) RT-PCR (reverse transcription polymerase chain reaction). Delta CT (threshold cycle) relative quantitation analysis revealed that glutathione synthetase gene (GSH-I) expression at the transcriptional level in the YSF2-19 strain was 9.9-fold greater than in the initial YS86. The shuffled yeast strain has a potential application in brewing, other food, and pharmaceutical industries. Simultaneously, the analysis of improved phenotypes will provide more valuable data for inverse metabolic engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Improving isopropanol tolerance and production of Clostridium beijerinckii DSM 6423 by random mutagenesis and genome shuffling.

PubMed

Gérando, H Máté de; Fayolle-Guichard, F; Rudant, L; Millah, S K; Monot, F; Ferreira, Nicolas Lopes; López-Contreras, A M

2016-06-01

Random mutagenesis and genome shuffling was applied to improve solvent tolerance and isopropanol/butanol/ethanol (IBE) production in the strictly anaerobic bacteria Clostridium beijerinckii DSM 6423. Following chemical mutagenesis with N-methyl-N-nitro-N-nitrosoguanidine (NTG), screening of putatively improved strains was done by submitting the mutants to toxic levels of inhibitory chemicals or by screening for their tolerance to isopropanol (>35 g/L). Suicide substrates, such as ethyl or methyl bromobutyrate or alcohol dehydrogenase inhibitors like allyl alcohol, were tested and, finally, 36 mutants were isolated. The fermentation profiles of these NTG mutant strains were characterized, and the best performing mutants were used for consecutive rounds of genome shuffling. Screening of strains with further enhancement in isopropanol tolerance at each recursive shuffling step was then used to spot additionally improved strains. Three highly tolerant strains were finally isolated and able to withstand up to 50 g/L isopropanol on plates. Even if increased tolerance to the desired end product was not always accompanied by higher production capabilities, some shuffled strains showed increased solvent titers compared to the parental strains and the original C. beijerinckii DSM 6423. This study confirms the efficiency of genome shuffling to generate improved strains toward a desired phenotype such as alcohol tolerance. This tool also offers the possibility of obtaining improved strains of Clostridium species for which targeted genetic engineering approaches have not been described yet.

Nucleotide exchange and excision technology DNA shuffling and directed evolution.

PubMed

Speck, Janina; Stebel, Sabine C; Arndt, Katja M; Müller, Kristian M

2011-01-01

Remarkable success in optimizing complex properties within DNA and proteins has been achieved by directed evolution. In contrast to various random mutagenesis methods and high-throughput selection methods, the number of available DNA shuffling procedures is limited, and protocols are often difficult to adjust. The strength of the nucleotide exchange and excision technology (NExT) DNA shuffling described here is the robust, efficient, and easily controllable DNA fragmentation step based on random incorporation of the so-called 'exchange nucleotides' by PCR. The exchange nucleotides are removed enzymatically, followed by chemical cleavage of the DNA backbone. The oligonucleotide pool is reassembled into full-length genes by internal primer extension, and the recombined gene library is amplified by standard PCR. The technique has been demonstrated by shuffling a defined gene library of chloramphenicol acetyltransferase variants using uridine as fragmentation defining exchange nucleotide. Substituting 33% of the dTTP with dUTP in the incorporation PCR resulted in shuffled clones with an average parental fragment size of 86 bases and revealed a mutation rate of only 0.1%. Additionally, a computer program (NExTProg) has been developed that predicts the fragment size distribution depending on the relative amount of the exchange nucleotide.

The combination of glycerol metabolic engineering and drug resistance marker-aided genome shuffling to improve very-high-gravity fermentation performances of industrial Saccharomyces cerevisiae.

PubMed

Wang, Pin-Mei; Zheng, Dao-Qiong; Liu, Tian-Zhe; Tao, Xiang-Lin; Feng, Ming-Guang; Min, Hang; Jiang, Xin-Hang; Wu, Xue-Chang

2012-03-01

A challenge associated with the ethanol productivity under very-high-gravity (VHG) conditions, optimizing multi-traits (i.e. byproduct formation and stress tolerance) of industrial yeast strains, is overcome by a combination of metabolic engineering and genome shuffling. First, industrial strain Y12 was deleted with a glycerol exporter Fps1p and hetero-expressed with glyceraldehydes-3-phosphate dehydrogenase, resulting in the modified strain YFG12 with lower glycerol yield. Second, YFG12 was subjected to three rounds of drug resistance marker-aided genome shuffling to increase its ethanol tolerance, and the best shuffled strain TS5 was obtained. Compared with wild strain Y12, shuffled strain TS5 not only decreased glycerol formation by 14.8%, but also increased fermentation rate and ethanol yield by 3.7% and 7.6%, respectively. Moreover, the system of genetic modification and Cre/loxP in aid of three different drug-resistance markers presented in the study significantly improved breeding efficiency and will facilitate the application of breeding technologies in prototrophic industrial microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Illumination discrimination in the absence of a fixed surface-reflectance layout

PubMed Central

Radonjić, Ana; Ding, Xiaomao; Krieger, Avery; Aston, Stacey; Hurlbert, Anya C.; Brainard, David H.

2018-01-01

Previous studies have shown that humans can discriminate spectral changes in illumination and that this sensitivity depends both on the chromatic direction of the illumination change and on the ensemble of surfaces in the scene. These studies, however, always used stimulus scenes with a fixed surface-reflectance layout. Here we compared illumination discrimination for scenes in which the surface reflectance layout remains fixed (fixed-surfaces condition) to those in which surface reflectances were shuffled randomly across scenes, but with the mean scene reflectance held approximately constant (shuffled-surfaces condition). Illumination discrimination thresholds in the fixed-surfaces condition were commensurate with previous reports. Thresholds in the shuffled-surfaces condition, however, were considerably elevated. Nonetheless, performance in the shuffled-surfaces condition exceeded that attainable through random guessing. Analysis of eye fixations revealed that in the fixed-surfaces condition, low illumination discrimination thresholds (across observers) were predicted by low overall fixation spread and high consistency of fixation location and fixated surface reflectances across trial intervals. Performance in the shuffled-surfaces condition was not systematically related to any of the eye-fixation characteristics we examined for that condition, but was correlated with performance in the fixed-surfaces condition. PMID:29904786

Symbiont shuffling linked to differential photochemical dynamics of Symbiodinium in three Caribbean reef corals

NASA Astrophysics Data System (ADS)

Cunning, Ross; Silverstein, Rachel N.; Baker, Andrew C.

2018-03-01

Dynamic symbioses with functionally diverse dinoflagellate algae in the genus Symbiodinium may allow some reef corals to alter their phenotypes through `symbiont shuffling', or changes in symbiont community composition. In particular, corals may become more bleaching resistant by increasing the relative abundance of thermally tolerant Symbiodinium in clade D after bleaching. Despite the immediate relevance of this phenomenon to corals living in warming oceans—and to interventions aimed at boosting coral resilience—the mechanisms governing how, why, and when symbiont shuffling occurs are still poorly understood. Here, we performed controlled thermal bleaching and recovery experiments on three species of Caribbean corals hosting mixtures of D1a ( S. trenchii) and other symbionts in clades B or C. We show that the degree of symbiont shuffling is related to (1) the duration of stress exposure and (2) the difference in photochemical efficiency ( F v /F m) of co-occurring symbionts under stress (i.e., the `photochemical advantage' of one symbiont over the other). The advantage of D1a under stress was greatest in Montastraea cavernosa, intermediate in Siderastrea siderea, and lowest in Orbicella faveolata and correlated positively with the magnitude of shuffling toward D1a. In holobionts where D1a had less of an advantage over co-occurring symbionts (i.e., only slightly higher F v /F m under stress), a longer stress duration was required to elicit commensurate increases in D1a abundance. In fact, across these three coral species, 92.9% of variation in the degree of symbiont shuffling could be explained by the time-integrated photochemical advantage of D1a under heat stress. Although F v /F m is governed by numerous factors that this study is unable to resolve mechanistically, its strong empirical relationship with symbiont shuffling helps elucidate general features that govern this process in reef corals, which will help refine predictions of coral responses to environmental change and inform interventions to manipulate symbiont communities to enhance coral resilience.

Complexity multiscale asynchrony measure and behavior for interacting financial dynamics

NASA Astrophysics Data System (ADS)

Yang, Ge; Wang, Jun; Niu, Hongli

2016-08-01

A stochastic financial price process is proposed and investigated by the finite-range multitype contact dynamical system, in an attempt to study the nonlinear behaviors of real asset markets. The viruses spreading process in a finite-range multitype system is used to imitate the interacting behaviors of diverse investment attitudes in a financial market, and the empirical research on descriptive statistics and autocorrelation behaviors of return time series is performed for different values of propagation rates. Then the multiscale entropy analysis is adopted to study several different shuffled return series, including the original return series, the corresponding reversal series, the random shuffled series, the volatility shuffled series and the Zipf-type shuffled series. Furthermore, we propose and compare the multiscale cross-sample entropy and its modification algorithm called composite multiscale cross-sample entropy. We apply them to study the asynchrony of pairs of time series under different time scales.

Enhanced production of fructosyltransferase in Aspergillus oryzae by genome shuffling.

PubMed

Wang, Shenghai; Duan, Mengjie; Liu, Yalan; Fan, Sen; Lin, Xiaoshan; Zhang, Yi

2017-03-01

To breed Aspergillus oryzae strains with high fructosyltransferase (FTase) activity using intraspecific protoplast fusion via genome-shuffling. A candidate library was developed using UV/LiCl of the conidia of A. oryzae SBB201. By screening for enzyme activity and cell biomass, two mutants (UV-11 and UV-76) were chosen for protoplast fusion and subsequent genome shuffling. After three rounds of genome recombination, a fusion mutant RIII-7 was obtained. Its FTase activity was 180 U g -1 , approximately double that of the original strain, and RIII-7 was genetically stable. In fermentation culture, FTase activity of the genome-shuffled strain reached a maximum of 353 U g -1 using substrate-feeding method, and this value was approximately 3.4-times higher than that of the original strain A. oryzae SBB201. Intraspecific protoplast fusion of A. oryzae significantly enhanced FTase activity and generated a potentially useful strain for industrial production.

Population shuffling between ground and high energy excited states

PubMed Central

Sabo, T Michael; Trent, John O; Lee, Donghan

2015-01-01

Stochastic processes powered by thermal energy lead to protein motions traversing time-scales from picoseconds to seconds. Fundamental to protein functionality is the utilization of these dynamics for tasks such as catalysis, folding, and allostery. A hierarchy of motion is hypothesized to connect and synergize fast and slow dynamics toward performing these essential activities. Population shuffling predicts a “top-down” temporal hierarchy, where slow time-scale conformational interconversion leads to a shuffling of the free energy landscape for fast time-scale events. Until now, population shuffling was only applied to interconverting ground states. Here, we extend the framework of population shuffling to be applicable for a system interconverting between low energy ground and high energy excited states, such as the SH3 domain mutants G48M and A39V/N53P/V55L from the Fyn tyrosine kinase, providing another tool for accessing the structural dynamics of high energy excited states. Our results indicate that the higher energy gauche− rotameric state for the leucine χ2 dihedral angle contributes significantly to the distribution of rotameric states in both the major and minor forms of the SH3 domain. These findings are corroborated with unrestrained molecular dynamics (MD) simulations on both the major and minor states of the SH3 domain demonstrating high correlations between experimental and back-calculated leucine χ2 rotameric populations. Taken together, we demonstrate how fast time-scale rotameric side-chain population distributions can be extracted from slow time-scale conformational exchange data further extending the scope and the applicability of the population shuffling model. PMID:26316263

Population shuffling between ground and high energy excited states.

PubMed

Sabo, T Michael; Trent, John O; Lee, Donghan

2015-11-01

Stochastic processes powered by thermal energy lead to protein motions traversing time-scales from picoseconds to seconds. Fundamental to protein functionality is the utilization of these dynamics for tasks such as catalysis, folding, and allostery. A hierarchy of motion is hypothesized to connect and synergize fast and slow dynamics toward performing these essential activities. Population shuffling predicts a "top-down" temporal hierarchy, where slow time-scale conformational interconversion leads to a shuffling of the free energy landscape for fast time-scale events. Until now, population shuffling was only applied to interconverting ground states. Here, we extend the framework of population shuffling to be applicable for a system interconverting between low energy ground and high energy excited states, such as the SH3 domain mutants G48M and A39V/N53P/V55L from the Fyn tyrosine kinase, providing another tool for accessing the structural dynamics of high energy excited states. Our results indicate that the higher energy gauche - rotameric state for the leucine χ2 dihedral angle contributes significantly to the distribution of rotameric states in both the major and minor forms of the SH3 domain. These findings are corroborated with unrestrained molecular dynamics (MD) simulations on both the major and minor states of the SH3 domain demonstrating high correlations between experimental and back-calculated leucine χ2 rotameric populations. Taken together, we demonstrate how fast time-scale rotameric side-chain population distributions can be extracted from slow time-scale conformational exchange data further extending the scope and the applicability of the population shuffling model. © 2015 The Protein Society.

Underwater sonar image detection: A combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm.

PubMed

Wang, Xingmei; Liu, Shu; Liu, Zhipeng

2017-01-01

This paper proposes a combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm to detect underwater objects in sonar images. Specifically, for the first time, the problem of inappropriate filtering degree parameter which commonly occurs in non-local spatial information and seriously affects the denoising performance in sonar images, was solved with the method utilizing a novel filtering degree parameter. Then, a quantum-inspired shuffled frog leaping algorithm based on new search mechanism (QSFLA-NSM) is proposed to precisely and quickly detect sonar images. Each frog individual is directly encoded by real numbers, which can greatly simplify the evolution process of the quantum-inspired shuffled frog leaping algorithm (QSFLA). Meanwhile, a fitness function combining intra-class difference with inter-class difference is adopted to evaluate frog positions more accurately. On this basis, recurring to an analysis of the quantum-behaved particle swarm optimization (QPSO) and the shuffled frog leaping algorithm (SFLA), a new search mechanism is developed to improve the searching ability and detection accuracy. At the same time, the time complexity is further reduced. Finally, the results of comparative experiments using the original sonar images, the UCI data sets and the benchmark functions demonstrate the effectiveness and adaptability of the proposed method.

Underwater sonar image detection: A combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm

PubMed Central

Liu, Zhipeng

2017-01-01

This paper proposes a combination of non-local spatial information and quantum-inspired shuffled frog leaping algorithm to detect underwater objects in sonar images. Specifically, for the first time, the problem of inappropriate filtering degree parameter which commonly occurs in non-local spatial information and seriously affects the denoising performance in sonar images, was solved with the method utilizing a novel filtering degree parameter. Then, a quantum-inspired shuffled frog leaping algorithm based on new search mechanism (QSFLA-NSM) is proposed to precisely and quickly detect sonar images. Each frog individual is directly encoded by real numbers, which can greatly simplify the evolution process of the quantum-inspired shuffled frog leaping algorithm (QSFLA). Meanwhile, a fitness function combining intra-class difference with inter-class difference is adopted to evaluate frog positions more accurately. On this basis, recurring to an analysis of the quantum-behaved particle swarm optimization (QPSO) and the shuffled frog leaping algorithm (SFLA), a new search mechanism is developed to improve the searching ability and detection accuracy. At the same time, the time complexity is further reduced. Finally, the results of comparative experiments using the original sonar images, the UCI data sets and the benchmark functions demonstrate the effectiveness and adaptability of the proposed method. PMID:28542266

Algorithms for optimizing cross-overs in DNA shuffling.

PubMed

He, Lu; Friedman, Alan M; Bailey-Kellogg, Chris

2012-03-21

DNA shuffling generates combinatorial libraries of chimeric genes by stochastically recombining parent genes. The resulting libraries are subjected to large-scale genetic selection or screening to identify those chimeras with favorable properties (e.g., enhanced stability or enzymatic activity). While DNA shuffling has been applied quite successfully, it is limited by its homology-dependent, stochastic nature. Consequently, it is used only with parents of sufficient overall sequence identity, and provides no control over the resulting chimeric library. This paper presents efficient methods to extend the scope of DNA shuffling to handle significantly more diverse parents and to generate more predictable, optimized libraries. Our CODNS (cross-over optimization for DNA shuffling) approach employs polynomial-time dynamic programming algorithms to select codons for the parental amino acids, allowing for zero or a fixed number of conservative substitutions. We first present efficient algorithms to optimize the local sequence identity or the nearest-neighbor approximation of the change in free energy upon annealing, objectives that were previously optimized by computationally-expensive integer programming methods. We then present efficient algorithms for more powerful objectives that seek to localize and enhance the frequency of recombination by producing "runs" of common nucleotides either overall or according to the sequence diversity of the resulting chimeras. We demonstrate the effectiveness of CODNS in choosing codons and allocating substitutions to promote recombination between parents targeted in earlier studies: two GAR transformylases (41% amino acid sequence identity), two very distantly related DNA polymerases, Pol X and β (15%), and beta-lactamases of varying identity (26-47%). Our methods provide the protein engineer with a new approach to DNA shuffling that supports substantially more diverse parents, is more deterministic, and generates more predictable and more diverse chimeric libraries.

Xylose-fermenting Pichia stipitis by genome shuffling for improved ethanol production.

PubMed

Shi, Jun; Zhang, Min; Zhang, Libin; Wang, Pin; Jiang, Li; Deng, Huiping

2014-03-01

Xylose fermentation is necessary for the bioconversion of lignocellulose to ethanol as fuel, but wild-type Saccharomyces cerevisiae strains cannot fully metabolize xylose. Several efforts have been made to obtain microbial strains with enhanced xylose fermentation. However, xylose fermentation remains a serious challenge because of the complexity of lignocellulosic biomass hydrolysates. Genome shuffling has been widely used for the rapid improvement of industrially important microbial strains. After two rounds of genome shuffling, a genetically stable, high-ethanol-producing strain was obtained. Designated as TJ2-3, this strain could ferment xylose and produce 1.5 times more ethanol than wild-type Pichia stipitis after fermentation for 96 h. The acridine orange and propidium iodide uptake assays showed that the maintenance of yeast cell membrane integrity is important for ethanol fermentation. This study highlights the importance of genome shuffling in P. stipitis as an effective method for enhancing the productivity of industrial strains. © 2013 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Methods and apparatuses for self-generating fault-tolerant keys in spread-spectrum systems

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

Moradi, Hussein; Farhang, Behrouz; Subramanian, Vijayarangam

Self-generating fault-tolerant keys for use in spread-spectrum systems are disclosed. At a communication device, beacon signals are received from another communication device and impulse responses are determined from the beacon signals. The impulse responses are circularly shifted to place a largest sample at a predefined position. The impulse responses are converted to a set of frequency responses in a frequency domain. The frequency responses are shuffled with a predetermined shuffle scheme to develop a set of shuffled frequency responses. A set of phase differences is determined as a difference between an angle of the frequency response and an angle ofmore » the shuffled frequency response at each element of the corresponding sets. Each phase difference is quantized to develop a set of secret-key quantized phases and a set of spreading codes is developed wherein each spreading code includes a corresponding phase of the set of secret-key quantized phases.« less

Improvement of industrially important microbial strains by genome shuffling: Current status and future prospects.

PubMed

Magocha, Tinashe Archbold; Zabed, H; Yang, Miaomiao; Yun, Junhua; Zhang, Huanhuan; Qi, Xianghui

2018-06-01

The growing demand for biotechnological products against limited metabolic capacity of industrially used microorganisms has led to an increased interest on strain-improvement over the last several decades, which aimed to enhance metabolite yield, substrate uptake and tolerance of the strains. Among a few techniques of strain-improvement, genome shuffling is the most recent and promising approach used for rapid strain-improvement that can yield a new strain by combining whole genomes of multi-parental microorganisms using the principles of protoplast fusion. Genome shuffling has brought a major breakthrough in the strain-improvement concept as it is found to be effective and reliable for expressing complex phenotypes. This review will discuss the technical aspects and applications of genome shuffling for various industrial strains to present its current status and recent progress. In the concluding remarks, a summary will be presented focusing on the major challenges and future outlooks of this technology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modified Shuffled Frog Leaping Optimization Algorithm Based Distributed Generation Rescheduling for Loss Minimization

NASA Astrophysics Data System (ADS)

Arya, L. D.; Koshti, Atul

2018-05-01

This paper investigates the Distributed Generation (DG) capacity optimization at location based on the incremental voltage sensitivity criteria for sub-transmission network. The Modified Shuffled Frog Leaping optimization Algorithm (MSFLA) has been used to optimize the DG capacity. Induction generator model of DG (wind based generating units) has been considered for study. Standard test system IEEE-30 bus has been considered for the above study. The obtained results are also validated by shuffled frog leaping algorithm and modified version of bare bones particle swarm optimization (BBExp). The performance of MSFLA has been found more efficient than the other two algorithms for real power loss minimization problem.

A Benes-like theorem for the shuffle-exchange graph

NASA Technical Reports Server (NTRS)

Schwabe, Eric J.

1992-01-01

One of the first theorems on permutation routing, proved by V. E. Beness (1965), shows that given a set of source-destination pairs in an N-node butterfly network with at most a constant number of sources or destinations in each column of the butterfly, there exists a set of paths of lengths O(log N) connecting each pair such that the total congestion is constant. An analogous theorem yielding constant-congestion paths for off-line routing in the shuffle-exchange graph is proved here. The necklaces of the shuffle-exchange graph play the same structural role as the columns of the butterfly in Beness' theorem.

Brain Modularity Mediates the Relation between Task Complexity and Performance

NASA Astrophysics Data System (ADS)

Ye, Fengdan; Yue, Qiuhai; Martin, Randi; Fischer-Baum, Simon; Ramos-Nuã+/-Ez, Aurora; Deem, Michael

Recent work in cognitive neuroscience has focused on analyzing the brain as a network, rather than a collection of independent regions. Prior studies taking this approach have found that individual differences in the degree of modularity of the brain network relate to performance on cognitive tasks. However, inconsistent results concerning the direction of this relationship have been obtained, with some tasks showing better performance as modularity increases, and other tasks showing worse performance. A recent theoretical model suggests that these inconsistencies may be explained on the grounds that high-modularity networks favor performance on simple tasks whereas low-modularity networks favor performance on complex tasks. The current study tests these predictions by relating modularity from resting-state fMRI to performance on a set of behavioral tasks. Complex and simple tasks were defined on the basis of whether they drew on executive attention. Consistent with predictions, we found a negative correlation between individuals' modularity and their performance on the complex tasks but a positive correlation with performance on the simple tasks. The results presented here provide a framework for linking measures of whole brain organization to cognitive processing.

Shared Subgenome Dominance Following Polyploidization Explains Grass Genome Evolutionary Plasticity from a Seven Protochromosome Ancestor with 16K Protogenes

PubMed Central

Murat, Florent; Zhang, Rongzhi; Guizard, Sébastien; Flores, Raphael; Armero, Alix; Pont, Caroline; Steinbach, Delphine; Quesneville, Hadi; Cooke, Richard; Salse, Jerome

2013-01-01

Modern plant genomes are diploidized paleopolyploids. We revisited grass genome paleohistory in response to the diploidization process through a detailed investigation of the evolutionary fate of duplicated blocks. Ancestrally duplicated genes can be conserved, deleted, and shuffled, defining dominant (bias toward duplicate retention) and sensitive (bias toward duplicate erosion) chromosomal fragments. We propose a new grass genome paleohistory deriving from an ancestral karyotype structured in seven protochromosomes containing 16,464 protogenes and following evolutionary rules where 1) ancestral shared polyploidizations shaped conserved dominant (D) and sensitive (S) subgenomes, 2) subgenome dominance is revealed by both gene deletion and shuffling from the S blocks, 3) duplicate deletion/movement may have been mediated by single-/double-stranded illegitimate recombination mechanisms, 4) modern genomes arose through centromeric fusion of protochromosomes, leading to functional monocentric neochromosomes, 5) the fusion of two dominant blocks leads to supradominant neochromosomes (D + D = D) with higher ancestral gene retention compared with D + S = D (i.e., fusion of blocks with opposite sensitivity) or even S + S = S (i.e., fusion of two sensitive ancestral blocks). A new user-friendly online tool named “PlantSyntenyViewer,” available at http://urgi.versailles.inra.fr/synteny-cereal, presents the refined comparative genomics data. PMID:24317974

Doing the Meiosis Shuffle.

ERIC Educational Resources Information Center

Krauskopf, Sara

1999-01-01

Presents a game called the Meiosis Shuffle that helps students simulate the process of meiosis in which homologous cards representing chromosomes pair up, line up, and split apart. Students respond well to the simulation and are better able to conceptualize what chromosomes do and how independent assortment causes genetic variation. (CCM)

Genome Shuffling and Gentamicin-Resistance to Improve ε-Poly-L-Lysine Productivity of Streptomyces albulus W-156.

PubMed

Wang, Liang; Chen, Xusheng; Wu, Guangyao; Zeng, Xin; Ren, Xidong; Li, Shu; Tang, Lei; Mao, Zhonggui

2016-12-01

Genome shuffling has been a recently effective method for screening the desirable phenotypes of industrial strains. Here, we combined genome shuffling and gentamicin resistance to improve the production of ε-poly-L-lysine in Streptomyces albulus W-156. Five starting mutants with higher ε-poly-L-lysine (ε-PL) productivities were firstly obtained by atmospheric and room temperature plasma (ARTP) mutagenesis. After three rounds of genome shuffling with increasing concentration of gentamicin for selection, S. albulus AG3-28, was finally got with a production of 3.43 g/L in shaking flask. In a 5-L fermenter, AG3-28 exhibited a higher ε-PL productivity (56.5 g/L) than the initial strain W-156 (37.5 g/L). Key enzyme activities in primary and secondary metabolic pathways were analyzed, and the transcription levels of hrdD and pls were determined by quantitative real time-polymerase chain reaction (qRT-PCR). Increase of key enzyme activities and the upregulation of the gene transcriptional levels demonstrated that ε-PL synthetic pathway in AG3-28 was obviously strengthened, which might be responsible for the high productivity. Moreover, hyper-yield strain AG3-28 was found to produce a slightly lower ε-PL polymerization degree than the parent strain. Amplified fragment length polymorphism (AFLP) analysis reflects the genetic diversity among the derivates after genome shuffling.

High efficiency family shuffling based on multi-step PCR and in vivo DNA recombination in yeast: statistical and functional analysis of a combinatorial library between human cytochrome P450 1A1 and 1A2.

PubMed

Abécassis, V; Pompon, D; Truan, G

2000-10-15

The design of a family shuffling strategy (CLERY: Combinatorial Libraries Enhanced by Recombination in Yeast) associating PCR-based and in vivo recombination and expression in yeast is described. This strategy was tested using human cytochrome P450 CYP1A1 and CYP1A2 as templates, which share 74% nucleotide sequence identity. Construction of highly shuffled libraries of mosaic structures and reduction of parental gene contamination were two major goals. Library characterization involved multiprobe hybridization on DNA macro-arrays. The statistical analysis of randomly selected clones revealed a high proportion of chimeric genes (86%) and a homogeneous representation of the parental contribution among the sequences (55.8 +/- 2.5% for parental sequence 1A2). A microtiter plate screening system was designed to achieve colorimetric detection of polycyclic hydrocarbon hydroxylation by transformed yeast cells. Full sequences of five randomly picked and five functionally selected clones were analyzed. Results confirmed the shuffling efficiency and allowed calculation of the average length of sequence exchange and mutation rates. The efficient and statistically representative generation of mosaic structures by this type of family shuffling in a yeast expression system constitutes a novel and promising tool for structure-function studies and tuning enzymatic activities of multicomponent eucaryote complexes involving non-soluble enzymes.

Mixing and Matching Siderophore Clusters: Structure and Biosynthesis of Serratiochelins from Serratia sp. V4

PubMed Central

2012-01-01

Interrogation of the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores—soluble, low molecular weight compounds—have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition to acquire iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of “odd” siderophores can reveal the evolutionary strategy that led to their creation. We report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well-known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholera vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores. PMID:22830960

Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4.

PubMed

Seyedsayamdost, Mohammad R; Cleto, Sara; Carr, Gavin; Vlamakis, Hera; João Vieira, Maria; Kolter, Roberto; Clardy, Jon

2012-08-22

Interrogation of the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores-soluble, low molecular weight compounds-have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition to acquire iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of "odd" siderophores can reveal the evolutionary strategy that led to their creation. We report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well-known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholera vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores.

Sequence-independent construction of ordered combinatorial libraries with predefined crossover points.

PubMed

Jézéquel, Laetitia; Loeper, Jacqueline; Pompon, Denis

2008-11-01

Combinatorial libraries coding for mosaic enzymes with predefined crossover points constitute useful tools to address and model structure-function relationships and for functional optimization of enzymes based on multivariate statistics. The presented method, called sequence-independent generation of a chimera-ordered library (SIGNAL), allows easy shuffling of any predefined amino acid segment between two or more proteins. This method is particularly well adapted to the exchange of protein structural modules. The procedure could also be well suited to generate ordered combinatorial libraries independent of sequence similarities in a robotized manner. Sequence segments to be recombined are first extracted by PCR from a single-stranded template coding for an enzyme of interest using a biotin-avidin-based method. This technique allows the reduction of parental template contamination in the final library. Specific PCR primers allow amplification of two complementary mosaic DNA fragments, overlapping in the region to be exchanged. Fragments are finally reassembled using a fusion PCR. The process is illustrated via the construction of a set of mosaic CYP2B enzymes using this highly modular approach.

Genome shuffling improves production of the low-temperature alkalophilic lipase by Acinetobacter johnsonii.

PubMed

Wang, HaiKuan; Zhang, Jie; Wang, XiaoJie; Qi, Wei; Dai, YuJie

2012-01-01

The production of a low-temperature alkalophilic lipase from Acinetobacter johnsonii was improved using genome shuffling. The starting populations, obtained by UV irradiation and diethyl sulfate mutagenesis, were subjected to recursive protoplast fusion. The optimal conditions for protoplast formation and regeneration were 0.15 mg lysozyme/ml for 45 min at 37°C. The protoplasts were inactivated under UV for 20 min or heated at 60°C for 60 min and a fusant probability of ~98% was observed. The positive colonies were created by fusing the inactivated protoplasts. After two rounds of genome shuffling, one strain, F22, with a lipase activity of 7 U/ml was obtained.

Post-Translational Modification of Bionanoparticles as a Modular Platform for Biosensor Assembly.

PubMed

Sun, Qing; Chen, Qi; Blackstock, Daniel; Chen, Wilfred

2015-08-25

Context driven biosensor assembly with modular targeting and detection moieties is gaining significant attentions. Although protein-based nanoparticles have emerged as an excellent platform for biosensor assembly, current strategies of decorating bionanoparticles with targeting and detection moieties often suffer from unfavorable spacing and orientation as well as bionanoparticle aggregation. Herein, we report a highly modular post-translational modification approach for biosensor assembly based on sortase A-mediated ligation. This approach enables the simultaneous modifications of the Bacillus stearothermophilus E2 nanoparticles with different functional moieties for antibody, enzyme, DNA aptamer, and dye decoration. The resulting easy-purification platform offers a high degree of targeting and detection modularity with signal amplification. This flexibility is demonstrated for the detection of both immobilized antigens and cancer cells.

A new approach for breeding low-temperature-resistant Volvariella volvacea strains: Genome shuffling in edible fungi.

PubMed

Zhu, Ziping; Wu, Xiao; Lv, Beibei; Wu, Guogan; Wang, Jinbin; Jiang, Wei; Li, Peng; He, Jianhua; Chen, Jianzhong; Chen, Mingjie; Bao, Dapeng; Zhang, Jinsong; Tan, Qi; Tang, Xueming

2016-09-01

Volvariella volvacea is difficult to store fresh because of the lack of low-temperature resistance. Many traditional mutagenic strategies have been applied in order to select out strains resistant to low temperature, but few commercially efficient strains have been produced. In order to break through the bottleneck of traditional breeding and significantly improve low-temperature resistance of the edible fungus V. volvacea, strains resistant to low temperature were constructed by genome shuffling. The optimum conditions of V. volvacea strain mutation, protoplast regeneration, and fusion were determined. After protoplasts were treated with 1% (v/v) ethylmethylsulfonate (EMS), 40 Sec of ultraviolet (UV) irradiation, 600 Gy electron beam implantation, and 750 Gy 60 Co-γ irradiation, separately, the lethality was within 70%-80%, which favored generating protoplasts being used in following forward mutation. Under these conditions, 16 strains of V. volvacea mutated by EMS, electron beam, UV irradiation, and 60 Co-γ irradiation were obtained. The 16 mutated protoplasts were selected to serve as the shuffling pool based on their excellent low-temperature resistance. After four rounds of genome shuffling and low-temperature resistance testing, three strains (VF 1 , VF 2 , and VF 3 ) with high genetic stability were screened. VF 1 , VF 2 , and VF 3 significantly enhanced fruit body shelf life to 20, 28, and 28 H at 10 °C, respectively, which exceeded 25%, 75%, and 75%, respectively, compared with the storage time of V23, the most low-temperature-resistant strain. Genome shuffling greatly improved the low-temperature resistance of V. volvacea, and shortened the course of screening required to generate desirable strains. To our knowledge, this is the first paper to apply genome shuffling to breeding new varieties of mushroom, and offers a new approach for breeding edible fungi with optimized phenotype. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

Self-similar grid patterns in free-space shuffle-exchange networks

NASA Astrophysics Data System (ADS)

Haney, Michael W.

1993-12-01

Self-similar grid patterns are proposed as an alternative to rectangular grid, array optoelectronic sources, and detectors of smart pixels. For shuffle based multistage interconnection networks, it is suggested that smart pixel should not be arrayed on a rectangular grid and that smart pixel unit cell should be the kernel of a self-similar grid pattern.

Linear motif-mediated interactions have contributed to the evolution of modularity in complex protein interaction networks.

PubMed

Kim, Inhae; Lee, Heetak; Han, Seong Kyu; Kim, Sanguk

2014-10-01

The modular architecture of protein-protein interaction (PPI) networks is evident in diverse species with a wide range of complexity. However, the molecular components that lead to the evolution of modularity in PPI networks have not been clearly identified. Here, we show that weak domain-linear motif interactions (DLIs) are more likely to connect different biological modules than strong domain-domain interactions (DDIs). This molecular division of labor is essential for the evolution of modularity in the complex PPI networks of diverse eukaryotic species. In particular, DLIs may compensate for the reduction in module boundaries that originate from increased connections between different modules in complex PPI networks. In addition, we show that the identification of biological modules can be greatly improved by including molecular characteristics of protein interactions. Our findings suggest that transient interactions have played a unique role in shaping the architecture and modularity of biological networks over the course of evolution.

Enhancement of ε-poly-lysine production in ε-poly-lysine-tolerant Streptomyces sp. by genome shuffling.

PubMed

Zhou, Yong-Peng; Ren, Xi-Dong; Wang, Liang; Chen, Xu-Sheng; Mao, Zhong-Gui; Tang, Lei

2015-09-01

ε-Poly-L-lysine (ε-PL) has been widely used as food additive. However, the self-inhibition of ε-PL on cell growth limits the accumulation of ε-PL in the wild-type strain. Here, we screened ε-PL-tolerant strain of Streptomyces sp. with higher ε-PL productivity by genome shuffling and studied the mechanism for the improvement. The initial mutant library was constructed by diethyl sulfate mutagenesis. After four rounds of protoplast fusion, a shuffled strain F4-22 with 3.11 g/L ε-PL productivity in shake flask, 1.81-fold in comparison with that of parent strain, was obtained. The higher aspartokinase activity was induced in F4-22 whereas no obvious changes have been found in ε-PL synthetic and degrading enzymes which indicated that the upstream reregulation of the precursor lysine synthesis rather than lysine polymerization or ε-PL degradation in shuffled strain accounted for the higher productivity. The activities of key enzymes in the central metabolic pathway were also enhanced in F4-22 which resulted in increased vigor of the strain and in delayed strain lysis during fermentation. These improved properties of shuffled strain led to the success of combining general two-stage fermentation into one-stage one in 5-L bioreactor with 32.7 % more ε-PL production than that of parent strain. The strategy used in this study provided a novel strain breeding approach of producers which suffered from ε-PL-like self-inhibition of the metabolites.

Improved wrist pannus volume measurement from contrast-enhanced MRI in rheumatoid arthritis using shuffle transform.

PubMed

Xanthopoulos, Emily; Hutchinson, Charles E; Adams, Judith E; Bruce, Ian N; Nash, Anthony F P; Holmes, Andrew P; Taylor, Christopher J; Waterton, John C

2007-01-01

Contrast-enhanced MRI is of value in assessing rheumatoid pannus in the hand, but the images are not always easy to quantitate. To develop and evaluate an improved measurement of volume of enhancing pannus (VEP) in the hand in human rheumatoid arthritis (RA). MR images of the hand and wrist were obtained for 14 patients with RA at 0, 1 and 13 weeks. Volume of enhancing pannus was measured on images created by subtracting precontrast T1-weighted images from contrast-enhanced T1-weighted images using a shuffle transformation technique. Maximum intensity projection (MIP) and 3D volume rendering of the images were used as a guide to identify the pannus and any contrast-enhanced veins. Visualisation of pannus was much improved following the shuffle transform. Between 0 weeks and 1 week, the mean value of the within-subject coefficient of variation (CoV) was 0.13 and the estimated total CoV was 0.15. There was no evidence of significant increased variability within the 13-week interval for the complete sample of patients. Volume of enhancing pannus can be measured reproducibly in the rheumatoid hand using 3D contrast-enhanced MRI and shuffle transform.

Directed evolution improves the fibrinolytic activity of nattokinase from Bacillus natto.

PubMed

Yongjun, Cai; Wei, Bao; Shujun, Jiang; Meizhi, Weng; Yan, Jia; Yan, Yin; Zhongliang, Zheng; Goulin, Zou

2011-12-01

Nattokinase (subtilisin NAT, NK) is a relatively effective microbial fibrinolytic enzyme that has been identified and characterized from Bacillus natto. In the current report, DNA family shuffling was used to improve the fibrinolytic activity of nattokinase. Three homologous genes from B. natto AS 1.107, Bacillus amyloliquefaciens CICC 20164 and Bacillus licheniformis CICC 10092 were shuffled to generate a mutant library. A plate-based method was used to screen the mutant libraries for improved activity. After three rounds of DNA shuffling, one desirable mutant with 16 amino acid substitutions was obtained. The mutant enzyme was purified and characterized. The kinetic measurements showed that the catalytic efficiency of the mutant NK was approximately 2.3 times higher than that of the wild-type nattokinase. In addition, the molecular modeling analysis suggested that the mutations affect the enzymatic function by changing the surface conformation of the substrate-binding pocket. The current study shows that the evolution of nattokinase with improved fibrinolytic activity by DNA family shuffling is feasible and provides useful references to facilitate the application of nattokinase in thrombolytic therapy. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

A Pebble-Bed Breed-and-Burn Reactor

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

Greenspan, Ehud

2016-03-31

The primary objective of this project is to use three-dimensional fuel shuffling in order to reduce the minimum peak radiation damage of ~550 dpa present Breed-and-Burn (B&B) fast nuclear reactor cores designs (they feature 2-D fuel shuffling) call for to as close as possible to the presently accepted value of 200 dpa thereby enabling earlier commercialization of B&B reactors which could make substantial contribution to energy sustainability and economic stability without need for fuel recycling. Another objective is increasing the average discharge burnup for the same peak discharge burnup thereby (1) increasing the fuel utilization of 2-D shuffled B&B reactorsmore » and (2) reducing the reprocessing capacity required to support a given capacity of FRs that are to recycle fuel.« less

Using peptide array to identify binding motifs and interaction networks for modular domains.

PubMed

Li, Shawn S-C; Wu, Chenggang

2009-01-01

Specific protein-protein interactions underlie all essential biological processes and form the basis of cellular signal transduction. The recognition of a short, linear peptide sequence in one protein by a modular domain in another represents a common theme of macromolecular recognition in cells, and the importance of this mode of protein-protein interaction is highlighted by the large number of peptide-binding domains encoded by the human genome. This phenomenon also provides a unique opportunity to identify protein-protein binding events using peptide arrays and complementary biochemical assays. Accordingly, high-density peptide array has emerged as a useful tool by which to map domain-mediated protein-protein interaction networks at the proteome level. Using the Src-homology 2 (SH2) and 3 (SH3) domains as examples, we describe the application of oriented peptide array libraries in uncovering specific motifs recognized by an SH2 domain and the use of high-density peptide arrays in identifying interaction networks mediated by the SH3 domain. Methods reviewed here could also be applied to other modular domains, including catalytic domains, that recognize linear peptide sequences.

Design, Synthesis, and Biological Functionality of a Dendrimer-based Modular Drug Delivery Platform

PubMed Central

Mullen, Douglas G.; McNerny, Daniel Q.; Desai, Ankur; Cheng, Xue-min; DiMaggio, Stassi C.; Kotlyar, Alina; Zhong, Yueyang; Qin, Suyang; Kelly, Christopher V.; Thomas, Thommey P.; Majoros, Istvan; Orr, Bradford G.; Baker, James R.; Banaszak Holl, Mark M.

2011-01-01

A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction (‘click’ chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate ‘click’ reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by 1H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the over-expressed folic acid receptor. PMID:21425790

Activity Augmentation of Amphioxus Peptidoglycan Recognition Protein BbtPGRP3 via Fusion with a Chitin Binding Domain

PubMed Central

Wang, Wen-Jie; Cheng, Wang; Luo, Ming; Yan, Qingyu; Yu, Hong-Mei; Li, Qiong; Cao, Dong-Dong; Huang, Shengfeng; Xu, Anlong; Mariuzza, Roy A.; Chen, Yuxing; Zhou, Cong-Zhao

2015-01-01

Peptidoglycan recognition proteins (PGRPs), which have been identified in most animals, are pattern recognition molecules that involve antimicrobial defense. Resulting from extraordinary expansion of innate immune genes, the amphioxus encodes many PGRPs of diverse functions. For instance, three isoforms of PGRP encoded by Branchiostoma belcheri tsingtauense, termed BbtPGRP1~3, are fused with a chitin binding domain (CBD) at the N-terminus. Here we report the 2.7 Å crystal structure of BbtPGRP3, revealing an overall structure of an N-terminal hevein-like CBD followed by a catalytic PGRP domain. Activity assays combined with site-directed mutagenesis indicated that the individual PGRP domain exhibits amidase activity towards both DAP-type and Lys-type peptidoglycans (PGNs), the former of which is favored. The N-terminal CBD not only has the chitin-binding activity, but also enables BbtPGRP3 to gain a five-fold increase of amidase activity towards the Lys-type PGNs, leading to a significantly broadened substrate spectrum. Together, we propose that modular evolution via domain shuffling combined with gene horizontal transfer makes BbtPGRP1~3 novel PGRPs of augmented catalytic activity and broad recognition spectrum. PMID:26479246

Evolution of transcriptional enhancers and animal diversity

PubMed Central

Rubinstein, Marcelo; de Souza, Flávio S. J.

2013-01-01

Deciphering the genetic bases that drive animal diversity is one of the major challenges of modern biology. Although four decades ago it was proposed that animal evolution was mainly driven by changes in cis-regulatory DNA elements controlling gene expression rather than in protein-coding sequences, only now are powerful bioinformatics and experimental approaches available to accelerate studies into how the evolution of transcriptional enhancers contributes to novel forms and functions. In the introduction to this Theme Issue, we start by defining the general properties of transcriptional enhancers, such as modularity and the coexistence of tight sequence conservation with transcription factor-binding site shuffling as different mechanisms that maintain the enhancer grammar over evolutionary time. We discuss past and current methods used to identify cell-type-specific enhancers and provide examples of how enhancers originate de novo, change and are lost in particular lineages. We then focus in the central part of this Theme Issue on analysing examples of how the molecular evolution of enhancers may change form and function. Throughout this introduction, we present the main findings of the articles, reviews and perspectives contributed to this Theme Issue that together illustrate some of the great advances and current frontiers in the field. PMID:24218630

Symbiosis Island Shuffling with Abundant Insertion Sequences in the Genomes of Extra-Slow-Growing Strains of Soybean Bradyrhizobia

PubMed Central

Iida, Takayuki; Itakura, Manabu; Anda, Mizue; Sugawara, Masayuki; Isawa, Tsuyoshi; Okubo, Takashi; Sato, Shusei; Chiba-Kakizaki, Kaori

2015-01-01

Extra-slow-growing bradyrhizobia from root nodules of field-grown soybeans harbor abundant insertion sequences (ISs) and are termed highly reiterated sequence-possessing (HRS) strains. We analyzed the genome organization of HRS strains with the focus on IS distribution and symbiosis island structure. Using pulsed-field gel electrophoresis, we consistently detected several plasmids (0.07 to 0.4 Mb) in the HRS strains (NK5, NK6, USDA135, 2281, USDA123, and T2), whereas no plasmids were detected in the non-HRS strain USDA110. The chromosomes of the six HRS strains (9.7 to 10.7 Mb) were larger than that of USDA110 (9.1 Mb). Using MiSeq sequences of 6 HRS and 17 non-HRS strains mapped to the USDA110 genome, we found that the copy numbers of ISRj1, ISRj2, ISFK1, IS1632, ISB27, ISBj8, and IS1631 were markedly higher in HRS strains. Whole-genome sequencing showed that the HRS strain NK6 had four small plasmids (136 to 212 kb) and a large chromosome (9,780 kb). Strong colinearity was found between 7.4-Mb core regions of the NK6 and USDA110 chromosomes. USDA110 symbiosis islands corresponded mainly to five small regions (S1 to S5) within two variable regions, V1 (0.8 Mb) and V2 (1.6 Mb), of the NK6 chromosome. The USDA110 nif gene cluster (nifDKENXSBZHQW-fixBCX) was split into two regions, S2 and S3, where ISRj1-mediated rearrangement occurred between nifS and nifB. ISs were also scattered in NK6 core regions, and ISRj1 insertion often disrupted some genes important for survival and environmental responses. These results suggest that HRS strains of soybean bradyrhizobia were subjected to IS-mediated symbiosis island shuffling and core genome degradation. PMID:25862225

Features Extraction of Flotation Froth Images and BP Neural Network Soft-Sensor Model of Concentrate Grade Optimized by Shuffled Cuckoo Searching Algorithm

PubMed Central

Wang, Jie-sheng; Han, Shuang; Shen, Na-na; Li, Shu-xia

2014-01-01

For meeting the forecasting target of key technology indicators in the flotation process, a BP neural network soft-sensor model based on features extraction of flotation froth images and optimized by shuffled cuckoo search algorithm is proposed. Based on the digital image processing technique, the color features in HSI color space, the visual features based on the gray level cooccurrence matrix, and the shape characteristics based on the geometric theory of flotation froth images are extracted, respectively, as the input variables of the proposed soft-sensor model. Then the isometric mapping method is used to reduce the input dimension, the network size, and learning time of BP neural network. Finally, a shuffled cuckoo search algorithm is adopted to optimize the BP neural network soft-sensor model. Simulation results show that the model has better generalization results and prediction accuracy. PMID:25133210

The MHC big bang.

PubMed

Abi Rached, L; McDermott, M F; Pontarotti, P

1999-02-01

The human Major Histocompatibility Complex (MHC) shares similarities with three other chromosome regions in human. This could be the vestige of ancestral large scale duplications. We discuss here the possibility i) that these duplications occurred during two rounds of tetraploidization supposed to have taken place during chordate evolution before the jawed vertebrate radiation, and ii) that one of the quadruplicate regions, relaxed of functional constraints, gave rise to the vertebrate MHC by a quick round of gene cis-duplication and cis-exon shuffling. These different rounds of cis-duplications and exon shufflings allowed the emergence of new genes participating in novel biological functions i.e. adaptive immune responses. Cis-duplications and cis-exon shufflings are ongoing processes in the evolution of some of these genes in this region as they have occurred and were fixed at different times and in different lineages during vertebrate evolution. In contrast, other genes within the MHC have remained stable since the emergence of jawed vertebrates.

Landau free energy for a bcc-hcp reconstructive phase transformation

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

Sanati, Mahdi; Saxena, A.; Lookman, T.

We study the bcc-hcp phase transition in Ti and Zr with the use of first-principles calculations. We have determined the complete energy surface from the bcc to hcp structure. The results are used to find an appropriate Landau free energy density for describing this transformation. The proposed Landau free energy density has two relevant order parameters: shear and shuffle. Through first-principles calculations, we show that the bcc structure is unstable with respect to the shuffle of atoms (TA{sub 1} N-point phonon) rather than the shear. Therefore, we reduce the two order parameter Landau free energy to an effective one ordermore » parameter (shuffle) potential, which is a reasonable approximation. In general, the effective Landau free energy is a triple-well potential. From the phonon dispersion data and the change in entropy at the transition temperature we find the free energy coefficients for Ti and Zr.« less

Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics.

PubMed

Sridharan, Gautham Vivek; Bruinsma, Bote Gosse; Bale, Shyam Sundhar; Swaminathan, Anandh; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

2017-11-13

Large-scale -omics data are now ubiquitously utilized to capture and interpret global responses to perturbations in biological systems, such as the impact of disease states on cells, tissues, and whole organs. Metabolomics data, in particular, are difficult to interpret for providing physiological insight because predefined biochemical pathways used for analysis are inherently biased and fail to capture more complex network interactions that span multiple canonical pathways. In this study, we introduce a nov-el approach coined Metabolomic Modularity Analysis (MMA) as a graph-based algorithm to systematically identify metabolic modules of reactions enriched with metabolites flagged to be statistically significant. A defining feature of the algorithm is its ability to determine modularity that highlights interactions between reactions mediated by the production and consumption of cofactors and other hub metabolites. As a case study, we evaluated the metabolic dynamics of discarded human livers using time-course metabolomics data and MMA to identify modules that explain the observed physiological changes leading to liver recovery during subnormothermic machine perfusion (SNMP). MMA was performed on a large scale liver-specific human metabolic network that was weighted based on metabolomics data and identified cofactor-mediated modules that would not have been discovered by traditional metabolic pathway analyses.

Exploring metazoan evolution through dynamic and holistic changes in protein families and domains

PubMed Central

2012-01-01

Background Proteins convey the majority of biochemical and cellular activities in organisms. Over the course of evolution, proteins undergo normal sequence mutations as well as large scale mutations involving domain duplication and/or domain shuffling. These events result in the generation of new proteins and protein families. Processes that affect proteome evolution drive species diversity and adaptation. Herein, change over the course of metazoan evolution, as defined by birth/death and duplication/deletion events within protein families and domains, was examined using the proteomes of 9 metazoan and two outgroup species. Results In studying members of the three major metazoan groups, the vertebrates, arthropods, and nematodes, we found that the number of protein families increased at the majority of lineages over the course of metazoan evolution where the magnitude of these increases was greatest at the lineages leading to mammals. In contrast, the number of protein domains decreased at most lineages and at all terminal lineages. This resulted in a weak correlation between protein family birth and domain birth; however, the correlation between domain birth and domain member duplication was quite strong. These data suggest that domain birth and protein family birth occur via different mechanisms, and that domain shuffling plays a role in the formation of protein families. The ratio of protein family birth to protein domain birth (domain shuffling index) suggests that shuffling had a more demonstrable effect on protein families in nematodes and arthropods than in vertebrates. Through the contrast of high and low domain shuffling indices at the lineages of Trichinella spiralis and Gallus gallus, we propose a link between protein redundancy and evolutionary changes controlled by domain shuffling; however, the speed of adaptation among the different lineages was relatively invariant. Evaluating the functions of protein families that appeared or disappeared at the last common ancestors (LCAs) of the three metazoan clades supports a correlation with organism adaptation. Furthermore, bursts of new protein families and domains in the LCAs of metazoans and vertebrates are consistent with whole genome duplications. Conclusion Metazoan speciation and adaptation were explored by birth/death and duplication/deletion events among protein families and domains. Our results provide insights into protein evolution and its bearing on metazoan evolution. PMID:22862991

The effect of progressive hypoxia on school structure and dynamics in Atlantic herring Clupea harengus.

PubMed

Domenici, Paolo; Ferrari, R Silvana; Steffensen, John F; Batty, Robert S

2002-10-22

The effect of progressive hypoxia on the structure and dynamics of herring (Clupea harengus) schools in laboratory conditions was investigated. The length, width and depth of schools of about 20 individuals were measured from video recordings to test the hypothesis that during hypoxia fish schools change their shape and volume. School shape (calculated as the ratios of length/depth, width/depth and length/width) did not change significantly during hypoxia. School length, width, depth, area and volume were all significantly increased at 20% oxygen saturation. Volume, area and width were more sensitive to hypoxia; volume and width were also increased at 25% and area at 30% oxygen saturation. The degree of position changing (shuffling) of individuals within the school was also analysed. Shuffling in normoxia was observed to occur largely through 'O-turn' manoeuvres, a 360( degrees )turn executed laterally to the school that allowed fishes in the front to move to the back. O-turn frequency during normoxia was 0.69 O-turns fish(-1) min(-1) but significantly decreased with hypoxia to 0.37 O-turns fish(-1) min(-1) at 30% oxygen saturation. Shuffling was also investigated by measuring the persistence time of individual herring in leading positions (i.e. the first half of the school). No significant changes occurred during hypoxia, indicating that the decrease in O-turn frequency does not affect shuffling rate during hypoxia, and that position shuffling in hypoxic conditions is mainly due to overtaking or falling back by individual fishes. School integrity and positional dynamics are the outcome of trade-offs among a number of biotic factors, such as food, predator defence, mating behaviour and various physical factors that may impose certain limits. Among these, our results indicate that oxygen level modulates schooling behaviour. Oxygen alters whole-school parameters at oxygen saturation values that can be encountered by herring in the field, indicating that oxygen availability is an important factor in the trade-offs that determine school volume. An increase in school volume in the wild may increase the oxygen available to each individual. However, shuffling rate is not affected by hypoxia, indicating that the internal dynamics of positioning is the result of the balance of other factors, for example related to the nutritional state of each individual fish as suggested by previous studies.

The Mathematics of Mixing Things Up

NASA Astrophysics Data System (ADS)

Diaconis, Persi

2011-08-01

How long should a Markov chain Monte Carlo algorithm be run? Using examples from statistical physics (Ehrenfest urn, Ising model, hard discs) as well as card shuffling, this tutorial paper gives an overview of a body of mathematical results that can give useful answers to practitioners (viz: seven shuffles suffice for practical purposes). It points to new techniques (path coupling, geometric inequalities, and Harris recurrence). The discovery of phase transitions in mixing times (the cutoff phenomenon) is emphasized.

Characterization of an alternative low energy fold for bovine α-lactalbumin formed by disulfide bond shuffling.

PubMed

Lewney, Sarah; Smith, Lorna J

2012-03-01

Bovine α-lactalbumin (αLA) forms a misfolded disulfide bond shuffled isomer, X-αLA. This X-αLA isomer contains two native disulfide bridges (Cys 6-Cys 120 and Cys 28-Cys 111) and two non-native disulfide bridges (Cys 61-Cys 73 and Cys 77-Cys 91). MD simulations have been used to characterize the X-αLA isomer and its formation via disulfide bond shuffling and to compare it with the native fold of αLA. In the simulations of the X-αLA isomer the structure of the α-domain of native αLA is largely retained in agreement with experimental data. However, there are significant rearrangements in the β-domain, including the loss of the native β-sheet and calcium binding site. Interestingly, the energies of X-αLA and native αLA in simulations in the absence of calcium are closely similar. Thus, the X-αLA isomer represents a different low energy fold for the protein. Calcium binding to native αLA is shown to help preserve the structure of the β-domain of the protein limiting possibilities for disulfide bond shuffling. Hence, binding calcium plays an important role in both maintaining the native structure of αLA and providing a mechanism for distinguishing between folded and misfolded species. Copyright © 2011 Wiley Periodicals, Inc.

The Feigin Tetrahedron

NASA Astrophysics Data System (ADS)

Rupel, Dylan

2015-03-01

The first goal of this note is to extend the well-known Feigin homomorphisms taking quantum groups to quantum polynomial algebras. More precisely, we define generalized Feigin homomorphisms from a quantum shuffle algebra to quantum polynomial algebras which extend the classical Feigin homomorphisms along the embedding of the quantum group into said quantum shuffle algebra. In a recent work of Berenstein and the author, analogous extensions of Feigin homomorphisms from the dual Hall-Ringel algebra of a valued quiver to quantum polynomial algebras were defined. To relate these constructions, we establish a homomorphism, dubbed the quantum shuffle character, from the dual Hall-Ringel algebra to the quantum shuffle algebra which relates the generalized Feigin homomorphisms. These constructions can be compactly described by a commuting tetrahedron of maps beginning with the quantum group and terminating in a quantum polynomial algebra. The second goal in this project is to better understand the dual canonical basis conjecture for skew-symmetrizable quantum cluster algebras. In the symmetrizable types it is known that dual canonical basis elements need not have positive multiplicative structure constants, while this is still suspected to hold for skew-symmetrizable quantum cluster algebras. We propose an alternate conjecture for the symmetrizable types: the cluster monomials should correspond to irreducible characters of a KLR algebra. Indeed, the main conjecture of this note would establish this ''KLR conjecture'' for acyclic skew-symmetrizable quantum cluster algebras: that is, we conjecture that the images of rigid representations under the quantum shuffle character give irreducible characters for KLR algebras. We sketch a proof in the symmetric case giving an alternative to the proof of Kimura-Qin that all non-initial cluster variables in an acyclic skew-symmetric quantum cluster algebra are contained in the dual canonical basis. With these results in mind we interpret the cluster mutations directly in terms of the representation theory of the KLR algebra.

Genome shuffling improves thermotolerance and glutamic acid production of Corynebacteria glutamicum.

PubMed

Zheng, Pu; Liu, Miao; Liu, Xiao-de; Du, Qiao-Yan; Ni, Ye; Sun, Zhi-Hao

2012-03-01

Genome shuffling was used to improve the thermotolerance of L: -glutamic acid-producing strain Corynebacteria glutamicum. Five strains with subtle improvements in high temperature tolerance and productivity were selected by ultraviolet irradiation and diethyl sulfate mutagenesis. An improved strain (F343) was obtained by three rounds of genome shuffling of the five strains as mentioned above. The cell density of F343 was four times higher than that of ancestor strains after 24 h of cultivation at 44°C, and importantly, the yield of L: -glutamic acid was increased by 1.8-times comparing with that of the ancestor strain at 38°C in a 5-L fermentor. With glucose supplement and two-stage pH control, the L: -glutamate acid concentration of F343 reached 119 g/L after fermentation for 30 h. The genetic diversity between F343 and its ancestors was also evaluated by amplified fragment length polymorphism analysis. Results suggest that the phenotypes for both thermotolerance and L: -glutamic acid production in F343 were evolved.

Interface structures and twinning mechanisms of {1¯012} twins in hexagonal metals

DOE PAGES

Gong, Mingyu; Hirth, John P.; Liu, Yue; ...

2017-06-07

In this paper, a controversy concerning the description of {1¯012} {1¯012} twinning, whether it is shear-shuffle or pure glide-shuffle or pure shuffle, has developed. There is disagreement about the interpretation of transmission electron microscopic observations, atomistic simulations and theories for twin growth. In this article, we highlight the atomic-level, characteristic, equilibrium and non-equilibrium boundaries and corresponding boundary defects associated with the three-dimensional ‘normal’, ‘forward’ and ‘lateral’ propagation of {1¯011} growth/annealing and deformation twins. Although deformation twin boundaries (TBs) after recovery exhibit some similarity to growth/annealing TBs because of the plastic accommodation of stress fields, there are important distinctions among them.more » These distinctions distinguish among the mechanisms of twin growth and resolve the controversy. In addition, a new type of disconnection, a glide disclination, is described for twinning. Synchroshear, seldom considered, is shown to be a likely mechanism for {1¯012} twinning.« less

bcc-to-hcp transformation pathways for iron versus hydrostatic pressure: Coupled shuffle and shear modes

NASA Astrophysics Data System (ADS)

Liu, J. B.; Johnson, D. D.

2009-04-01

Using density-functional theory, we calculate the potential-energy surface (PES), minimum-energy pathway (MEP), and transition state (TS) versus hydrostatic pressure σhyd for the reconstructive transformation in Fe from body-centered cubic (bcc) to hexagonal closed-packed (hcp). At fixed σhyd , the PES is described by coupled shear (γ) and shuffle (η) modes and is determined from structurally minimized hcp-bcc energy differences at a set of (η,γ) . We fit the PES using symmetry-adapted polynomials, permitting the MEP to be found analytically. The MEP is continuous and fully explains the transformation and its associated magnetization and volume discontinuity at TS. We show that σhyd (while not able to induce shear) dramatically alters the MEP to drive reconstruction by a shuffle-only mode at ≤30GPa , as observed. Finally, we relate our polynomial-based results to Landau and nudge-elastic-band approaches and show they yield incorrect MEP in general.

PrecisePrimer: an easy-to-use web server for designing PCR primers for DNA library cloning and DNA shuffling.

PubMed

Pauthenier, Cyrille; Faulon, Jean-Loup

2014-07-01

PrecisePrimer is a web-based primer design software made to assist experimentalists in any repetitive primer design task such as preparing, cloning and shuffling DNA libraries. Unlike other popular primer design tools, it is conceived to generate primer libraries with popular PCR polymerase buffers proposed as pre-set options. PrecisePrimer is also meant to design primers in batches, such as for DNA libraries creation of DNA shuffling experiments and to have the simplest interface possible. It integrates the most up-to-date melting temperature algorithms validated with experimental data, and cross validated with other computational tools. We generated a library of primers for the extraction and cloning of 61 genes from yeast DNA genomic extract using default parameters. All primer pairs efficiently amplified their target without any optimization of the PCR conditions. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Soluble expression of an amebic cysteine protease in the cytoplasm of Escherichia coli SHuffle Express cells and purification of active enzyme.

PubMed

Jalomo-Khayrova, Ekaterina; Mares, Rosa E; Muñoz, Patricia L A; Meléndez-López, Samuel G; Rivero, Ignacio A; Ramos, Marco A

2018-04-03

Recombinant production of amebic cysteine proteases using Escherichia coli cells as the bacterial system has become a challenging effort, with protein insolubility being the most common issue. Since many of these enzymes need a native conformation stabilized by disulfide bonds, an elaborate process of oxidative folding is usually demanded to get a functional protein. The cytoplasm of E. coli SHuffle Express cells owns an enhanced ability to properly fold proteins with disulfide bonds. Because of this cellular feature, it was possible to assume that this strain represents a reliable expression system and worthwhile been considered as an efficient bacterial host for the recombinant production of amebic cysteine proteases. Using E. coli SHuffle Express cells as the bacterial system, we efficiently produce soluble recombinant EhCP1protein. Enzymatic and inhibition analyses revealed that it exhibits proper catalytic abilities, proceeds effectively over the substrate (following an apparent Michaelis-Menten kinetics), and displays a typical inhibition profile. We report the first feasibility study of the recombinant production of amebic cysteine proteases using E. coli SHuffle Express as the bacterial host. We present a simple protocol for the recombinant expression and purification of fully soluble and active EhCP1 enzyme. We confirm the suitability of recombinant EhCP1 as a therapeutic target. We propose an approachable bacterial system for the recombinant production of amebic proteins, particularly for those with a need for proper oxidative folding.

Increased xylose affinity of Hxt2 through gene shuffling of hexose transporters in Saccharomyces cerevisiae.

PubMed

Nijland, J G; Shin, H Y; de Waal, P P; Klaassen, P; Driessen, A J M

2018-02-01

Optimizing D-xylose transport in Saccharomyces cerevisiae is essential for efficient bioethanol production from cellulosic materials. We have used a gene shuffling approach of hexose (Hxt) transporters in order to increase the affinity for D-xylose. Various libraries were transformed to a hexose transporter deletion strain, and shuffled genes were selected via growth on low concentrations of D-xylose. This screening yielded two homologous fusion proteins (fusions 9,4 and 9,6), both consisting of the major central part of Hxt2 and various smaller parts of other Hxt proteins. Both chimeric proteins showed the same increase in D-xylose affinity (8·1 ± 3·0 mmol l -1 ) compared with Hxt2 (23·7 ± 2·1 mmol l -1 ). The increased D-xylose affinity could be related to the C terminus, more specifically to a cysteine to proline mutation at position 505 in Hxt2. The Hxt2 C505P mutation increased the affinity for D-xylose for Hxt2, thus providing a way to increase D-xylose transport flux at low D-xylose concentration. The gene shuffling protocol using the highly homologues hexose transporters family provides a powerful tool to enhance the D-xylose affinity of Hxt transporters in S. cerevisiae, thus providing a means to increase the D-xylose uptake flux at low D-xylose concentrations. © 2017 The Society for Applied Microbiology.

Latent change models of adult cognition: are changes in processing speed and working memory associated with changes in episodic memory?

PubMed

Hertzog, Christopher; Dixon, Roger A; Hultsch, David F; MacDonald, Stuart W S

2003-12-01

The authors used 6-year longitudinal data from the Victoria Longitudinal Study (VLS) to investigate individual differences in amount of episodic memory change. Latent change models revealed reliable individual differences in cognitive change. Changes in episodic memory were significantly correlated with changes in other cognitive variables, including speed and working memory. A structural equation model for the latent change scores showed that changes in speed and working memory predicted changes in episodic memory, as expected by processing resource theory. However, these effects were best modeled as being mediated by changes in induction and fact retrieval. Dissociations were detected between cross-sectional ability correlations and longitudinal changes. Shuffling the tasks used to define the Working Memory latent variable altered patterns of change correlations.

Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases.

PubMed

Xu, Yuquan; Zhou, Tong; Zhang, Shuwei; Espinosa-Artiles, Patricia; Wang, Luoyi; Zhang, Wei; Lin, Min; Gunatilaka, A A Leslie; Zhan, Jixun; Molnár, István

2014-08-26

Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases (iPKSs) offers a test case for the modularization of secondary metabolic pathways into "build-couple-pair" combinatorial synthetic schemes. Expression of random pairs of iPKS subunits from four BDL model systems in a yeast heterologous host created a diverse library of BDL congeners, including a polyketide with an unnatural skeleton and heat shock response-inducing activity. Pairwise heterocombinations of the iPKS subunits also helped to illuminate the innate, idiosyncratic programming of these enzymes. Even in combinatorial contexts, these biosynthetic programs remained largely unchanged, so that the iPKSs built their cognate biosynthons, coupled these building blocks into chimeric polyketide intermediates, and catalyzed intramolecular pairing to release macrocycles or α-pyrones. However, some heterocombinations also provoked stuttering, i.e., the relaxation of iPKSs chain length control to assemble larger homologous products. The success of such a plug and play approach to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural polyketides for drug discovery.

Enhanced succinic acid production by Actinobacillus succinogenes after genome shuffling.

PubMed

Zheng, Pu; Zhang, Kunkun; Yan, Qiang; Xu, Yan; Sun, Zhihao

2013-08-01

Succinic acid is an important platform chemical for synthesis of C4 compounds. We applied genome shuffling to improve fermentative production of succinic acid by A. succinogenes. Using a screening strategy composed of selection in fermentation broth, cultured in 96-deep-well plates, and condensed HPLC screening, a starting population of 11 mutants producing a higher succinic acid concentration was selected and subjected to recursive protoplasts fusion. After three rounds of genome shuffling, strain F3-II-3-F was obtained, producing succinic acid at 1.99 g/l/h with a yield of 95.6 g/l. The genome shuffled strain had about a 73 % improvement in succinic acid production compared to the parent strain after 48 h in fed-batch fermentation. The genomic variability of F3-II-3-F was confirmed by amplified fragment-length polymorphism. The activity levels of key enzymes involved in end-product formation from glucose and metabolic flux distribution during succinic acid production were compared between A. succinogenes CGMCC 1593 and F3-II-3-F. Increased activity of glucokinase, fructose-1,6-bisphosphate aldolase, PEP carboxykinase and fumarase, as well as decreased activity of pyruvate kinase, pyruvate formate-lyase, and acetate kinase explained the enhanced succinic acid production and decreased acetic acid formation. Metabolic flux analysis suggested that increased flux to NADH was the main reason for increased activity of the C4 pathway resulting in increased yields of succinic acid. The present work will be propitious to the development of a bio-succinic acid fermentation industry.

An improved shuffled frog leaping algorithm based evolutionary framework for currency exchange rate prediction

NASA Astrophysics Data System (ADS)

Dash, Rajashree

2017-11-01

Forecasting purchasing power of one currency with respect to another currency is always an interesting topic in the field of financial time series prediction. Despite the existence of several traditional and computational models for currency exchange rate forecasting, there is always a need for developing simpler and more efficient model, which will produce better prediction capability. In this paper, an evolutionary framework is proposed by using an improved shuffled frog leaping (ISFL) algorithm with a computationally efficient functional link artificial neural network (CEFLANN) for prediction of currency exchange rate. The model is validated by observing the monthly prediction measures obtained for three currency exchange data sets such as USD/CAD, USD/CHF, and USD/JPY accumulated within same period of time. The model performance is also compared with two other evolutionary learning techniques such as Shuffled frog leaping algorithm and Particle Swarm optimization algorithm. Practical analysis of results suggest that, the proposed model developed using the ISFL algorithm with CEFLANN network is a promising predictor model for currency exchange rate prediction compared to other models included in the study.

A copyright protection scheme for digital images based on shuffled singular value decomposition and visual cryptography.

PubMed

Devi, B Pushpa; Singh, Kh Manglem; Roy, Sudipta

2016-01-01

This paper proposes a new watermarking algorithm based on the shuffled singular value decomposition and the visual cryptography for copyright protection of digital images. It generates the ownership and identification shares of the image based on visual cryptography. It decomposes the image into low and high frequency sub-bands. The low frequency sub-band is further divided into blocks of same size after shuffling it and then the singular value decomposition is applied to each randomly selected block. Shares are generated by comparing one of the elements in the first column of the left orthogonal matrix with its corresponding element in the right orthogonal matrix of the singular value decomposition of the block of the low frequency sub-band. The experimental results show that the proposed scheme clearly verifies the copyright of the digital images, and is robust to withstand several image processing attacks. Comparison with the other related visual cryptography-based algorithms reveals that the proposed method gives better performance. The proposed method is especially resilient against the rotation attack.

Exon Shuffling and Origin of Scorpion Venom Biodiversity

PubMed Central

Wang, Xueli; Gao, Bin; Zhu, Shunyi

2016-01-01

Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences. PMID:28035955

Exon Shuffling and Origin of Scorpion Venom Biodiversity.

PubMed

Wang, Xueli; Gao, Bin; Zhu, Shunyi

2016-12-26

Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences.

Random domain name and address mutation (RDAM) for thwarting reconnaissance attacks

PubMed Central

Chen, Xi; Zhu, Yuefei

2017-01-01

Network address shuffling is a novel moving target defense (MTD) that invalidates the address information collected by the attacker by dynamically changing or remapping the host’s network addresses. However, most network address shuffling methods are limited by the limited address space and rely on the host’s static domain name to map to its dynamic address; therefore these methods cannot effectively defend against random scanning attacks, and cannot defend against an attacker who knows the target’s domain name. In this paper, we propose a network defense method based on random domain name and address mutation (RDAM), which increases the scanning space of the attacker through a dynamic domain name method and reduces the probability that a host will be hit by an attacker scanning IP addresses using the domain name system (DNS) query list and the time window methods. Theoretical analysis and experimental results show that RDAM can defend against scanning attacks and worm propagation more effectively than general network address shuffling methods, while introducing an acceptable operational overhead. PMID:28489910

Subunit architecture and functional modular rearrangements of the transcriptional Mediator complex

PubMed Central

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2014-01-01

SUMMARY The multisubunit Mediator comprising ~30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. PMID:24882805

Why do proteases mess up with antigen presentation by re-shuffling antigen sequences?

PubMed

Liepe, Juliane; Ovaa, Huib; Mishto, Michele

2018-04-30

The sequence of a large number of MHC-presented epitopes is not present as such in the original antigen because it has been re-shuffled by the proteasome or other proteases. Why do proteases throw a spanner in the works of our model of antigen tagging and immune recognition? We describe in this review what we know about the immunological relevance of post-translationally spliced epitopes and why proteases seem to have a second (dark) personality, which is keen to create new peptide bonds. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Principal Component Analysis Based Measure of Structural Holes

NASA Astrophysics Data System (ADS)

Deng, Shiguo; Zhang, Wenqing; Yang, Huijie

2013-02-01

Based upon principal component analysis, a new measure called compressibility coefficient is proposed to evaluate structural holes in networks. This measure incorporates a new effect from identical patterns in networks. It is found that compressibility coefficient for Watts-Strogatz small-world networks increases monotonically with the rewiring probability and saturates to that for the corresponding shuffled networks. While compressibility coefficient for extended Barabasi-Albert scale-free networks decreases monotonically with the preferential effect and is significantly large compared with that for corresponding shuffled networks. This measure is helpful in diverse research fields to evaluate global efficiency of networks.

Improved Adaptive LSB Steganography Based on Chaos and Genetic Algorithm

NASA Astrophysics Data System (ADS)

Yu, Lifang; Zhao, Yao; Ni, Rongrong; Li, Ting

2010-12-01

We propose a novel steganographic method in JPEG images with high performance. Firstly, we propose improved adaptive LSB steganography, which can achieve high capacity while preserving the first-order statistics. Secondly, in order to minimize visual degradation of the stego image, we shuffle bits-order of the message based on chaos whose parameters are selected by the genetic algorithm. Shuffling message's bits-order provides us with a new way to improve the performance of steganography. Experimental results show that our method outperforms classical steganographic methods in image quality, while preserving characteristics of histogram and providing high capacity.

Using Hydrazine to Link Ferrocene with Re(CO)3: A Modular Approach.

PubMed

Chanawanno, Kullapa; Rhoda, Hannah M; Hasheminasab, Abed; Crandall, Laura A; King, Alexander J; Herrick, Richard S; Nemykin, Victor N; Ziegler, Christopher J

2016-09-01

Acetyl ferrocene and diacetyl ferrocene both readily react with an excess of hydrazine to afford the corresponding hydrazone compounds. These compounds can then be linked to Re(CO) 3 via a metal-mediated Schiff base reaction, resulting in a series of ferrocene-Re(CO) 3 conjugates with different stoichiometries. Conjugates with 1:1, 1:2, and 2:1 ferrocene: Re(CO) 3 ratios can be produced via this "modular" type synthesis approach. Several examples of these conjugates were structurally characterized, and their spectroscopic, electrochemical, and spectroelectrochemical behaviors were investigated. The electronic structures of these compounds were also probed using DFT and TDDFT calculations.

Malleable machines in transcription regulation: the mediator complex.

PubMed

Tóth-Petróczy, Agnes; Oldfield, Christopher J; Simon, István; Takagi, Yuichiro; Dunker, A Keith; Uversky, Vladimir N; Fuxreiter, Monika

2008-12-01

The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs) to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs) distinguished by a high protein-protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the arrangements of the disordered regions and their embedded interaction sites are quite similar in the two organisms. All of these data suggest an integral role for intrinsic disorder in Mediator's function.

In Vitro and In Vivo Gene Therapy Vector Evolution via Multispecies Interbreeding and Retargeting of Adeno-Associated Viruses ▿ †

PubMed Central

Grimm, Dirk; Lee, Joyce S.; Wang, Lora; Desai, Tushar; Akache, Bassel; Storm, Theresa A.; Kay, Mark A.

2008-01-01

Adeno-associated virus (AAV) serotypes differ broadly in transduction efficacies and tissue tropisms and thus hold enormous potential as vectors for human gene therapy. In reality, however, their use in patients is restricted by prevalent anti-AAV immunity or by their inadequate performance in specific targets, exemplified by the AAV type 2 (AAV-2) prototype in the liver. Here, we attempted to merge desirable qualities of multiple natural AAV isolates by an adapted DNA family shuffling technology to create a complex library of hybrid capsids from eight different wild-type viruses. Selection on primary or transformed human hepatocytes yielded pools of hybrids from five of the starting serotypes: 2, 4, 5, 8, and 9. More stringent selection with pooled human antisera (intravenous immunoglobulin [IVIG]) then led to the selection of a single type 2/type 8/type 9 chimera, AAV-DJ, distinguished from its closest natural relative (AAV-2) by 60 capsid amino acids. Recombinant AAV-DJ vectors outperformed eight standard AAV serotypes in culture and greatly surpassed AAV-2 in livers of naïve and IVIG-immunized mice. A heparin binding domain in AAV-DJ was found to limit biodistribution to the liver (and a few other tissues) and to affect vector dose response and antibody neutralization. Moreover, we report the first successful in vivo biopanning of AAV capsids by using a new AAV-DJ-derived viral peptide display library. Two peptides enriched after serial passaging in mouse lungs mediated the retargeting of AAV-DJ vectors to distinct alveolar cells. Our study validates DNA family shuffling and viral peptide display as two powerful and compatible approaches to the molecular evolution of novel AAV vectors for human gene therapy applications. PMID:18400866

Physical activity monitoring in patients with peripheral arterial disease: validation of an activity monitor.

PubMed

Fokkenrood, H J P; Verhofstad, N; van den Houten, M M L; Lauret, G J; Wittens, C; Scheltinga, M R M; Teijink, J A W

2014-08-01

The daily life physical activity (PA) of patients with peripheral arterial disease (PAD) may be severely hampered by intermittent claudication (IC). From a therapeutic, as well as research, point of view, it may be more relevant to determine improvement in PA as an outcome measure in IC. The aim of this study was to validate daily activities using a novel type of tri-axial accelerometer (Dynaport MoveMonitor) in patients with IC. Patients with IC were studied during a hospital visit. Standard activities (locomotion, lying, sitting, standing, shuffling, number of steps and "not worn" detection) were video recorded and compared with activities scored by the MoveMonitor. Inter-rater reliability (expressed in intraclass correlation coefficients [ICC]), sensitivity, specificity, and positive predictive values (PPV) were calculated for each activity. Twenty-eight hours of video observation were analysed (n = 21). Our video annotation method (the gold standard method) appeared to be accurate for most postures (ICC > 0.97), except for shuffling (ICC = 0.38). The MoveMonitor showed a high sensitivity (>86%), specificity (>91%), and PPV (>88%) for locomotion, lying, sitting, and "not worn" detection. Moderate accuracy was found for standing (46%), while shuffling appeared to be undetectable (18%). A strong correlation was found between video recordings and the MoveMonitor with regard to the calculation of the "number of steps" (ICC = 0.90). The MoveMonitor provides accurate information on a diverse set of postures, daily activities, and number of steps in IC patients. However, the detection of low amplitude movements, such as shuffling and "sitting to standing" transfers, is a matter of concern. This tool is useful in assessing the role of PA as a novel, clinically relevant outcome parameter in IC. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks

PubMed Central

Bi, Zedong; Zhou, Changsong

2016-01-01

Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations) influence the efficacy variability under pair-wise additive spike-timing dependent plasticity (STDP) and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded), by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF) neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy). PMID:27555816

Enhanced degradation of perfluorooctanoic acid by a genome shuffling-modified Pseudomonas parafulva YAB-1.

PubMed

Yi, Langbo; Peng, Qingzhong; Liu, Deming; Zhou, Lulu; Tang, Chongjian; Zhou, Yaoyu; Chai, Liyuan

2018-05-02

Perfluorooctanoic acid (PFOA) as an emerging persistent organic pollutant is hard to be degraded by conventional methods because of its stable physical and chemical properties. Microbial transformation is an attractive remediation approach to prevent and clean up PFOA contamination. To date, several strains of wild microbes have been reported to have limited capacity to degrade PFOA, selection of superior strains degrading PFOA become urgently necessary. Here, we report the application of genome shuffling to improve the PFOA-degrading bacterium Pseudomonas Parafulva YAB-1. The initial mutant populations of strain YAB1 were generated by nitrosoguanidine and ultraviolet irradiation mutagenesis respectively, resulting in mutants YM-9 and YM-19 with slightly improved PFOA-degrading ability. YM-9 and YM-19 were used as the starting strains for three rounds of recursive protoplast fusion. The positive mutants were screened on inorganic salt medium plates containing different concentrations of PFOA and selected based on their PFOA degradability in shake-flask fermentation test. The best performing recombinant F3-52 was isolated after three rounds of genome shuffling. In batch fermentation, the PFOA degradation rate of mutant F3-52 was up to 58.6%, which was 1.8-fold higher than that of the parent strain YAB1, and 1.6-fold higher than the initial mutants YM-9 and YM-19. Pass-generation test indicated that the heredity character of F3-52 was stable. The results demonstrated that genome shuffling was an efficient method for improving PFOA degradation of Pseudomonas Parafulva YAB1. The bred mutant F3-52 with 58.6% PFOA-degrading rate could be used for the environmental control of PFOA pollutant.

Enhancement and Analysis of Human Antiaflatoxin B1 (AFB1) scFv Antibody-Ligand Interaction Using Chain Shuffling.

PubMed

Rangnoi, Kuntalee; Choowongkomon, Kiattawee; O'Kennedy, Richard; Rüker, Florian; Yamabhai, Montarop

2018-06-06

A human antiaflatoxin B1 (AFB1) scFv antibody (yAFB1-c3), selected from a naı̈ve human phage-displayed scFv library, was used as a template for improving and analysis of antibody-ligand interactions using the chain-shuffling technique. The variable-heavy and variable-light (VH/VL)-shuffled library was constructed from the VH of 25 preselected clones recombined with the VL of yAFB1-c3 and vice versa. Affinity selection from these libraries demonstrated that the VH domain played an important role in the binding of scFv to free AFB1. Therefore, in the next step, VH-shuffled scFv library was constructed from variable-heavy (VH) chain repertoires, amplified from the naı̈ve library, recombined with the variable-light (VL) chain of the clone yAFB1-c3. This library was then used to select a specific scFv antibody against soluble AFB1 by a standard biopanning method. Three clones that showed improved binding properties were isolated. Amino acid sequence analysis indicated that the improved clones have amino acid mutations in framework 1 (FR1) and the complementarity determining region (CDR1) of the VH chain. One clone, designated sAFH-3e3, showed 7.5-fold improvement in sensitivity over the original scFv clone and was selected for molecular binding studies with AFB1. Homology modeling and molecular docking were used to compare the binding of this and the original clones. The results confirmed that VH is more important than VL for AFB1 binding.

Vertical transportation systems embedded on shuffled frog leaping algorithm for manufacturing optimisation problems in industries.

PubMed

Aungkulanon, Pasura; Luangpaiboon, Pongchanun

2016-01-01

Response surface methods via the first or second order models are important in manufacturing processes. This study, however, proposes different structured mechanisms of the vertical transportation systems or VTS embedded on a shuffled frog leaping-based approach. There are three VTS scenarios, a motion reaching a normal operating velocity, and both reaching and not reaching transitional motion. These variants were performed to simultaneously inspect multiple responses affected by machining parameters in multi-pass turning processes. The numerical results of two machining optimisation problems demonstrated the high performance measures of the proposed methods, when compared to other optimisation algorithms for an actual deep cut design.

Residual Shuffling Convolutional Neural Networks for Deep Semantic Image Segmentation Using Multi-Modal Data

NASA Astrophysics Data System (ADS)

Chen, K.; Weinmann, M.; Gao, X.; Yan, M.; Hinz, S.; Jutzi, B.; Weinmann, M.

2018-05-01

In this paper, we address the deep semantic segmentation of aerial imagery based on multi-modal data. Given multi-modal data composed of true orthophotos and the corresponding Digital Surface Models (DSMs), we extract a variety of hand-crafted radiometric and geometric features which are provided separately and in different combinations as input to a modern deep learning framework. The latter is represented by a Residual Shuffling Convolutional Neural Network (RSCNN) combining the characteristics of a Residual Network with the advantages of atrous convolution and a shuffling operator to achieve a dense semantic labeling. Via performance evaluation on a benchmark dataset, we analyze the value of different feature sets for the semantic segmentation task. The derived results reveal that the use of radiometric features yields better classification results than the use of geometric features for the considered dataset. Furthermore, the consideration of data on both modalities leads to an improvement of the classification results. However, the derived results also indicate that the use of all defined features is less favorable than the use of selected features. Consequently, data representations derived via feature extraction and feature selection techniques still provide a gain if used as the basis for deep semantic segmentation.

Biometrics based key management of double random phase encoding scheme using error control codes

NASA Astrophysics Data System (ADS)

Saini, Nirmala; Sinha, Aloka

2013-08-01

In this paper, an optical security system has been proposed in which key of the double random phase encoding technique is linked to the biometrics of the user to make it user specific. The error in recognition due to the biometric variation is corrected by encoding the key using the BCH code. A user specific shuffling key is used to increase the separation between genuine and impostor Hamming distance distribution. This shuffling key is then further secured using the RSA public key encryption to enhance the security of the system. XOR operation is performed between the encoded key and the feature vector obtained from the biometrics. The RSA encoded shuffling key and the data obtained from the XOR operation are stored into a token. The main advantage of the present technique is that the key retrieval is possible only in the simultaneous presence of the token and the biometrics of the user which not only authenticates the presence of the original input but also secures the key of the system. Computational experiments showed the effectiveness of the proposed technique for key retrieval in the decryption process by using the live biometrics of the user.

Strain improvement of Sporolactobacillus inulinus ATCC 15538 for acid tolerance and production of D-lactic acid by genome shuffling.

PubMed

Zheng, Huijie; Gong, Jixian; Chen, Tao; Chen, Xun; Zhao, Xueming

2010-02-01

Improvement of acid tolerance and production of D-lactic acid by Sporolactobacillus inulinus ATCC 15538 was performed by using recursive protoplast fusion in a genome shuffling format. The starting population was generated by ultraviolet irradiation, diethyl sulfate mutagenesis, and pH-gradient filter and then, subjected for the recursive protoplast fusion. The concentration of lysozyme, time, and temperature for enzyme treatment were optimized by response surface methodology based on the central composite design. Based on contour plots and variance analysis, the model predicted a maximum Y (multiply protoplasts formation ratio by protoplasts regeneration ratio), 60.4%, and the corresponding above used values were 7.75 mg/ml lysozyme, 1.59 h, and 38 degrees C. A pH-5-resistant recombinant, F3-4, was obtained after three rounds of genome shuffling and its production of D-lactic acid reached 93.4 g/l in a 5 L bioreactor, which was increased by 39.8% and 119% in comparison with that of UV generated strain and the original strain S. inulinus ATCC 15538, respectively. The subculture experiments indicated that F3-4 was genetically stable.

Anthropogenic climate change drives shift and shuffle in North Atlantic phytoplankton communities.

PubMed

Barton, Andrew D; Irwin, Andrew J; Finkel, Zoe V; Stock, Charles A

2016-03-15

Anthropogenic climate change has shifted the biogeography and phenology of many terrestrial and marine species. Marine phytoplankton communities appear sensitive to climate change, yet understanding of how individual species may respond to anthropogenic climate change remains limited. Here, using historical environmental and phytoplankton observations, we characterize the realized ecological niches for 87 North Atlantic diatom and dinoflagellate taxa and project changes in species biogeography between mean historical (1951-2000) and future (2051-2100) ocean conditions. We find that the central positions of the core range of 74% of taxa shift poleward at a median rate of 12.9 km per decade (km⋅dec(-1)), and 90% of taxa shift eastward at a median rate of 42.7 km⋅dec(-1) The poleward shift is faster than previously reported for marine taxa, and the predominance of longitudinal shifts is driven by dynamic changes in multiple environmental drivers, rather than a strictly poleward, temperature-driven redistribution of ocean habitats. A century of climate change significantly shuffles community composition by a basin-wide median value of 16%, compared with seasonal variations of 46%. The North Atlantic phytoplankton community appears poised for marked shift and shuffle, which may have broad effects on food webs and biogeochemical cycles.

The Fractal Patterns of Words in a Text: A Method for Automatic Keyword Extraction.

PubMed

Najafi, Elham; Darooneh, Amir H

2015-01-01

A text can be considered as a one dimensional array of words. The locations of each word type in this array form a fractal pattern with certain fractal dimension. We observe that important words responsible for conveying the meaning of a text have dimensions considerably different from one, while the fractal dimensions of unimportant words are close to one. We introduce an index quantifying the importance of the words in a given text using their fractal dimensions and then ranking them according to their importance. This index measures the difference between the fractal pattern of a word in the original text relative to a shuffled version. Because the shuffled text is meaningless (i.e., words have no importance), the difference between the original and shuffled text can be used to ascertain degree of fractality. The degree of fractality may be used for automatic keyword detection. Words with the degree of fractality higher than a threshold value are assumed to be the retrieved keywords of the text. We measure the efficiency of our method for keywords extraction, making a comparison between our proposed method and two other well-known methods of automatic keyword extraction.

The Fractal Patterns of Words in a Text: A Method for Automatic Keyword Extraction

PubMed Central

Najafi, Elham; Darooneh, Amir H.

2015-01-01

A text can be considered as a one dimensional array of words. The locations of each word type in this array form a fractal pattern with certain fractal dimension. We observe that important words responsible for conveying the meaning of a text have dimensions considerably different from one, while the fractal dimensions of unimportant words are close to one. We introduce an index quantifying the importance of the words in a given text using their fractal dimensions and then ranking them according to their importance. This index measures the difference between the fractal pattern of a word in the original text relative to a shuffled version. Because the shuffled text is meaningless (i.e., words have no importance), the difference between the original and shuffled text can be used to ascertain degree of fractality. The degree of fractality may be used for automatic keyword detection. Words with the degree of fractality higher than a threshold value are assumed to be the retrieved keywords of the text. We measure the efficiency of our method for keywords extraction, making a comparison between our proposed method and two other well-known methods of automatic keyword extraction. PMID:26091207

RNA damage in biological conflicts and the diversity of responding RNA repair systems

PubMed Central

Burroughs, A. Maxwell; Aravind, L.

2016-01-01

RNA is targeted in biological conflicts by enzymatic toxins or effectors. A vast diversity of systems which repair or ‘heal’ this damage has only recently become apparent. Here, we summarize the known effectors, their modes of action, and RNA targets before surveying the diverse systems which counter this damage from a comparative genomics viewpoint. RNA-repair systems show a modular organization with extensive shuffling and displacement of the constituent domains; however, a general ‘syntax’ is strongly maintained whereby systems typically contain: a RNA ligase (either ATP-grasp or RtcB superfamilies), nucleotidyltransferases, enzymes modifying RNA-termini for ligation (phosphatases and kinases) or protection (methylases), and scaffold or cofactor proteins. We highlight poorly-understood or previously-uncharacterized repair systems and components, e.g. potential scaffolding cofactors (Rot/TROVE and SPFH/Band-7 modules) with their respective cognate non-coding RNAs (YRNAs and a novel tRNA-like molecule) and a novel nucleotidyltransferase associating with diverse ligases. These systems have been extensively disseminated by lateral transfer between distant prokaryotic and microbial eukaryotic lineages consistent with intense inter-organismal conflict. Components have also often been ‘institutionalized’ for non-conflict roles, e.g. in RNA-splicing and in RNAi systems (e.g. in kinetoplastids) which combine a distinct family of RNA-acting prim-pol domains with DICER-like proteins. PMID:27536007

Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

PubMed

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2014-06-05

The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

De novo design of protein homo-oligomers with modular hydrogen bond network-mediated specificity

PubMed Central

Boyken, Scott E.; Chen, Zibo; Groves, Benjamin; Langan, Robert A.; Oberdorfer, Gustav; Ford, Alex; Gilmore, Jason; Xu, Chunfu; DiMaio, Frank; Pereira, Jose Henrique; Sankaran, Banumathi; Seelig, Georg; Zwart, Peter H.; Baker, David

2017-01-01

In nature, structural specificity in DNA and proteins is encoded quite differently: in DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen bond networks with atomic accuracy is a milestone for protein design and enables the programming of protein interaction specificity for a broad range of synthetic biology applications. PMID:27151862

De Novo Computational Design of Retro-Aldol Enzymes

PubMed Central

Jiang, Lin; Althoff, Eric A.; Clemente, Fernando R.; Doyle, Lindsey; Röthlisberger, Daniela; Zanghellini, Alexandre; Gallaher, Jasmine L.; Betker, Jamie L.; Tanaka, Fujie; Barbas, Carlos F.; Hilvert, Donald; Houk, Kendall N.; Stoddard, Barry L.; Baker, David

2012-01-01

The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, we designed retro-aldolases that use four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a nonnatural substrate. Of the 72 designs that were experimentally characterized, 32, spanning a range of protein folds, had detectable retro-aldolase activity. Designs that used an explicit water molecule to mediate proton shuffling were significantly more successful, with rate accelerations of up to four orders of magnitude and multiple turnovers, than those involving charged side-chain networks. The atomic accuracy of the design process was confirmed by the x-ray crystal structure of active designs embedded in two protein scaffolds, both of which were nearly superimposable on the design model. PMID:18323453

Simultaneous targeting of prostate stem cell antigen and prostate-specific membrane antigen improves the killing of prostate cancer cells using a novel modular T cell-retargeting system.

PubMed

Arndt, Claudia; Feldmann, Anja; Koristka, Stefanie; Cartellieri, Marc; Dimmel, Maria; Ehninger, Armin; Ehninger, Gerhard; Bachmann, Michael

2014-09-01

Recently, we described a novel modular platform technology in which T cell-recruitment and tumor-targeting domains of conventional bispecific antibodies are split to independent components, a universal effector module (EM) and replaceable monospecific/monovalent target modules (TMs) that form highly efficient T cell-retargeting complexes. Theoretically, our unique strategy should allow us to simultaneously retarget T cells to different tumor antigens by combining the EM with two or more different monovalent/monospecific TMs or even with bivalent/bispecific TMs, thereby overcoming limitations of a monospecific treatment such as the selection of target-negative tumor escape variants. In order to advance our recently introduced prostate stem cell antigen (PSCA)-specific modular system for a dual-targeting of prostate cancer cells, two additional TMs were constructed: a monovalent/monospecific TM directed against the prostate-specific membrane antigen (PSMA) and a bivalent/bispecific TM (bsTM) with specificity for PSMA and PSCA. The functionality of the novel dual-targeting strategies was analyzed by performing T cell activation and chromium release assays. Similar to the PSCA-specific modular system, the novel PSMA-specific modular system mediates an efficient target-dependent and -specific tumor cell lysis at low E:T ratios and picomolar Ab concentrations. Moreover, by combination of the EM with either the bispecific TM directed to PSMA and PSCA or both monospecifc TMs directed to either PSCA or PSMA, dual-specific targeting complexes were formed which allowed us to kill potential escape variants expressing only one or the other target antigen. Overall, the novel modular system represents a promising tool for multiple tumor targeting. © 2014 Wiley Periodicals, Inc.

Topological distortion and reorganized modular structure of gut microbial co-occurrence networks in inflammatory bowel disease

NASA Astrophysics Data System (ADS)

Baldassano, Steven N.; Bassett, Danielle S.

2016-05-01

The gut microbiome plays a key role in human health, and alterations of the normal gut flora are associated with a variety of distinct disease states. Yet, the natural dependencies between microbes in healthy and diseased individuals remain far from understood. Here we use a network-based approach to characterize microbial co-occurrence in individuals with inflammatory bowel disease (IBD) and healthy (non-IBD control) individuals. We find that microbial networks in patients with IBD differ in both global structure and local connectivity patterns. While a “core” microbiome is preserved, network topology of other densely interconnected microbe modules is distorted, with potent inflammation-mediating organisms assuming roles as integrative and highly connected inter-modular hubs. We show that while both networks display a rich-club organization, in which a small set of microbes commonly co-occur, the healthy network is more easily disrupted by elimination of a small number of key species. Further investigation of network alterations in disease might offer mechanistic insights into the specific pathogens responsible for microbiome-mediated inflammation in IBD.

Evolutionary Novelty in a Butterfly Wing Pattern through Enhancer Shuffling

PubMed Central

Pardo-Diaz, Carolina; Hanly, Joseph J.; Martin, Simon H.; Mallet, James; Dasmahapatra, Kanchon K.; Salazar, Camilo; Joron, Mathieu; Nadeau, Nicola; McMillan, W. Owen; Jiggins, Chris D.

2016-01-01

An important goal in evolutionary biology is to understand the genetic changes underlying novel morphological structures. We investigated the origins of a complex wing pattern found among Amazonian Heliconius butterflies. Genome sequence data from 142 individuals across 17 species identified narrow regions associated with two distinct red colour pattern elements, dennis and ray. We hypothesise that these modules in non-coding sequence represent distinct cis-regulatory loci that control expression of the transcription factor optix, which in turn controls red pattern variation across Heliconius. Phylogenetic analysis of the two elements demonstrated that they have distinct evolutionary histories and that novel adaptive morphological variation was created by shuffling these cis-regulatory modules through recombination between divergent lineages. In addition, recombination of modules into different combinations within species further contributes to diversity. Analysis of the timing of diversification in these two regions supports the hypothesis of introgression moving regulatory modules between species, rather than shared ancestral variation. The dennis phenotype introgressed into Heliconius melpomene at about the same time that ray originated in this group, while ray introgressed back into H. elevatus much more recently. We show that shuffling of existing enhancer elements both within and between species provides a mechanism for rapid diversification and generation of novel morphological combinations during adaptive radiation. PMID:26771987

Evolutionary Novelty in a Butterfly Wing Pattern through Enhancer Shuffling.

PubMed

Wallbank, Richard W R; Baxter, Simon W; Pardo-Diaz, Carolina; Hanly, Joseph J; Martin, Simon H; Mallet, James; Dasmahapatra, Kanchon K; Salazar, Camilo; Joron, Mathieu; Nadeau, Nicola; McMillan, W Owen; Jiggins, Chris D

2016-01-01

An important goal in evolutionary biology is to understand the genetic changes underlying novel morphological structures. We investigated the origins of a complex wing pattern found among Amazonian Heliconius butterflies. Genome sequence data from 142 individuals across 17 species identified narrow regions associated with two distinct red colour pattern elements, dennis and ray. We hypothesise that these modules in non-coding sequence represent distinct cis-regulatory loci that control expression of the transcription factor optix, which in turn controls red pattern variation across Heliconius. Phylogenetic analysis of the two elements demonstrated that they have distinct evolutionary histories and that novel adaptive morphological variation was created by shuffling these cis-regulatory modules through recombination between divergent lineages. In addition, recombination of modules into different combinations within species further contributes to diversity. Analysis of the timing of diversification in these two regions supports the hypothesis of introgression moving regulatory modules between species, rather than shared ancestral variation. The dennis phenotype introgressed into Heliconius melpomene at about the same time that ray originated in this group, while ray introgressed back into H. elevatus much more recently. We show that shuffling of existing enhancer elements both within and between species provides a mechanism for rapid diversification and generation of novel morphological combinations during adaptive radiation.

Mutation by DNA shuffling of 5-enolpyruvylshikimate-3-phosphate synthase from Malus domestica for improved glyphosate resistance.

PubMed

Tian, Yong-Sheng; Xu, Jing; Peng, Ri-He; Xiong, Ai-Sheng; Xu, Hu; Zhao, Wei; Fu, Xiao-Yan; Han, Hong-Juan; Yao, Quan-Hong

2013-09-01

A new 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene from Malus domestica (MdEPSPS) was cloned and characterized by rapid amplification of cDNA ends to identify an EPSPS gene appropriate for the development of transgenic glyphosate-tolerant plants. However, wild-type MdEPSPS is not suitable for the development of transgenic glyphosate-tolerant plants because of its poor glyphosate resistance. Thus, we performed DNA shuffling on MdEPSPS, and one highly glyphosate-resistant mutant with mutations in eight amino acids (N63D, N86S, T101A, A187T, D230G, H317R, Y399R and C413A.) was identified after five rounds of DNA shuffling and screening. Among the eight amino acid substitutions on this mutant, only two residue changes (T101A and A187T) were identified by site-directed mutagenesis as essential and additive in altering glyphosate resistance, which was further confirmed by kinetic analyses. The single-site A187T mutation has also never been previously reported as an important residue for glyphosate resistance. Furthermore, transgenic rice was used to confirm the potential of MdEPSPS mutant in developing glyphosate-resistant crops. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Antimicrobial activity predictors benchmarking analysis using shuffled and designed synthetic peptides.

PubMed

Porto, William F; Pires, Állan S; Franco, Octavio L

2017-08-07

The antimicrobial activity prediction tools aim to help the novel antimicrobial peptides (AMP) sequences discovery, utilizing machine learning methods. Such approaches have gained increasing importance in the generation of novel synthetic peptides by means of rational design techniques. This study focused on predictive ability of such approaches to determine the antimicrobial sequence activities, which were previously characterized at the protein level by in vitro studies. Using four web servers and one standalone software, we evaluated 78 sequences generated by the so-called linguistic model, being 40 designed and 38 shuffled sequences, with ∼60 and ∼25% of identity to AMPs, respectively. The ab initio molecular modelling of such sequences indicated that the structure does not affect the predictions, as both sets present similar structures. Overall, the systems failed on predicting shuffled versions of designed peptides, as they are identical in AMPs composition, which implies in accuracies below 30%. The prediction accuracy is negatively affected by the low specificity of all systems here evaluated, as they, on the other hand, reached 100% of sensitivity. Our results suggest that complementary approaches with high specificity, not necessarily high accuracy, should be developed to be used together with the current systems, overcoming their limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

A protein domain-based interactome network for C. elegans early embryogenesis

PubMed Central

Boxem, Mike; Maliga, Zoltan; Klitgord, Niels; Li, Na; Lemmens, Irma; Mana, Miyeko; de Lichtervelde, Lorenzo; Mul, Joram D.; van de Peut, Diederik; Devos, Maxime; Simonis, Nicolas; Yildirim, Muhammed A.; Cokol, Murat; Kao, Huey-Ling; de Smet, Anne-Sophie; Wang, Haidong; Schlaitz, Anne-Lore; Hao, Tong; Milstein, Stuart; Fan, Changyu; Tipsword, Mike; Drew, Kevin; Galli, Matilde; Rhrissorrakrai, Kahn; Drechsel, David; Koller, Daphne; Roth, Frederick P.; Iakoucheva, Lilia M.; Dunker, A. Keith; Bonneau, Richard; Gunsalus, Kristin C.; Hill, David E.; Piano, Fabio; Tavernier, Jan; van den Heuvel, Sander; Hyman, Anthony A.; Vidal, Marc

2008-01-01

Summary Many protein-protein interactions are mediated through independently folding modular domains. Proteome-wide efforts to model protein-protein interaction or “interactome” networks have largely ignored this modular organization of proteins. We developed an experimental strategy to efficiently identify interaction domains and generated a domain-based interactome network for proteins involved in C. elegans early embryonic cell divisions. Minimal interacting regions were identified for over 200 proteins, providing important information on their domain organization. Furthermore, our approach increased the sensitivity of the two-hybrid system, resulting in a more complete interactome network. This interactome modeling strategy revealed new insights into C. elegans centrosome function and is applicable to other biological processes in this and other organisms. PMID:18692475

Foot pressure and center of pressure in athletes with ankle instability during lateral shuffling and running gait.

PubMed

Huang, P-Y; Lin, C-F; Kuo, L-C; Liao, J-C

2011-12-01

This study evaluates foot pressure and center of pressure (COP) patterns in individuals with ankle instability during running and lateral shuffling. Eleven participants with ankle instability (AI) and 11 normal subjects (Normal) performed running and lateral shuffling tasks. The outcome measures were foot progression angle, peak pressure, and displacement of COP during stance phase. During running, the foot progression angle, that is, the angle of foot abduction, was lower in the AI group (Normal: 13.46° ± 4.45°; AI: 8.78° ± 3.91°), and the 1st metatarsal contact pressure (Normal: 0.76 ± 0.47 N/cm(2)·kg; AI: 1.05 ± 0.70 N/cm(2)·kg) and the 3rd metatarsal peak pressure were higher in the AI (Normal: 0.96 ± 0.60 N/cm(2)·kg; AI: 1.54 ± 0.68 N/cm(2)·kg). The medial-lateral (M-L) COP in the late-stance phase of running for the AI group transferred faster from lateral to medial foot than the Normal group. For lateral shuffling, the AI group had greater peak pressure at the 1st (Normal: 0.76 ± 0.67 N/cm(2)·kg; AI: 1.49 ± 1.04 N/cm(2)·kg), 2nd (Normal: 0.57 ± 0.39 N/cm(2)·kg; AI: 0.87 ± 0.68 N/cm(2)·kg), 3rd (Normal: 0.70 ± 0.54 N/cm(2)·kg; AI: 1.42 ± 0.87 N/cm(2)·kg), and 4th (Normal: 0.52 ± 0.38 N/cm(2)·kg; AI: 1.12 ± 0.78 N/cm(2)·kg) metatarsal areas than the Normal group. The M-L COP located more laterally from the early to mid-stance phase in the AI compared with the Normal group. The findings suggest that COP displacement during lateral shuffle may be a factor in ankle instability while the foot progression angle during running may be a compensatory strategy. © 2011 John Wiley & Sons A/S.

Interspecies Interactions Determine the Impact of the Gut Microbiota on Nutrient Allocation in Drosophila melanogaster

PubMed Central

Douglas, Angela E.

2014-01-01

The animal gut is perpetually exposed to microorganisms, and this microbiota affects development, nutrient allocation, and immune homeostasis. A major challenge is to understand the contribution of individual microbial species and interactions among species in shaping these microbe-dependent traits. Using the Drosophila melanogaster gut microbiota, we tested whether microbe-dependent performance and nutritional traits of Drosophila are functionally modular, i.e., whether the impact of each microbial taxon on host traits is independent of the presence of other microbial taxa. Gnotobiotic flies were constructed with one or a set of five of the Acetobacter and Lactobacillus species which dominate the gut microbiota of conventional flies (Drosophila with untreated microbiota). Axenic (microbiota-free) flies exhibited prolonged development time and elevated glucose and triglyceride contents. The low glucose content of conventional flies was recapitulated in gnotobiotic Drosophila flies colonized with any of the 5 bacterial taxa tested. In contrast, the development rates and triglyceride levels in monocolonized flies varied depending on the taxon present: Acetobacter species supported the largest reductions, while most Lactobacillus species had no effect. Only flies with both Acetobacter and Lactobacillus had triglyceride contents restored to the level in conventional flies. This could be attributed to two processes: Lactobacillus-mediated promotion of Acetobacter abundance in the fly and a significant negative correlation between fly triglyceride content and Acetobacter abundance. We conclude that the microbial basis of host traits varies in both specificity and modularity; microbe-mediated reduction in glucose is relatively nonspecific and modular, while triglyceride content is influenced by interactions among microbes. PMID:24242251

Psychoeducation as a Mediator of Treatment Approach on Parent Engagement in Child Psychotherapy for Disruptive Behavior.

PubMed

Martinez, Jonathan I; Lau, Anna S; Chorpita, Bruce F; Weisz, John R

2017-01-01

Parent engagement in treatment for child disruptive behavior has been associated with improved child outcomes in care. However, many families who enter care do not receive an adequate dose of treatment, and parents are often not involved. We examined therapists' use of psychoeducation, a therapeutic practice used to present factual information about target problems and treatments, and its association with parent engagement in child psychotherapy. Participants were drawn from the Child System and Treatment Enhancement Projects' multisite trial contrasting standard evidence-based treatments, modular treatment, or usual care. We included an ethnically diverse sample of 46 youth (ages 7-13) who received treatment for disruptive behavior in modular treatment or usual care. A reliable observational coding system was developed to assess therapists' in-session use of psychoeducation strategies (e.g., discussing causes of misbehavior, describing and providing rationale for treatment, etc.), as well as other engagement strategies (e.g., collaborative goal setting, managing expectations, etc.), in the early phase of treatment. Findings revealed that modular treatment therapists provided more psychoeducation and other engagement strategies compared with usual care therapists. Furthermore, psychoeducation strategies employed by therapists early on uniquely predicted subsequent parent involvement in treatment, over and above the use of other engagement strategies. Finally, therapists' use of the psychoeducation strategy of discussing causes of child's misbehavior mediated the effect of treatment condition on parent involvement in their child's therapy. These findings suggest that the implementation of psychoeducation strategies upon entry into care promotes parent involvement in child psychotherapy for disruptive behavior.

Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines.

PubMed

Porciani, David; Cardwell, Leah N; Tawiah, Kwaku D; Alam, Khalid K; Lange, Margaret J; Daniels, Mark A; Burke, Donald H

2018-06-11

Large RNAs and ribonucleoprotein complexes have powerful therapeutic potential, but effective cell-targeted delivery tools are limited. Aptamers that internalize into target cells can deliver siRNAs (<15 kDa, 19-21 nt/strand). We demonstrate a modular nanostructure for cellular delivery of large, functional RNA payloads (50-80 kDa, 175-250 nt) by aptamers that recognize multiple human B cell cancer lines and transferrin receptor-expressing cells. Fluorogenic RNA reporter payloads enable accelerated testing of platform designs and rapid evaluation of assembly and internalization. Modularity is demonstrated by swapping in different targeting and payload aptamers. Both modules internalize into leukemic B cell lines and remained colocalized within endosomes. Fluorescence from internalized RNA persists for ≥2 h, suggesting a sizable window for aptamer payloads to exert influence upon targeted cells. This demonstration of aptamer-mediated, cell-internalizing delivery of large RNAs with retention of functional structure raises the possibility of manipulating endosomes and cells by delivering large aptamers and regulatory RNAs.

Modular Activating Receptors in Innate and Adaptive Immunity.

PubMed

Berry, Richard; Call, Matthew E

2017-03-14

Triggering of cell-mediated immunity is largely dependent on the recognition of foreign or abnormal molecules by a myriad of cell surface-bound receptors. Many activating immune receptors do not possess any intrinsic signaling capacity but instead form noncovalent complexes with one or more dimeric signaling modules that communicate with a common set of kinases to initiate intracellular information-transfer pathways. This modular architecture, where the ligand binding and signaling functions are detached from one another, is a common theme that is widely employed throughout the innate and adaptive arms of immune systems. The evolutionary advantages of this highly adaptable platform for molecular recognition are visible in the variety of ligand-receptor interactions that can be linked to common signaling pathways, the diversification of receptor modules in response to pathogen challenges, and the amplification of cellular responses through incorporation of multiple signaling motifs. Here we provide an overview of the major classes of modular activating immune receptors and outline the current state of knowledge regarding how these receptors assemble, recognize their ligands, and ultimately trigger intracellular signal transduction pathways that activate immune cell effector functions.

Mediator: A key regulator of plant development.

PubMed

Buendía-Monreal, Manuel; Gillmor, C Stewart

2016-11-01

Mediator is a multiprotein complex that regulates transcription at the level of RNA pol II assembly, as well as through regulation of chromatin architecture, RNA processing and recruitment of epigenetic marks. Though its modular structure is conserved in eukaryotes, its subunit composition has diverged during evolution and varies in response to environmental and tissue-specific inputs, suggesting different functions for each subunit and/or Mediator conformation. In animals, Mediator has been implicated in the control of differentiation and morphogenesis through modulation of numerous signaling pathways. In plants, studies have revealed roles for Mediator in regulation of cell division, cell fate and organogenesis, as well as developmental timing and hormone responses. We begin this review with an overview of biochemical mechanisms of yeast and animal Mediator that are likely to be conserved in all eukaryotes, as well as a brief discussion of the role of Mediator in animal development. We then present a comprehensive review of studies of the role of Mediator in plant development. Finally, we point to important questions for future research on the role of Mediator as a master coordinator of development. Copyright © 2016 Elsevier Inc. All rights reserved.

Tracking down the path of memory: eye scanpaths facilitate retrieval of visuospatial information.

PubMed

Bochynska, Agata; Laeng, Bruno

2015-09-01

Recent research points to a crucial role of eye fixations on the same spatial locations where an item appeared when learned, for the successful retrieval of stored information (e.g., Laeng et al. in Cognition 131:263-283, 2014. doi: 10.1016/j.cognition.2014.01.003 ). However, evidence about whether the specific temporal sequence (i.e., scanpath) of these eye fixations is also relevant for the accuracy of memory remains unclear. In the current study, eye fixations were recorded while looking at a checkerboard-like pattern. In a recognition session (48 h later), animations were shown where each square that formed the pattern was presented one by one, either according to the same, idiosyncratic, temporal sequence in which they were originally viewed by each participant or in a shuffled sequence although the squares were, in both conditions, always in their correct positions. Afterward, participants judged whether they had seen the same pattern before or not. Showing the elements serially according to the original scanpath's sequence yielded a significantly better recognition performance than the shuffled condition. In a forced fixation condition, where the gaze was maintained on the center of the screen, the advantage of memory accuracy for same versus shuffled scanpaths disappeared. Concluding, gaze scanpaths (i.e., the order of fixations and not simply their positions) are functional to visual memory and physical reenacting of the original, embodied, perception can facilitate retrieval.

Comparative study on fermentation performance in the genome shuffled Candida versatilis and wild-type salt tolerant yeast strain.

PubMed

Qi, Wei; Guo, Hong-Lian; Wang, Chun-Ling; Hou, Li-Hua; Cao, Xiao-Hong; Liu, Jin-Fu; Lu, Fu-Ping

2017-01-01

The fermentation performance of a genome-shuffled strain of Candida versatilis S3-5, isolated for improved tolerance to salt, and wild-type (WT) strain were analysed. The fermentation parameters, such as growth, reducing sugar, ethanol, organic acids and volatile compounds, were detected during soy sauce fermentation process. The results showed that ethanol produced by the genome shuffled strain S3-5 was increasing at a faster rate and to a greater extent than WT. At the end of the fermentation, malic acid, citric acid and succinic acid formed in tricarboxylic acid cycle after S3-5 treatment elevated by 39.20%, 6.85% and 17.09% compared to WT, respectively. Moreover, flavour compounds such as phenethyl acetate, ethyl vanillate, ethyl acetate, isoamyl acetate, ethyl myristate, ethyl pentadecanoate, ethyl palmitate and phenylacetaldehyde produced by S3-5 were 2.26, 2.12, 2.87, 34.41, 6.32, 13.64, 2.23 and 78.85 times as compared to WT. S3-5 exhibited enhanced metabolic ability as compared to the wild-type strain, improved conversion of sugars to ethanol, metabolism of organic acid and formation of volatile compounds, especially esters, Moreover, S3-5 might be an ester-flavour type salt-tolerant yeast. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Development of a Modularized and Mediated Course Design in Altered Physiological Systems: An Exercise in Faculty Development.

ERIC Educational Resources Information Center

Garten, Edward D.

An innovative, off-campus course offered by the nursing department at Moorhead State University in Minnesota is described. The course was implemented to meet the requirements of nursing students living in rural towns located some distance from the university department of nursing. This curriculum innovation is examined as a change process that was…

Complex networks with scale-free nature and hierarchical modularity

NASA Astrophysics Data System (ADS)

Shekatkar, Snehal M.; Ambika, G.

2015-09-01

Generative mechanisms which lead to empirically observed structure of networked systems from diverse fields like biology, technology and social sciences form a very important part of study of complex networks. The structure of many networked systems like biological cell, human society and World Wide Web markedly deviate from that of completely random networks indicating the presence of underlying processes. Often the main process involved in their evolution is the addition of links between existing nodes having a common neighbor. In this context we introduce an important property of the nodes, which we call mediating capacity, that is generic to many networks. This capacity decreases rapidly with increase in degree, making hubs weak mediators of the process. We show that this property of nodes provides an explanation for the simultaneous occurrence of the observed scale-free structure and hierarchical modularity in many networked systems. This also explains the high clustering and small-path length seen in real networks as well as non-zero degree-correlations. Our study also provides insight into the local process which ultimately leads to emergence of preferential attachment and hence is also important in understanding robustness and control of real networks as well as processes happening on real networks.

Reconstitution of active human core Mediator complex reveals a pivotal role of the MED14 subunit

PubMed Central

Cevher, Murat A.; Shi, Yi; Li, Dan; Chait, Brian T.; Malik, Sohail; Roeder, Robert G.

2014-01-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here, we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to mass spectrometry (CX-MS). Whereas the reconstituted head and middle modules can stably associate, only with incorporation of MED14 into the bi-modular complex does it acquire basal and coactivator functions. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematically dissecting the multiple layers of functionalities associated with the Mediator complex. PMID:25383669

Determination of allergen specificity by heavy chains in grass pollen allergen-specific IgE antibodies.

PubMed

Gadermaier, Elisabeth; Flicker, Sabine; Lupinek, Christian; Steinberger, Peter; Valenta, Rudolf

2013-04-01

Affinity and clonality of allergen-specific IgE antibodies are important determinants for the magnitude of IgE-mediated allergic inflammation. We sought to analyze the contribution of heavy and light chains of human allergen-specific IgE antibodies for allergen specificity and to test whether promiscuous pairing of heavy and light chains with different allergen specificity allows binding and might affect affinity. Ten IgE Fabs specific for 3 non-cross-reactive major timothy grass pollen allergens (Phl p 1, Phl p 2, and Phl p 5) obtained by means of combinatorial cloning from patients with grass pollen allergy were used to construct stable recombinant single chain variable fragments (ScFvs) representing the original Fabs and shuffled ScFvs in which heavy chains were recombined with light chains from IgE Fabs with specificity for other allergens by using the pCANTAB 5 E expression system. Possible ancestor genes for the heavy chain and light chain variable region-encoding genes were determined by using sequence comparison with the ImMunoGeneTics database, and their chromosomal locations were determined. Recombinant ScFvs were tested for allergen specificity and epitope recognition by means of direct and sandwich ELISA, and affinity by using surface plasmon resonance experiments. The shuffling experiments demonstrate that promiscuous pairing of heavy and light chains is possible and maintains allergen specificity, which is mainly determined by the heavy chains. ScFvs consisting of different heavy and light chains exhibited different affinities and even epitope specificity for the corresponding allergen. Our results indicate that allergen specificity of allergen-specific IgE is mainly determined by the heavy chains. Different heavy and light chain pairings in allergen-specific IgE antibodies affect affinity and epitope specificity and thus might influence clinical reactivity to allergens. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Modes of Large-Scale Brain Network Organization during Threat Processing and Posttraumatic Stress Disorder Symptom Reduction during TF-CBT among Adolescent Girls.

PubMed

Cisler, Josh M; Sigel, Benjamin A; Kramer, Teresa L; Smitherman, Sonet; Vanderzee, Karin; Pemberton, Joy; Kilts, Clinton D

2016-01-01

Posttraumatic stress disorder (PTSD) is often chronic and disabling across the lifespan. The gold standard treatment for adolescent PTSD is Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT), though treatment response is variable and mediating neural mechanisms are not well understood. Here, we test whether PTSD symptom reduction during TF-CBT is associated with individual differences in large-scale brain network organization during emotion processing. Twenty adolescent girls, aged 11-16, with PTSD related to assaultive violence completed a 12-session protocol of TF-CBT. Participants completed an emotion processing task, in which neutral and fearful facial expressions were presented either overtly or covertly during 3T fMRI, before and after treatment. Analyses focused on characterizing network properties of modularity, assortativity, and global efficiency within an 824 region-of-interest brain parcellation separately during each of the task blocks using weighted functional connectivity matrices. We similarly analyzed an existing dataset of healthy adolescent girls undergoing an identical emotion processing task to characterize normative network organization. Pre-treatment individual differences in modularity, assortativity, and global efficiency during covert fear vs neutral blocks predicted PTSD symptom reduction. Patients who responded better to treatment had greater network modularity and assortativity but lesser efficiency, a pattern that closely resembled the control participants. At a group level, greater symptom reduction was associated with greater pre-to-post-treatment increases in network assortativity and modularity, but this was more pronounced among participants with less symptom improvement. The results support the hypothesis that modularized and resilient brain organization during emotion processing operate as mechanisms enabling symptom reduction during TF-CBT.

Stochastic modular analysis for gene circuits: interplay among retroactivity, nonlinearity, and stochasticity.

PubMed

Kim, Kyung Hyuk; Sauro, Herbert M

2015-01-01

This chapter introduces a computational analysis method for analyzing gene circuit dynamics in terms of modules while taking into account stochasticity, system nonlinearity, and retroactivity. (1) ANALOG ELECTRICAL CIRCUIT REPRESENTATION FOR GENE CIRCUITS: A connection between two gene circuit components is often mediated by a transcription factor (TF) and the connection signal is described by the TF concentration. The TF is sequestered to its specific binding site (promoter region) and regulates downstream transcription. This sequestration has been known to affect the dynamics of the TF by increasing its response time. The downstream effect-retroactivity-has been shown to be explicitly described in an electrical circuit representation, as an input capacitance increase. We provide a brief review on this topic. (2) MODULAR DESCRIPTION OF NOISE PROPAGATION: Gene circuit signals are noisy due to the random nature of biological reactions. The noisy fluctuations in TF concentrations affect downstream regulation. Thus, noise can propagate throughout the connected system components. This can cause different circuit components to behave in a statistically dependent manner, hampering a modular analysis. Here, we show that the modular analysis is still possible at the linear noise approximation level. (3) NOISE EFFECT ON MODULE INPUT-OUTPUT RESPONSE: We investigate how to deal with a module input-output response and its noise dependency. Noise-induced phenotypes are described as an interplay between system nonlinearity and signal noise. Lastly, we provide the comprehensive approach incorporating the above three analysis methods, which we call "stochastic modular analysis." This method can provide an analysis framework for gene circuit dynamics when the nontrivial effects of retroactivity, stochasticity, and nonlinearity need to be taken into account.

Analysis of nonuniformity in intron phase distribution.

PubMed Central

Fedorov, A; Suboch, G; Bujakov, M; Fedorova, L

1992-01-01

The distribution of different intron groups with respect to phases has been analyzed. It has been established that group II introns and nuclear introns have a minimum frequency of phase 2 introns. Since the phase of introns is an extremely conservative measure the observed minimum reflects evolutionary processes. A sample of all known, group I introns was too small to provide a valid characteristic of their phase distribution. The findings observed for the unequal distribution of phases cannot be explained solely on the basis of the mobile properties of introns. One of the most likely explanations for this nonuniformity in the intron phase distribution is the process of exon shuffling. It is proposed that group II introns originated at the early stages of evolution and were involved in the process of exon shuffling. PMID:1598214

A novel high-throughput (HTP) cloning strategy for site-directed designed chimeragenesis and mutation using the Gateway cloning system

PubMed Central

Suzuki, Yasuhiro; Kagawa, Naoko; Fujino, Toru; Sumiya, Tsuyoshi; Andoh, Taichi; Ishikawa, Kumiko; Kimura, Rie; Kemmochi, Kiyokazu; Ohta, Tsutomu; Tanaka, Shigeo

2005-01-01

There is an increasing demand for easy, high-throughput (HTP) methods for protein engineering to support advances in the development of structural biology, bioinformatics and drug design. Here, we describe an N- and C-terminal cloning method utilizing Gateway cloning technology that we have adopted for chimeric and mutant genes production as well as domain shuffling. This method involves only three steps: PCR, in vitro recombination and transformation. All three processes consist of simple handling, mixing and incubation steps. We have characterized this novel HTP method on 96 targets with >90% success. Here, we also discuss an N- and C-terminal cloning method for domain shuffling and a combination of mutation and chimeragenesis with two types of plasmid vectors. PMID:16009811

A parallel approximate string matching under Levenshtein distance on graphics processing units using warp-shuffle operations

PubMed Central

Ho, ThienLuan; Oh, Seung-Rohk

2017-01-01

Approximate string matching with k-differences has a number of practical applications, ranging from pattern recognition to computational biology. This paper proposes an efficient memory-access algorithm for parallel approximate string matching with k-differences on Graphics Processing Units (GPUs). In the proposed algorithm, all threads in the same GPUs warp share data using warp-shuffle operation instead of accessing the shared memory. Moreover, we implement the proposed algorithm by exploiting the memory structure of GPUs to optimize its performance. Experiment results for real DNA packages revealed that the performance of the proposed algorithm and its implementation archived up to 122.64 and 1.53 times compared to that of sequential algorithm on CPU and previous parallel approximate string matching algorithm on GPUs, respectively. PMID:29016700

Characterization of Monomethyihydrazine (MMH) Non-Volatile Residue

NASA Technical Reports Server (NTRS)

Davis, Chuck; Howard, Philip M.

2009-01-01

The Space Shuttle program has a unique propellant purity requirement for determination of nonvolatile residue (NVR) in monomethylhydrazine (MMH). TIis requirement differs from the Military Specification procurement specification by requiring a NVR analysis with a limit of less than or equal to 10 milligrams per liter. In June 2008, a routine MMH replenishment delivery was transferred into a NASA KSC owned tanker for future delivery to the Space Shuffle pad MMH storage tank. Per Shuffle standard operating procedure, the receiving tanker was sampled and analyzed for purity and surprisingly it failed the Shuttle use NVR specification limit. Detailed examination of the NVR revealed that it was fundamentally different than the typical MMH NVR. This paper will examine various aspects of NVR determination in MMH and the analytical characterization processes used to identify the NVR.

Transcription regulation by the Mediator complex.

PubMed

Soutourina, Julie

2018-04-01

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

A versatile modular vector system for rapid combinatorial mammalian genetics.

PubMed

Albers, Joachim; Danzer, Claudia; Rechsteiner, Markus; Lehmann, Holger; Brandt, Laura P; Hejhal, Tomas; Catalano, Antonella; Busenhart, Philipp; Gonçalves, Ana Filipa; Brandt, Simone; Bode, Peter K; Bode-Lesniewska, Beata; Wild, Peter J; Frew, Ian J

2015-04-01

Here, we describe the multiple lentiviral expression (MuLE) system that allows multiple genetic alterations to be introduced simultaneously into mammalian cells. We created a toolbox of MuLE vectors that constitute a flexible, modular system for the rapid engineering of complex polycistronic lentiviruses, allowing combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced short palindromic repeats) gene mutation, together with expression of fluorescent or enzymatic reporters for cellular assays and animal imaging. Examples of tumor engineering were used to illustrate the speed and versatility of performing combinatorial genetics using the MuLE system. By transducing cultured primary mouse cells with single MuLE lentiviruses, we engineered tumors containing up to 5 different genetic alterations, identified genetic dependencies of molecularly defined tumors, conducted genetic interaction screens, and induced the simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes. Intramuscular injection of MuLE viruses expressing oncogenic H-RasG12V together with combinations of knockdowns of the tumor suppressors cyclin-dependent kinase inhibitor 2A (Cdkn2a), transformation-related protein 53 (Trp53), and phosphatase and tensin homolog (Pten) allowed the generation of 3 murine sarcoma models, demonstrating that genetically defined autochthonous tumors can be rapidly generated and quantitatively monitored via direct injection of polycistronic MuLE lentiviruses into mouse tissues. Together, our results demonstrate that the MuLE system provides genetic power for the systematic investigation of the molecular mechanisms that underlie human diseases.

Multivariate Statistical Postprocessing of Ensemble Forcasts of Precipitation and Temperature over four River Basins in California

NASA Astrophysics Data System (ADS)

Scheuerer, Michael; Hamill, Thomas M.; Whitin, Brett; He, Minxue; Henkel, Arthur

2017-04-01

Hydrological forecasts strongly rely on predictions of precipitation amounts and temperature as meteorological inputs to hydrological models. Ensemble weather predictions provide a number of different scenarios that reflect the uncertainty about these meteorological inputs, but are often biased and underdispersive, and therefore require statistical postprocessing. In hydrological applications it is crucial that spatial and temporal (i.e. between different forecast lead times) dependencies as well as dependence between the two weather variables is adequately represented by the recalibrated forecasts. We present a study with temperature and precipitation forecasts over four river basins over California that are postprocessed with a variant of the nonhomogeneous Gaussian regression method (Gneiting et al., 2005) and the censored, shifted gamma distribution approach (Scheuerer and Hamill, 2015) respectively. For modelling spatial, temporal and inter-variable dependence we propose a variant of the Schaake Shuffle (Clark et al., 2005) that uses spatio-temporal trajectories of observed temperture and precipitation as a dependence template, and chooses the historic dates in such a way that the divergence between the marginal distributions of these trajectories and the univariate forecast distributions is minimized. For the four river basins considered in our study, this new multivariate modelling technique consistently improves upon the Schaake Shuffle and yields reliable spatio-temporal forecast trajectories of temperature and precipitation that can be used to force hydrological forecast systems. References: Clark, M., Gangopadhyay, S., Hay, L., Rajagopalan, B., Wilby, R., 2004. The Schaake Shuffle: A method for reconstructing space-time variability in forecasted precipitation and temperature fields. Journal of Hydrometeorology, 5, pp.243-262. Gneiting, T., Raftery, A.E., Westveld, A.H., Goldman, T., 2005. Calibrated probabilistic forecasting using ensemble model output statistics and minimum CRPS. Monthly Weather Review, 133, pp.1098-1118. Scheuerer, M., Hamill, T.M., 2015. Statistical postprocessing of ensemble precipitation forecasts by fitting censored, shifted gamma distributions. Monthly Weather Review, 143, pp.4578-4596. Scheuerer, M., Hamill, T.M., Whitin, B., He, M., and Henkel, A., 2016: A method for preferential selection of dates in the Schaake shuffle approach to constructing spatio-temporal forecast fields of temperature and precipitation. Water Resources Research, submitted.

A Quantum Shuffling Game for Teaching Statistical Mechanics

ERIC Educational Resources Information Center

Black, P. J.; And Others

1971-01-01

A game simulating an Einstein model of a crystal producing a Boltzmann distribution. Computer-made films present the results with large distributions showing heat flow and some applications to entropy. (TS)

Modular protein expression by RNA trans-splicing enables flexible expression of antibody formats in mammalian cells from a dual-host phage display vector.

PubMed

Shang, Yonglei; Tesar, Devin; Hötzel, Isidro

2015-10-01

A recently described dual-host phage display vector that allows expression of immunoglobulin G (IgG) in mammalian cells bypasses the need for subcloning of phage display clone inserts to mammalian vectors for IgG expression in large antibody discovery and optimization campaigns. However, antibody discovery and optimization campaigns usually need different antibody formats for screening, requiring reformatting of the clones in the dual-host phage display vector to an alternative vector. We developed a modular protein expression system mediated by RNA trans-splicing to enable the expression of different antibody formats from the same phage display vector. The heavy-chain region encoded by the phage display vector is directly and precisely fused to different downstream heavy-chain sequences encoded by complementing plasmids simply by joining exons in different pre-mRNAs by trans-splicing. The modular expression system can be used to efficiently express structurally correct IgG and Fab fragments or other antibody formats from the same phage display clone in mammalian cells without clone reformatting. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Adaptive Grouping Cloud Model Shuffled Frog Leaping Algorithm for Solving Continuous Optimization Problems

PubMed Central

Liu, Haorui; Yi, Fengyan; Yang, Heli

2016-01-01

The shuffled frog leaping algorithm (SFLA) easily falls into local optimum when it solves multioptimum function optimization problem, which impacts the accuracy and convergence speed. Therefore this paper presents grouped SFLA for solving continuous optimization problems combined with the excellent characteristics of cloud model transformation between qualitative and quantitative research. The algorithm divides the definition domain into several groups and gives each group a set of frogs. Frogs of each region search in their memeplex, and in the search process the algorithm uses the “elite strategy” to update the location information of existing elite frogs through cloud model algorithm. This method narrows the searching space and it can effectively improve the situation of a local optimum; thus convergence speed and accuracy can be significantly improved. The results of computer simulation confirm this conclusion. PMID:26819584

Intraspecific protoplast fusion of Brettanomyces anomalus for improved production of an extracellular β-glucosidase.

PubMed

Wu, Peng; Zhao, Xihong; Pan, Siyi

2014-09-03

Improvement of production of an extracellular β-glucosidase with high activity by Brettanomyces anomalus PSY-001 was performed by using recursive protoplast fusion in a genome-shuffling format. The initial population was generated by ultraviolet irradiation, ultrasonic mutagenesis and, then, subjected to recursive protoplast fusion. Mutant strains exhibiting significantly higher β-glucosidase activities in liquid media were isolated. The best mutant strain showed increased cell growth in a flask culture, as well as increased β-glucosidase production. A recombinant strain, F3-25, was obtained after three rounds of genome shuffling and its production of β-glucosidase activity reached 4790 U L -1 , which was a nearly eightfold increase compared to the original strain B. anomalus PSY-001. The subculture experiments indicated that F3-25 was genetically stable.

Intraspecific protoplast fusion of Brettanomyces anomalus for improved production of an extracellular β-glucosidase

PubMed Central

Wu, Peng; Zhao, Xihong; Pan, Siyi

2014-01-01

Improvement of production of an extracellular β-glucosidase with high activity by Brettanomyces anomalus PSY-001 was performed by using recursive protoplast fusion in a genome-shuffling format. The initial population was generated by ultraviolet irradiation, ultrasonic mutagenesis and, then, subjected to recursive protoplast fusion. Mutant strains exhibiting significantly higher β-glucosidase activities in liquid media were isolated. The best mutant strain showed increased cell growth in a flask culture, as well as increased β-glucosidase production. A recombinant strain, F3-25, was obtained after three rounds of genome shuffling and its production of β-glucosidase activity reached 4790 U L−1, which was a nearly eightfold increase compared to the original strain B. anomalus PSY-001. The subculture experiments indicated that F3-25 was genetically stable. PMID:26019572

An amodal shared resource model of language-mediated visual attention

PubMed Central

Smith, Alastair C.; Monaghan, Padraic; Huettig, Falk

2013-01-01

Language-mediated visual attention describes the interaction of two fundamental components of the human cognitive system, language and vision. Within this paper we present an amodal shared resource model of language-mediated visual attention that offers a description of the information and processes involved in this complex multimodal behavior and a potential explanation for how this ability is acquired. We demonstrate that the model is not only sufficient to account for the experimental effects of Visual World Paradigm studies but also that these effects are emergent properties of the architecture of the model itself, rather than requiring separate information processing channels or modular processing systems. The model provides an explicit description of the connection between the modality-specific input from language and vision and the distribution of eye gaze in language-mediated visual attention. The paper concludes by discussing future applications for the model, specifically its potential for investigating the factors driving observed individual differences in language-mediated eye gaze. PMID:23966967

Identification of amino acids important for substrate specificity in sucrose transporters using gene shuffling.

PubMed

Reinders, Anke; Sun, Ye; Karvonen, Kayla L; Ward, John M

2012-08-31

Plant sucrose transporters (SUTs) are H(+)-coupled uptake transporters. Type I and II (SUTs) are phylogenetically related but have different substrate specificities. Type I SUTs transport sucrose, maltose, and a wide range of natural and synthetic α- and β-glucosides. Type II SUTs are more selective for sucrose and maltose. Here, we investigated the structural basis for this difference in substrate specificity. We used a novel gene shuffling method called synthetic template shuffling to introduce 62 differentially conserved amino acid residues from type I SUTs into OsSUT1, a type II SUT from rice. The OsSUT1 variants were tested for their ability to transport the fluorescent coumarin β-glucoside esculin when expressed in yeast. Fluorescent yeast cells were selected using fluorescence-activated cell sorting (FACS). Substitution of five amino acids present in type I SUTs in OsSUT1 was found to be sufficient to confer esculin uptake activity. The changes clustered in two areas of the OsSUT1 protein: in the first loop and the top of TMS2 (T80L and A86K) and in TMS5 (S220A, S221A, and T224Y). The substrate specificity of this OsSUT1 variant was almost identical to that of type I SUTs. Corresponding changes in the sugarcane type II transporter ShSUT1 also changed substrate specificity, indicating that these residues contribute to substrate specificity in type II SUTs in general.

Identification of Amino Acids Important for Substrate Specificity in Sucrose Transporters Using Gene Shuffling*

PubMed Central

Reinders, Anke; Sun, Ye; Karvonen, Kayla L.; Ward, John M.

2012-01-01

Plant sucrose transporters (SUTs) are H+-coupled uptake transporters. Type I and II (SUTs) are phylogenetically related but have different substrate specificities. Type I SUTs transport sucrose, maltose, and a wide range of natural and synthetic α- and β-glucosides. Type II SUTs are more selective for sucrose and maltose. Here, we investigated the structural basis for this difference in substrate specificity. We used a novel gene shuffling method called synthetic template shuffling to introduce 62 differentially conserved amino acid residues from type I SUTs into OsSUT1, a type II SUT from rice. The OsSUT1 variants were tested for their ability to transport the fluorescent coumarin β-glucoside esculin when expressed in yeast. Fluorescent yeast cells were selected using fluorescence-activated cell sorting (FACS). Substitution of five amino acids present in type I SUTs in OsSUT1 was found to be sufficient to confer esculin uptake activity. The changes clustered in two areas of the OsSUT1 protein: in the first loop and the top of TMS2 (T80L and A86K) and in TMS5 (S220A, S221A, and T224Y). The substrate specificity of this OsSUT1 variant was almost identical to that of type I SUTs. Corresponding changes in the sugarcane type II transporter ShSUT1 also changed substrate specificity, indicating that these residues contribute to substrate specificity in type II SUTs in general. PMID:22807445

Domain Shuffling in a Sensor Protein Contributed to the Evolution of Insect Pathogenicity in Plant-Beneficial Pseudomonas protegens

PubMed Central

Kupferschmied, Peter; Péchy-Tarr, Maria; Imperiali, Nicola; Maurhofer, Monika; Keel, Christoph

2014-01-01

Pseudomonas protegens is a biocontrol rhizobacterium with a plant-beneficial and an insect pathogenic lifestyle, but it is not understood how the organism switches between the two states. Here, we focus on understanding the function and possible evolution of a molecular sensor that enables P. protegens to detect the insect environment and produce a potent insecticidal toxin specifically during insect infection but not on roots. By using quantitative single cell microscopy and mutant analysis, we provide evidence that the sensor histidine kinase FitF is a key regulator of insecticidal toxin production. Our experimental data and bioinformatic analyses indicate that FitF shares a sensing domain with DctB, a histidine kinase regulating carbon uptake in Proteobacteria. This suggested that FitF has acquired its specificity through domain shuffling from a common ancestor. We constructed a chimeric DctB-FitF protein and showed that it is indeed functional in regulating toxin expression in P. protegens. The shuffling event and subsequent adaptive modifications of the recruited sensor domain were critical for the microorganism to express its potent insect toxin in the observed host-specific manner. Inhibition of the FitF sensor during root colonization could explain the mechanism by which P. protegens differentiates between the plant and insect host. Our study establishes FitF of P. protegens as a prime model for molecular evolution of sensor proteins and bacterial pathogenicity. PMID:24586167

Comparison of plantar pressure distribution between three different shoes and three common movements in futsal.

PubMed

Teymouri, Meghdad; Halabchi, Farzin; Mirshahi, Maryam; Mansournia, Mohammad Ali; Mousavi Ahranjani, Ali; Sadeghi, Amir

2017-01-01

Analysis of in-shoe pressure distribution during sport-specific movements may provide a clue to improve shoe design and prevent injuries. This study compared the mean and the peak pressures over the whole foot and ten separate areas of the foot, wearing different shoes during specific movements. Nine male adult recreational futsal players performed three trials of three sport-specific movements (shuffle, sprint and penalty kick), while they were wearing three brands of futsal shoes (Adidas, Lotto and Tiger). Plantar pressures on dominant feet were collected using the F-SCAN system. Peak and mean pressures for whole foot and each separate area were extracted. For statistical analysis, the mean differences in outcome variables between different shoes and movements were estimated using random-effects regression model using STATA ver.10. In the average calculation of the three movements, the peak pressure on the whole foot in Adidas shoe was less than Lotto [8.8% (CI95%: 4.1-13.6%)] and Tiger shoes [11.8% (CI95%:7-16.7%)], (P<0.001). Also, the recorded peak pressure on the whole foot in penalty kick was 61.1% (CI95%: 56.3-65.9%) and 57.6% (CI95%: 52.8-62.3%) less than Shuffle and Sprint tests, respectively (P<0.001). Areas with the highest peak pressure during all 3 movements were not different between all shoes. This area was medial forefoot in cases of shuffle and sprint movements and medial heel in case of penalty kick.

A chimeric virus created by DNA shuffling of the capsid genes of different subtypes of porcine circovirus type 2 (PCV2) in the backbone of the non-pathogenic PCV1 induces protective immunity against the predominant PCV2b and the emerging PCV2d in pigs.

PubMed

Matzinger, Shannon R; Opriessnig, Tanja; Xiao, Chao-Ting; Catanzaro, Nicholas; Beach, Nathan M; Slade, David E; Nitzel, Gregory P; Meng, Xiang-Jin

2016-11-01

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease (PCVAD). Available commercial vaccines all target PCV2a subtype, although the circulating predominant subtype worldwide is PCV2b, and the emerging PCV2d subtype is also increasingly associated with PCVAD. Here we molecularly bred genetically-divergent strains representing PCV2a, PCV2b, PCV2c, PCV2d, and "divergent PCV2a" subtypes by DNA-shuffling of the capsid genes to produce a chimeric virus representing PCV2 global genetic diversity. When placed in the PCV2a backbone, one chimeric virus (PCV2-3cl14) induced higher neutralizing antibody titers against different PCV2 subtypes. Subsequently, a candidate vaccine (PCV1-3cl14) was produced by cloning the shuffled 3cl14 capsid into the backbone of the non-pathogenic PCV1. A vaccine efficacy study revealed that chimeric virus PCV1-3cl14 induces protective immunity against challenge with PCV2b or PCV2d in pigs. The chimeric PCV1-3cl14 virus is a strong candidate for a novel vaccine in pigs infected with variable PCV2 strains. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 38412 - Drawbridge Operation Regulations; Chicago River, Chicago, IL

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

... Shuffle 8K Run, Rock N Roll Chicago Half Marathon, Illinois Special Olympics Rubber Duck Race, Chicago Triathlon, Ready to Run Chicago Marathon, Bank of America Chicago Marathon, Men's Health Urbanathlon, and...

A synthetic biology approach for evaluating the functional contribution of designer cellulosome components to deconstruction of cellulosic substrates

PubMed Central

2013-01-01

Background Select cellulolytic bacteria produce multi-enzymatic cellulosome complexes that bind to the plant cell wall and catalyze its efficient degradation. The multi-modular interconnecting cellulosomal subunits comprise dockerin-containing enzymes that bind cohesively to cohesin-containing scaffoldins. The organization of the modules into functional polypeptides is achieved by intermodular linkers of different lengths and composition, which provide flexibility to the complex and determine its overall architecture. Results Using a synthetic biology approach, we systematically investigated the spatial organization of the scaffoldin subunit and its effect on cellulose hydrolysis by designing a combinatorial library of recombinant trivalent designer scaffoldins, which contain a carbohydrate-binding module (CBM) and 3 divergent cohesin modules. The positions of the individual modules were shuffled into 24 different arrangements of chimaeric scaffoldins. This basic set was further extended into three sub-sets for each arrangement with intermodular linkers ranging from zero (no linkers), 5 (short linkers) and native linkers of 27–35 amino acids (long linkers). Of the 72 possible scaffoldins, 56 were successfully cloned and 45 of them expressed, representing 14 full sets of chimaeric scaffoldins. The resultant 42-component scaffoldin library was used to assemble designer cellulosomes, comprising three model C. thermocellum cellulases. Activities were examined using Avicel as a pure microcrystalline cellulose substrate and pretreated cellulose-enriched wheat straw as a model substrate derived from a native source. All scaffoldin combinations yielded active trivalent designer cellulosome assemblies on both substrates that exceeded the levels of the free enzyme systems. A preferred modular arrangement for the trivalent designer scaffoldin was not observed for the three enzymes used in this study, indicating that they could be integrated at any position in the designer cellulosome without significant effect on cellulose-degrading activity. Designer cellulosomes assembled with the long-linker scaffoldins achieved higher levels of activity, compared to those assembled with short-and no-linker scaffoldins. Conclusions The results demonstrate the robustness of the cellulosome system. Long intermodular scaffoldin linkers are preferable, thus leading to enhanced degradation of cellulosic substrates, presumably due to the increased flexibility and spatial positioning of the attached enzymes in the complex. These findings provide a general basis for improved designer cellulosome systems as a platform for bioethanol production. PMID:24341331

The Conundrum of Functional Brain Networks: Small-World Efficiency or Fractal Modularity

PubMed Central

Gallos, Lazaros K.; Sigman, Mariano; Makse, Hernán A.

2012-01-01

The human brain has been studied at multiple scales, from neurons, circuits, areas with well-defined anatomical and functional boundaries, to large-scale functional networks which mediate coherent cognition. In a recent work, we addressed the problem of the hierarchical organization in the brain through network analysis. Our analysis identified functional brain modules of fractal structure that were inter-connected in a small-world topology. Here, we provide more details on the use of network science tools to elaborate on this behavior. We indicate the importance of using percolation theory to highlight the modular character of the functional brain network. These modules present a fractal, self-similar topology, identified through fractal network methods. When we lower the threshold of correlations to include weaker ties, the network as a whole assumes a small-world character. These weak ties are organized precisely as predicted by theory maximizing information transfer with minimal wiring costs. PMID:22586406

Loop models, modular invariance, and three-dimensional bosonization

NASA Astrophysics Data System (ADS)

Goldman, Hart; Fradkin, Eduardo

2018-05-01

We consider a family of quantum loop models in 2+1 spacetime dimensions with marginally long-ranged and statistical interactions mediated by a U (1 ) gauge field, both purely in 2+1 dimensions and on a surface in a (3+1)-dimensional bulk system. In the absence of fractional spin, these theories have been shown to be self-dual under particle-vortex duality and shifts of the statistical angle of the loops by 2 π , which form a subgroup of the modular group, PSL (2 ,Z ) . We show that careful consideration of fractional spin in these theories completely breaks their statistical periodicity and describe how this occurs, resolving a disagreement with the conformal field theories they appear to approach at criticality. We show explicitly that incorporation of fractional spin leads to loop model dualities which parallel the recent web of (2+1)-dimensional field theory dualities, providing a nontrivial check on its validity.

High-Dimensional Mutant and Modular Thermodynamic Cycles, Molecular Switching, and Free Energy Transduction

PubMed Central

Carter, Charles W.

2017-01-01

Understanding how distinct parts of proteins produce coordinated behavior has driven and continues to drive advances in protein science and enzymology. However, despite consensus about the conceptual basis for allostery, the idiosyncratic nature of allosteric mechanisms resists general approaches. Computational methods can identify conformational transition states from structural changes, revealing common switching mechanisms that impose multistate behavior. Thermodynamic cycles use factorial perturbations to measure coupling energies between side chains in molecular switches that mediate shear during domain motion. Such cycles have now been complemented by modular cycles that measure energetic coupling between separable domains. For one model system, energetic coupling between domains has been shown to be quantitatively equivalent to that between dynamic side chains. Linkages between domain motion, switching residues, and catalysis make nucleoside triphosphate hydrolysis conditional on domain movement, confirming an essential yet neglected aspect of free energy transduction and suggesting the potential generality of these studies. PMID:28375734

A Helitron transposon reconstructed from bats reveals a novel mechanism of genome shuffling in eukaryotes.

PubMed

Grabundzija, Ivana; Messing, Simon A; Thomas, Jainy; Cosby, Rachel L; Bilic, Ilija; Miskey, Csaba; Gogol-Döring, Andreas; Kapitonov, Vladimir; Diem, Tanja; Dalda, Anna; Jurka, Jerzy; Pritham, Ellen J; Dyda, Fred; Izsvák, Zsuzsanna; Ivics, Zoltán

2016-03-02

Helitron transposons capture and mobilize gene fragments in eukaryotes, but experimental evidence for their transposition is lacking in the absence of an isolated active element. Here we reconstruct Helraiser, an ancient element from the bat genome, and use this transposon as an experimental tool to unravel the mechanism of Helitron transposition. A hairpin close to the 3'-end of the transposon functions as a transposition terminator. However, the 3'-end can be bypassed by the transposase, resulting in transduction of flanking sequences to new genomic locations. Helraiser transposition generates covalently closed circular intermediates, suggestive of a replicative transposition mechanism, which provides a powerful means to disseminate captured transcriptional regulatory signals across the genome. Indeed, we document the generation of novel transcripts by Helitron promoter capture both experimentally and by transcriptome analysis in bats. Our results provide mechanistic insight into Helitron transposition, and its impact on diversification of gene function by genome shuffling.

Inversions and Gene Order Shuffling in Anopheles gambiae and A. funestus

NASA Astrophysics Data System (ADS)

Sharakhov, Igor V.; Serazin, Andrew C.; Grushko, Olga G.; Dana, Ali; Lobo, Neil; Hillenmeyer, Maureen E.; Westerman, Richard; Romero-Severson, Jeanne; Costantini, Carlo; Sagnon, N'Fale; Collins, Frank H.; Besansky, Nora J.

2002-10-01

In tropical Africa, Anopheles funestus is one of the three most important malaria vectors. We physically mapped 157 A. funestus complementary DNAs (cDNAs) to the polytene chromosomes of this species. Sequences of the cDNAs were mapped in silico to the A. gambiae genome as part of a comparative genomic study of synteny, gene order, and sequence conservation between A. funestus and A. gambiae. These species are in the same subgenus and diverged about as recently as humans and chimpanzees. Despite nearly perfect preservation of synteny, we found substantial shuffling of gene order along corresponding chromosome arms. Since the divergence of these species, at least 70 chromosomal inversions have been fixed, the highest rate of rearrangement of any eukaryote studied to date. The high incidence of paracentric inversions and limited colinearity suggests that locating genes in one anopheline species based on gene order in another may be limited to closely related taxa.

The zoom lens of attention: Simulating shuffled versus normal text reading using the SWIFT model

PubMed Central

Schad, Daniel J.; Engbert, Ralf

2012-01-01

Assumptions on the allocation of attention during reading are crucial for theoretical models of eye guidance. The zoom lens model of attention postulates that attentional deployment can vary from a sharp focus to a broad window. The model is closely related to the foveal load hypothesis, i.e., the assumption that the perceptual span is modulated by the difficulty of the fixated word. However, these important theoretical concepts for cognitive research have not been tested quantitatively in eye movement models. Here we show that the zoom lens model, implemented in the SWIFT model of saccade generation, captures many important patterns of eye movements. We compared the model's performance to experimental data from normal and shuffled text reading. Our results demonstrate that the zoom lens of attention might be an important concept for eye movement control in reading. PMID:22754295

Solving Energy-Aware Real-Time Tasks Scheduling Problem with Shuffled Frog Leaping Algorithm on Heterogeneous Platforms

PubMed Central

Zhang, Weizhe; Bai, Enci; He, Hui; Cheng, Albert M.K.

2015-01-01

Reducing energy consumption is becoming very important in order to keep battery life and lower overall operational costs for heterogeneous real-time multiprocessor systems. In this paper, we first formulate this as a combinatorial optimization problem. Then, a successful meta-heuristic, called Shuffled Frog Leaping Algorithm (SFLA) is proposed to reduce the energy consumption. Precocity remission and local optimal avoidance techniques are proposed to avoid the precocity and improve the solution quality. Convergence acceleration significantly reduces the search time. Experimental results show that the SFLA-based energy-aware meta-heuristic uses 30% less energy than the Ant Colony Optimization (ACO) algorithm, and 60% less energy than the Genetic Algorithm (GA) algorithm. Remarkably, the running time of the SFLA-based meta-heuristic is 20 and 200 times less than ACO and GA, respectively, for finding the optimal solution. PMID:26110406

Baseline shifts in coral skeletal oxygen isotopic composition: a signature of symbiont shuffling?

NASA Astrophysics Data System (ADS)

Carilli, J. E.; Charles, C. D.; Garren, M.; McField, M.; Norris, R. D.

2013-06-01

Decades-long records of the stable isotopic composition of coral skeletal cores were analyzed from four sites on the Mesoamerican Reef. Two of the sites exhibited baseline shifts in oxygen isotopic composition after known coral bleaching events. Changes in pH at the calcification site caused by a change in the associated symbiont community are invoked to explain the observed shift in the isotopic composition. To test the hypothesis that changes in symbiont clade could affect skeletal chemistry, additional coral samples were collected from Belize for paired Symbiodinium identification and skeletal stable isotopic analysis. We found some evidence that skeletal stable isotopic composition may be affected by symbiont clade and suggest this is an important topic for future investigation. If different Symbiodinium clades leave consistent signatures in skeletal geochemical composition, the signature will provide a method to quantify past symbiont shuffling events, important for understanding how corals are likely to respond to climate change.

Achieving Integrated Care for Older People: Shuffling the Deckchairs or Making the System Watertight For the Future?

PubMed Central

Harvey, Gill; Dollard, Joanne; Marshall, Amy; Mittinty, Manasi Murthy

2018-01-01

Integrated care has been recognised as a key initiative to resolve the issues surrounding care for older people living with multi-morbidity. Multiple strategies and policies have been implemented to increase coordination of care globally however, evidence of effectiveness remains mixed. The reasons for this are complex and multifactorial, yet many strategies deal with parts of the problem rather than taking a whole systems view with the older person clearly at the centre. This approach of fixing parts of the system may be akin to shuffling the deckchairs on the Titanic, rather than dealing with the fundamental reasons why the ship is sinking. Attempts to make the ship more watertight need to be firmly centred on the older person, pay close attention to implementation and embrace approaches that promote collaborative working between all the stakeholders involved. PMID:29626395

Fast hydrological model calibration based on the heterogeneous parallel computing accelerated shuffled complex evolution method

NASA Astrophysics Data System (ADS)

Kan, Guangyuan; He, Xiaoyan; Ding, Liuqian; Li, Jiren; Hong, Yang; Zuo, Depeng; Ren, Minglei; Lei, Tianjie; Liang, Ke

2018-01-01

Hydrological model calibration has been a hot issue for decades. The shuffled complex evolution method developed at the University of Arizona (SCE-UA) has been proved to be an effective and robust optimization approach. However, its computational efficiency deteriorates significantly when the amount of hydrometeorological data increases. In recent years, the rise of heterogeneous parallel computing has brought hope for the acceleration of hydrological model calibration. This study proposed a parallel SCE-UA method and applied it to the calibration of a watershed rainfall-runoff model, the Xinanjiang model. The parallel method was implemented on heterogeneous computing systems using OpenMP and CUDA. Performance testing and sensitivity analysis were carried out to verify its correctness and efficiency. Comparison results indicated that heterogeneous parallel computing-accelerated SCE-UA converged much more quickly than the original serial version and possessed satisfactory accuracy and stability for the task of fast hydrological model calibration.

Footprinting reveals that nogalamycin and actinomycin shuffle between DNA binding sites.

PubMed Central

Fox, K R; Waring, M J

1986-01-01

The hypothesis that sequence-selective DNA-binding antibiotics locate their preferred binding sites by a process involving migration from nonspecific sites has been tested by footprinting with DNAase I. Footprinting patterns on the tyrT DNA fragment produced by nogalamycin and actinomycin change with time after mixing the antibiotic with the DNA. Sites of protection as well as enhanced cleavage are seen to develop in a fashion which is both temperature and concentration-dependent. At certain sites cutting is transiently enhanced, then blocked. Limited evidence for slow reaction with echinomycin and mithramycin is presented, but the kinetics of footprinting with daunomycin and distamycin appear instantaneous. The feasibility of adducing direct evidence for shuffling by footprinting seems to be governed by slow dissociation of the antibiotic-DNA complex. It may also be dependent upon the mode of binding, be it intercalative or non-intercalative in character. Images PMID:2421246

Finite state model and compatibility theory - New analysis tools for permutation networks

NASA Technical Reports Server (NTRS)

Huang, S.-T.; Tripathi, S. K.

1986-01-01

A simple model to describe the fundamental operation theory of shuffle-exchange-type permutation networks, the finite permutation machine (FPM), is described, and theorems which transform the control matrix result to a continuous compatible vector result are developed. It is found that only 2n-1 shuffle exchange passes are necessary, and that 3n-3 passes are sufficient, to realize all permutations, reducing the sufficient number of passes by two from previous results. The flexibility of the approach is demonstrated by the description of a stack permutation machine (SPM) which can realize all permutations, and by showing that the FPM corresponding to the Benes (1965) network belongs to the SPM. The FPM corresponding to the network with two cascaded reverse-exchange networks is found to realize all permutations, and a simple mechanism to verify several equivalence relationships of various permutation networks is discussed.

Nod-shuffle 3D spectroscopy with PMAS

NASA Astrophysics Data System (ADS)

Roth, Martin M.; Fechner, Thomas; Becker, Thomas; Kelz, Andreas

2004-09-01

PMAS is a versatile integral field spectrograph based on the principle of a fiber-coupled lens array type of IFU. The instrument was commissioned at the Calar Alto 3.5m Telescope in May 2001. PMAS is offered as a common user instrument at Calar Alto since 2002. However, it has remained flexible enough to be used as a testbed for new observing techniques. Since the instrument is sensitive in the wavelength range from 0.35 to 1 μm, it is being used to experiment with faint object 3D spectroscopy for a variety of objects in stellar and extragalactic astronomy. Among these experiments, we have implemented a nod-shuffle mode of operation, which is a beam switching technique to achieve a high degree of sky subtraction accuracy. We describe the technical details of the special solution found for PMAS and first results obtained in test observations of faint haloes of planetary nebulae.

Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes

PubMed Central

Huang, Shengfeng; Chen, Zelin; Yan, Xinyu; Yu, Ting; Huang, Guangrui; Yan, Qingyu; Pontarotti, Pierre Antoine; Zhao, Hongchen; Li, Jie; Yang, Ping; Wang, Ruihua; Li, Rui; Tao, Xin; Deng, Ting; Wang, Yiquan; Li, Guang; Zhang, Qiujin; Zhou, Sisi; You, Leiming; Yuan, Shaochun; Fu, Yonggui; Wu, Fenfang; Dong, Meiling; Chen, Shangwu; Xu, Anlong

2014-01-01

Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE). Modern vertebrates also lost substantial transposable element (TE) diversity, whereas lancelets preserve high TE diversity that includes even the long-sought RAG transposon. Lancelets also exhibit rapid gene turnover, pervasive transcription, fastest exon shuffling in metazoans and substantial TE methylation not observed in other invertebrates. These new lancelet genome sequences provide new insights into the chordate ancestral state and the vertebrate evolution. PMID:25523484

Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes.

PubMed

Huang, Shengfeng; Chen, Zelin; Yan, Xinyu; Yu, Ting; Huang, Guangrui; Yan, Qingyu; Pontarotti, Pierre Antoine; Zhao, Hongchen; Li, Jie; Yang, Ping; Wang, Ruihua; Li, Rui; Tao, Xin; Deng, Ting; Wang, Yiquan; Li, Guang; Zhang, Qiujin; Zhou, Sisi; You, Leiming; Yuan, Shaochun; Fu, Yonggui; Wu, Fenfang; Dong, Meiling; Chen, Shangwu; Xu, Anlong

2014-12-19

Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE). Modern vertebrates also lost substantial transposable element (TE) diversity, whereas lancelets preserve high TE diversity that includes even the long-sought RAG transposon. Lancelets also exhibit rapid gene turnover, pervasive transcription, fastest exon shuffling in metazoans and substantial TE methylation not observed in other invertebrates. These new lancelet genome sequences provide new insights into the chordate ancestral state and the vertebrate evolution.

Comparison of plantar pressure distribution between three different shoes and three common movements in futsal

PubMed Central

Teymouri, Meghdad; Mirshahi, Maryam; Mansournia, Mohammad Ali; Mousavi Ahranjani, Ali; Sadeghi, Amir

2017-01-01

Introduction Analysis of in-shoe pressure distribution during sport-specific movements may provide a clue to improve shoe design and prevent injuries. This study compared the mean and the peak pressures over the whole foot and ten separate areas of the foot, wearing different shoes during specific movements. Methods Nine male adult recreational futsal players performed three trials of three sport-specific movements (shuffle, sprint and penalty kick), while they were wearing three brands of futsal shoes (Adidas, Lotto and Tiger). Plantar pressures on dominant feet were collected using the F-SCAN system. Peak and mean pressures for whole foot and each separate area were extracted. For statistical analysis, the mean differences in outcome variables between different shoes and movements were estimated using random-effects regression model using STATA ver.10. Results In the average calculation of the three movements, the peak pressure on the whole foot in Adidas shoe was less than Lotto [8.8% (CI95%: 4.1–13.6%)] and Tiger shoes [11.8% (CI95%:7–16.7%)], (P<0.001). Also, the recorded peak pressure on the whole foot in penalty kick was 61.1% (CI95%: 56.3–65.9%) and 57.6% (CI95%: 52.8–62.3%) less than Shuffle and Sprint tests, respectively (P<0.001). Conclusion Areas with the highest peak pressure during all 3 movements were not different between all shoes. This area was medial forefoot in cases of shuffle and sprint movements and medial heel in case of penalty kick. PMID:29088278

The episodic evolution of fibritin: traces of ancient global environmental alterations may remain in the genomes of T4-like phages

PubMed Central

Letarov, A V; Krisch, H M

2013-01-01

The evolutionary adaptation of bacteriophages to their environment is achieved by alterations of their genomes involving a combination of both point mutations and lateral gene transfer. A phylogenetic analysis of a large set of collar fiber protein (fibritin) loci from diverse T4-like phages indicates that nearly all the modular swapping involving the C-terminal domain of this gene occurred in the distant past and has since ceased. In phage T4, this fibritin domain encodes the sequence that mediates both the attachment of the long tail fibers to the virion and also controls, in an environmentally sensitive way, the phage's ability to infect its host bacteria. Subsequent to its distant period of modular exchange, the evolution of fibritin has proceeded primarily by the slow vertical divergence mechanism. We suggest that ancient and sudden changes in the environment forced the T4-like phages to alter fibritin's mode of action or function. The genome's response to such episodes of rapid environmental change could presumably only be achieved quickly enough by employing the modular evolution mechanism. A phylogenetic analysis of the fibritin locus reveals the possible traces of such events within the T4 superfamily's genomes. PMID:24223296

MOCASSIN-prot: A multi-objective clustering approach for protein similarity networks

USDA-ARS?s Scientific Manuscript database

Motivation: Proteins often include multiple conserved domains. Various evolutionary events including duplication and loss of domains, domain shuffling, as well as sequence divergence contribute to generating complexities in protein structures, and consequently, in their functions. The evolutionary h...

A Healthy Brain in a Healthy Body: Brain Network Correlates of Physical and Mental Fitness

PubMed Central

Douw, Linda; Nieboer, Dagmar; van Dijk, Bob W.; Stam, Cornelis J.; Twisk, Jos W. R.

2014-01-01

A healthy lifestyle is an important focus in today's society. The physical benefits of regular exercise are abundantly clear, but physical fitness is also associated with better cognitive performance. How these two factors together relate to characteristics of the brain is still incompletely understood. By applying mathematical concepts from ‘network theory’, insights in the organization and dynamics of brain functioning can be obtained. We test the hypothesis that neural network organization mediates the association between cardio respiratory fitness (i.e. VO2 max) and cognitive functioning. A healthy cohort was studied (n = 219, 113 women, age range 41–44 years). Subjects underwent resting-state eyes-closed magneto-encephalography (MEG). Five artifact-free epochs were analyzed and averaged in six frequency bands (delta-gamma). The phase lag index (PLI) was used as a measure of functional connectivity between all sensors. Modularity analysis was performed, and both within and between-module connectivity of each sensor was calculated. Subjects underwent a maximum oxygen uptake (VO2 max) measurement as an indicator of cardio respiratory fitness. All subjects were tested with a commonly used Dutch intelligence test. Intelligence quotient (IQ) was related to VO2 max. In addition, VO2 max was negatively associated with upper alpha and beta band modularity. Particularly increased intermodular connectivity in the beta band was associated with higher VO2 max and IQ, further indicating a benefit of more global network integration as opposed to local connections. Within-module connectivity showed a spatially varied pattern of correlation, while average connectivity did not show significant results. Mediation analysis was not significant. The occurrence of less modularity in the resting-state is associated with better cardio respiratory fitness, while having increased intermodular connectivity, as opposed to within-module connections, is related to better physical and mental fitness. PMID:24498438

Genome-wide association of mediator and RNA polymerase II in wild-type and mediator mutant yeast.

PubMed

Paul, Emily; Zhu, Z Iris; Landsman, David; Morse, Randall H

2015-01-01

Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genome-Wide Association of Mediator and RNA Polymerase II in Wild-Type and Mediator Mutant Yeast

PubMed Central

Paul, Emily; Zhu, Z. Iris

2014-01-01

Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences. PMID:25368384

Cytosolic delivery of multi-domain cargos by the N-terminus of Pasteurella multocida toxin.

PubMed

Clemons, Nathan C; Bannai, Yuka; Haywood, Elizabeth E; Xu, Yiting; Buschbach, James D; Ho, Mengfei; Wilson, Brenda A

2018-05-21

The zoonotic pathogen Pasteurella multocida produces a 146-kDa modular toxin (PMT) that enters host cells and manipulates intracellular signaling through action on its Gα-protein targets. The N-terminus of PMT (PMT-N) mediates cellular uptake through receptor-mediated endocytosis, followed by delivery of the C-terminal catalytic domain from acidic endosomes into the cytosol. The putative native cargo of PMT consists of a 710-residue polypeptide of three distinct modular subdomains (C1-C2-C3), where C1 contains a membrane localization domain (MLD), C2 has as-of-yet undefined function, and C3 catalyzes deamidation of a specific active-site glutamine residue in Gα-protein targets. However, whether the three cargo subdomains are delivered intact or undergo further proteolytic processing during or after translocation from the late endosome is unclear. Here, we demonstrate that PMT-N mediates delivery of its native C-terminal cargo as a single polypeptide, corresponding to C1-C2-C3, including the MLD, with no evidence of cleavage between subdomains. We show that PMT-N also delivers into the cytosol non-native GFP cargo, further supporting that the receptor-binding and translocation functions reside within PMT-N. Our findings further show that PMT-N can deliver C1-C2 alone but that the presence of C1-C2 is important for cytosolic delivery of the catalytic C3 subdomain by PMT-N. In addition, we further refine the minimum C3 domain required for intracellular activity as comprising residues 1105-1278. These findings reinforce that PMT-N serves as the cytosolic delivery vehicle for C-terminal cargo and demonstrate that its native cargo is delivered intact as C1-C2-C3. Copyright © 2018 American Society for Microbiology.

Modular MLV-VLPs co-displaying ovalbumin peptides and GM-CSF effectively induce expansion of CD11b+ APC and antigen-specific T cell responses in vitro.

PubMed

Gogesch, Patricia; Schülke, Stefan; Scheurer, Stephan; Mühlebach, Michael D; Waibler, Zoe

2018-05-28

The development of novel vaccination strategies is a persistent challenge to provide effective prophylactic treatments to encounter viral infections. In general, the physical conjugation of selected vaccine components, e.g. antigen and adjuvant, has been shown to enhance the immunogenicity and hence, can increase effectiveness of the vaccine. In our proof-of-concept study, we generated non-infectious, replication deficient Murine Leukemia Virus (MLV)-derived virus-like particles (VLPs) that physically link antigen and adjuvant in a modular fashion by co-displaying them on their surface. For this purpose, we selected the immunodominant peptides of the model antigen ovalbumin (OVA) and the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) as non-classical adjuvant. Our results show that murine GM-CSF displayed on MLV-VLPs mediates expansion and proliferation of CD11b + cells within murine bone marrow and total spleen cells. Moreover, we show increased immunogenicity of modular VLPs co-displaying OVA peptides and GM-CSF by their elevated capacity to induce OVA-specific T cell-activation and -proliferation within OT-I and OT-II splenocyte cultures. These enhanced effects were not achieved by using an equimolar mixture of VLPs displaying either OVA or GM-CSF. Taken together, OVA and GM-CSF co-displaying MLV-VLPs are able to target and expand antigen presenting cells which in turn results in enhanced antigen-specific T cell activation and proliferation in vitro. These data suggest MLV-VLPs to be an attractive platform to flexibly combine antigen and adjuvant for novel modular vaccination approaches. Copyright © 2018 Elsevier Ltd. All rights reserved.

Directed evolution of glutathione transferases towards a selective glutathione-binding site and improved oxidative stability.

PubMed

Axarli, Irine; Muleta, Abdi W; Chronopoulou, Evangelia G; Papageorgiou, Anastassios C; Labrou, Nikolaos E

2017-01-01

Glutathione transferases (GSTs) are a family of detoxification enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic compounds. A library of alpha class GSTs was constructed by DNA shuffling using the DNA encoding the human glutathione transferase A1-1 (hGSTA1-1) and the rat glutathione transferase A1-1 (rGSTA1-1). Activity screening of the library allowed the selection of a chimeric enzyme variant (GSTD4) that displayed high affinity towards GSH and GSH-Sepharose affinity adsorbent, higher k cat /K m and improved thermal stability, compared to the parent enzymes. The crystal structures of the GSTD4 enzyme in free form and in complex with GSH were determined to 1.6Šand 2.3Šresolution, respectively. Analysis of the GSTD4 structure showed subtle conformational changes in the GSH-binding site and in electron-sharing network that may contribute to the increased GSH affinity. The shuffled variant GSTD4 was further optimized for improved oxidative stability employing site-saturation mutagenesis. The Cys112Ser mutation confers optimal oxidative stability and kinetic properties in the GSTD4 enzyme. DNA shuffling allowed the creation of a chimeric enzyme variant with improved properties, compared to the parent enzymes. X-ray crystallography shed light on how recombination of a specific segment from homologous GSTA1-1 together with point mutations gives rise to a new functionally competent enzyme with improved binding, catalytic properties and stability. Such an engineered GST would be useful in biotechnology as affinity tool in affinity chromatography as well as a biocatalytic matrix for the construction of biochips or enzyme biosensors. Copyright © 2016 Elsevier B.V. All rights reserved.

Scaling behaviors of precipitation over China

NASA Astrophysics Data System (ADS)

Jiang, Lei; Li, Nana; Zhao, Xia

2017-04-01

Scaling behaviors in the precipitation time series derived from 1951 to 2009 over China are investigated by detrended fluctuation analysis (DFA) method. The results show that there exists long-term memory for the precipitation time series in some stations, where the values of the scaling exponent α are less than 0.62, implying weak persistence characteristics. The values of scaling exponent in other stations indicate random behaviors. In addition, the scaling exponent α in precipitation records varies from station to station over China. A numerical test is made to verify the significance in DFA exponents by shuffling the data records many times. We think it is significant when the values of scaling exponent before shuffled precipitation records are larger than the interval threshold for 95 % confidence level after shuffling precipitation records many times. By comparison, the daily precipitation records exhibit weak positively long-range correlation in a power law fashion mainly at the stations taking on zonal distributions in south China, upper and middle reaches of the Yellow River, northern part of northeast China. This may be related to the subtropical high. Furthermore, the values of scaling exponent which cannot pass the significance test do not show a clear distribution pattern. It seems that the stations are mainly distributed in coastal areas, southwest China, and southern part of north China. In fact, many complicated factors may affect the scaling behaviors of precipitation such as the system of the east and south Asian monsoon, the interaction between sea and land, and the big landform of the Tibetan Plateau. These results may provide a better prerequisite to long-term predictor of precipitation time series for different regions over China.

A Novel Strategy to Construct Yeast Saccharomyces cerevisiae Strains for Very High Gravity Fermentation

PubMed Central

Liu, Tianzhe; Wang, Pinmei; Zhao, Wenpeng; Zhu, Muyuan; Jiang, Xinhang; Zhao, Yuhua; Wu, Xuechang

2012-01-01

Very high gravity (VHG) fermentation is aimed to considerably increase both the fermentation rate and the ethanol concentration, thereby reducing capital costs and the risk of bacterial contamination. This process results in critical issues, such as adverse stress factors (ie., osmotic pressure and ethanol inhibition) and high concentrations of metabolic byproducts which are difficult to overcome by a single breeding method. In the present paper, a novel strategy that combines metabolic engineering and genome shuffling to circumvent these limitations and improve the bioethanol production performance of Saccharomyces cerevisiae strains under VHG conditions was developed. First, in strain Z5, which performed better than other widely used industrial strains, the gene GPD2 encoding glycerol 3-phosphate dehydrogenase was deleted, resulting in a mutant (Z5ΔGPD2) with a lower glycerol yield and poor ethanol productivity. Second, strain Z5ΔGPD2 was subjected to three rounds of genome shuffling to improve its VHG fermentation performance, and the best performing strain SZ3-1 was obtained. Results showed that strain SZ3-1 not only produced less glycerol, but also increased the ethanol yield by up to 8% compared with the parent strain Z5. Further analysis suggested that the improved ethanol yield in strain SZ3-1 was mainly contributed by the enhanced ethanol tolerance of the strain. The differences in ethanol tolerance between strains Z5 and SZ3-1 were closely associated with the cell membrane fatty acid compositions and intracellular trehalose concentrations. Finally, genome rearrangements in the optimized strain were confirmed by karyotype analysis. Hence, a combination of genome shuffling and metabolic engineering is an efficient approach for the rapid improvement of yeast strains for desirable industrial phenotypes. PMID:22363590

Design and characterizations of two novel cellulases through single-gene shuffling of Cel12A (EG3) gene from Trichoderma reseei.

PubMed

Yenenler, Asli; Sezerman, Osman Ugur

2016-06-01

Cellulases have great potential to be widely used for industrial applications. In general, naturally occurring cellulases are not optimized and limited to meet the industrial needs. These limitations lead to demand for novel cellulases with enhanced enzymatic properties. Here, we describe the enzymatic and structural properties of two novel enzymes, EG3_S1 and EG3_S2, obtained through the single-gene shuffling approach of Cel12A(EG3) gene from Trichoderma reseei EG3_S1 and EG3_S2 shuffled enzymes display 59 and 75% identity in protein sequence with respect to native, respectively. Toward 4-MUC, the minimum activity of EG3_S1 was reported as 5.9-fold decrease in native at 35°C, whereas the maximum activity of EG3_S2 was reported as 15.4-fold increase in native activity at 40°C. Also, the diminished enzyme activity of EG3_S1 was reported within range of 0.6- to 0.8-fold of native and within range of 0.5- to 0.7-fold of native toward CMC and Na-CMC, respectively. For EG3_S2 enzyme, the improved enzymatic activities within range of 1.1- to 1.4-fold of native and within range of 1.1- to 1.6-fold of native were reported toward CMC and Na-CMC, respectively. Moreover, we have reported 6.5-fold increase in the kcat/Km ratio of EG3_S2 with respect to native and suggested EG3_S2 enzyme as more efficient catalysis for hydrolysis reactions than its native counterpart. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

In-shoe plantar tri-axial stress profiles during maximum-effort cutting maneuvers.

PubMed

Cong, Yan; Lam, Wing Kai; Cheung, Jason Tak-Man; Zhang, Ming

2014-12-18

Soft tissue injuries, such as anterior cruciate ligament rupture, ankle sprain and foot skin problems, frequently occur during cutting maneuvers. These injuries are often regarded as associated with abnormal joint torque and interfacial friction caused by excessive external and in-shoe shear forces. This study simultaneously investigated the dynamic in-shoe localized plantar pressure and shear stress during lateral shuffling and 45° sidestep cutting maneuvers. Tri-axial force transducers were affixed at the first and second metatarsal heads, lateral forefoot, and heel regions in the midsole of a basketball shoe. Seventeen basketball players executed both cutting maneuvers with maximum efforts. Lateral shuffling cutting had a larger mediolateral braking force than 45° sidestep cutting. This large braking force was concentrated at the first metatarsal head, as indicated by its maximum medial shear stress (312.2 ± 157.0 kPa). During propulsion phase, peak shear stress occurred at the second metatarsal head (271.3 ± 124.3 kPa). Compared with lateral shuffling cutting, 45° sidestep cutting produced larger peak propulsion shear stress (463.0 ± 272.6 kPa) but smaller peak braking shear stress (184.8 ± 181.7 kPa), of which both were found at the first metatarsal head. During both cutting maneuvers, maximum medial and posterior shear stress occurred at the first metatarsal head, whereas maximum pressure occurred at the second metatarsal head. The first and second metatarsal heads sustained relatively high pressure and shear stress and were expected to be susceptible to plantar tissue discomfort or injury. Due to different stress distribution, distinct pressure and shear cushioning mechanisms in basketball footwear might be considered over different foot regions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estimation of beech pyrolysis kinetic parameters by Shuffled Complex Evolution.

PubMed

Ding, Yanming; Wang, Changjian; Chaos, Marcos; Chen, Ruiyu; Lu, Shouxiang

2016-01-01

The pyrolysis kinetics of a typical biomass energy feedstock, beech, was investigated based on thermogravimetric analysis over a wide heating rate range from 5K/min to 80K/min. A three-component (corresponding to hemicellulose, cellulose and lignin) parallel decomposition reaction scheme was applied to describe the experimental data. The resulting kinetic reaction model was coupled to an evolutionary optimization algorithm (Shuffled Complex Evolution, SCE) to obtain model parameters. To the authors' knowledge, this is the first study in which SCE has been used in the context of thermogravimetry. The kinetic parameters were simultaneously optimized against data for 10, 20 and 60K/min heating rates, providing excellent fits to experimental data. Furthermore, it was shown that the optimized parameters were applicable to heating rates (5 and 80K/min) beyond those used to generate them. Finally, the predicted results based on optimized parameters were contrasted with those based on the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Visual mismatch negativity indicates automatic, task-independent detection of artistic image composition in abstract artworks.

PubMed

Menzel, Claudia; Kovács, Gyula; Amado, Catarina; Hayn-Leichsenring, Gregor U; Redies, Christoph

2018-05-06

In complex abstract art, image composition (i.e., the artist's deliberate arrangement of pictorial elements) is an important aesthetic feature. We investigated whether the human brain detects image composition in abstract artworks automatically (i.e., independently of the experimental task). To this aim, we studied whether a group of 20 original artworks elicited a visual mismatch negativity when contrasted with a group of 20 images that were composed of the same pictorial elements as the originals, but in shuffled arrangements, which destroy artistic composition. We used a passive oddball paradigm with parallel electroencephalogram recordings to investigate the detection of image type-specific properties. We observed significant deviant-standard differences for the shuffled and original images, respectively. Furthermore, for both types of images, differences in amplitudes correlated with the behavioral ratings of the images. In conclusion, we show that the human brain can detect composition-related image properties in visual artworks in an automatic fashion. Copyright © 2018 Elsevier B.V. All rights reserved.

A new maximum power tracking in PV system during partially shaded conditions based on shuffled frog leap algorithm

NASA Astrophysics Data System (ADS)

Sridhar, R.; Jeevananthan, S.; Dash, S. S.; Vishnuram, Pradeep

2017-05-01

Maximum Power Point Trackers (MPPTs) are power electronic conditioners used in photovoltaic (PV) system to ensure that PV structures feed maximum power for the given ambient temperature and sun's irradiation. When the PV panels are shaded by a fraction due to any environment hindrances then, conventional MPPT trackers may fail in tracking the appropriate peak power as there will be multi power peaks. In this work, a shuffled frog leap algorithm (SFLA) is proposed and it successfully identifies the global maximum power point among other local maxima. The SFLA MPPT is compared with a well-entrenched conventional perturb and observe (P&O) MPPT algorithm and a global search particle swarm optimisation (PSO) MPPT. The simulation results reveal that the proposed algorithm is highly advantageous than P&O, as it tracks nearly 30% more power for a given shading pattern. The credible nature of the proposed SFLA is ensured when it outplays PSO MPPT in convergence. The whole system is realised in MATLAB/Simulink environment.

An Effective Hybrid Cuckoo Search Algorithm with Improved Shuffled Frog Leaping Algorithm for 0-1 Knapsack Problems

PubMed Central

Wang, Gai-Ge; Feng, Qingjiang; Zhao, Xiang-Jun

2014-01-01

An effective hybrid cuckoo search algorithm (CS) with improved shuffled frog-leaping algorithm (ISFLA) is put forward for solving 0-1 knapsack problem. First of all, with the framework of SFLA, an improved frog-leap operator is designed with the effect of the global optimal information on the frog leaping and information exchange between frog individuals combined with genetic mutation with a small probability. Subsequently, in order to improve the convergence speed and enhance the exploitation ability, a novel CS model is proposed with considering the specific advantages of Lévy flights and frog-leap operator. Furthermore, the greedy transform method is used to repair the infeasible solution and optimize the feasible solution. Finally, numerical simulations are carried out on six different types of 0-1 knapsack instances, and the comparative results have shown the effectiveness of the proposed algorithm and its ability to achieve good quality solutions, which outperforms the binary cuckoo search, the binary differential evolution, and the genetic algorithm. PMID:25404940

Cumulants, free cumulants and half-shuffles

PubMed Central

Ebrahimi-Fard, Kurusch; Patras, Frédéric

2015-01-01

Free cumulants were introduced as the proper analogue of classical cumulants in the theory of free probability. There is a mix of similarities and differences, when one considers the two families of cumulants. Whereas the combinatorics of classical cumulants is well expressed in terms of set partitions, that of free cumulants is described and often introduced in terms of non-crossing set partitions. The formal series approach to classical and free cumulants also largely differs. The purpose of this study is to put forward a different approach to these phenomena. Namely, we show that cumulants, whether classical or free, can be understood in terms of the algebra and combinatorics underlying commutative as well as non-commutative (half-)shuffles and (half-) unshuffles. As a corollary, cumulants and free cumulants can be characterized through linear fixed point equations. We study the exponential solutions of these linear fixed point equations, which display well the commutative, respectively non-commutative, character of classical and free cumulants. PMID:27547078

A computational module assembled from different protease family motifs identifies PI PLC from Bacillus cereus as a putative prolyl peptidase with a serine protease scaffold.

PubMed

Rendón-Ramírez, Adela; Shukla, Manish; Oda, Masataka; Chakraborty, Sandeep; Minda, Renu; Dandekar, Abhaya M; Ásgeirsson, Bjarni; Goñi, Félix M; Rao, Basuthkar J

2013-01-01

Proteolytic enzymes have evolved several mechanisms to cleave peptide bonds. These distinct types have been systematically categorized in the MEROPS database. While a BLAST search on these proteases identifies homologous proteins, sequence alignment methods often fail to identify relationships arising from convergent evolution, exon shuffling, and modular reuse of catalytic units. We have previously established a computational method to detect functions in proteins based on the spatial and electrostatic properties of the catalytic residues (CLASP). CLASP identified a promiscuous serine protease scaffold in alkaline phosphatases (AP) and a scaffold recognizing a β-lactam (imipenem) in a cold-active Vibrio AP. Subsequently, we defined a methodology to quantify promiscuous activities in a wide range of proteins. Here, we assemble a module which encapsulates the multifarious motifs used by protease families listed in the MEROPS database. Since APs and proteases are an integral component of outer membrane vesicles (OMV), we sought to query other OMV proteins, like phospholipase C (PLC), using this search module. Our analysis indicated that phosphoinositide-specific PLC from Bacillus cereus is a serine protease. This was validated by protease assays, mass spectrometry and by inhibition of the native phospholipase activity of PI-PLC by the well-known serine protease inhibitor AEBSF (IC50 = 0.018 mM). Edman degradation analysis linked the specificity of the protease activity to a proline in the amino terminal, suggesting that the PI-PLC is a prolyl peptidase. Thus, we propose a computational method of extending protein families based on the spatial and electrostatic congruence of active site residues.

A molecular dynamics study of tilt grain boundary resistance to slip and heat transfer in nanocrystalline silicon

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

Chen, Xiang; Chen, Youping; Xiong, Liming

2014-12-28

We present a molecular dynamics study of grain boundary (GB) resistance to dislocation-mediated slip transfer and phonon-mediated heat transfer in nanocrystalline silicon bicrystal. Three most stable 〈110〉 tilt GBs in silicon are investigated. Under mechanical loading, the nucleation and growth of hexagonal-shaped shuffle dislocation loops are reproduced. The resistances of different GBs to slip transfer are quantified through their constitutive responses. Results show that the Σ3 coherent twin boundary (CTB) in silicon exhibits significantly higher resistance to dislocation motion than the Σ9 GB in glide symmetry and the Σ19 GB in mirror symmetry. The distinct GB strengths are explained bymore » the atomistic details of the dislocation-GB interaction. Under thermal loading, based on a thermostat-induced heat pulse model, the resistances of the GBs to transient heat conduction in ballistic-diffusive regime are characterized. In contrast to the trend found in the dislocation-GB interaction in bicrystal models with different GBs, the resistances of the same three GBs to heat transfer are strikingly different. The strongest dislocation barrier Σ3 CTB is almost transparent to heat conduction, while the dislocation-permeable Σ9 and Σ19 GBs exhibit larger resistance to heat transfer. In addition, simulation results suggest that the GB thermal resistance not only depends on the GB energy but also on the detailed atomic structure along the GBs.« less

Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy.

PubMed

You, Mingxu; Zhu, Guizhi; Chen, Tao; Donovan, Michael J; Tan, Weihong

2015-01-21

The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery

NASA Astrophysics Data System (ADS)

Badeau, Barry A.; Comerford, Michael P.; Arakawa, Christopher K.; Shadish, Jared A.; Deforest, Cole A.

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Remote entanglement stabilization for modular quantum computing

NASA Astrophysics Data System (ADS)

Didier, Nicolas; Shankar, S.; Mirrahimi, M.

Quantum information processing in a modular architecture requires to distribute and stabilize entanglement in a qubit network. We present autonomous entanglement stabilization protocols between two qubits that are coupled to distant cavities. The cavities coupling is mediated and controlled via a three-wave mixing device that generates either a delocalized mode or a two-mode squeezed state between the remote cavities depending on the pump frequency. Local drives on the qubits and the cavities steer and maintain the system to the desired qubit Bell state. We show that these reservoir-engineering based protocols stabilize entanglement in presence of qubit-cavity asymmetries and losses. Most spectacularly, even a weakly-squeezed state can stabilize a maximally entangled Bell state of two distant qubits through entanglement accumulation. This research was supported by the Agence Nationale de la Recherche under Grant ANR-14-CE26-0018, by Inria's DPEI under the TAQUILLA associated team and by ARO under Grant No. W911NF-14-1-0011.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery.

PubMed

Badeau, Barry A; Comerford, Michael P; Arakawa, Christopher K; Shadish, Jared A; DeForest, Cole A

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

How to remain nonfolded and pliable: the linkers in modular α-amylases as a case study.

PubMed

Feller, Georges; Dehareng, Dominique; Lage, Jean-Luc Da

2011-07-01

The primary structure of linkers in a new class of modular α-amylases constitutes a paradigm of the structural basis that allows a polypeptide to remain nonfolded, extended and pliable. Unfolding is mediated through a depletion of hydrophobic residues and an enrichment of hydrophilic residues, amongst which Ser and Thr are over-represented. An extended and flexible conformation is promoted by the sequential arrangement of Pro and Gly, which are the most abundant residues in these linkers. This is complemented by charge repulsion, charge clustering and disulfide-bridged loops. Molecular dynamics simulations suggest the existence of conformational transitions resulting from a transient and localized hydrophobic collapse, arising from the peculiar composition of the linkers. Accordingly, these linkers should not be regarded as fully disordered, but rather as possessing various discrete structural patterns allowing them to fulfill their biological function as a free energy reservoir for concerted motions between structured domains. © 2011 The Authors Journal compilation © 2011 FEBS.

Modular evolution of phosphorylation-based signalling systems

PubMed Central

Jin, Jing; Pawson, Tony

2012-01-01

Phosphorylation sites are formed by protein kinases (‘writers’), frequently exert their effects following recognition by phospho-binding proteins (‘readers’) and are removed by protein phosphatases (‘erasers’). This writer–reader–eraser toolkit allows phosphorylation events to control a broad range of regulatory processes, and has been pivotal in the evolution of new functions required for the development of multi-cellular animals. The proteins that comprise this system of protein kinases, phospho-binding targets and phosphatases are typically modular in organization, in the sense that they are composed of multiple globular domains and smaller peptide motifs with binding or catalytic properties. The linkage of these binding and catalytic modules in new ways through genetic recombination, and the selection of particular domain combinations, has promoted the evolution of novel, biologically useful processes. Conversely, the joining of domains in aberrant combinations can subvert cell signalling and be causative in diseases such as cancer. Major inventions such as phosphotyrosine (pTyr)-mediated signalling that flourished in the first multi-cellular animals and their immediate predecessors resulted from stepwise evolutionary progression. This involved changes in the binding properties of interaction domains such as SH2 and their linkage to new domain types, and alterations in the catalytic specificities of kinases and phosphatases. This review will focus on the modular aspects of signalling networks and the mechanism by which they may have evolved. PMID:22889906

Plasmodium cysteine repeat modular proteins 1-4: complex proteins with roles throughout the malaria parasite life cycle.

PubMed

Thompson, Joanne; Fernandez-Reyes, Delmiro; Sharling, Lisa; Moore, Sally G; Eling, Wijnand M; Kyes, Sue A; Newbold, Christopher I; Kafatos, Fotis C; Janse, Chris J; Waters, Andrew P

2007-06-01

The Cysteine Repeat Modular Proteins (PCRMP1-4) of Plasmodium, are encoded by a small gene family that is conserved in malaria and other Apicomplexan parasites. They are very large, predicted surface proteins with multipass transmembrane domains containing motifs that are conserved within families of cysteine-rich, predicted surface proteins in a range of unicellular eukaryotes, and a unique combination of protein-binding motifs, including a >100 kDa cysteine-rich modular region, an epidermal growth factor-like domain and a Kringle domain. PCRMP1 and 2 are expressed in life cycle stages in both the mosquito and vertebrate. They colocalize with PfEMP1 (P. falciparum Erythrocyte Membrane Antigen-1) during its export from P. falciparum blood-stage parasites and are exposed on the surface of haemolymph- and salivary gland-sporozoites in the mosquito, consistent with a role in host tissue targeting and invasion. Gene disruption of pcrmp1 and 2 in the rodent malaria model, P. berghei, demonstrated that both are essential for transmission of the parasite from the mosquito to the mouse and has established their discrete and important roles in sporozoite targeting to the mosquito salivary gland. The unprecedented expression pattern and structural features of the PCRMPs thus suggest a variety of roles mediating host-parasite interactions throughout the parasite life cycle.

A modular Human Exposure Model (HEM) framework to ...

EPA Pesticide Factsheets

Life Cycle Impact Analysis (LCIA) has proven to be a valuable tool for systematically comparing processes and products, and has been proposed for use in Chemical Alternatives Analysis (CAA). The exposure assessment portion of the human health impact scores of LCIA has historically focused on far-field sources (environmentally mediated exposures) while research has shown that use related exposures, (near-field exposures) typically dominate population exposure. Characterizing the human health impacts of chemicals in consumer products over the life cycle of these products requires an evaluation of both near-field as well far-field sources. Assessing the impacts of the near-field exposures requires bridging the scientific and technical gaps that currently prevent the harmonious use of the best available methods and tools from the fields of LCIA and human health exposure and risk assessment. The U.S. EPA’s Chemical Safety and Sustainability LC-HEM project is developing the Human Exposure Model (HEM) to assess near-field exposures to chemicals that occur to various populations over the life cycle of a commercial product. The HEM will be a publically available, web-based, modular system which will allow for the evaluation of chemical/product impacts in a LCIA framework to support CAA. We present here an overview of the framework for the modular HEM system. The framework includes a data flow diagram of in-progress and future planned modules, the definition of each mod

Grain-size considerations for optoelectronic multistage interconnection networks.

PubMed

Krishnamoorthy, A V; Marchand, P J; Kiamilev, F E; Esener, S C

1992-09-10

This paper investigates, at the system level, the performance-cost trade-off between optical and electronic interconnects in an optoelectronic interconnection network. The specific system considered is a packet-switched, free-space optoelectronic shuffle-exchange multistage interconnection network (MIN). System bandwidth is used as the performance measure, while system area, system power, and system volume constitute the cost measures. A detailed design and analysis of a two-dimensional (2-D) optoelectronic shuffle-exchange routing network with variable grain size K is presented. The architecture permits the conventional 2 x 2 switches or grains to be generalized to larger K x K grain sizes by replacing optical interconnects with electronic wires without affecting the functionality of the system. Thus the system consists of log(k) N optoelectronic stages interconnected with free-space K-shuffles. When K = N, the MIN consists of a single electronic stage with optical input-output. The system design use an effi ient 2-D VLSI layout and a single diffractive optical element between stages to provide the 2-D K-shuffle interconnection. Results indicate that there is an optimum range of grain sizes that provides the best performance per cost. For the specific VLSI/GaAs multiple quantum well technology and system architecture considered, grain sizes larger than 256 x 256 result in a reduced performance, while grain sizes smaller than 16 x 16 have a high cost. For a network with 4096 channels, the useful range of grain sizes corresponds to approximately 250-400 electronic transistors per optical input-output channel. The effect of varying certain technology parameters such as the number of hologram phase levels, the modulator driving voltage, the minimum detectable power, and VLSI minimum feature size on the optimum grain-size system is studied. For instance, results show that using four phase levels for the interconnection hologram is a good compromise for the cost functions mentioned above. As VLSI minimum feature sizes decrease, the optimum grain size increases, whereas, if optical interconnect performance in terms of the detector power or modulator driving voltage requirements improves, the optimum grain size may be reduced. Finally, several architectural modifications to the system, such as K x K contention-free switches and sorting networks, are investigated and optimized for grain size. Results indicate that system bandwidth can be increased, but at the price of reduced performance/cost. The optoelectronic MIN architectures considered thus provide a broad range of performance/cost alternatives and offer a superior performance over purely electronic MIN's.

Theory for the Emergence of Modularity in Complex Systems

NASA Astrophysics Data System (ADS)

Deem, Michael; Park, Jeong-Man

2013-03-01

Biological systems are modular, and this modularity evolves over time and in different environments. A number of observations have been made of increased modularity in biological systems under increased environmental pressure. We here develop a theory for the dynamics of modularity in these systems. We find a principle of least action for the evolved modularity at long times. In addition, we find a fluctuation dissipation relation for the rate of change of modularity at short times. We discuss a number of biological and social systems that can be understood with this framework. The modularity of the protein-protein interaction network increases when yeast are exposed to heat shock, and the modularity of the protein-protein networks in both yeast and E. coli appears to have increased over evolutionary time. Food webs in low-energy, stressful environments are more modular than those in plentiful environments, arid ecologies are more modular during droughts, and foraging of sea otters is more modular when food is limiting. The modularity of social networks changes over time: stock brokers instant messaging networks are more modular under stressful market conditions, criminal networks are more modular under increased police pressure, and world trade network modularity has decreased

Shuffling the Operational Deck: Future Requirements for the Plans, Operations, Medical Intelligence (POMI) Community

DTIC Science & Technology

2011-04-11

countries. PepsiCo, IBM and Nike are current examples of the so-called "game planning" approach to succession and talent ~anagement.21 Annual...Rothwell and associates, inc .; a full-service consulting Succession Planning finn provides other partner industries with the value of strategic

Synthesis of Nitriles via Palladium-Catalyzed Water Shuffling from Amides to Acetonitrile

PubMed Central

Zhang, Wandi; Haskins, Christopher W.; Yang, Yang; Dai, Mingji

2014-01-01

Palladium-catalyzed synthesis of nitriles from amides has been described. Two similar, but complementary reaction conditions have been identified to convert various amides including α,β,γ,δ-unsaturated amides, cinnamides, aromatic amides and alkyl amides to the corresponding nitriles in good to excellent yield. PMID:25316145

Synthesis of nitriles via palladium-catalyzed water shuffling from amides to acetonitrile.

PubMed

Zhang, Wandi; Haskins, Christopher W; Yang, Yang; Dai, Mingji

2014-12-07

Palladium-catalyzed synthesis of nitriles from amides has been described. Two similar, but complementary reaction conditions have been identified to convert various amides including α,β,γ,δ-unsaturated amides, cinnamides, aromatic amides and alkyl amides to the corresponding nitriles in good to excellent yield.

Acoustic indicators for targeted detection of stored product and urban insect pests by inexpensive infrared, acoustic, and virbrational detection of movement

USDA-ARS?s Scientific Manuscript database

Crawling or running, scraping or shuffling, and wriggling activity of three stored-product pests, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), and Stegobium paniceum (L.) (Coleoptera: Anobiidae), and two urban pests, Blattella germanic...

Twelve Great Basketball Offenses.

ERIC Educational Resources Information Center

Healey, William A.; Hartley, Joseph W.

Features and merits of twelve offensive basketball patterns are presented in this volume. Plays described are: (1) single pivot-post offense; (2) double pivot-post offense; (3) weak-side cutter series (reverse action offense); (4) 1-3-1 offense (hi-lo offense); (5) Illinois continuity offense; (6) rotation offense; (7) shuffle offense; (8) pick…

76 FR 10378 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-24

... Disulfide Bonds in the Cytosol of E. coli Description of Technology: Many proteins of biomedical importance... of E. coli to alter the redox potential of the cytosol (such as ``Origami'' or ``Shuffle'' cells... improve the yield of correctly oxidized recombinant proteins in the cytosol of E. coli. By overproducing...

The role of somatic recombination in natural populations of the root pathogen Armillaria mellea

USDA-ARS?s Scientific Manuscript database

Fungi have evolved various mechanisms of shuffling genetic material, which can occur in the absence of fruiting and meiosis. In the homobasidiomycete Armillaria (causal agent of Armillaria root disease), the predominant vegetative stage is diploid. Diploid and haploid mycelia can fuse and undergo ka...

Revealing misassembled segments in the bovine reference genome by high resolution linkage disequilibrium scan

USDA-ARS?s Scientific Manuscript database

Misassembly signatures, created by shuffling the order of sequences while assembling a genome, can be easily seen by analyzing the unexpected behaviour of the linkage disequilibrium (LD) decay. A heuristic process was proposed to identify those misassembly signatures and presented the ones found in ...

Bacteriocins from Gram-Negative Bacteria: A Classification?

NASA Astrophysics Data System (ADS)

Rebuffat, Sylvie

Bacteria produce an arsenal of toxic peptides and proteins, which are termed bacteriocins and play a role in mediating the dynamics of microbial populations and communities. Bacteriocins from Gram-negative bacteria arise mainly from Enterobacteriaceae. They assemble into two main families: high molecular mass modular proteins (30-80 kDa) termed colicins and low molecular mass peptides (between 1 and 10 kDa) termed microcins. The production of colicins is mediated by the SOS response regulon, which plays a role in the response of many bacteria to DNA damages. Microcins are highly stable hydrophobic peptides that are produced under stress conditions, particularly nutrient depletion. Colicins and microcins are found essentially in Escherichia coli, but several other Gram-negative species also produce bacteriocin-like substances. This chapter presents the basis of a classification of colicins and microcins.

Harm mediates the disgust-immorality link.

PubMed

Schein, Chelsea; Ritter, Ryan S; Gray, Kurt

2016-09-01

Many acts are disgusting, but only some of these acts are immoral. Dyadic morality predicts that disgusting acts should be judged as immoral to the extent that they seem harmful. Consistent with this prediction, 3 studies reveal that perceived harm mediates the link between feelings of disgust and moral condemnation-even for ostensibly harmless "purity" violations. In many cases, accounting for perceived harm completely eliminates the link between disgust and moral condemnation. Analyses also reveal the predictive power of anger and typicality/weirdness in moral judgments of disgusting acts. The mediation of disgust by harm holds across diverse acts including gay marriage, sex acts, and religious blasphemy. Revealing the endogenous presence and moral relevance of harm within disgusting-but-ostensibly harmless acts argues against modular accounts of moral cognition such as moral foundations theory. Instead, these data support pluralistic conceptions of harm and constructionist accounts of morality and emotion. Implications for moral cognition and the concept of "purity" are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Survey of Modular Military Vehicles: Benefits and Burdens

DTIC Science & Technology

2016-01-01

Survey of Modular Military Vehicles: BENEFITS and BURDENS Jean M. Dasch and David J. Gorsich Modularity in military vehicle design is generally...considered a positive attribute that promotes adaptability, resilience, and cost savings. The benefits and burdens of modularity are considered by...Engineering Center, vehicles were considered based on horizontal modularity , vertical modularity , and distributed modularity . Examples were given for each

Mobile DNA and evolution in the 21st century

PubMed Central

2010-01-01

Scientific history has had a profound effect on the theories of evolution. At the beginning of the 21st century, molecular cell biology has revealed a dense structure of information-processing networks that use the genome as an interactive read-write (RW) memory system rather than an organism blueprint. Genome sequencing has documented the importance of mobile DNA activities and major genome restructuring events at key junctures in evolution: exon shuffling, changes in cis-regulatory sites, horizontal transfer, cell fusions and whole genome doublings (WGDs). The natural genetic engineering functions that mediate genome restructuring are activated by multiple stimuli, in particular by events similar to those found in the DNA record: microbial infection and interspecific hybridization leading to the formation of allotetraploids. These molecular genetic discoveries, plus a consideration of how mobile DNA rearrangements increase the efficiency of generating functional genomic novelties, make it possible to formulate a 21st century view of interactive evolutionary processes. This view integrates contemporary knowledge of the molecular basis of genetic change, major genome events in evolution, and stimuli that activate DNA restructuring with classical cytogenetic understanding about the role of hybridization in species diversification. PMID:20226073

Superbinder SH2 domains act as antagonists of cell signaling.

PubMed

Kaneko, Tomonori; Huang, Haiming; Cao, Xuan; Li, Xing; Li, Chengjun; Voss, Courtney; Sidhu, Sachdev S; Li, Shawn S C

2012-09-25

Protein-ligand interactions mediated by modular domains, which often play important roles in regulating cellular functions, are generally of moderate affinities. We examined the Src homology 2 (SH2) domain, a modular domain that recognizes phosphorylated tyrosine (pTyr) residues, to investigate how the binding affinity of a modular domain for its ligand influences the structure and cellular function of the protein. We used the phage display method to perform directed evolution of the pTyr-binding residues in the SH2 domain of the tyrosine kinase Fyn and identified three amino acid substitutions that critically affected binding. We generated three SH2 domain triple-point mutants that were "superbinders" with much higher affinities for pTyr-containing peptides than the natural domain. Crystallographic analysis of one of these superbinders revealed that the superbinder SH2 domain recognized the pTyr moiety in a bipartite binding mode: A hydrophobic surface encompassed the phenyl ring, and a positively charged site engaged the phosphate. When expressed in mammalian cells, the superbinder SH2 domains blocked epidermal growth factor receptor signaling and inhibited anchorage-independent cell proliferation, suggesting that pTyr superbinders might be explored for therapeutic applications and useful as biological research tools. Although the SH2 domain fold can support much higher affinity for its ligand than is observed in nature, our results suggest that natural SH2 domains are not optimized for ligand binding but for specificity and flexibility, which are likely properties important for their function in signaling and regulatory processes.

No Child Left Behind? Sociology Ignored!

ERIC Educational Resources Information Center

Karen, David

2005-01-01

Too many American children are segregated into schools without standards, shuffled from grade-to-grade because of their age, regard less of their knowledge. This is discrimination, pure and simple--the soft bigotry of low expectations. And our nation should treat it like other forms of discrimination. We should end it. One size does not fit all…

The Psychometric Anatomy of Two Unidimensional Workload Scales

DTIC Science & Technology

2004-10-01

for the subjects to complete. In Task I, the subject takes a deck of shuffled flashcards , each card having one of the scale’s descriptors printed on...workload scale. The size of the flashcards is somewhat arbitrary, but 2.5 by 3 inches should accommodate the length of most descriptors. Task I is

Evolution of Enzymes Required for Biodegradation of Pentachlorophenol in Sphingobium Chlorophenolicum

DTIC Science & Technology

2007-06-15

1883-1888. 3 Schopfer, L. M.; Massey, V. "Kinetic and mechanistic studies on the oxidation of the melilotate hydroxylase-2-OH- cinnamate complex by...del Cardayré. 2002. Genome shuffling of Lactobacillus for improved acid tolerance. Nature Biotechnol. 20: 707-712. 14 Zhang, Y.-X., K. Perry, V

A Water Workout Is Fun! Give It a Try!

ERIC Educational Resources Information Center

Waters, Liz

2008-01-01

When a family faces the particular challenge of a debilitating illness, disorder, or other disability that is affecting a child, life becomes complicated. Suddenly the need for medications and therapies takes center stage, and things like summer swimming lessons and lazy days poolside can get lost in the shuffle. In this article, the author…

Protecting and Expanding the Honors Budget in Hard Times

ERIC Educational Resources Information Center

Railsback, Brian

2012-01-01

In difficult budget times, especially at state colleges and universities, honors programs might seem too easy for budget-cutters to reduce, cut, or lose in the shuffle of administrative reorganization. Recent years have been financially perilous and hardly an easy time for honors programs or colleges to increase budgets. Using Western Carolina…

Efect of tri-species chromosome shuffling on agronomic and fiber traits in Upland cotton

USDA-ARS?s Scientific Manuscript database

Gossypium barbadense (L.), G. tomentosum (Seem.), G. mustelinum (Watt.) and G. darwinii (Watt.) are in the primary gene pool of Upland cotton (G. hirsutum). They share a common chromosome number (2n=52), similar AD-genome architecture, and form reasonably fertile F1 hybrids. However, reduced transm...

The Parity Theorem Shuffle

ERIC Educational Resources Information Center

Smith, Michael D.

2016-01-01

The Parity Theorem states that any permutation can be written as a product of transpositions, but no permutation can be written as a product of both an even number and an odd number of transpositions. Most proofs of the Parity Theorem take several pages of mathematical formalism to complete. This article presents an alternative but equivalent…

The Influence of Bilingualism on Cognitive Development and Cognitive Strategy.

ERIC Educational Resources Information Center

Ben-Zeev, Sandra

This dissertation abstract summarizes a research study which investigated the hypothesis that bilingualism in children would result in: (1) increased ability to analyze syntax; (2) acceleration in the time of arrival of the stage of concrete operational thinking; and (3) an increase in cognitive flexibility or ability to mentally shuffle material.…

Biogeography and body size shuffling of aquatic salamander communities on a shifting refuge

PubMed Central

Bonett, Ronald M.; Trujano-Alvarez, Ana Lilia; Williams, Michael J.; Timpe, Elizabeth K.

2013-01-01

Freshwater habitats of coastal plains are refugia for many divergent vertebrate lineages, yet these environments are highly vulnerable to sea-level fluctuations, which suggest that resident communities have endured dynamic histories. Using the fossil record and a multi-locus nuclear phylogeny, we examine divergence times, biogeography, body size evolution and patterns of community assembly of aquatic salamanders from North American coastal plains since the Late Cretaceous. At least five salamander families occurred on the extensive Western Interior Coastal Plain (WICP), which existed from the Late Cretaceous through the Eocene. Four of these families subsequently colonized the emergent Southeastern Coastal Plain (SECP) by the Early Oligocene to Late Miocene. Three families ultimately survived and underwent extensive body size evolution in situ on the SECP. This included at least two major size reversals in recent taxa that are convergent with confamilial WICP ancestors. Dynamics of the coastal plain, major lineage extinctions and frequent extreme changes in body size have resulted in significant shuffling of the size structure of aquatic salamander communities on this shifting refuge since the Cretaceous. PMID:23466988

A comparative analysis of swarm intelligence techniques for feature selection in cancer classification.

PubMed

Gunavathi, Chellamuthu; Premalatha, Kandasamy

2014-01-01

Feature selection in cancer classification is a central area of research in the field of bioinformatics and used to select the informative genes from thousands of genes of the microarray. The genes are ranked based on T-statistics, signal-to-noise ratio (SNR), and F-test values. The swarm intelligence (SI) technique finds the informative genes from the top-m ranked genes. These selected genes are used for classification. In this paper the shuffled frog leaping with Lévy flight (SFLLF) is proposed for feature selection. In SFLLF, the Lévy flight is included to avoid premature convergence of shuffled frog leaping (SFL) algorithm. The SI techniques such as particle swarm optimization (PSO), cuckoo search (CS), SFL, and SFLLF are used for feature selection which identifies informative genes for classification. The k-nearest neighbour (k-NN) technique is used to classify the samples. The proposed work is applied on 10 different benchmark datasets and examined with SI techniques. The experimental results show that the results obtained from k-NN classifier through SFLLF feature selection method outperform PSO, CS, and SFL.

The effect of normalization of Partial Directed Coherence on the statistical assessment of connectivity patterns: a simulation study.

PubMed

Toppi, J; Petti, M; Vecchiato, G; Cincotti, F; Salinari, S; Mattia, D; Babiloni, F; Astolfi, L

2013-01-01

Partial Directed Coherence (PDC) is a spectral multivariate estimator for effective connectivity, relying on the concept of Granger causality. Even if its original definition derived directly from information theory, two modifies were introduced in order to provide better physiological interpretations of the estimated networks: i) normalization of the estimator according to rows, ii) squared transformation. In the present paper we investigated the effect of PDC normalization on the performances achieved by applying the statistical validation process on investigated connectivity patterns under different conditions of Signal to Noise ratio (SNR) and amount of data available for the analysis. Results of the statistical analysis revealed an effect of PDC normalization only on the percentages of type I and type II errors occurred by using Shuffling procedure for the assessment of connectivity patterns. No effects of the PDC formulation resulted on the performances achieved during the validation process executed instead by means of Asymptotic Statistic approach. Moreover, the percentages of both false positives and false negatives committed by Asymptotic Statistic are always lower than those achieved by Shuffling procedure for each type of normalization.

Magnetic shuffling of coronal downdrafts

NASA Astrophysics Data System (ADS)

Petralia, A.; Reale, F.; Orlando, S.

2017-02-01

Context. Channelled fragmented downflows are ubiquitous in magnetized atmospheres, and have recently been addressed based on an observation after a solar eruption. Aims: We study the possible back-effect of the magnetic field on the propagation of confined flows. Methods: We compared two 3D magnetohydrodynamic simulations of dense supersonic plasma blobs that fall down along a coronal magnetic flux tube. In one, the blobs move strictly along the field lines; in the other, the initial velocity of the blobs is not perfectly aligned with the magnetic field and the field is weaker. Results: The aligned blobs remain compact while flowing along the tube, with the generated shocks. The misaligned blobs are disrupted and merge through the chaotic shuffling of the field lines. They are structured into thinner filaments. Alfvén wave fronts are generated together with shocks ahead of the dense moving front. Conclusions: Downflowing plasma fragments can be chaotically and efficiently mixed if their motion is misaligned with field lines, with broad implications for disk accretion in protostars, coronal eruptions, and rain, for example. Movies associated to Figs. 2 and 3 are available at http://www.aanda.org

In Search of Determinism-Sensitive Region to Avoid Artefacts in Recurrence Plots

NASA Astrophysics Data System (ADS)

Wendi, Dadiyorto; Marwan, Norbert; Merz, Bruno

As an effort to reduce parameter uncertainties in constructing recurrence plots, and in particular to avoid potential artefacts, this paper presents a technique to derive artefact-safe region of parameter sets. This technique exploits both deterministic (incl. chaos) and stochastic signal characteristics of recurrence quantification (i.e. diagonal structures). It is useful when the evaluated signal is known to be deterministic. This study focuses on the recurrence plot generated from the reconstructed phase space in order to represent many real application scenarios when not all variables to describe a system are available (data scarcity). The technique involves random shuffling of the original signal to destroy its original deterministic characteristics. Its purpose is to evaluate whether the determinism values of the original and the shuffled signal remain closely together, and therefore suggesting that the recurrence plot might comprise artefacts. The use of such determinism-sensitive region shall be accompanied by standard embedding optimization approaches, e.g. using indices like false nearest neighbor and mutual information, to result in a more reliable recurrence plot parameterization.

Generalized Hurst exponent and multifractal function of original and translated texts mapped into frequency and length time series

NASA Astrophysics Data System (ADS)

Ausloos, M.

2012-09-01

A nonlinear dynamics approach can be used in order to quantify complexity in written texts. As a first step, a one-dimensional system is examined: two written texts by one author (Lewis Carroll) are considered, together with one translation into an artificial language (i.e., Esperanto) are mapped into time series. Their corresponding shuffled versions are used for obtaining a baseline. Two different one-dimensional time series are used here: one based on word lengths (LTS), the other on word frequencies (FTS). It is shown that the generalized Hurst exponent h(q) and the derived f(α) curves of the original and translated texts show marked differences. The original texts are far from giving a parabolic f(α) function, in contrast to the shuffled texts. Moreover, the Esperanto text has more extreme values. This suggests cascade model-like, with multiscale time-asymmetric features as finally written texts. A discussion of the difference and complementarity of mapping into a LTS or FTS is presented. The FTS f(α) curves are more opened than the LTS ones.

Generalized Hurst exponent and multifractal function of original and translated texts mapped into frequency and length time series.

PubMed

Ausloos, M

2012-09-01

A nonlinear dynamics approach can be used in order to quantify complexity in written texts. As a first step, a one-dimensional system is examined: two written texts by one author (Lewis Carroll) are considered, together with one translation into an artificial language (i.e., Esperanto) are mapped into time series. Their corresponding shuffled versions are used for obtaining a baseline. Two different one-dimensional time series are used here: one based on word lengths (LTS), the other on word frequencies (FTS). It is shown that the generalized Hurst exponent h(q) and the derived f(α) curves of the original and translated texts show marked differences. The original texts are far from giving a parabolic f(α) function, in contrast to the shuffled texts. Moreover, the Esperanto text has more extreme values. This suggests cascade model-like, with multiscale time-asymmetric features as finally written texts. A discussion of the difference and complementarity of mapping into a LTS or FTS is presented. The FTS f(α) curves are more opened than the LTS ones.

Advancing Metabolic Engineering of Saccharomyces cerevisiae Using the CRISPR/Cas System

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

Lian, Jiazhang; HamediRad, Mohammad; Zhao, Huimin

Thanks to its ease of use, modularity, and scalability, the clustered regularly interspaced short palindromic repeats (CRISPR) system has been increasingly used in the design and engineering of Saccharomyces cerevisiae, one of the most popular hosts for industrial biotechnology. This review summarizes the recent development of this disruptive technology for metabolic engineering applications, including CRISPR-mediated gene knock-out and knock-in as well as transcriptional activation and interference. More importantly, multi-functional CRISPR systems that combine both gain- and loss-of-function modulations for combinatorial metabolic engineering are highlighted.

Advancing Metabolic Engineering of Saccharomyces cerevisiae Using the CRISPR/Cas System

DOE PAGES

Lian, Jiazhang; HamediRad, Mohammad; Zhao, Huimin

2018-04-18

Thanks to its ease of use, modularity, and scalability, the clustered regularly interspaced short palindromic repeats (CRISPR) system has been increasingly used in the design and engineering of Saccharomyces cerevisiae, one of the most popular hosts for industrial biotechnology. This review summarizes the recent development of this disruptive technology for metabolic engineering applications, including CRISPR-mediated gene knock-out and knock-in as well as transcriptional activation and interference. More importantly, multi-functional CRISPR systems that combine both gain- and loss-of-function modulations for combinatorial metabolic engineering are highlighted.

MC EMiNEM maps the interaction landscape of the Mediator.

PubMed

Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C; Martin, Dietmar E; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

2012-01-01

The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

The relative efficiency of modular and non-modular networks of different size

PubMed Central

Tosh, Colin R.; McNally, Luke

2015-01-01

Most biological networks are modular but previous work with small model networks has indicated that modularity does not necessarily lead to increased functional efficiency. Most biological networks are large, however, and here we examine the relative functional efficiency of modular and non-modular neural networks at a range of sizes. We conduct a detailed analysis of efficiency in networks of two size classes: ‘small’ and ‘large’, and a less detailed analysis across a range of network sizes. The former analysis reveals that while the modular network is less efficient than one of the two non-modular networks considered when networks are small, it is usually equally or more efficient than both non-modular networks when networks are large. The latter analysis shows that in networks of small to intermediate size, modular networks are much more efficient that non-modular networks of the same (low) connective density. If connective density must be kept low to reduce energy needs for example, this could promote modularity. We have shown how relative functionality/performance scales with network size, but the precise nature of evolutionary relationship between network size and prevalence of modularity will depend on the costs of connectivity. PMID:25631996

SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm

PubMed Central

2012-01-01

Background Production of correctly disulfide bonded proteins to high yields remains a challenge. Recombinant protein expression in Escherichia coli is the popular choice, especially within the research community. While there is an ever growing demand for new expression strains, few strains are dedicated to post-translational modifications, such as disulfide bond formation. Thus, new protein expression strains must be engineered and the parameters involved in producing disulfide bonded proteins must be understood. Results We have engineered a new E. coli protein expression strain named SHuffle, dedicated to producing correctly disulfide bonded active proteins to high yields within its cytoplasm. This strain is based on the trxB gor suppressor strain SMG96 where its cytoplasmic reductive pathways have been diminished, allowing for the formation of disulfide bonds in the cytoplasm. We have further engineered a major improvement by integrating into its chromosome a signal sequenceless disulfide bond isomerase, DsbC. We probed the redox state of DsbC in the oxidizing cytoplasm and evaluated its role in assisting the formation of correctly folded multi-disulfide bonded proteins. We optimized protein expression conditions, varying temperature, induction conditions, strain background and the co-expression of various helper proteins. We found that temperature has the biggest impact on improving yields and that the E. coli B strain background of this strain was superior to the K12 version. We also discovered that auto-expression of substrate target proteins using this strain resulted in higher yields of active pure protein. Finally, we found that co-expression of mutant thioredoxins and PDI homologs improved yields of various substrate proteins. Conclusions This work is the first extensive characterization of the trxB gor suppressor strain. The results presented should help researchers design the appropriate protein expression conditions using SHuffle strains. PMID:22569138

Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan.

PubMed

Chiou, Chien-Shun; Wang, You-Wun; Chen, Pei-Ling; Wang, Wan-Ling; Wu, Ping-Fuai; Wei, Hsiao-Lun

2009-06-01

The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2-3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. The occurrences of scarlet fever in central Taiwan in 2000-2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003.

Measuring efficiency of international crude oil markets: A multifractality approach

NASA Astrophysics Data System (ADS)

Niere, H. M.

2015-01-01

The three major international crude oil markets are treated as complex systems and their multifractal properties are explored. The study covers daily prices of Brent crude, OPEC reference basket and West Texas Intermediate (WTI) crude from January 2, 2003 to January 2, 2014. A multifractal detrended fluctuation analysis (MFDFA) is employed to extract the generalized Hurst exponents in each of the time series. The generalized Hurst exponent is used to measure the degree of multifractality which in turn is used to quantify the efficiency of the three international crude oil markets. To identify whether the source of multifractality is long-range correlations or broad fat-tail distributions, shuffled data and surrogated data corresponding to each of the time series are generated. Shuffled data are obtained by randomizing the order of the price returns data. This will destroy any long-range correlation of the time series. Surrogated data is produced using the Fourier-Detrended Fluctuation Analysis (F-DFA). This is done by randomizing the phases of the price returns data in Fourier space. This will normalize the distribution of the time series. The study found that for the three crude oil markets, there is a strong dependence of the generalized Hurst exponents with respect to the order of fluctuations. This shows that the daily price time series of the markets under study have signs of multifractality. Using the degree of multifractality as a measure of efficiency, the results show that WTI is the most efficient while OPEC is the least efficient market. This implies that OPEC has the highest likelihood to be manipulated among the three markets. This reflects the fact that Brent and WTI is a very competitive market hence, it has a higher level of complexity compared against OPEC, which has a large monopoly power. Comparing with shuffled data and surrogated data, the findings suggest that for all the three crude oil markets, the multifractality is mainly due to long-range correlations.

Modelling Biogeochemistry Across Domains with The Modular System for Shelves and Coasts (MOSSCO)

NASA Astrophysics Data System (ADS)

Burchard, H.; Lemmen, C.; Hofmeister, R.; Knut, K.; Nasermoaddeli, M. H.; Kerimoglu, O.; Koesters, F.; Wirtz, K.

2016-02-01

Coastal biogeochemical processes extend from the atmosphere through the water column and the epibenthos into the ocean floor, laterally they are determined by freshwater inflows and open water exchange, and in situ they are mediated by physical, chemical and biological interactions. We use the new Modular System for Shelves and Coasts (MOSSCO, http://www.mossco.de) to obtain an integrated view of coastal biogeochemistry. MOSSCO is a coupling framework that builds on existing coupling technologies like the Earth System Modeling Framework (ESMF, for domain-coupling) and the Framework for Aquatic Biogeochemistry (FABM, for process coupling). MOSSCO facilitates the communication about and the integration of existing and of new process models into a threedimensional regional coastal modelling context. In the MOSSCO concept, the integrating framework imposes very few restrictions on contributed data or models; in fact, there is no distinction made between data and models. The few requirements are: (1) principle coupleability, i.e. access to I/O and timing information in submodels, which has recently been referred to as the Basic Model Interface (BMI) (2) open source/open data access and licencing and (3) communication of metadata, such as spatiotemporal information, naming conventions, and physical units. These requirements suffice to integrate different models and data sets into the MOSSCO infrastructure and subsequently built a modular integrated modeling tool that can span a diversity of processes and domains. Here, we demonstrate a MOSSCO application for the southern North Sea, where atmospheric deposition, biochemical processing in the water column and the ocean floor, lateral nutrient replenishment, and wave- and current-dependent remobilization from sediments are accounted for by modular components. A multi-annual simulation yields realistic succession of the spatial gradients of dissolved nutrients, of chlorophyll variability and gross primary production rates and of benthic denitrification rates for this intriguing coastal system.

A Fly's Eye View of Natural and Drug Reward.

PubMed

Lowenstein, Eve G; Velazquez-Ulloa, Norma A

2018-01-01

Animals encounter multiple stimuli each day. Some of these stimuli are innately appetitive or aversive, while others are assigned valence based on experience. Drugs like ethanol can elicit aversion in the short term and attraction in the long term. The reward system encodes the predictive value for different stimuli, mediating anticipation for attractive or punishing stimuli and driving animal behavior to approach or avoid conditioned stimuli. The neurochemistry and neurocircuitry of the reward system is partly evolutionarily conserved. In both vertebrates and invertebrates, including Drosophila melanogaster , dopamine is at the center of a network of neurotransmitters and neuromodulators acting in concert to encode rewards. Behavioral assays in D. melanogaster have become increasingly sophisticated, allowing more direct comparison with mammalian research. Moreover, recent evidence has established the functional modularity of the reward neural circuits in Drosophila . This functional modularity resembles the organization of reward circuits in mammals. The powerful genetic and molecular tools for D. melanogaster allow characterization and manipulation at the single-cell level. These tools are being used to construct a detailed map of the neural circuits mediating specific rewarding stimuli and have allowed for the identification of multiple genes and molecular pathways that mediate the effects of reinforcing stimuli, including their rewarding effects. This report provides an overview of the research on natural and drug reward in D. melanogaster , including natural rewards such as sugar and other food nutrients, and drug rewards including ethanol, cocaine, amphetamine, methamphetamine, and nicotine. We focused mainly on the known genetic and neural mechanisms underlying appetitive reward for sugar and reward for ethanol. We also include genes, molecular pathways, and neural circuits that have been identified using assays that test the palatability of the rewarding stimulus, the preference for the rewarding stimulus, or other effects of the stimulus that indicate how it can modify behavior. Commonalities between mechanisms of natural and drug reward are highlighted and future directions are presented, putting forward questions best suited for research using D. melanogaster as a model organism.

A Modular Library of Small Molecule Signals Regulates Social Behaviors in Caenorhabditis elegans

PubMed Central

Bose, Neelanjan; Zaslaver, Alon; Mahanti, Parag; Ho, Margaret C.; O'Doherty, Oran G.; Edison, Arthur S.; Sternberg, Paul W.; Schroeder, Frank C.

2012-01-01

The nematode C. elegans is an important model for the study of social behaviors. Recent investigations have shown that a family of small molecule signals, the ascarosides, controls population density sensing and mating behavior. However, despite extensive studies of C. elegans aggregation behaviors, no intraspecific signals promoting attraction or aggregation of wild-type hermaphrodites have been identified. Using comparative metabolomics, we show that the known ascarosides are accompanied by a series of derivatives featuring a tryptophan-derived indole moiety. Behavioral assays demonstrate that these indole ascarosides serve as potent intraspecific attraction and aggregation signals for hermaphrodites, in contrast to ascarosides lacking the indole group, which are repulsive. Hermaphrodite attraction to indole ascarosides depends on the ASK amphid sensory neurons. Downstream of the ASK sensory neuron, the interneuron AIA is required for mediating attraction to indole ascarosides instead of the RMG interneurons, which previous studies have shown to integrate attraction and aggregation signals from ASK and other sensory neurons. The role of the RMG interneuron in mediating aggregation and attraction is thought to depend on the neuropeptide Y-like receptor NPR-1, because solitary and social C. elegans strains are distinguished by different npr-1 variants. We show that indole ascarosides promote attraction and aggregation in both solitary and social C. elegans strains. The identification of indole ascarosides as aggregation signals reveals unexpected complexity of social signaling in C. elegans, which appears to be based on a modular library of ascarosides integrating building blocks derived from lipid β-oxidation and amino-acid metabolism. Variation of modules results in strongly altered signaling content, as addition of a tryptophan-derived indole unit to repellent ascarosides produces strongly attractive indole ascarosides. Our findings show that the library of ascarosides represents a highly developed chemical language integrating different neurophysiological pathways to mediate social communication in C. elegans. PMID:22253572

A Fly’s Eye View of Natural and Drug Reward

PubMed Central

Lowenstein, Eve G.; Velazquez-Ulloa, Norma A.

2018-01-01

Animals encounter multiple stimuli each day. Some of these stimuli are innately appetitive or aversive, while others are assigned valence based on experience. Drugs like ethanol can elicit aversion in the short term and attraction in the long term. The reward system encodes the predictive value for different stimuli, mediating anticipation for attractive or punishing stimuli and driving animal behavior to approach or avoid conditioned stimuli. The neurochemistry and neurocircuitry of the reward system is partly evolutionarily conserved. In both vertebrates and invertebrates, including Drosophila melanogaster, dopamine is at the center of a network of neurotransmitters and neuromodulators acting in concert to encode rewards. Behavioral assays in D. melanogaster have become increasingly sophisticated, allowing more direct comparison with mammalian research. Moreover, recent evidence has established the functional modularity of the reward neural circuits in Drosophila. This functional modularity resembles the organization of reward circuits in mammals. The powerful genetic and molecular tools for D. melanogaster allow characterization and manipulation at the single-cell level. These tools are being used to construct a detailed map of the neural circuits mediating specific rewarding stimuli and have allowed for the identification of multiple genes and molecular pathways that mediate the effects of reinforcing stimuli, including their rewarding effects. This report provides an overview of the research on natural and drug reward in D. melanogaster, including natural rewards such as sugar and other food nutrients, and drug rewards including ethanol, cocaine, amphetamine, methamphetamine, and nicotine. We focused mainly on the known genetic and neural mechanisms underlying appetitive reward for sugar and reward for ethanol. We also include genes, molecular pathways, and neural circuits that have been identified using assays that test the palatability of the rewarding stimulus, the preference for the rewarding stimulus, or other effects of the stimulus that indicate how it can modify behavior. Commonalities between mechanisms of natural and drug reward are highlighted and future directions are presented, putting forward questions best suited for research using D. melanogaster as a model organism. PMID:29720947

Programmable and Multiparameter DNA-Based Logic Platform For Cancer Recognition and Targeted Therapy

PubMed Central

2014-01-01

The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy. PMID:25361164

Spider wrapping silk fibre architecture arising from its modular soluble protein precursor

NASA Astrophysics Data System (ADS)

Tremblay, Marie-Laurence; Xu, Lingling; Lefèvre, Thierry; Sarker, Muzaddid; Orrell, Kathleen E.; Leclerc, Jérémie; Meng, Qing; Pézolet, Michel; Auger, Michèle; Liu, Xiang-Qin; Rainey, Jan K.

2015-06-01

Spiders store spidroins in their silk glands as high concentration aqueous solutions, spinning these dopes into fibres with outstanding mechanical properties. Aciniform (or wrapping) silk is the toughest spider silk and is devoid of the short amino acid sequence motifs characteristic of the other spidroins. Using solution-state NMR spectroscopy, we demonstrate that the 200 amino acid Argiope trifasciata AcSp1 repeat unit contrasts with previously characterized spidroins, adopting a globular 5-helix bundle flanked by intrinsically disordered N- and C-terminal tails. Split-intein-mediated segmental NMR-active isotope-enrichment allowed unambiguous demonstration of modular and malleable “beads-on-a-string” concatemeric behaviour. Concatemers form fibres upon manual drawing with silk-like morphology and mechanical properties, alongside secondary structuring and orientation consistent with native AcSp1 fibres. AcSp1 structural stability varies locally, with the fifth helix denaturing most readily. The structural transition of aciniform spidroin from a mostly α-helical dope to a mixed α-helix/β-sheet-containing fibre can be directly related to spidroin architecture and stability.

Adaptive multi-resolution Modularity for detecting communities in networks

NASA Astrophysics Data System (ADS)

Chen, Shi; Wang, Zhi-Zhong; Bao, Mei-Hua; Tang, Liang; Zhou, Ji; Xiang, Ju; Li, Jian-Ming; Yi, Chen-He

2018-02-01

Community structure is a common topological property of complex networks, which attracted much attention from various fields. Optimizing quality functions for community structures is a kind of popular strategy for community detection, such as Modularity optimization. Here, we introduce a general definition of Modularity, by which several classical (multi-resolution) Modularity can be derived, and then propose a kind of adaptive (multi-resolution) Modularity that can combine the advantages of different Modularity. By applying the Modularity to various synthetic and real-world networks, we study the behaviors of the methods, showing the validity and advantages of the multi-resolution Modularity in community detection. The adaptive Modularity, as a kind of multi-resolution method, can naturally solve the first-type limit of Modularity and detect communities at different scales; it can quicken the disconnecting of communities and delay the breakup of communities in heterogeneous networks; and thus it is expected to generate the stable community structures in networks more effectively and have stronger tolerance against the second-type limit of Modularity.

Product modular design incorporating preventive maintenance issues

NASA Astrophysics Data System (ADS)

Gao, Yicong; Feng, Yixiong; Tan, Jianrong

2016-03-01

Traditional modular design methods lead to product maintenance problems, because the module form of a system is created according to either the function requirements or the manufacturing considerations. For solving these problems, a new modular design method is proposed with the considerations of not only the traditional function related attributes, but also the maintenance related ones. First, modularity parameters and modularity scenarios for product modularity are defined. Then the reliability and economic assessment models of product modularity strategies are formulated with the introduction of the effective working age of modules. A mathematical model used to evaluate the difference among the modules of the product so that the optimal module of the product can be established. After that, a multi-objective optimization problem based on metrics for preventive maintenance interval different degrees and preventive maintenance economics is formulated for modular optimization. Multi-objective GA is utilized to rapidly approximate the Pareto set of optimal modularity strategy trade-offs between preventive maintenance cost and preventive maintenance interval difference degree. Finally, a coordinate CNC boring machine is adopted to depict the process of product modularity. In addition, two factorial design experiments based on the modularity parameters are constructed and analyzed. These experiments investigate the impacts of these parameters on the optimal modularity strategies and the structure of module. The research proposes a new modular design method, which may help to improve the maintainability of product in modular design.

Development of modularity in the neural activity of childrenʼs brains

NASA Astrophysics Data System (ADS)

Chen, Man; Deem, Michael W.

2015-02-01

We study how modularity of the human brain changes as children develop into adults. Theory suggests that modularity can enhance the response function of a networked system subject to changing external stimuli. Thus, greater cognitive performance might be achieved for more modular neural activity, and modularity might likely increase as children develop. The value of modularity calculated from functional magnetic resonance imaging (fMRI) data is observed to increase during childhood development and peak in young adulthood. Head motion is deconvolved from the fMRI data, and it is shown that the dependence of modularity on age is independent of the magnitude of head motion. A model is presented to illustrate how modularity can provide greater cognitive performance at short times, i.e. task switching. A fitness function is extracted from the model. Quasispecies theory is used to predict how the average modularity evolves with age, illustrating the increase of modularity during development from children to adults that arises from selection for rapid cognitive function in young adults. Experiments exploring the effect of modularity on cognitive performance are suggested. Modularity may be a potential biomarker for injury, rehabilitation, or disease.

An Examination of Stimulus Control in Fluency-Based Strategies: SAFMEDS and Generalization

ERIC Educational Resources Information Center

Meindl, James N.; Ivy, Jonathan W.; Miller, Neal; Neef, Nancy A.; Williamson, Robert L.

2013-01-01

Fluency-based strategies such as Say All Fast a Minute Each Day Shuffled (SAFMEDS) effectively promote fluent responding (i.e., high rate and accuracy). It is possible, however, that the stimulus control developed through these activities inhibits stimulus generalization. We investigated this concern in a two-part study with college students.…

Piaget's Developmental Theories Used in an Early Childhood Program for Mentally Retarded Students.

ERIC Educational Resources Information Center

Francis Christi, Sister

The author describes a Piaget based curriculum involving three main themes (classification, number measurement/space, and seriation) for young mentally retarded children. Students solve problems by doing something physically and mentally to the data, shuffling the facts about in their minds, so that they will come to a logical solution. Language…

The Reference Statistic Shuffle: Finding a Tool That Not Only Adds Stuff up but Improves Results

ERIC Educational Resources Information Center

Northam, Sarah H.

2012-01-01

Reference librarians are constantly balancing their reference duties against other duties, for example, collection development and departmental liaison. The author works as a reference librarian at Texas A&M University-Commerce Libraries in Commerce, Texas. The university has approximately 11,000 students, a large number of whom are…

Dynamics of modularity of neural activity in the brain during development

NASA Astrophysics Data System (ADS)

Deem, Michael; Chen, Man

2014-03-01

Theory suggests that more modular systems can have better response functions at short times. This theory suggests that greater cognitive performance may be achieved for more modular neural activity, and that modularity of neural activity may, therefore, likely increase with development in children. We study the relationship between age and modularity of brain neural activity in developing children. The value of modularity calculated from fMRI data is observed to increase during childhood development and peak in young adulthood. We interpret these results as evidence of selection for plasticity in the cognitive function of the human brain. We present a model to illustrate how modularity can provide greater cognitive performance at short times and enhance fast, low-level, automatic cognitive processes. Conversely, high-level, effortful, conscious cognitive processes may not benefit from modularity. We use quasispecies theory to predict how the average modularity evolves with age, given a fitness function extracted from the model. We suggest further experiments exploring the effect of modularity on cognitive performance and suggest that modularity may be a potential biomarker for injury, rehabilitation, or disease.

Modular Courses in British Higher Education: A Critical Assessment

ERIC Educational Resources Information Center

Church, Clive

1975-01-01

The trends towards modular course structures is examined. British conceptions of modularization are compared with American interpretations of modular instruction, the former shown to be concerned almost exclusively with content, the latter attempting more radical changes in students' learning behavior. Rationales for British modular schemes are…

MC EMiNEM Maps the Interaction Landscape of the Mediator

PubMed Central

Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C.; Martin, Dietmar E.; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

2012-01-01

The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors. PMID:22737066

Dissociation of modular total hip arthroplasty at the neck-stem interface without dislocation.

PubMed

Kouzelis, A; Georgiou, C S; Megas, P

2012-12-01

Modular femoral and acetabular components are now widely used, but only a few complications related to the modularity itself have been reported. We describe a case of dissociation of the modular total hip arthroplasty (THA) at the femoral neck-stem interface during walking. The possible causes of this dissociation are discussed. Successful treatment was provided with surgical revision and replacement of the modular neck components. Surgeons who use modular components in hip arthroplasties should be aware of possible early complications in which the modularity of the prostheses is the major factor of failure.

Quasispecies theory for evolution of modularity.

PubMed

Park, Jeong-Man; Niestemski, Liang Ren; Deem, Michael W

2015-01-01

Biological systems are modular, and this modularity evolves over time and in different environments. A number of observations have been made of increased modularity in biological systems under increased environmental pressure. We here develop a quasispecies theory for the dynamics of modularity in populations of these systems. We show how the steady-state fitness in a randomly changing environment can be computed. We derive a fluctuation dissipation relation for the rate of change of modularity and use it to derive a relationship between rate of environmental changes and rate of growth of modularity. We also find a principle of least action for the evolved modularity at steady state. Finally, we compare our predictions to simulations of protein evolution and find them to be consistent.

The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics.

PubMed

Goswami, Anjali; Binder, Wendy J; Meachen, Julie; O'Keefe, F Robin

2015-04-21

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because they provide the only information on deep-time developmental and evolutionary dynamics, including trends in trait relationships and their role in shaping organismal diversity. Here, we demonstrate the important perspective on phenotypic integration provided by the fossil record with a study of Smilodon fatalis (saber-toothed cats) and Canis dirus (dire wolves). We quantified temporal trends in size, variance, phenotypic integration, and direct developmental integration (fluctuating asymmetry) through 27,000 y of Late Pleistocene climate change. Both S. fatalis and C. dirus showed a gradual decrease in magnitude of phenotypic integration and an increase in variance and the correlation between fluctuating asymmetry and overall integration through time, suggesting that developmental integration mediated morphological response to environmental change in the later populations of these species. These results are consistent with experimental studies and represent, to our knowledge, the first deep-time validation of the importance of developmental integration in stabilizing morphological evolution through periods of environmental change.

The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics

PubMed Central

Goswami, Anjali; Binder, Wendy J.; Meachen, Julie; O’Keefe, F. Robin

2015-01-01

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because they provide the only information on deep-time developmental and evolutionary dynamics, including trends in trait relationships and their role in shaping organismal diversity. Here, we demonstrate the important perspective on phenotypic integration provided by the fossil record with a study of Smilodon fatalis (saber-toothed cats) and Canis dirus (dire wolves). We quantified temporal trends in size, variance, phenotypic integration, and direct developmental integration (fluctuating asymmetry) through 27,000 y of Late Pleistocene climate change. Both S. fatalis and C. dirus showed a gradual decrease in magnitude of phenotypic integration and an increase in variance and the correlation between fluctuating asymmetry and overall integration through time, suggesting that developmental integration mediated morphological response to environmental change in the later populations of these species. These results are consistent with experimental studies and represent, to our knowledge, the first deep-time validation of the importance of developmental integration in stabilizing morphological evolution through periods of environmental change. PMID:25901310

D-amphetamine stimulates unconditioned exploration/approach behaviors in crayfish: towards a conserved evolutionary function of ancestral drug reward

PubMed Central

Alcaro, Antonio; Panksepp, Jaak; Huber, Robert

2012-01-01

In mammals, rewarding properties of drugs depend on their capacity to activate a dopamine-mediated appetitive motivational seeking state—a system that allows animals to pursue and find all kinds of objects and events needed for survival. With such states strongly conserved in evolution, invertebrates have recently been developed into a powerful model in addiction research, where a shared ancestral brain system for the acquisition of reward can mediate drug addiction in many species. A conditioned place preference paradigm has illustrated that crayfish seek out environments that had previously been paired with psychostimulant and opioid administration. The present work demonstrates that the administration of d-amphetamine stimulates active explorative behaviors in crayfish through the action of the drug within their head ganglion. Crayfish, with a modularly organized and experimentally accessible, ganglionic nervous system offers a unique model to investigate (1) the fundamental, biological mechanisms of addictive drug reward; (2) how an appetitive/seeking disposition is implemented in a simple neural system, and (3) how it mediates the rewarding actions of major drugs of abuse. PMID:21504757

Emergence of the Epidemic Methicillin-Resistant Staphylococcus aureus Strain USA300 Coincides with Horizontal Transfer of the Arginine Catabolic Mobile Element and speG-mediated Adaptations for Survival on Skin

PubMed Central

Planet, Paul J.; LaRussa, Samuel J.; Dana, Ali; Smith, Hannah; Xu, Amy; Ryan, Chanelle; Uhlemann, Anne-Catrin; Boundy, Sam; Goldberg, Julia; Narechania, Apurva; Kulkarni, Ritwij; Ratner, Adam J.; Geoghegan, Joan A.; Kolokotronis, Sergios-Orestis; Prince, Alice

2013-01-01

ABSTRACT The arginine catabolic mobile element (ACME) is the largest genomic region distinguishing epidemic USA300 strains of methicillin-resistant Staphylococcus aureus (MRSA) from other S. aureus strains. However, the functional relevance of ACME to infection and disease has remained unclear. Using phylogenetic analysis, we have shown that the modular segments of ACME were assembled into a single genetic locus in Staphylococcus epidermidis and then horizontally transferred to the common ancestor of USA300 strains in an extremely recent event. Acquisition of one ACME gene, speG, allowed USA300 strains to withstand levels of polyamines (e.g., spermidine) produced in skin that are toxic to other closely related S. aureus strains. speG-mediated polyamine tolerance also enhanced biofilm formation, adherence to fibrinogen/fibronectin, and resistance to antibiotic and keratinocyte-mediated killing. We suggest that these properties gave USA300 a major selective advantage during skin infection and colonization, contributing to the extraordinary evolutionary success of this clone. PMID:24345744

Self-organized modularization in evolutionary algorithms.

PubMed

Dauscher, Peter; Uthmann, Thomas

2005-01-01

The principle of modularization has proven to be extremely successful in the field of technical applications and particularly for Software Engineering purposes. The question to be answered within the present article is whether mechanisms can also be identified within the framework of Evolutionary Computation that cause a modularization of solutions. We will concentrate on processes, where modularization results only from the typical evolutionary operators, i.e. selection and variation by recombination and mutation (and not, e.g., from special modularization operators). This is what we call Self-Organized Modularization. Based on a combination of two formalizations by Radcliffe and Altenberg, some quantitative measures of modularity are introduced. Particularly, we distinguish Built-in Modularity as an inherent property of a genotype and Effective Modularity, which depends on the rest of the population. These measures can easily be applied to a wide range of present Evolutionary Computation models. It will be shown, both theoretically and by simulation, that under certain conditions, Effective Modularity (as defined within this paper) can be a selection factor. This causes Self-Organized Modularization to take place. The experimental observations emphasize the importance of Effective Modularity in comparison with Built-in Modularity. Although the experimental results have been obtained using a minimalist toy model, they can lead to a number of consequences for existing models as well as for future approaches. Furthermore, the results suggest a complex self-amplification of highly modular equivalence classes in the case of respected relations. Since the well-known Holland schemata are just the equivalence classes of respected relations in most Simple Genetic Algorithms, this observation emphasizes the role of schemata as Building Blocks (in comparison with arbitrary subsets of the search space).

[Modular enteral nutrition in pediatrics].

PubMed

Murillo Sanchís, S; Prenafeta Ferré, M T; Sempere Luque, M D

1991-01-01

Modular Enteral Nutrition may be a substitute for Parenteral Nutrition in children with different pathologies. Study of 4 children with different pathologies selected from a group of 40 admitted to the Maternal-Childrens Hospital "Valle de Hebrón" in Barcelona, who received modular enteral nutrition. They were monitored on a daily basis by the Dietician Service. Modular enteral nutrition consists of modules of proteins, peptides, lipids, glucids and mineral salts-vitamins. 1.--Craneo-encephalic traumatisms with loss of consciousness, Feeding with a combination of parenteral nutrition and modular enteral nutrition for 7 days. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended and modular enteral nutrition alone used up to a total of 43 days. 2.--55% burns with 36 days of hyperproteic modular enteral nutrition together with normal feeding. A more rapid recovery was achieved with an increase in total proteins and albumin. 3.--Persistent diarrhoea with 31 days of modular enteral nutrition, 5 days on parenteral nutrition alone and 8 days on combined parenteral nutrition and modular enteral nutrition. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended. 4.--Mucoviscidosis with a total of 19 days on modular enteral nutrition, 12 of which were exclusively on modular enteral nutrition and 7 as a night supplement to normal feeding. We administered proteic intakes of up to 20% of the total calorific intake and in concentrations of up to 1.2 calories/ml of the final preparation, always with a good tolerance. Modular enteral nutrition can and should be used as a substitute for parenteral nutrition in children with different pathologies, thus preventing the complications inherent in parenteral nutrition.

Convergent evolution of modularity in metabolic networks through different community structures.

PubMed

Zhou, Wanding; Nakhleh, Luay

2012-09-14

It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of the modularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxonomy. We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct) enzymes in the organism's metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability). Further, our results call for exploring new measures of modularity and network communities that better correspond to functional categorizations.

Continuous-flow synthesis of functionalized phenols by aerobic oxidation of Grignard reagents.

PubMed

He, Zhi; Jamison, Timothy F

2014-03-24

Phenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas-liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation-sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne-mediated in-line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three-step, one-flow process, capable of preparing 2-functionalized phenols in a modular fashion, is established. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Storytime Using Ipods: Using Technology to Reach All Learners

ERIC Educational Resources Information Center

Boeglin-Quintana, Brenda; Donovan, Loretta

2013-01-01

Many educators would agree that one way to enhance reading fluency is by being read to by fluent readers. The purpose of this study was to examine the impact of providing students with audio books via an iPod Shuffle during silent reading time at school. For six weeks, Kindergarten participants spent time either silent reading or listening to a…

When a Challenge Becomes a Gift of Inspiration

ERIC Educational Resources Information Center

Johnson, Lauren

2017-01-01

When he entered the building, the buzz of speculations quickly traveled throughout the halls. Where did he come from? What is wrong with him? What grade is he in? Who is has the lowest number? As everyone secretly hopes the new student deemed a "challenge" won't be placed in their classroom, the tall, thin shadow shuffles past your room…

Shuffling the Deck To Ensure Fairness in Dealing: A Commentary on Some Issues of Equity and Mathematics Education from the Perspective of the QUASAR Project.

ERIC Educational Resources Information Center

Silver, Edward A.

This paper is a reaction to a plenary address, "Fairness in Dealing: Diversity, Psychology, and Mathematics Education" by Suzanne Damarin (SE 057 179). The issues of intentionality, institutional and instructional practices, identity development, and assessment are addressed in regard to the Quantitative Understanding: Amplifying Student…

Children's Preference for Sequenced Accompaniments: The Influence of Style and Perceived Tempo.

ERIC Educational Resources Information Center

Brittin, Ruth V.

2000-01-01

Explores the influence of tempo on musical preference for students in grades 2-6, focusing on the effects of various styles using a MIDI keyboard. Explains that the students listened to 10 musical selections identifying their preferences and perceptions of tempo. Reveals that the preferred styles were Hip-Hop, Heavy Rock Shuffle, Samba, and Funk2.…

Implicit Contractive Mappings in Modular Metric and Fuzzy Metric Spaces

PubMed Central

Hussain, N.; Salimi, P.

2014-01-01

The notion of modular metric spaces being a natural generalization of classical modulars over linear spaces like Lebesgue, Orlicz, Musielak-Orlicz, Lorentz, Orlicz-Lorentz, and Calderon-Lozanovskii spaces was recently introduced. In this paper we investigate the existence of fixed points of generalized α-admissible modular contractive mappings in modular metric spaces. As applications, we derive some new fixed point theorems in partially ordered modular metric spaces, Suzuki type fixed point theorems in modular metric spaces and new fixed point theorems for integral contractions. In last section, we develop an important relation between fuzzy metric and modular metric and deduce certain new fixed point results in triangular fuzzy metric spaces. Moreover, some examples are provided here to illustrate the usability of the obtained results. PMID:25003157

Mean wind speed persistence over China

NASA Astrophysics Data System (ADS)

Jiang, Lei

2018-07-01

The wind speed persistence is an important factor in the assessment of wind energy potential. In this paper, we explore the persistence of Mean Wind Speed (MWS) with many years of record using Detrended Fluctuation Analysis (DFA) over China. The results illustrate that there exist irregular high-frequency fluctuations for daily MWS anomaly records. Long-term persistence of MWS is found for all meteorological observed sites. We also make some numerical tests in order to verify the significance of long-term persistence by shuffling the data records many times. These facts prove that the MWS anomaly records have long-term persistence over all the stations in China. The mean value 0.64 in DFA-exponents for all stations over China is also obviously higher than the value 0.53 according to interval threshold of 95% confidence level after shuffling the MWS records many times. In addition, the values of scaling exponent vary from station to station over China. Long-term persistence of MWS in spatial distributions seems to be downward trends from east to west China. Many factors may affect long-term persistence of MWS such as southwest monsoon, Tibetan Plateau landform and atmosphere-ocean-land interaction and so on. Possible physical mechanism need further analysis in the future.

Robust watermarking scheme for binary images using a slice-based large-cluster algorithm with a Hamming Code

NASA Astrophysics Data System (ADS)

Chen, Wen-Yuan; Liu, Chen-Chung

2006-01-01

The problems with binary watermarking schemes are that they have only a small amount of embeddable space and are not robust enough. We develop a slice-based large-cluster algorithm (SBLCA) to construct a robust watermarking scheme for binary images. In SBLCA, a small-amount cluster selection (SACS) strategy is used to search for a feasible slice in a large-cluster flappable-pixel decision (LCFPD) method, which is used to search for the best location for concealing a secret bit from a selected slice. This method has four major advantages over the others: (a) SBLCA has a simple and effective decision function to select appropriate concealment locations, (b) SBLCA utilizes a blind watermarking scheme without the original image in the watermark extracting process, (c) SBLCA uses slice-based shuffling capability to transfer the regular image into a hash state without remembering the state before shuffling, and finally, (d) SBLCA has enough embeddable space that every 64 pixels could accommodate a secret bit of the binary image. Furthermore, empirical results on test images reveal that our approach is a robust watermarking scheme for binary images.

Editing disulphide bonds: error correction using redox currencies.

PubMed

Ito, Koreaki

2010-01-01

The disulphide bond-introducing enzyme of bacteria, DsbA, sometimes oxidizes non-native cysteine pairs. DsbC should rearrange the resulting incorrect disulphide bonds into those with correct connectivity. DsbA and DsbC receive oxidizing and reducing equivalents, respectively, from respective redox components (quinones and NADPH) of the cell. Two mechanisms of disulphide bond rearrangement have been proposed. In the redox-neutral 'shuffling' mechanism, the nucleophilic cysteine in the DsbC active site forms a mixed disulphide with a substrate and induces disulphide shuffling within the substrate part of the enzyme-substrate complex, followed by resolution into a reduced enzyme and a disulphide-rearranged substrate. In the 'reduction-oxidation' mechanism, DsbC reduces those substrates with wrong disulphides so that DsbA can oxidize them again. In this issue of Molecular Microbiology, Berkmen and his collaborators show that a disulphide reductase, TrxP, from an anaerobic bacterium can substitute for DsbC in Escherichia coli. They propose that the reduction-oxidation mechanism of disulphide rearrangement can indeed operate in vivo. An implication of this work is that correcting errors in disulphide bonds can be coupled to cellular metabolism and is conceptually similar to the proofreading processes observed with numerous synthesis and maturation reactions of biological macromolecules.

Using Meteorological Analogues for Reordering Postprocessed Precipitation Ensembles in Hydrological Forecasting

NASA Astrophysics Data System (ADS)

Bellier, Joseph; Bontron, Guillaume; Zin, Isabella

2017-12-01

Meteorological ensemble forecasts are nowadays widely used as input of hydrological models for probabilistic streamflow forecasting. These forcings are frequently biased and have to be statistically postprocessed, using most of the time univariate techniques that apply independently to individual locations, lead times and weather variables. Postprocessed ensemble forecasts therefore need to be reordered so as to reconstruct suitable multivariate dependence structures. The Schaake shuffle and ensemble copula coupling are the two most popular methods for this purpose. This paper proposes two adaptations of them that make use of meteorological analogues for reconstructing spatiotemporal dependence structures of precipitation forecasts. Performances of the original and adapted techniques are compared through a multistep verification experiment using real forecasts from the European Centre for Medium-Range Weather Forecasts. This experiment evaluates not only multivariate precipitation forecasts but also the corresponding streamflow forecasts that derive from hydrological modeling. Results show that the relative performances of the different reordering methods vary depending on the verification step. In particular, the standard Schaake shuffle is found to perform poorly when evaluated on streamflow. This emphasizes the crucial role of the precipitation spatiotemporal dependence structure in hydrological ensemble forecasting.

Dual Liquid Flyback Booster for the Space Shuttle

NASA Technical Reports Server (NTRS)

Blum, C.; Jones, P.; Meinders, B.

1998-01-01

Liquid Flyback Boosters provide an opportunity to improve shuttle safety, increase performance, and reduce operating costs. The objective of the LFBB study is to establish the viability of a LFBB configuration to integrate into the shuffle vehicle and meet the goals of the Space Shuttle upgrades program. The design of a technically viable LFBB must integrate into the shuffle vehicle with acceptable impacts to the vehicle elements, i.e. orbiter and external tank and the shuttle operations infrastructure. The LFBB must also be capable of autonomous return to the launch site. The smooth integration of the LFBB into the space shuttle vehicle and the ability of the LFBB to fly back to the launch site are not mutually compatible capabilities. LFBB wing configurations optimized for ascent must also provide flight quality during the powered return back to the launch site. This paper will focus on the core booster design and ascent performance. A companion paper 'Conceptual Design for a Space Shuttle Liquid Flyback Booster' will focus on the flyback system design and performance. The LFBB study developed design and aerodynamic data to demonstrate the viability of a dual booster configuration to meet the shuttle upgrade goals, i.e. enhanced safety, improved performance and reduced operations costs.

ARTP mutation and genome shuffling of ABE fermentation symbiotic system for improvement of butanol production.

PubMed

Gu, Chunkai; Wang, Genyu; Mai, Shuai; Wu, Pengfei; Wu, Jianrong; Wang, Gehua; Liu, Hongjuan; Zhang, Jianan

2017-03-01

Butanol is an ideal renewable biofuel which possesses superior fuel properties. Previously, butanol-producing symbiotic system TSH06 was isolated in our lab, with microoxygen tolerance ability. To boost butanol yield for large-scale industrial production, TSH06 was used as parental strain and subjected to atmospheric and room temperature plasma (ARTP) and four rounds of genome shuffling (GS). ARTP mutant and GS strain were co-cultured with facultative anaerobic Bacillus cereus TSH2 to form a symbiotic system with microoxygen tolerance, which was then subjected to fermentation. Relative messenger RNA (mRNA) level of key enzyme gene was measured by real-time PCR. The highest butanol titer of TS4-30 reached 15.63 g/L, which was 34% higher than TSH06 (12.19 g/L). Compared with parental strain, mRNA of acid-forming gene in TS4-30 decreased in acidogenesis phase, while solvent-forming gene increased in solventogenesis phase. This gene expression pattern was consistent with high butanol yield and low acid level in TS4-30. In summary, symbiotic system TS4-30 was obtained with butanol titer improvement and microoxygen tolerance.

Modular Power Standard for Space Explorations Missions

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Gardner, Brent G.

2016-01-01

Future human space exploration will most likely be composed of assemblies of multiple modular spacecraft elements with interconnected electrical power systems. An electrical system composed of a standardized set modular building blocks provides significant development, integration, and operational cost advantages. The modular approach can also provide the flexibility to configure power systems to meet the mission needs. A primary goal of the Advanced Exploration Systems (AES) Modular Power System (AMPS) project is to establish a Modular Power Standard that is needed to realize these benefits. This paper is intended to give the space exploration community a "first look" at the evolving Modular Power Standard and invite their comments and technical contributions.

Configurable double-sided modular jet impingement assemblies for electronics cooling

DOEpatents

Zhou, Feng; Dede, Ercan Mehmet

2018-05-22

A modular jet impingement assembly includes an inlet tube fluidly coupled to a fluid inlet, an outlet tube fluidly coupled to a fluid outlet, and a modular manifold having a first distribution recess extending into a first side of the modular manifold, a second distribution recess extending into a second side of the modular manifold, a plurality of inlet connection tubes positioned at an inlet end of the modular manifold, and a plurality of outlet connection tubes positioned at an outlet end of the modular manifold. A first manifold insert is removably positioned within the first distribution recess, a second manifold insert is removably positioned within the second distribution recess, and a first and second heat transfer plate each removably coupled to the modular manifold. The first and second heat transfer plates each comprise an impingement surface.

Isolation of a human anti-epidermal growth factor receptor Fab antibody, EG-19-11, with subnanomolar affinity from naïve immunoglobulin repertoires using a hierarchical antibody library system.

PubMed

Hur, Byung-ung; Yoon, Jae-bong; Liu, Li-Kun; Cha, Sang-hoon

2010-11-30

Specific antibodies that possess a subnanomolar affinity are very difficult to obtain from human naïve immunoglobulin repertoires without the use of lengthy affinity optimization procedures. Here, we designed a hierarchical phage-displayed antibody library system to generate an enormous diversity of combinatorial Fab fragments (6×10(17)) and attempted to isolate high-affinity Fabs against the human epidermal growth factor receptor (EGFR). A primary antibody library, designated HuDVFab-8L, comprising 4.5×10(9) human naïve heavy chains and eight unspecified human naïve light chains was selected against the EGFR-Fc protein by biopanning, and four anti-EGFR Fab clones were isolated. Because one of the Fab clones, denoted EG-L2-11, recognized a native EGFR expressed on A431 cells, the heavy chain of the Fab was shuffled with a human naïve light chain repertoire with a diversity of 1.4×10(8) and selected a second time against the EGFR-Fc protein again. One EG-L2-11 variant, denoted EG-19-11, recognized an EGFR epitope that was almost the same as that bound by cetuximab and had a K(D) of approximately 540 pM for soluble EGFR, which is about 7-fold higher than that of the FabC225 derived from cetuximab. This variant was also internalized by A431 cells, likely via receptor-mediated endocytosis, and it efficiently inhibited EGF-mediated tyrosine phosphorylation of the EGFR. These results demonstrate that the use of our hierarchical antibody library system is advantageous in generating fully human antibodies especially with a therapeutic purpose. Copyright © 2010 Elsevier B.V. All rights reserved.

Massive amplification of rolling-circle transposons in the lineage of the bat Myotis lucifugus

PubMed Central

Pritham, Ellen J.; Feschotte, Cédric

2007-01-01

Rolling-circle (RC) transposons, or Helitrons, are a newly recognized group of eukaryotic transposable elements abundant in the genomes of plants, invertebrates, and zebrafish. We provide evidence for the colonization of a mammalian genome by Helitrons, which has not been reported previously. We identified and characterized two families of Helitrons in the little brown bat Myotis lucifugus. The consensus sequence for the first family, HeliBat1, displays the hallmarks of an autonomous Helitron, including coding capacity for an ≈1,500-aa protein with an RC replication motif and a region related to the SF1 superfamily of DNA helicases. The HeliBatN1 family is a nonautonomous Helitron family that is only distantly related to HeliBat1. The two HeliBat families have attained high copy numbers (≈15,000 and > 100,000 copies, respectively) and make up at least ≈3% of the M. lucifugus genome. Sequence divergence and cross-species analyses indicate that both HeliBat families have amplified within the last ≈30–36 million years and are restricted to the lineage of vesper bats. We could not detect the presence of Helitrons in any other order of placental mammals, despite the broad representation of these taxa in the databases. We describe an instance of HeliBat-mediated transduction of a host gene fragment that was subsequently dispersed in ≈1,000 copies throughout the M. lucifugus genome. Given the demonstrated propensity of RC transposons to mediate the duplication and shuffling of host genes in bacteria and maize, it is tempting to speculate that the massive amplification of Helitrons in vesper bats has influenced the evolutionary trajectory of these mammals. PMID:17261799

Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker

PubMed Central

Schmohl, Joerg U.; Felices, Martin; Todhunter, Deborah; Taras, Elizabeth; Miller, Jeffrey S.; Vallera, Daniel A.

2016-01-01

Background The design of a highly effective anti-cancer immune-engager would include targeting of highly drug refractory cancer stem cells (CSC). The design would promote effective antibody-dependent cell-mediated cytotoxicity (ADCC) and simultaneously promote costimulation to expand and self-sustain the effector NK cell population. Based on our bispecific NK cell engager platform we constructed a tetraspecific killer engager (TetraKE) comprising single-chain variable fragments (scFvs) binding FcγRIII (CD16) on NK cells, EpCAM on carcinoma cells and CD133 on cancer stem cells in order to promote ADCC. Furthermore, an Interleukin (IL)-15-crosslinker enhanced NK cell related proliferation resulting in a highly active drug termed 1615EpCAM133. Results Proliferation assays showed TetraKE promoted proliferation and enhanced NK cell survival. Drug-target binding, NK cell related degranulation, and IFN-γ production was specific for both tumor related antigens in EpCAM and CD133 bearing cancer cell lines. The TetraKE showed higher killing activity and superior dose dependent degranulation. Cytokine profiling showed a moderately enhanced IFN-γ production, enhanced GM-CSF production, but no evidence of induction of excessive cytokine release. Methods Assembly and synthesis of hybrid genes encoding the TetraKE were performed using DNA shuffling and ligation. The TetraKE was tested for efficacy, specificity, proliferation, survival, and cytokine production using carcinoma cell lines and functional assays measuring NK cell activity. Conclusion 1615EpCAM133 combines improved induction of ADCC with enhanced proliferation, limited cytokine response, and prolonged survival and proliferation of NK cells. By linking scFv-related targeting of carcinoma and CSCs with a sustaining IL-15 signal, our new construct shows great promise to target cancer and CSCs. PMID:27650544

Convergent evolution of modularity in metabolic networks through different community structures

PubMed Central

2012-01-01

Background It has been reported that the modularity of metabolic networks of bacteria is closely related to the variability of their living habitats. However, given the dependency of the modularity score on the community structure, it remains unknown whether organisms achieve certain modularity via similar or different community structures. Results In this work, we studied the relationship between similarities in modularity scores and similarities in community structures of the metabolic networks of 1021 species. Both similarities are then compared against the genetic distances. We revisited the association between modularity and variability of the microbial living environments and extended the analysis to other aspects of their life style such as temperature and oxygen requirements. We also tested both topological and biological intuition of the community structures identified and investigated the extent of their conservation with respect to the taxomony. Conclusions We find that similar modularities are realized by different community structures. We find that such convergent evolution of modularity is closely associated with the number of (distinct) enzymes in the organism’s metabolome, a consequence of different life styles of the species. We find that the order of modularity is the same as the order of the number of the enzymes under the classification based on the temperature preference but not on the oxygen requirement. Besides, inspection of modularity-based communities reveals that these communities are graph-theoretically meaningful yet not reflective of specific biological functions. From an evolutionary perspective, we find that the community structures are conserved only at the level of kingdoms. Our results call for more investigation into the interplay between evolution and modularity: how evolution shapes modularity, and how modularity affects evolution (mainly in terms of fitness and evolvability). Further, our results call for exploring new measures of modularity and network communities that better correspond to functional categorizations. PMID:22974099

Modular jet impingement assemblies with passive and active flow control for electronics cooling

DOEpatents

Zhou, Feng; Dede, Ercan Mehmet; Joshi, Shailesh

2016-09-13

Power electronics modules having modular jet impingement assembly utilized to cool heat generating devices are disclosed. The modular jet impingement assemblies include a modular manifold having a distribution recess, one or more angled inlet connection tubes positioned at an inlet end of the modular manifold that fluidly couple the inlet tube to the distribution recess and one or more outlet connection tubes positioned at an outlet end of the modular manifold that fluidly coupling the outlet tube to the distribution recess. The modular jet impingement assemblies include a manifold insert removably positioned within the distribution recess and include one or more inlet branch channels each including an impinging slot and one or more outlet branch channels each including a collecting slot. Further a heat transfer plate coupled to the modular manifold, the heat transfer plate comprising an impingement surface including an array of fins that extend toward the manifold insert.

Modular cathode assemblies and methods of using the same for electrochemical reduction

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

Wiedmeyer, Stanley G.; Barnes, Laurel A.; Williamson, Mark A.

Modular cathode assemblies are useable in electrolytic reduction systems and include a basket through which fluid electrolyte may pass and exchange charge with a material to be reduced in the basket. The basket can be divided into upper and lower sections to provide entry for the material. Example embodiment cathode assemblies may have any shape to permit modular placement at any position in reduction systems. Modular cathode assemblies include a cathode plate in the basket, to which unique and opposite electrical power may be supplied. Example embodiment modular cathode assemblies may have standardized electrical connectors. Modular cathode assemblies may bemore » supported by a top plate of an electrolytic reduction system. Electrolytic oxide reduction systems are operated by positioning modular cathode and anode assemblies at desired positions, placing a material in the basket, and charging the modular assemblies to reduce the metal oxide.« less

Modular cathode assemblies and methods of using the same for electrochemical reduction

DOEpatents

Wiedmeyer, Stanley G; Barnes, Laurel A; Williamson, Mark A; Willit, James L

2014-12-02

Modular cathode assemblies are useable in electrolytic reduction systems and include a basket through which fluid electrolyte may pass and exchange charge with a material to be reduced in the basket. The basket can be divided into upper and lower sections to provide entry for the material. Example embodiment cathode assemblies may have any shape to permit modular placement at any position in reduction systems. Modular cathode assemblies include a cathode plate in the basket, to which unique and opposite electrical power may be supplied. Example embodiment modular cathode assemblies may have standardized electrical connectors. Modular cathode assemblies may be supported by a top plate of an electrolytic reduction system. Electrolytic oxide reduction systems are operated by positioning modular cathode and anode assemblies at desired positions, placing a material in the basket, and charging the modular assemblies to reduce the metal oxide.

The Current Status of Modular Coordination. A Research Correlation Conference of Building Research Institute, Division of Engineering and Industrial Research (Fall 1959).

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC.

Publication of conference presentations include--(1) a brief review of current modular standard development, (2) the statistical status of modular practice, (3) availability of modular products, and (4) educational programs on modular coordination. Included are--(1) explanatory diagrams, (2) text of an open panel discussion, and (3) a list of…

The Vibrio cholerae Colonization Factor GbpA Possesses a Modular Structure that Governs Binding to Different Host Surfaces

PubMed Central

Wong, Edmond; Vaaje-Kolstad, Gustav; Ghosh, Avishek; Hurtado-Guerrero, Ramon; Konarev, Peter V.; Ibrahim, Adel F. M.; Svergun, Dmitri I.; Eijsink, Vincent G. H.; Chatterjee, Nabendu S.; van Aalten, Daan M. F.

2012-01-01

Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mammalian intestinal mucin through an unknown molecular mechanism. We report structural studies that reveal that GbpA possesses an unusual, elongated, four-domain structure, with domains 1 and 4 showing structural homology to chitin binding domains. A glycan screen revealed that GbpA binds to GlcNAc oligosaccharides. Structure-guided GbpA truncation mutants show that domains 1 and 4 of GbpA interact with chitin in vitro, whereas in vivo complementation studies reveal that domain 1 is also crucial for mucin binding and intestinal colonization. Bacterial binding studies show that domains 2 and 3 bind to the V. cholerae surface. Finally, mouse virulence assays show that only the first three domains of GbpA are required for colonization. These results explain how GbpA provides structural/functional modular interactions between V. cholerae, intestinal epithelium and chitinous exoskeletons. PMID:22253590

Atomically precise arrays of fluorescent silver clusters: a modular approach for metal cluster photonics on DNA nanostructures.

PubMed

Copp, Stacy M; Schultz, Danielle E; Swasey, Steven; Gwinn, Elisabeth G

2015-03-24

The remarkable precision that DNA scaffolds provide for arraying nanoscale optical elements enables optical phenomena that arise from interactions of metal nanoparticles, dye molecules, and quantum dots placed at nanoscale separations. However, control of ensemble optical properties has been limited by the difficulty of achieving uniform particle sizes and shapes. Ligand-stabilized metal clusters offer a route to atomically precise arrays that combine desirable attributes of both metals and molecules. Exploiting the unique advantages of the cluster regime requires techniques to realize controlled nanoscale placement of select cluster structures. Here we show that atomically monodisperse arrays of fluorescent, DNA-stabilized silver clusters can be realized on a prototypical scaffold, a DNA nanotube, with attachment sites separated by <10 nm. Cluster attachment is mediated by designed DNA linkers that enable isolation of specific clusters prior to assembly on nanotubes and preserve cluster structure and spectral purity after assembly. The modularity of this approach generalizes to silver clusters of diverse sizes and DNA scaffolds of many types. Thus, these silver cluster nano-optical elements, which themselves have colors selected by their particular DNA templating oligomer, bring unique dimensions of control and flexibility to the rapidly expanding field of nano-optics.

Modular Design in Treaty Verification Equipment

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

Macarthur, Duncan Whittemore; Benz, Jacob; Tolk, Keith

2015-01-27

It is widely believed that modular design is a good thing. However, there are often few explicit arguments, or even an agreed range of definitions, to back up this belief. In this paper, we examine the potential range of design modularity, the implications of various amounts of modularity, and the advantages and disadvantages of each level of modular construction. We conclude with a comparison of the advantages and disadvantages of each type, as well as discuss many caveats that should be observed to take advantage of the positive features of modularity and minimize the effects of the negative. The tradeoffsmore » described in this paper will be evaluated during the conceptual design to determine what amount of modularity should be included.« less

Sea shell diversity and rapidly evolving secretomes: insights into the evolution of biomineralization.

PubMed

Kocot, Kevin M; Aguilera, Felipe; McDougall, Carmel; Jackson, Daniel J; Degnan, Bernard M

2016-01-01

An external skeleton is an essential part of the body plan of many animals and is thought to be one of the key factors that enabled the great expansion in animal diversity and disparity during the Cambrian explosion. Molluscs are considered ideal to study the evolution of biomineralization because of their diversity of highly complex, robust and patterned shells. The molluscan shell forms externally at the interface of animal and environment, and involves controlled deposition of calcium carbonate within a framework of macromolecules that are secreted from the dorsal mantle epithelium. Despite its deep conservation within Mollusca, the mantle is capable of producing an incredible diversity of shell patterns, and macro- and micro-architectures. Here we review recent developments within the field of molluscan biomineralization, focusing on the genes expressed in the mantle that encode secreted proteins. The so-called mantle secretome appears to regulate shell deposition and patterning and in some cases becomes part of the shell matrix. Recent transcriptomic and proteomic studies have revealed marked differences in the mantle secretomes of even closely-related molluscs; these typically exceed expected differences based on characteristics of the external shell. All mantle secretomes surveyed to date include novel genes encoding lineage-restricted proteins and unique combinations of co-opted ancient genes. A surprisingly large proportion of both ancient and novel secreted proteins containing simple repetitive motifs or domains that are often modular in construction. These repetitive low complexity domains (RLCDs) appear to further promote the evolvability of the mantle secretome, resulting in domain shuffling, expansion and loss. RLCD families further evolve via slippage and other mechanisms associated with repetitive sequences. As analogous types of secreted proteins are expressed in biomineralizing tissues in other animals, insights into the evolution of the genes underlying molluscan shell formation may be applied more broadly to understanding the evolution of metazoan biomineralization.

Structure of the human CD97 gene: Exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily

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

Hamann, J.; Van Lier, R.A.W.; Hartmann, E.

1996-02-15

This article reports on the structure and genetic mapping of the human CD97 gene, a homologue to the secretin receptor superfamily of cell surface proteins. The detailed organization of the gene, which maps to the short arm of chromosome 19, is given. 18 refs., 1 fig., 1 tab.

What is your Cosmic Connection to the Elements?

NASA Technical Reports Server (NTRS)

White, Nicholas E. (Technical Monitor); Lochner, James; Rohrbach, Gail; Cochrane, Kim

2003-01-01

This information and activity booklet describes the roles of the Big Bang, types of stars, supernovae, cosmic ray interactions, and radioactive decay in the formation of the elements. The booklet includes instructions for the following classroom activities, intended for students in Grades 9-12: Grandma's Apple Pie; Cosmic Shuffle; Nickel-odeon; Kinesthetic Big Bang; Elemental Haiku; Cosmic Ray Collisions; Cosmic Abundances; and What's Out There.

High-Speed Optical Wide-Area Data-Communication Network

NASA Technical Reports Server (NTRS)

Monacos, Steve P.

1994-01-01

Proposed fiber-optic wide-area network (WAN) for digital communication balances input and output flows of data with its internal capacity by routing traffic via dynamically interconnected routing planes. Data transmitted optically through network by wavelength-division multiplexing in synchronous or asynchronous packets. WAN implemented with currently available technology. Network is multiple-ring cyclic shuffle exchange network ensuring traffic reaches its destination with minimum number of hops.

Lessons Learned from the Great Recession: Layoffs and the RIF-Induced Teacher Shuffle

ERIC Educational Resources Information Center

Goldhaber, Dan; Strunk, Katharine O.; Brown, Nate; Knight, David S.

2016-01-01

One consequence of the Great Recession is that teacher layoffs occurred at a scale previously unseen. In this article, we assess the effects of receiving a layoff notice on teacher mobility using data from Los Angeles and Washington State. Our analyses are based on 6-year panels of data in each site, including 4 years of layoffs. We find that the…

Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan

PubMed Central

2009-01-01

Background The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. Results A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2–3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. Conclusion The occurrences of scarlet fever in central Taiwan in 2000–2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003. PMID:19486515

Principles of auditory processing differ between sensory and premotor structures of the songbird forebrain

PubMed Central

Vicario, David S.

2017-01-01

Sensory and motor brain structures work in collaboration during perception. To evaluate their respective contributions, the present study recorded neural responses to auditory stimulation at multiple sites simultaneously in both the higher-order auditory area NCM and the premotor area HVC of the songbird brain in awake zebra finches (Taeniopygia guttata). Bird’s own song (BOS) and various conspecific songs (CON) were presented in both blocked and shuffled sequences. Neural responses showed plasticity in the form of stimulus-specific adaptation, with markedly different dynamics between the two structures. In NCM, the response decrease with repetition of each stimulus was gradual and long-lasting and did not differ between the stimuli or the stimulus presentation sequences. In contrast, HVC responses to CON stimuli decreased much more rapidly in the blocked than in the shuffled sequence. Furthermore, this decrease was more transient in HVC than in NCM, as shown by differential dynamics in the shuffled sequence. Responses to BOS in HVC decreased more gradually than to CON stimuli. The quality of neural representations, computed as the mutual information between stimuli and neural activity, was higher in NCM than in HVC. Conversely, internal functional correlations, estimated as the coherence between recording sites, were greater in HVC than in NCM. The cross-coherence between the two structures was weak and limited to low frequencies. These findings suggest that auditory communication signals are processed according to very different but complementary principles in NCM and HVC, a contrast that may inform study of the auditory and motor pathways for human speech processing. NEW & NOTEWORTHY Neural responses to auditory stimulation in sensory area NCM and premotor area HVC of the songbird forebrain show plasticity in the form of stimulus-specific adaptation with markedly different dynamics. These two structures also differ in stimulus representations and internal functional correlations. Accordingly, NCM seems to process the individually specific complex vocalizations of others based on prior familiarity, while HVC responses appear to be modulated by transitions and/or timing in the ongoing sequence of sounds. PMID:28031398

Analysis of Advanced Modular Power Systems (AMPS) for Deep Space Exploration

NASA Technical Reports Server (NTRS)

Oeftering, Richard; Soeder, James F.; Beach, Ray

2014-01-01

The Advanced Modular Power Systems (AMPS) project is developing a modular approach to spacecraft power systems for exploration beyond Earth orbit. AMPS is intended to meet the need of reducing the cost of design development, test and integration and also reducing the operational logistics cost of supporting exploration missions. AMPS seeks to establish modular power building blocks with standardized electrical, mechanical, thermal and data interfaces that can be applied across multiple exploration vehicles. The presentation discusses the results of a cost analysis that compares the cost of the modular approach against a traditional non-modular approach.

In Silico Investigation of a Surgical Interface for Remote Control of Modular Miniature Robots in Minimally Invasive Surgery

PubMed Central

Zygomalas, Apollon; Giokas, Konstantinos; Koutsouris, Dimitrios

2014-01-01

Aim. Modular mini-robots can be used in novel minimally invasive surgery techniques like natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single site (LESS) surgery. The control of these miniature assistants is complicated. The aim of this study is the in silico investigation of a remote controlling interface for modular miniature robots which can be used in minimally invasive surgery. Methods. The conceptual controlling system was developed, programmed, and simulated using professional robotics simulation software. Three different modes of control were programmed. The remote controlling surgical interface was virtually designed as a high scale representation of the respective modular mini-robot, therefore a modular controlling system itself. Results. With the proposed modular controlling system the user could easily identify the conformation of the modular mini-robot and adequately modify it as needed. The arrangement of each module was always known. The in silico investigation gave useful information regarding the controlling mode, the adequate speed of rearrangements, and the number of modules needed for efficient working tasks. Conclusions. The proposed conceptual model may promote the research and development of more sophisticated modular controlling systems. Modular surgical interfaces may improve the handling and the dexterity of modular miniature robots during minimally invasive procedures. PMID:25295187

In silico investigation of a surgical interface for remote control of modular miniature robots in minimally invasive surgery.

PubMed

Zygomalas, Apollon; Giokas, Konstantinos; Koutsouris, Dimitrios

2014-01-01

Aim. Modular mini-robots can be used in novel minimally invasive surgery techniques like natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single site (LESS) surgery. The control of these miniature assistants is complicated. The aim of this study is the in silico investigation of a remote controlling interface for modular miniature robots which can be used in minimally invasive surgery. Methods. The conceptual controlling system was developed, programmed, and simulated using professional robotics simulation software. Three different modes of control were programmed. The remote controlling surgical interface was virtually designed as a high scale representation of the respective modular mini-robot, therefore a modular controlling system itself. Results. With the proposed modular controlling system the user could easily identify the conformation of the modular mini-robot and adequately modify it as needed. The arrangement of each module was always known. The in silico investigation gave useful information regarding the controlling mode, the adequate speed of rearrangements, and the number of modules needed for efficient working tasks. Conclusions. The proposed conceptual model may promote the research and development of more sophisticated modular controlling systems. Modular surgical interfaces may improve the handling and the dexterity of modular miniature robots during minimally invasive procedures.

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus‐like particle

PubMed Central

Tekewe, Alemu; Connors, Natalie K.; Middelberg, Anton P. J.

2016-01-01

Abstract Virus‐like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co‐expression of unmodified VP1 and modular VP1‐RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. PMID:27222486

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus-like particle.

PubMed

Tekewe, Alemu; Connors, Natalie K; Middelberg, Anton P J; Lua, Linda H L

2016-08-01

Virus-like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co-expression of unmodified VP1 and modular VP1-RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. © 2016 The Protein Society.

Modular workcells: modern methods for laboratory automation.

PubMed

Felder, R A

1998-12-01

Laboratory automation is beginning to become an indispensable survival tool for laboratories facing difficult market competition. However, estimates suggest that only 8% of laboratories will be able to afford total laboratory automation systems. Therefore, automation vendors have developed alternative hardware configurations called 'modular automation', to fit the smaller laboratory. Modular automation consists of consolidated analyzers, integrated analyzers, modular workcells, and pre- and post-analytical automation. These terms will be defined in this paper. Using a modular automation model, the automated core laboratory will become a site where laboratory data is evaluated by trained professionals to provide diagnostic information to practising physicians. Modem software information management and process control tools will complement modular hardware. Proper standardization that will allow vendor-independent modular configurations will assure success of this revolutionary new technology.

The Modular need for the Division Signal Battalion

DTIC Science & Technology

2017-06-09

findings and analyzes them to expand on them. It is with these findings and subsequent analysis that the case studies shape the answer to the three...These case studies focus on the signal leadership development and how it occurred in the pre-modular force structure, during modularity, and the...the comparative case study research. The case studies focus on signal leader development in a pre-modular signal force, a modular signal force, and

Modular Fixturing System

NASA Technical Reports Server (NTRS)

Littell, Justin Anderson (Inventor); Street, Jon P. (Inventor)

2017-01-01

The modular fixturing system of the present invention is modular, reusable and capable of significant customization, both in terms of system radius and system height, allowing it to be arranged and rearranged in numerous unique configurations. The system includes multiple modular stanchions having stanchion shafts and stanchion feet that removably attach to apertures in a table. Angle brackets attached to the modular stanchions support shelves. These shelves in turn provide support to work pieces during fabrication processes such as welding.

A Modularized Counselor-Education Program.

ERIC Educational Resources Information Center

Miller, Thomas V.; Dimattia, Dominic J.

1978-01-01

Counselor-education programs may be enriched through the use of modularized learning experiences. This article notes several recent articles on competency-based counselor education, the concepts of simulation and modularization, and describes the process of developing a modularized master's program at the University of Bridgeport in Connecticut.…

On the classification of weakly integral modular categories

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

Bruillard, Paul; Galindo, César; Ng, Siu-Hung

In this paper we classify all modular categories of dimension 4m, where m is an odd square-free integer, and all rank 6 and rank 7 weakly integral modular categories. This completes the classification of weakly integral modular categories through rank 7. In particular, our results imply that all integral modular categories of rank at most 7 are pointed (that is, every simple object has dimension 1). All the non-integral (but weakly integral) modular categories of ranks 6 and 7 have dimension 4m, with m an odd square free integer, so their classification is an application of our main result. Themore » classification of rank 7 integral modular categories is facilitated by an analysis of the two group actions on modular categories: the Galois group of the field generated by the entries of the S-matrix and the group of invertible isomorphism classes of objects. We derive some valuable arithmetic consequences from these actions.« less

Modular interdependency in complex dynamical systems.

PubMed

Watson, Richard A; Pollack, Jordan B

2005-01-01

Herbert A. Simon's characterization of modularity in dynamical systems describes subsystems as having dynamics that are approximately independent of those of other subsystems (in the short term). This fits with the general intuition that modules must, by definition, be approximately independent. In the evolution of complex systems, such modularity may enable subsystems to be modified and adapted independently of other subsystems, whereas in a nonmodular system, modifications to one part of the system may result in deleterious side effects elsewhere in the system. But this notion of modularity and its effect on evolvability is not well quantified and is rather simplistic. In particular, modularity need not imply that intermodule dependences are weak or unimportant. In dynamical systems this is acknowledged by Simon's suggestion that, in the long term, the dynamical behaviors of subsystems do interact with one another, albeit in an "aggregate" manner--but this kind of intermodule interaction is omitted in models of modularity for evolvability. In this brief discussion we seek to unify notions of modularity in dynamical systems with notions of how modularity affects evolvability. This leads to a quantifiable measure of modularity and a different understanding of its effect on evolvability.

Individual differences and time-varying features of modular brain architecture.

PubMed

Liao, Xuhong; Cao, Miao; Xia, Mingrui; He, Yong

2017-05-15

Recent studies have suggested that human brain functional networks are topologically organized into functionally specialized but inter-connected modules to facilitate efficient information processing and highly flexible cognitive function. However, these studies have mainly focused on group-level network modularity analyses using "static" functional connectivity approaches. How these extraordinary modular brain structures vary across individuals and spontaneously reconfigure over time remain largely unknown. Here, we employed multiband resting-state functional MRI data (N=105) from the Human Connectome Project and a graph-based modularity analysis to systematically investigate individual variability and dynamic properties in modular brain networks. We showed that the modular structures of brain networks dramatically vary across individuals, with higher modular variability primarily in the association cortex (e.g., fronto-parietal and attention systems) and lower variability in the primary systems. Moreover, brain regions spontaneously changed their module affiliations on a temporal scale of seconds, which cannot be simply attributable to head motion and sampling error. Interestingly, the spatial pattern of intra-subject dynamic modular variability largely overlapped with that of inter-subject modular variability, both of which were highly reproducible across repeated scanning sessions. Finally, the regions with remarkable individual/temporal modular variability were closely associated with network connectors and the number of cognitive components, suggesting a potential contribution to information integration and flexible cognitive function. Collectively, our findings highlight individual modular variability and the notable dynamic characteristics in large-scale brain networks, which enhance our understanding of the neural substrates underlying individual differences in a variety of cognition and behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Modular Apparatus and Method for Attaching Multiple Devices

NASA Technical Reports Server (NTRS)

Okojie, Robert S (Inventor)

2015-01-01

A modular apparatus for attaching sensors and electronics is disclosed. The modular apparatus includes a square recess including a plurality of cavities and a reference cavity such that a pressure sensor can be connected to the modular apparatus. The modular apparatus also includes at least one voltage input hole and at least one voltage output hole operably connected to each of the plurality of cavities such that voltage can be applied to the pressure sensor and received from the pressure sensor.

Robotic hand with modular extensions

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

Salisbury, Curt Michael; Quigley, Morgan

A robotic device is described herein. The robotic device includes a frame that comprises a plurality of receiving regions that are configured to receive a respective plurality of modular robotic extensions. The modular robotic extensions are removably attachable to the frame at the respective receiving regions by way of respective mechanical fuses. Each mechanical fuse is configured to trip when a respective modular robotic extension experiences a predefined load condition, such that the respective modular robotic extension detaches from the frame when the load condition is met.

You Can Teach an Old Magician New Tricks

ERIC Educational Resources Information Center

Bonomo, John P.

2008-01-01

Mathematics forms the basis for many types of card tricks. One of the best-known works as follows: Take any 15 cards out of a deck and ask a volunteer to select one of the cards and place it back in the deck. After shuffling the cards, you deal out three piles of cards and ask the volunteer which pile his or her card is in. You collect up the…

Developing of Library for Proofs of Data Possession in Charm

DTIC Science & Technology

2013-06-01

INTENTIONALLY LEFT BLANK x LIST OF ACRONYMS AND ABBREVIATIONS API Application Programmer Interface DTP Datatype -preserving Encryption FedRAMP U.S...proposed block-cipher mode for Datatype -Preserving Encryption (DTP) uses the Knuth Shuffle in one of its steps [19]. It may be advantageous to...http://www.clustal.org/omega/clustalo-api/util_8c.html. [19] U. T. Mattsson, “Format-controlling encryption using datatype -preserving encryption

Nonlinear Rayleigh wave inversion based on the shuffled frog-leaping algorithm

NASA Astrophysics Data System (ADS)

Sun, Cheng-Yu; Wang, Yan-Yan; Wu, Dun-Shi; Qin, Xiao-Jun

2017-12-01

At present, near-surface shear wave velocities are mainly calculated through Rayleigh wave dispersion-curve inversions in engineering surface investigations, but the required calculations pose a highly nonlinear global optimization problem. In order to alleviate the risk of falling into a local optimal solution, this paper introduces a new global optimization method, the shuffle frog-leaping algorithm (SFLA), into the Rayleigh wave dispersion-curve inversion process. SFLA is a swarm-intelligence-based algorithm that simulates a group of frogs searching for food. It uses a few parameters, achieves rapid convergence, and is capability of effective global searching. In order to test the reliability and calculation performance of SFLA, noise-free and noisy synthetic datasets were inverted. We conducted a comparative analysis with other established algorithms using the noise-free dataset, and then tested the ability of SFLA to cope with data noise. Finally, we inverted a real-world example to examine the applicability of SFLA. Results from both synthetic and field data demonstrated the effectiveness of SFLA in the interpretation of Rayleigh wave dispersion curves. We found that SFLA is superior to the established methods in terms of both reliability and computational efficiency, so it offers great potential to improve our ability to solve geophysical inversion problems.

Molecular Approaches to Improve the Insecticidal Activity of Bacillus thuringiensis Cry Toxins

PubMed Central

Lucena, Wagner A.; Pelegrini, Patrícia B.; Martins-de-Sa, Diogo; Fonseca, Fernando C. A.; Gomes, Jose E.; de Macedo, Leonardo L. P.; da Silva, Maria Cristina M.; Oliveira, Raquel S.; Grossi-de-Sa, Maria F.

2014-01-01

Bacillus thuringiensis (Bt) is a gram-positive spore-forming soil bacterium that is distributed worldwide. Originally recognized as a pathogen of the silkworm, several strains were found on epizootic events in insect pests. In the 1960s, Bt began to be successfully used to control insect pests in agriculture, particularly because of its specificity, which reflects directly on their lack of cytotoxicity to human health, non-target organisms and the environment. Since the introduction of transgenic plants expressing Bt genes in the mid-1980s, numerous methodologies have been used to search for and improve toxins derived from native Bt strains. These improvements directly influence the increase in productivity and the decreased use of chemical insecticides on Bt-crops. Recently, DNA shuffling and in silico evaluations are emerging as promising tools for the development and exploration of mutant Bt toxins with enhanced activity against target insect pests. In this report, we describe natural and in vitro evolution of Cry toxins, as well as their relevance in the mechanism of action for insect control. Moreover, the use of DNA shuffling to improve two Bt toxins will be discussed together with in silico analyses of the generated mutations to evaluate their potential effect on protein structure and cytotoxicity. PMID:25123558

Understanding of how Propionibacterium acidipropionici respond to propionic acid stress at the level of proteomics

PubMed Central

Guan, Ningzi; Shin, Hyun-dong; Chen, Rachel R.; Li, Jianghua; Liu, Long; Du, Guocheng; Chen, Jian

2014-01-01

Propionic acid (PA) is an important platform chemical in the food, agriculture, and pharmaceutical industries and is mainly biosynthesized by propionibacteria. Acid tolerance in PA-producing strains is crucial. In previous work, we investigated the acid tolerance mechanism of Propionibacterium acidipropionici at microenvironmental levels by analyzing physiological changes in the parental strain and three PA-tolerant mutants obtained by genome shuffling. However, the molecular mechanism of PA tolerance in P. acidipropionici remained unclear. Here, we performed a comparative proteomics study of P. acidipropionici CGMCC 1.2230 and the acid-tolerant mutant P. acidipropionici WSH1105; MALDI-TOF/MS identified 24 proteins that significantly differed between the parental and shuffled strains. The differentially expressed proteins were mainly categorized as key components of crucial biological processes and the acid stress response. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to confirm differential expression of nine key proteins. Overexpression of the secretory protein glyceraldehyde-3-phosphate dehydrogenase and ATP synthase subunit α in Escherichia coli BL21 improved PA and acetic acid tolerance; overexpression of NADH dehydrogenase and methylmalonyl-CoA epimerase improved PA tolerance. These results provide new insights into the acid tolerance of P. acidipropionici and will facilitate the development of PA production through fermentation by propionibacteria. PMID:25377721

PTESFinder: a computational method to identify post-transcriptional exon shuffling (PTES) events.

PubMed

Izuogu, Osagie G; Alhasan, Abd A; Alafghani, Hani M; Santibanez-Koref, Mauro; Elliott, David J; Elliot, David J; Jackson, Michael S

2016-01-13

Transcripts, which have been subject to Post-transcriptional exon shuffling (PTES), have an exon order inconsistent with the underlying genomic sequence. These have been identified in a wide variety of tissues and cell types from many eukaryotes, and are now known to be mostly circular, cytoplasmic, and non-coding. Although there is no uniformly ascribed function, several have been shown to be involved in gene regulation. Accurate identification of these transcripts can, however, be difficult due to artefacts from a wide variety of sources. Here, we present a computational method, PTESFinder, to identify these transcripts from high throughput RNAseq data. Uniquely, it systematically excludes potential artefacts emanating from pseudogenes, segmental duplications, and template switching, and outputs both PTES and canonical exon junction counts to facilitate comparative analyses. In comparison with four existing methods, PTESFinder achieves highest specificity and comparable sensitivity at a variety of read depths. PTESFinder also identifies between 13 % and 41.6 % more structures, compared to publicly available methods recently used to identify human circular RNAs. With high sensitivity and specificity, user-adjustable filters that target known sources of false positives, and tailored output to facilitate comparison of transcript levels, PTESFinder will facilitate the discovery and analysis of these poorly understood transcripts.

Buried mine detection using fractal geometry analysis to the LWIR successive line scan data image

NASA Astrophysics Data System (ADS)

Araki, Kan

2012-06-01

We have engaged in research on buried mine/IED detection by remote sensing method using LWIR camera. A IR image of a ground, containing buried objects can be assumed as a superimposed pattern including thermal scattering which may depend on the ground surface roughness, vegetation canopy, and effect of the sun light, and radiation due to various heat interaction caused by differences in specific heat, size, and buried depth of the objects and local temperature of their surrounding environment. In this cumbersome environment, we introduce fractal geometry for analyzing from an IR image. Clutter patterns due to these complex elements have oftentimes low ordered fractal dimension of Hausdorff Dimension. On the other hand, the target patterns have its tendency of obtaining higher ordered fractal dimension in terms of Information Dimension. Random Shuffle Surrogate method or Fourier Transform Surrogate method is used to evaluate fractional statistics by applying shuffle of time sequence data or phase of spectrum. Fractal interpolation to each line scan was also applied to improve the signal processing performance in order to evade zero division and enhance information of data. Some results of target extraction by using relationship between low and high ordered fractal dimension are to be presented.

Evolution of EF-hand calcium-modulated proteins. IV. Exon shuffling did not determine the domain compositions of EF-hand proteins

NASA Technical Reports Server (NTRS)

Kretsinger, R. H.; Nakayama, S.

1993-01-01

In the previous three reports in this series we demonstrated that the EF-hand family of proteins evolved by a complex pattern of gene duplication, transposition, and splicing. The dendrograms based on exon sequences are nearly identical to those based on protein sequences for troponin C, the essential light chain myosin, the regulatory light chain, and calpain. This validates both the computational methods and the dendrograms for these subfamilies. The proposal of congruence for calmodulin, troponin C, essential light chain, and regulatory light chain was confirmed. There are, however, significant differences in the calmodulin dendrograms computed from DNA and from protein sequences. In this study we find that introns are distributed throughout the EF-hand domain and the interdomain regions. Further, dendrograms based on intron type and distribution bear little resemblance to those based on protein or on DNA sequences. We conclude that introns are inserted, and probably deleted, with relatively high frequency. Further, in the EF-hand family exons do not correspond to structural domains and exon shuffling played little if any role in the evolution of this widely distributed homolog family. Calmodulin has had a turbulent evolution. Its dendrograms based on protein sequence, exon sequence, 3'-tail sequence, intron sequences, and intron positions all show significant differences.

Detection of inter-frame forgeries in digital videos.

PubMed

K, Sitara; Mehtre, B M

2018-05-26

Videos are acceptable as evidence in the court of law, provided its authenticity and integrity are scientifically validated. Videos recorded by surveillance systems are susceptible to malicious alterations of visual content by perpetrators locally or remotely. Such malicious alterations of video contents (called video forgeries) are categorized into inter-frame and intra-frame forgeries. In this paper, we propose inter-frame forgery detection techniques using tamper traces from spatio-temporal and compressed domains. Pristine videos containing frames that are recorded during sudden camera zooming event, may get wrongly classified as tampered videos leading to an increase in false positives. To address this issue, we propose a method for zooming detection and it is incorporated in video tampering detection. Frame shuffling detection, which was not explored so far is also addressed in our work. Our method is capable of differentiating various inter-frame tamper events and its localization in the temporal domain. The proposed system is tested on 23,586 videos of which 2346 are pristine and rest of them are candidates of inter-frame forged videos. Experimental results show that we have successfully detected frame shuffling with encouraging accuracy rates. We have achieved improved accuracy on forgery detection in frame insertion, frame deletion and frame duplication. Copyright © 2018. Published by Elsevier B.V.

Modular femoral neck fracture after primary total hip arthroplasty.

PubMed

Sotereanos, Nicholas G; Sauber, Timothy J; Tupis, Todd T

2013-01-01

The use of modular femoral stems in primary total hip arthroplasty has increased considerably in recent years. These modular components offer the surgeon the ability to independently alter version, offset, and length of the femoral component of a hip arthroplasty. This increases the surgeon's ability to accurately recreate the relevant anatomy but increases the possibilities of corrosion and fracture. Multiple case reports have highlighted fractures of these modular components. We present a case of a fracture of a modular design that has had no previously reported modular neck fractures. The patient was informed that data concerning the case would be submitted, and he consented. Copyright © 2013 Elsevier Inc. All rights reserved.

Modular properties of 6d (DELL) systems

NASA Astrophysics Data System (ADS)

Aminov, G.; Mironov, A.; Morozov, A.

2017-11-01

If super-Yang-Mills theory possesses the exact conformal invariance, there is an additional modular invariance under the change of the complex bare charge [InlineMediaObject not available: see fulltext.]. The low-energy Seiberg-Witten prepotential ℱ( a), however, is not explicitly invariant, because the flat moduli also change a - → a D = ∂ℱ/∂ a. In result, the prepotential is not a modular form and depends also on the anomalous Eisenstein series E 2. This dependence is usually described by the universal MNW modular anomaly equation. We demonstrate that, in the 6 d SU( N) theory with two independent modular parameters τ and \\widehat{τ} , the modular anomaly equation changes, because the modular transform of τ is accompanied by an ( N -dependent!) shift of \\widehat{τ} and vice versa. This is a new peculiarity of double-elliptic systems, which deserves further investigation.

Towards a Formal Basis for Modular Safety Cases

NASA Technical Reports Server (NTRS)

Denney, Ewen; Pai, Ganesh

2015-01-01

Safety assurance using argument-based safety cases is an accepted best-practice in many safety-critical sectors. Goal Structuring Notation (GSN), which is widely used for presenting safety arguments graphically, provides a notion of modular arguments to support the goal of incremental certification. Despite the efforts at standardization, GSN remains an informal notation whereas the GSN standard contains appreciable ambiguity especially concerning modular extensions. This, in turn, presents challenges when developing tools and methods to intelligently manipulate modular GSN arguments. This paper develops the elements of a theory of modular safety cases, leveraging our previous work on formalizing GSN arguments. Using example argument structures we highlight some ambiguities arising through the existing guidance, present the intuition underlying the theory, clarify syntax, and address modular arguments, contracts, well-formedness and well-scopedness of modules. Based on this theory, we have a preliminary implementation of modular arguments in our toolset, AdvoCATE.

Brain modularity controls the critical behavior of spontaneous activity.

PubMed

Russo, R; Herrmann, H J; de Arcangelis, L

2014-03-13

The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

Why Go Modular? A Review of Modular A-Level Mathematics.

ERIC Educational Resources Information Center

Taverner, Sally; Wright, Martin

1997-01-01

Attitudes, academic intentions, and attainment of students gaining a grade in A-level (Advanced level) mathematics were compared for those who followed a modular course and those assessed at the end of two years of study. Overall, the final grades of those assessed modularly were half a grade higher. (JOW)

On Classification of Modular Categories by Rank: Table A.1

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

Bruillard, Paul; Ng, Siu-Hung; Rowell, Eric C.

2016-04-10

The feasibility of a classification-by-rank program for modular categories follows from the Rank-Finiteness Theorem. We develop arithmetic, representation theoretic and algebraic methods for classifying modular categories by rank. As an application, we determine all possible fusion rules for all rank=5 modular categories and describe the corresponding monoidal equivalence classes.

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells.

PubMed

Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A; Schmid, Michael C; Schröder, Gunnar; Vergunst, Annette C; Carena, Ilaria; Dehio, Christoph

2005-01-18

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells.

Unraveling the disease consequences and mechanisms of modular structure in animal social networks

PubMed Central

Leu, Stephan T.; Cross, Paul C.; Hudson, Peter J.; Bansal, Shweta

2017-01-01

Disease risk is a potential cost of group living. Although modular organization is thought to reduce this cost in animal societies, empirical evidence toward this hypothesis has been conflicting. We analyzed empirical social networks from 43 animal species to motivate our study of the epidemiological consequences of modular structure in animal societies. From these empirical studies, we identified the features of interaction patterns associated with network modularity and developed a theoretical network model to investigate when and how subdivisions in social networks influence disease dynamics. Contrary to prior work, we found that disease risk is largely unaffected by modular structure, although social networks beyond a modular threshold experience smaller disease burden and longer disease duration. Our results illustrate that the lowering of disease burden in highly modular social networks is driven by two mechanisms of modular organization: network fragmentation and subgroup cohesion. Highly fragmented social networks with cohesive subgroups are able to structurally trap infections within a few subgroups and also cause a structural delay to the spread of disease outbreaks. Finally, we show that network models incorporating modular structure are necessary only when prior knowledge suggests that interactions within the population are highly subdivided. Otherwise, null networks based on basic knowledge about group size and local contact heterogeneity may be sufficient when data-limited estimates of epidemic consequences are necessary. Overall, our work does not support the hypothesis that modular structure universally mitigates the disease impact of group living. PMID:28373567

Unraveling the disease consequences and mechanisms of modular structure in animal social networks

USGS Publications Warehouse

Sah, Pratha; Leu, Stephan T.; Cross, Paul C.; Hudson, Peter J.; Bansal, Shweta

2017-01-01

Disease risk is a potential cost of group living. Although modular organization is thought to reduce this cost in animal societies, empirical evidence toward this hypothesis has been conflicting. We analyzed empirical social networks from 43 animal species to motivate our study of the epidemiological consequences of modular structure in animal societies. From these empirical studies, we identified the features of interaction patterns associated with network modularity and developed a theoretical network model to investigate when and how subdivisions in social networks influence disease dynamics. Contrary to prior work, we found that disease risk is largely unaffected by modular structure, although social networks beyond a modular threshold experience smaller disease burden and longer disease duration. Our results illustrate that the lowering of disease burden in highly modular social networks is driven by two mechanisms of modular organization: network fragmentation and subgroup cohesion. Highly fragmented social networks with cohesive subgroups are able to structurally trap infections within a few subgroups and also cause a structural delay to the spread of disease outbreaks. Finally, we show that network models incorporating modular structure are necessary only when prior knowledge suggests that interactions within the population are highly subdivided. Otherwise, null networks based on basic knowledge about group size and local contact heterogeneity may be sufficient when data-limited estimates of epidemic consequences are necessary. Overall, our work does not support the hypothesis that modular structure universally mitigates the disease impact of group living.

Unraveling the disease consequences and mechanisms of modular structure in animal social networks.

PubMed

Sah, Pratha; Leu, Stephan T; Cross, Paul C; Hudson, Peter J; Bansal, Shweta

2017-04-18

Disease risk is a potential cost of group living. Although modular organization is thought to reduce this cost in animal societies, empirical evidence toward this hypothesis has been conflicting. We analyzed empirical social networks from 43 animal species to motivate our study of the epidemiological consequences of modular structure in animal societies. From these empirical studies, we identified the features of interaction patterns associated with network modularity and developed a theoretical network model to investigate when and how subdivisions in social networks influence disease dynamics. Contrary to prior work, we found that disease risk is largely unaffected by modular structure, although social networks beyond a modular threshold experience smaller disease burden and longer disease duration. Our results illustrate that the lowering of disease burden in highly modular social networks is driven by two mechanisms of modular organization: network fragmentation and subgroup cohesion. Highly fragmented social networks with cohesive subgroups are able to structurally trap infections within a few subgroups and also cause a structural delay to the spread of disease outbreaks. Finally, we show that network models incorporating modular structure are necessary only when prior knowledge suggests that interactions within the population are highly subdivided. Otherwise, null networks based on basic knowledge about group size and local contact heterogeneity may be sufficient when data-limited estimates of epidemic consequences are necessary. Overall, our work does not support the hypothesis that modular structure universally mitigates the disease impact of group living.

Modular assembly for supporting, straining, and directing flow to a core in a nuclear reactor

DOEpatents

Pennell, William E.

1977-01-01

A reactor core support arrangement for supporting, straining, and providing fluid flow to the core and periphery of a nuclear reactor during normal operation. A plurality of removable inlet modular units are contained within permanent liners in the lower supporting plate of the reactor vessel lower internals. During normal operation (1) each inlet modular unit directs main coolant flow to a plurality of core assemblies, the latter being removably supported in receptacles in the upper portion of the modular unit and (2) each inlet modular unit may direct bypass flow to a low pressure annular region of the reactor vessel. Each inlet modular unit may include special fluid seals interposed between mating surfaces of the inlet modular units and the core assemblies and between the inlet modular units and the liners, to minimize leakage and achieve an hydraulic balance. Utilizing the hydraulic balance, the modular units are held in the liners and the assemblies are held in the modular unit receptacles by their own respective weight. Included as part of the permanent liners below the horizontal support plate are generally hexagonal axial debris barriers. The axial debris barriers collectively form a bottom boundary of a secondary high pressure plenum, the upper boundary of which is the bottom surface of the horizontal support plate. Peripheral liners include radial debris barriers which collectively form a barrier against debris entry radially. During normal operation primary coolant inlet openings in the liner, below the axial debris barriers, pass a large amount of coolant into the inlet modular units, and secondary coolant inlet openings in the portion of the liners within the secondary plenum pass a small amount of coolant into the inlet modular units. The secondary coolant inlet openings also provide alternative coolant inlet flow paths in the unlikely event of blockage of the primary inlet openings. The primary inlet openings have characteristics which limit the entry of debris and minimize the potential for debris entering the primary inlets blocking the secondary inlets from inside the modular unit.

Portable modular detection system

DOEpatents

Brennan, James S [Rodeo, CA; Singh, Anup [Danville, CA; Throckmorton, Daniel J [Tracy, CA; Stamps, James F [Livermore, CA

2009-10-13

Disclosed herein are portable and modular detection devices and systems for detecting electromagnetic radiation, such as fluorescence, from an analyte which comprises at least one optical element removably attached to at least one alignment rail. Also disclosed are modular detection devices and systems having an integrated lock-in amplifier and spatial filter and assay methods using the portable and modular detection devices.

Modularity-like objective function in annotated networks

NASA Astrophysics Data System (ADS)

Xie, Jia-Rong; Wang, Bing-Hong

2017-12-01

We ascertain the modularity-like objective function whose optimization is equivalent to the maximum likelihood in annotated networks. We demonstrate that the modularity-like objective function is a linear combination of modularity and conditional entropy. In contrast with statistical inference methods, in our method, the influence of the metadata is adjustable; when its influence is strong enough, the metadata can be recovered. Conversely, when it is weak, the detection may correspond to another partition. Between the two, there is a transition. This paper provides a concept for expanding the scope of modularity methods.

Modular organization and hospital performance.

PubMed

Kuntz, Ludwig; Vera, Antonio

2007-02-01

The concept of modularization represents a modern form of organization, which contains the vertical disaggregation of the firm and the use of market mechanisms within hierarchies. The objective of this paper is to examine whether the use of modular structures has a positive effect on hospital performance. The empirical section makes use of multiple regression analyses and leads to the main result that modularization does not have a positive effect on hospital performance. However, the analysis also finds out positive efficiency effects of two central ideas of modularization, namely process orientation and internal market mechanisms.

Modular analysis of biological networks.

PubMed

Kaltenbach, Hans-Michael; Stelling, Jörg

2012-01-01

The analysis of complex biological networks has traditionally relied on decomposition into smaller, semi-autonomous units such as individual signaling pathways. With the increased scope of systems biology (models), rational approaches to modularization have become an important topic. With increasing acceptance of de facto modularity in biology, widely different definitions of what constitutes a module have sparked controversies. Here, we therefore review prominent classes of modular approaches based on formal network representations. Despite some promising research directions, several important theoretical challenges remain open on the way to formal, function-centered modular decompositions for dynamic biological networks.

Full characterization of modular values for finite-dimensional systems

NASA Astrophysics Data System (ADS)

Ho, Le Bin; Imoto, Nobuyuki

2016-06-01

Kedem and Vaidman obtained a relationship between the spin-operator modular value and its weak value for specific coupling strengths [14]. Here we give a general expression for the modular value in the n-dimensional Hilbert space using the weak values up to (n - 1)th order of an arbitrary observable for any coupling strength, assuming non-degenerated eigenvalues. For two-dimensional case, it shows a linear relationship between the weak value and the modular value. We also relate the modular value of the sum of observables to the weak value of their product.

On the role of sparseness in the evolution of modularity in gene regulatory networks

PubMed Central

2018-01-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases. PMID:29775459

On the role of sparseness in the evolution of modularity in gene regulatory networks.

PubMed

Espinosa-Soto, Carlos

2018-05-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

Anatomical Network Analysis Shows Decoupling of Modular Lability and Complexity in the Evolution of the Primate Skull

PubMed Central

Esteve-Altava, Borja; Boughner, Julia C.; Diogo, Rui; Villmoare, Brian A.; Rasskin-Gutman, Diego

2015-01-01

Modularity and complexity go hand in hand in the evolution of the skull of primates. Because analyses of these two parameters often use different approaches, we do not know yet how modularity evolves within, or as a consequence of, an also-evolving complex organization. Here we use a novel network theory-based approach (Anatomical Network Analysis) to assess how the organization of skull bones constrains the co-evolution of modularity and complexity among primates. We used the pattern of bone contacts modeled as networks to identify connectivity modules and quantify morphological complexity. We analyzed whether modularity and complexity evolved coordinately in the skull of primates. Specifically, we tested Herbert Simon’s general theory of near-decomposability, which states that modularity promotes the evolution of complexity. We found that the skulls of extant primates divide into one conserved cranial module and up to three labile facial modules, whose composition varies among primates. Despite changes in modularity, statistical analyses reject a positive feedback between modularity and complexity. Our results suggest a decoupling of complexity and modularity that translates to varying levels of constraint on the morphological evolvability of the primate skull. This study has methodological and conceptual implications for grasping the constraints that underlie the developmental and functional integration of the skull of humans and other primates. PMID:25992690

Programming Saposin-Mediated Compensatory Metabolic Sinks for Enhanced Ubiquinone Production.

PubMed

Xu, Wen; Yuan, Jifeng; Yang, Shuiyun; Ching, Chi-Bun; Liu, Jiankang

2016-12-16

Microbial synthesis of ubiquinone by fermentation processes has been emerging in recent years. However, as ubiquinone is a primary metabolite that is tightly regulated by the host central metabolism, tweaking the individual pathway components could only result in a marginal improvement on the ubiquinone production. Given that ubiquinone is stored in the lipid bilayer, we hypothesized that introducing additional metabolic sink for storing ubiquinone might improve the CoQ 10 production. As human lipid binding/transfer protein saposin B (hSapB) was reported to extract ubiquinone from the lipid bilayer and form the water-soluble complex, hSapB was chosen to build a compensatory metabolic sink for the ubiquinone storage. As a proof-of-concept, hSapB-mediated metabolic sink systems were devised and systematically investigated in the model organism of Escherichia coli. The hSapB-mediated periplasmic sink resulted in more than 200% improvement of CoQ 8 over the wild type strain. Further investigation revealed that hSapB-mediated sink systems could also improve the CoQ 10 production in a CoQ 10 -hyperproducing E. coli strain obtained by a modular pathway rewiring approach. As the design principles and the engineering strategies reported here are generalizable to other microbes, compensatory sink systems will be a method of significant interest to the synthetic biology community.

iELM—a web server to explore short linear motif-mediated interactions

PubMed Central

Weatheritt, Robert J.; Jehl, Peter; Dinkel, Holger; Gibson, Toby J.

2012-01-01

The recent expansion in our knowledge of protein–protein interactions (PPIs) has allowed the annotation and prediction of hundreds of thousands of interactions. However, the function of many of these interactions remains elusive. The interactions of Eukaryotic Linear Motif (iELM) web server provides a resource for predicting the function and positional interface for a subset of interactions mediated by short linear motifs (SLiMs). The iELM prediction algorithm is based on the annotated SLiM classes from the Eukaryotic Linear Motif (ELM) resource and allows users to explore both annotated and user-generated PPI networks for SLiM-mediated interactions. By incorporating the annotated information from the ELM resource, iELM provides functional details of PPIs. This can be used in proteomic analysis, for example, to infer whether an interaction promotes complex formation or degradation. Furthermore, details of the molecular interface of the SLiM-mediated interactions are also predicted. This information is displayed in a fully searchable table, as well as graphically with the modular architecture of the participating proteins extracted from the UniProt and Phospho.ELM resources. A network figure is also presented to aid the interpretation of results. The iELM server supports single protein queries as well as large-scale proteomic submissions and is freely available at http://i.elm.eu.org. PMID:22638578

Modular Mayhem? A Case Study of the Development of the A-Level Science Curriculum in England

ERIC Educational Resources Information Center

Hayward, Geoff; McNicholl, Jane

2007-01-01

This article investigates the costs and benefits of the increased use of modular or unitized qualification designs through a case study of the GCE A-level science curriculum in England. Following a brief review of the development of modular A-levels, the various proposed advantages of modularity--short-term goals and regular feedback, flexibility…

Simulation of value stream mapping and discrete optimization of energy consumption in modular construction

NASA Astrophysics Data System (ADS)

Chowdhury, Md Mukul

With the increased practice of modularization and prefabrication, the construction industry gained the benefits of quality management, improved completion time, reduced site disruption and vehicular traffic, and improved overall safety and security. Whereas industrialized construction methods, such as modular and manufactured buildings, have evolved over decades, core techniques used in prefabrication plants vary only slightly from those employed in traditional site-built construction. With a focus on energy and cost efficient modular construction, this research presents the development of a simulation, measurement and optimization system for energy consumption in the manufacturing process of modular construction. The system is based on Lean Six Sigma principles and loosely coupled system operation to identify the non-value adding tasks and possible causes of low energy efficiency. The proposed system will also include visualization functions for demonstration of energy consumption in modular construction. The benefits of implementing this system include a reduction in the energy consumption in production cost, decrease of energy cost in the production of lean-modular construction, and increase profit. In addition, the visualization functions will provide detailed information about energy efficiency and operation flexibility in modular construction. A case study is presented to validate the reliability of the system.

Framework for Defining and Assessing Benefits of a Modular Assembly Design Approach for Exploration Systems

NASA Technical Reports Server (NTRS)

Dorsey, John T.; Collins, Timothy J.; Moe, Rud V.; Doggett,. William R.

2006-01-01

A comprehensive modular assembly system model has been proposed that extends the art from modular hardware, to include in-space assembly, servicing and repair and it s critical components of infrastructure, agents and assembly operations. Benefits of modular assembly have been identified and a set of metrics defined that extends the art beyond the traditional measures of performance, with emphasis on criteria that allow life-cycle mission costs to be used as a figure of merit (and include all substantive terms that have an impact on the evaluation). The modular assembly approach was used as a basis for developing a Solar Electric Transfer Vehicle (SETV) concept and three modular assembly scenarios were developed. The modular assembly approach also allows the SETV to be entered into service much earlier than competing conventional configurations and results in a great deal of versatility in accommodating different launch vehicle payload capabilities, allowing for modules to be pre-assembled before launch or assembled on orbit, without changing the space vehicle design.

Modular Knowledge Representation and Reasoning in the Semantic Web

NASA Astrophysics Data System (ADS)

Serafini, Luciano; Homola, Martin

Construction of modular ontologies by combining different modules is becoming a necessity in ontology engineering in order to cope with the increasing complexity of the ontologies and the domains they represent. The modular ontology approach takes inspiration from software engineering, where modularization is a widely acknowledged feature. Distributed reasoning is the other side of the coin of modular ontologies: given an ontology comprising of a set of modules, it is desired to perform reasoning by combination of multiple reasoning processes performed locally on each of the modules. In the last ten years, a number of approaches for combining logics has been developed in order to formalize modular ontologies. In this chapter, we survey and compare the main formalisms for modular ontologies and distributed reasoning in the Semantic Web. We select four formalisms build on formal logical grounds of Description Logics: Distributed Description Logics, ℰ-connections, Package-based Description Logics and Integrated Distributed Description Logics. We concentrate on expressivity and distinctive modeling features of each framework. We also discuss reasoning capabilities of each framework.

Classification of functional interactions from multi-electrodes data using conditional modularity analysis

NASA Astrophysics Data System (ADS)

Makhtar, Siti Noormiza; Senik, Mohd Harizal

2018-02-01

The availability of massive amount of neuronal signals are attracting widespread interest in functional connectivity analysis. Functional interactions estimated by multivariate partial coherence analysis in the frequency domain represent the connectivity strength in this study. Modularity is a network measure for the detection of community structure in network analysis. The discovery of community structure for the functional neuronal network was implemented on multi-electrode array (MEA) signals recorded from hippocampal regions in isoflurane-anaesthetized Lister-hooded rats. The analysis is expected to show modularity changes before and after local unilateral kainic acid (KA)-induced epileptiform activity. The result is presented using color-coded graphic of conditional modularity measure for 19 MEA nodes. This network is separated into four sub-regions to show the community detection within each sub-region. The results show that classification of neuronal signals into the inter- and intra-modular nodes is feasible using conditional modularity analysis. Estimation of segregation properties using conditional modularity analysis may provide further information about functional connectivity from MEA data.

Recognition of Isolated Non-Speech Sounds.

DTIC Science & Technology

1987-05-31

stapler could be presented within a set of paper shuffling sounds and within a set of sounds characteristic of entering a room. The former context...should act in a top down manner to suggest a stapler event for the sound whereas the latter context will suggest that a light has been switched on. Such...Moulton Street Cambridge, MA 02238 " Department of the Army Or. William B. Rouse School of Industrial and Systems Director, Organizations and Systems

Scalable Wrap-Around Shuffle Exchange Network with Deflection Routing

NASA Technical Reports Server (NTRS)

Monacos, Steve P. (Inventor)

1997-01-01

The invention in one embodiment is a communication network including plural non-blocking crossbar nodes, first apparatus for connecting the nodes in a first layer of connecting links, and second apparatus for connecting links independent of the first layer, whereby each layer is connected to the other layer at each point of the nodes. Preferably, each one of the layers of connecting links corresponds to one recirculating network topology that closes in on itself.

A Formal Theory for Modular ERDF Ontologies

NASA Astrophysics Data System (ADS)

Analyti, Anastasia; Antoniou, Grigoris; Damásio, Carlos Viegas

The success of the Semantic Web is impossible without any form of modularity, encapsulation, and access control. In an earlier paper, we extended RDF graphs with weak and strong negation, as well as derivation rules. The ERDF #n-stable model semantics of the extended RDF framework (ERDF) is defined, extending RDF(S) semantics. In this paper, we propose a framework for modular ERDF ontologies, called modular ERDF framework, which enables collaborative reasoning over a set of ERDF ontologies, while support for hidden knowledge is also provided. In particular, the modular ERDF stable model semantics of modular ERDF ontologies is defined, extending the ERDF #n-stable model semantics. Our proposed framework supports local semantics and different points of view, local closed-world and open-world assumptions, and scoped negation-as-failure. Several complexity results are provided.

Future Concepts for Modular, Intelligent Aerospace Power Systems

NASA Technical Reports Server (NTRS)

Button, Robert M.; Soeder, James F.

2004-01-01

Nasa's resent commitment to Human and Robotic Space Exploration obviates the need for more affordable and sustainable systems and missions. Increased use of modularity and on-board intelligent technologies will enable these lofty goals. To support this new paradigm, an advanced technology program to develop modular, intelligent power management and distribution (PMAD) system technologies is presented. The many benefits to developing and including modular functionality in electrical power components and systems are shown to include lower costs and lower mass for highly reliable systems. The details of several modular technologies being developed by NASA are presented, broken down into hierarchical levels. Modularity at the device level, including the use of power electronic building blocks, is shown to provide benefits in lowering the development time and costs of new power electronic components.

Modular multiplication in GF(p) for public-key cryptography

NASA Astrophysics Data System (ADS)

Olszyna, Jakub

Modular multiplication forms the basis of modular exponentiation which is the core operation of the RSA cryptosystem. It is also present in many other cryptographic algorithms including those based on ECC and HECC. Hence, an efficient implementation of PKC relies on efficient implementation of modular multiplication. The paper presents a survey of most common algorithms for modular multiplication along with hardware architectures especially suitable for cryptographic applications in energy constrained environments. The motivation for studying low-power and areaefficient modular multiplication algorithms comes from enabling public-key security for ultra-low power devices that can perform under constrained environments like wireless sensor networks. Serial architectures for GF(p) are analyzed and presented. Finally proposed architectures are verified and compared according to the amount of power dissipated throughout the operation.

Modular space station Phase B extension preliminary performance specification. Volume 2: Project

NASA Technical Reports Server (NTRS)

1971-01-01

The four systems of the modular space station project are described, and the interfaces between this project and the shuttle project, the tracking and data relay satellite project, and an arbitrarily defined experiment project are defined. The experiment project was synthesized from internal experiments, detached research and application modules, and attached research and application modules to derive a set of interface requirements which will support multiple combinations of these elements expected during the modular space station mission. The modular space station project element defines a 6-man orbital program capable of growth to a 12-man orbital program capability. The modular space station project element specification defines the modular space station system, the premission operations support system, the mission operations support system, and the cargo module system and their interfaces.

Z-Score-Based Modularity for Community Detection in Networks

PubMed Central

Miyauchi, Atsushi; Kawase, Yasushi

2016-01-01

Identifying community structure in networks is an issue of particular interest in network science. The modularity introduced by Newman and Girvan is the most popular quality function for community detection in networks. In this study, we identify a problem in the concept of modularity and suggest a solution to overcome this problem. Specifically, we obtain a new quality function for community detection. We refer to the function as Z-modularity because it measures the Z-score of a given partition with respect to the fraction of the number of edges within communities. Our theoretical analysis shows that Z-modularity mitigates the resolution limit of the original modularity in certain cases. Computational experiments using both artificial networks and well-known real-world networks demonstrate the validity and reliability of the proposed quality function. PMID:26808270

Ground-based studies of tropisms in hardware developed for the European Modular Cultivation System (EMCS)

NASA Astrophysics Data System (ADS)

Correll, Melanie J.; Edelmann, Richard E.; Hangarter, Roger P.; Mullen, Jack L.; Kiss, John Z.

Phototropism and gravitropism play key roles in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. The blue-light response is controlled by the phototropins while the red-light response is mediated by the phytochrome family of photoreceptors. In order to better characterize root phototropism, we plan to perform experiments in microgravity so that this tropism can be more effectively studied without the interactions with the gravity response. Our experiments are to be performed on the European Modular Cultivation System (EMCS), which provides an incubator, lighting system, and high resolution video that are on a centrifuge palette. These experiments will be performed at μg, 1g (control) and fractional g-levels. In order to ensure success of this mission on the International Space Station, we have been conducting ground-based studies on growth, phototropism, and gravitropism in experimental unique equipment (EUE) that was designed for our experiments with Arabidopsis seedlings. Currently, the EMCS and our EUE are scheduled for launch on space shuttle mission STS-121. This project should provide insight into how the blue- and red-light signaling systems interact with each other and with the gravisensing system.

Spaceflight studies of tropisms in the European Modular Cultivation System

NASA Astrophysics Data System (ADS)

Kiss, J. Z.; Correll, M. J.; Edelmann, R. E.

Phototropism and gravitropism play key roles in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. The blue-light response is controlled by the phototropins while the red-light response is mediated by the phytochrome family of photoreceptors. In order to better characterize root phototropism, we plan to perform experiments in microgravity so that this tropism can be more effectively studied without the interactions with the gravity response. Our experiments are to be performed on the European Modular Cultivation System (EMCS), which provides an incubator, lighting system, and high resolution video that are on a centrifuge palette. These experiments will be performed at μ g, 1g (control) and fractional g-levels. In order to ensure success of this mission on the International Space Station (ISS), we have been performing ground-based studies on growth, phototropism, and gravitropism in experimental unique equipment (EUE) that was designed for our experiments that will use Arabidopsis seedlings. Currently, the EMCS and our EUE are scheduled for launch on space shuttle mission STS-121. This project should provide insight into how the blue-light and red-light signaling systems interact with each other, and also with the gravisensing system.

BASIC: A Simple and Accurate Modular DNA Assembly Method.

PubMed

Storch, Marko; Casini, Arturo; Mackrow, Ben; Ellis, Tom; Baldwin, Geoff S

2017-01-01

Biopart Assembly Standard for Idempotent Cloning (BASIC) is a simple, accurate, and robust DNA assembly method. The method is based on linker-mediated DNA assembly and provides highly accurate DNA assembly with 99 % correct assemblies for four parts and 90 % correct assemblies for seven parts [1]. The BASIC standard defines a single entry vector for all parts flanked by the same prefix and suffix sequences and its idempotent nature means that the assembled construct is returned in the same format. Once a part has been adapted into the BASIC format it can be placed at any position within a BASIC assembly without the need for reformatting. This allows laboratories to grow comprehensive and universal part libraries and to share them efficiently. The modularity within the BASIC framework is further extended by the possibility of encoding ribosomal binding sites (RBS) and peptide linker sequences directly on the linkers used for assembly. This makes BASIC a highly versatile library construction method for combinatorial part assembly including the construction of promoter, RBS, gene variant, and protein-tag libraries. In comparison with other DNA assembly standards and methods, BASIC offers a simple robust protocol; it relies on a single entry vector, provides for easy hierarchical assembly, and is highly accurate for up to seven parts per assembly round [2].

Revealing hidden insect-fungus interactions; moderately specialized, modular and anti-nested detritivore networks.

PubMed

Jacobsen, Rannveig M; Sverdrup-Thygeson, Anne; Kauserud, Håvard; Birkemoe, Tone

2018-04-11

Ecological networks are composed of interacting communities that influence ecosystem structure and function. Fungi are the driving force for ecosystem processes such as decomposition and carbon sequestration in terrestrial habitats, and are strongly influenced by interactions with invertebrates. Yet, interactions in detritivore communities have rarely been considered from a network perspective. In the present study, we analyse the interaction networks between three functional guilds of fungi and insects sampled from dead wood. Using DNA metabarcoding to identify fungi, we reveal a diversity of interactions differing in specificity in the detritivore networks, involving three guilds of fungi. Plant pathogenic fungi were relatively unspecialized in their interactions with insects inhabiting dead wood, while interactions between the insects and wood-decay fungi exhibited the highest degree of specialization, which was similar to estimates for animal-mediated seed dispersal networks in previous studies. The low degree of specialization for insect symbiont fungi was unexpected. In general, the pooled insect-fungus networks were significantly more specialized, more modular and less nested than randomized networks. Thus, the detritivore networks had an unusual anti-nested structure. Future studies might corroborate whether this is a common aspect of networks based on interactions with fungi, possibly owing to their often intense competition for substrate. © 2018 The Author(s).

Mild and modular surface modification of cellulose via hetero Diels-Alder (HDA) cycloaddition.

PubMed

Goldmann, Anja S; Tischer, Thomas; Barner, Leonie; Bruns, Michael; Barner-Kowollik, Christopher

2011-04-11

A combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and hetero Diels-Alder (HDA) cycloaddition was used to effect, under mild (T ≈ 20 °C), fast, and modular conditions, the grafting of poly(isobornyl acrylate) (M(n) = 9800 g mol(-1), PDI = 1.19) onto a solid cellulose substrate. The active hydroxyl groups expressed on the cellulose fibers were converted to tosylate leaving groups, which were subsequently substituted by a highly reactive cyclopentadienyl functionality (Cp). By employing the reactive Cp-functionality as a diene, thiocarbonyl thio-capped poly(isobornyl acrylate) synthesized via RAFT polymerization (mediated by benzyl pyridine-2-yldithioformiate (BPDF)) was attached to the surface under ambient conditions by an HDA cycloaddition (reaction time: 15 h). The surface-modified cellulose samples were analyzed in-depth by X-ray photoelectron spectroscopy, scanning electron microscopy, elemental analysis, Fourier transform infrared (FT-IR) spectroscopy as well as Fourier transform infrared microscopy employing a focal plane array detector for imaging purposes. The analytical results provide strong evidence that the reaction of suitable dienophiles with Cp-functional cellulose proceeds under mild reaction conditions (T ≈ 20 °C) in an efficient fashion. In particular, the visualization of individual modified cellulose fibers via high-resolution FT-IR microscopy corroborates the homogeneous distribution of the polymer film on the cellulose fibers.

Portable or Modular? There Is a Difference....

ERIC Educational Resources Information Center

Morton, Mike

2002-01-01

Describes differences between two types of school facilities: portable (prebuilt, temporary wood structure installed on site) and modular (method of construction for permanent buildings). Provides details of modular construction. (PKP)

Highly-Efficient and Modular Medium-Voltage Converters

DTIC Science & Technology

2015-09-28

HVDC modular multilevel converter in decoupled double synchronous reference frame for voltage oscillation reduction," IEEE Trans. Ind...Electron., vol. 29, pp. 77-88, Jan 2014. [10] M. Guan and Z. Xu, "Modeling and control of a modular multilevel converter -based HVDC system under...34 Modular multilevel converter design for VSC HVDC applications," IEEE Journal of Emerging and Selected Topics in Power Electronics, vol. 3, pp.

Toward modular biological models: defining analog modules based on referent physiological mechanisms

PubMed Central

2014-01-01

Background Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project’s requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. Results We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale. Conclusions This report demonstrates the feasibility of PMMs and their usefulness across multiple model use cases. The pharmacodynamic response module developed here is robust to changes in model context and flexible in its ability to achieve validation targets in the face of considerable experimental uncertainty. Adopting the modularization methods presented here is expected to facilitate model reuse and integration, thereby accelerating the pace of biomedical research. PMID:25123169

Toward modular biological models: defining analog modules based on referent physiological mechanisms.

PubMed

Petersen, Brenden K; Ropella, Glen E P; Hunt, C Anthony

2014-08-16

Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project's requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale. This report demonstrates the feasibility of PMMs and their usefulness across multiple model use cases. The pharmacodynamic response module developed here is robust to changes in model context and flexible in its ability to achieve validation targets in the face of considerable experimental uncertainty. Adopting the modularization methods presented here is expected to facilitate model reuse and integration, thereby accelerating the pace of biomedical research.

A modular optical sensor

NASA Astrophysics Data System (ADS)

Conklin, John Albert

This dissertation presents the design of a modular, fiber-optic sensor and the results obtained from testing the modular sensor. The modular fiber-optic sensor is constructed in such manner that the sensor diaphragm can be replaced with different configurations to detect numerous physical phenomena. Additionally, different fiber-optic detection systems can be attached to the sensor. Initially, the modular sensor was developed to be used by university of students to investigate realistic optical sensors and detection systems to prepare for advance studies of micro-optical mechanical systems (MOMS). The design accomplishes this by doing two things. First, the design significantly lowers the costs associated with studying optical sensors by modularizing the sensor design. Second, the sensor broadens the number of physical phenomena that students can apply optical sensing techniques to in a fiber optics sensor course. The dissertation is divided into seven chapters covering the historical development of fiber-optic sensors, a theoretical overview of fiber-optic sensors, the design, fabrication, and the testing of the modular sensor developed in the course of this work. Chapter 1 discusses, in detail, how this dissertation is organized and states the purpose of the dissertation. Chapter 2 presents an historical overview of the development of optical fibers, optical pressure sensors, and fibers, optical pressure sensors, and optical microphones. Chapter 3 reviews the theory of multi-fiber optic detection systems, optical microphones, and pressure sensors. Chapter 4 presents the design details of the modular, optical sensor. Chapter 5 delves into how the modular sensor is fabricated and how the detection systems are constructed. Chapter 6 presents the data collected from the microphone and pressure sensor configurations of the modular sensor. Finally, Chapter 7 discusses the data collected and draws conclusions about the design based on the data collected. Chapter 7 also presents future work needed to expand the functionality and utility of the modular sensor.

Translating emotion theory and research into preventive interventions.

PubMed

Izard, Carroll E

2002-09-01

Scientific advances in the field of emotions suggest a framework for conceptualizing the emotion-related aspects of prevention programs that aim to enhance children's socioemotional competence and prevent the emergence of behavior problems and psychopathology. A conception of emotions as inherently adaptive and motivational and the related empirical evidence from several disciplines and specialities suggest 7 principles for developing preventive interventions: the utilization of positive and negative emotions, emotion modulation as a mediator of emotion utilization, emotion patterns in states and traits, different processes of emotion activation, emotion communication in early life, and the development of connections for the modular and relatively independent emotions and cognitive systems. Each principle's practical implications and application in current prevention programs are discussed.

Modular High Voltage Power Supply

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

Newell, Matthew R.

The goal of this project is to develop a modular high voltage power supply that will meet the needs of safeguards applications and provide a modular plug and play supply for use with standard electronic racks.

Hierarchical functional modularity in the resting-state human brain.

PubMed

Ferrarini, Luca; Veer, Ilya M; Baerends, Evelinda; van Tol, Marie-José; Renken, Remco J; van der Wee, Nic J A; Veltman, Dirk J; Aleman, André; Zitman, Frans G; Penninx, Brenda W J H; van Buchem, Mark A; Reiber, Johan H C; Rombouts, Serge A R B; Milles, Julien

2009-07-01

Functional magnetic resonance imaging (fMRI) studies have shown that anatomically distinct brain regions are functionally connected during the resting state. Basic topological properties in the brain functional connectivity (BFC) map have highlighted the BFC's small-world topology. Modularity, a more advanced topological property, has been hypothesized to be evolutionary advantageous, contributing to adaptive aspects of anatomical and functional brain connectivity. However, current definitions of modularity for complex networks focus on nonoverlapping clusters, and are seriously limited by disregarding inclusive relationships. Therefore, BFC's modularity has been mainly qualitatively investigated. Here, we introduce a new definition of modularity, based on a recently improved clustering measurement, which overcomes limitations of previous definitions, and apply it to the study of BFC in resting state fMRI of 53 healthy subjects. Results show hierarchical functional modularity in the brain. Copyright 2009 Wiley-Liss, Inc

Directional selection can drive the evolution of modularity in complex traits

PubMed Central

Melo, Diogo; Marroig, Gabriel

2015-01-01

Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection. PMID:25548154

Directional selection can drive the evolution of modularity in complex traits.

PubMed

Melo, Diogo; Marroig, Gabriel

2015-01-13

Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection.

Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

PubMed Central

Richards, Stephen; Liu, Yue; Bettencourt, Brian R.; Hradecky, Pavel; Letovsky, Stan; Nielsen, Rasmus; Thornton, Kevin; Hubisz, Melissa J.; Chen, Rui; Meisel, Richard P.; Couronne, Olivier; Hua, Sujun; Smith, Mark A.; Zhang, Peili; Liu, Jing; Bussemaker, Harmen J.; van Batenburg, Marinus F.; Howells, Sally L.; Scherer, Steven E.; Sodergren, Erica; Matthews, Beverly B.; Crosby, Madeline A.; Schroeder, Andrew J.; Ortiz-Barrientos, Daniel; Rives, Catharine M.; Metzker, Michael L.; Muzny, Donna M.; Scott, Graham; Steffen, David; Wheeler, David A.; Worley, Kim C.; Havlak, Paul; Durbin, K. James; Egan, Amy; Gill, Rachel; Hume, Jennifer; Morgan, Margaret B.; Miner, George; Hamilton, Cerissa; Huang, Yanmei; Waldron, Lenée; Verduzco, Daniel; Clerc-Blankenburg, Kerstin P.; Dubchak, Inna; Noor, Mohamed A.F.; Anderson, Wyatt; White, Kevin P.; Clark, Andrew G.; Schaeffer, Stephen W.; Gelbart, William; Weinstock, George M.; Gibbs, Richard A.

2005-01-01

We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each arm gene order has been extensively reshuffled, leading to a minimum of 921 syntenic blocks shared between the species. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 25–55 million years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences between the species—but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila. PMID:15632085

Microbial contributions to the persistence of coral reefs.

PubMed

Webster, Nicole S; Reusch, Thorsten B H

2017-10-01

On contemplating the adaptive capacity of reef organisms to a rapidly changing environment, the microbiome offers significant and greatly unrecognised potential. Microbial symbionts contribute to the physiology, development, immunity and behaviour of their hosts, and can respond very rapidly to changing environmental conditions, providing a powerful mechanism for acclimatisation and also possibly rapid evolution of coral reef holobionts. Environmentally acquired fluctuations in the microbiome can have significant functional consequences for the holobiont phenotype upon which selection can act. Environmentally induced changes in microbial abundance may be analogous to host gene duplication, symbiont switching / shuffling as a result of environmental change can either remove or introduce raw genetic material into the holobiont; and horizontal gene transfer can facilitate rapid evolution within microbial strains. Vertical transmission of symbionts is a key feature of many reef holobionts and this would enable environmentally acquired microbial traits to be faithfully passed to future generations, ultimately facilitating microbiome-mediated transgenerational acclimatisation (MMTA) and potentially even adaptation of reef species in a rapidly changing climate. In this commentary, we highlight the capacity and mechanisms for MMTA in reef species, propose a modified Price equation as a framework for assessing MMTA and recommend future areas of research to better understand how microorganisms contribute to the transgenerational acclimatisation of reef organisms, which is essential if we are to reliably predict the consequences of global change for reef ecosystems.

Modular Universal Scalable Ion-trap Quantum Computer

DTIC Science & Technology

2016-06-02

SECURITY CLASSIFICATION OF: The main goal of the original MUSIQC proposal was to construct and demonstrate a modular and universally- expandable ion...Distribution Unlimited UU UU UU UU 02-06-2016 1-Aug-2010 31-Jan-2016 Final Report: Modular Universal Scalable Ion-trap Quantum Computer The views...P.O. Box 12211 Research Triangle Park, NC 27709-2211 Ion trap quantum computation, scalable modular architectures REPORT DOCUMENTATION PAGE 11

Adapt Design: A Methodology for Enabling Modular Design for Mission Specific SUAS

DTIC Science & Technology

2016-08-24

ADAPT DESIGN: A METHODOLOGY FOR ENABLING MODULAR DESIGN FOR MISSION SPECIFIC SUAS Zachary C. Fisher David Locascio K. Daniel Cooksey...vehicle’s small scale. This paper considers a different approach to SUAS design aimed at addressing this issue. In this approach, a hybrid modular and...Two types of platforms have been identified: scalable platforms where variants are produced by varying scalable design variables, and modular

The effects of predictor method factors on selection outcomes: A modular approach to personnel selection procedures.

PubMed

Lievens, Filip; Sackett, Paul R

2017-01-01

Past reviews and meta-analyses typically conceptualized and examined selection procedures as holistic entities. We draw on the product design literature to propose a modular approach as a complementary perspective to conceptualizing selection procedures. A modular approach means that a product is broken down into its key underlying components. Therefore, we start by presenting a modular framework that identifies the important measurement components of selection procedures. Next, we adopt this modular lens for reviewing the available evidence regarding each of these components in terms of affecting validity, subgroup differences, and applicant perceptions, as well as for identifying new research directions. As a complement to the historical focus on holistic selection procedures, we posit that the theoretical contributions of a modular approach include improved insight into the isolated workings of the different components underlying selection procedures and greater theoretical connectivity among different selection procedures and their literatures. We also outline how organizations can put a modular approach into operation to increase the variety in selection procedures and to enhance the flexibility in designing them. Overall, we believe that a modular perspective on selection procedures will provide the impetus for programmatic and theory-driven research on the different measurement components of selection procedures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event.

PubMed

Kyndt, Tina; Haegeman, Annelies; Gheysen, Godelieve

2008-11-03

Endo-1,4-beta-glucanases or cellulases from the glycosyl hydrolase family 5 (GHF5) have been found in numerous bacteria and fungi, and recently also in higher eukaryotes, particularly in plant-parasitic nematodes (PPN). The origin of these genes has been attributed to horizontal gene transfer from bacteria, although there still is a lot of uncertainty about the origin and structure of the ancestral GHF5 PPN endoglucanase. It is not clear whether this ancestral endoglucanase consisted of the whole gene cassette, containing a catalytic domain and a carbohydrate-binding module (CBM, type 2 in PPN and bacteria) or only of the catalytic domain while the CBM2 was retrieved by domain shuffling later in evolution. Previous studies on the evolution of these genes have focused primarily on data of sedentary nematodes, while in this study, extra data from migratory nematodes were included. Two new endoglucanases from the migratory nematodes Pratylenchus coffeae and Ditylenchus africanus were included in this study. The latter one is the first gene isolated from a PPN of a different superfamily (Sphaerularioidea); all previously known nematode endoglucanases belong to the superfamily Tylenchoidea (order Rhabditida). Phylogenetic analyses were conducted with the PPN GHF5 endoglucanases and homologous endoglucanases from bacterial and other eukaryotic lineages such as beetles, fungi and plants. No statistical incongruence between the phylogenetic trees deduced from the catalytic domain and the CBM2 was found, which could suggest that both domains have evolved together. Furthermore, based on gene structure data, we inferred a model for the evolution of the GHF5 endoglucanase gene structure in plant-parasitic nematodes. Our data confirm a close relationship between Pratylenchus spp. and the root knot nematodes, while some Radopholus similis endoglucanases are more similar to cyst nematode genes. We conclude that the ancestral PPN GHF5 endoglucanase gene most probably consisted of the whole gene cassette, i.e. the GHF5 catalytic domain and the CBM2, rather than that it evolved by domain shuffling. Our evolutionary model for the gene structure in PPN GHF5 endoglucanases implies the occurrence of an early duplication event, and more recent gene duplications at genus or species level.

Space biology initiative program definition review. Trade study 4: Design modularity and commonality

NASA Technical Reports Server (NTRS)

Jackson, L. Neal; Crenshaw, John, Sr.; Davidson, William L.; Herbert, Frank J.; Bilodeau, James W.; Stoval, J. Michael; Sutton, Terry

1989-01-01

The relative cost impacts (up or down) of developing Space Biology hardware using design modularity and commonality is studied. Recommendations for how the hardware development should be accomplished to meet optimum design modularity requirements for Life Science investigation hardware will be provided. In addition, the relative cost impacts of implementing commonality of hardware for all Space Biology hardware are defined. Cost analysis and supporting recommendations for levels of modularity and commonality are presented. A mathematical or statistical cost analysis method with the capability to support development of production design modularity and commonality impacts to parametric cost analysis is provided.

Comprehensive benefits analysis of steel structure modular residence based on the entropy evaluation

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxiao; Wang, Li; Jiang, Pengming

2017-04-01

Steel structure modular residence is the outstanding residential industrialization. It has many advantages, such as the low whole cost, high resource recovery, a high degree of industrialization. This paper compares the comprehensive benefits of steel structural in modular buildings with prefabricated reinforced concrete residential from economic benefits, environmental benefits, social benefits and technical benefits by the method of entropy evaluation. Finally, it is concluded that the comprehensive benefits of steel structural in modular buildings is better than that of prefabricated reinforced concrete residential. The conclusion of this study will provide certain reference significance to the development of steel structural in modular buildings in China.

Modularity and the spread of perturbations in complex dynamical systems

NASA Astrophysics Data System (ADS)

Kolchinsky, Artemy; Gates, Alexander J.; Rocha, Luis M.

2015-12-01

We propose a method to decompose dynamical systems based on the idea that modules constrain the spread of perturbations. We find partitions of system variables that maximize "perturbation modularity," defined as the autocovariance of coarse-grained perturbed trajectories. The measure effectively separates the fast intramodular from the slow intermodular dynamics of perturbation spreading (in this respect, it is a generalization of the "Markov stability" method of network community detection). Our approach captures variation of modular organization across different system states, time scales, and in response to different kinds of perturbations: aspects of modularity which are all relevant to real-world dynamical systems. It offers a principled alternative to detecting communities in networks of statistical dependencies between system variables (e.g., "relevance networks" or "functional networks"). Using coupled logistic maps, we demonstrate that the method uncovers hierarchical modular organization planted in a system's coupling matrix. Additionally, in homogeneously coupled map lattices, it identifies the presence of self-organized modularity that depends on the initial state, dynamical parameters, and type of perturbations. Our approach offers a powerful tool for exploring the modular organization of complex dynamical systems.

Modularity and the spread of perturbations in complex dynamical systems.

PubMed

Kolchinsky, Artemy; Gates, Alexander J; Rocha, Luis M

2015-12-01

We propose a method to decompose dynamical systems based on the idea that modules constrain the spread of perturbations. We find partitions of system variables that maximize "perturbation modularity," defined as the autocovariance of coarse-grained perturbed trajectories. The measure effectively separates the fast intramodular from the slow intermodular dynamics of perturbation spreading (in this respect, it is a generalization of the "Markov stability" method of network community detection). Our approach captures variation of modular organization across different system states, time scales, and in response to different kinds of perturbations: aspects of modularity which are all relevant to real-world dynamical systems. It offers a principled alternative to detecting communities in networks of statistical dependencies between system variables (e.g., "relevance networks" or "functional networks"). Using coupled logistic maps, we demonstrate that the method uncovers hierarchical modular organization planted in a system's coupling matrix. Additionally, in homogeneously coupled map lattices, it identifies the presence of self-organized modularity that depends on the initial state, dynamical parameters, and type of perturbations. Our approach offers a powerful tool for exploring the modular organization of complex dynamical systems.

Modularity: An Application of General Systems Theory to Military Force Development

DTIC Science & Technology

2005-01-01

1999). Context, modularity, and the cultural constitution of development. In P. Lloyd & C. Fernyhough (Eds.), Lev Vygotsky : Critical assessments...of General Systems Theory to Military Force Development 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Prescribed by ANSI Std Z39-18 MODULARITY: AN APPLICATION OF GENERAL SYSTEMS THEORY TO MILITARY FORCE DEVELOPMENT 279 R SEARCH MODULARITY: AN APPLICATION OF

Gone to Fiddler’s Green: Reconnaissance and Security for the Corps

DTIC Science & Technology

2011-05-01

based reconnaissance and security organization. A U.S. corps in major combat operations must contend with an enemy’s armored advance guard or...screen, guard, and cover. Andrew D. Goldin, “ Ruminations on Modular Cavalry,” Armor Magazine, (September-October 2006): 14. 22 Goldin, “ Ruminations ...on Modular Cavalry,” 15. 23 Goldin, “ Ruminations on Modular Cavalry,” 16. 10 capabilities compared to modular force brigade combat teams in support

Local modular Hamiltonians from the quantum null energy condition

NASA Astrophysics Data System (ADS)

Koeller, Jason; Leichenauer, Stefan; Levine, Adam; Shahbazi-Moghaddam, Arvin

2018-03-01

The vacuum modular Hamiltonian K of the Rindler wedge in any relativistic quantum field theory is given by the boost generator. Here we investigate the modular Hamiltonian for more general half-spaces which are bounded by an arbitrary smooth cut of a null plane. We derive a formula for the second derivative of the modular Hamiltonian with respect to the coordinates of the cut which schematically reads K''=Tv v . This formula can be integrated twice to obtain a simple expression for the modular Hamiltonian. The result naturally generalizes the standard expression for the Rindler modular Hamiltonian to this larger class of regions. Our primary assumptions are the quantum null energy condition—an inequality between the second derivative of the von Neumann entropy of a region and the stress tensor—and its saturation in the vacuum for these regions. We discuss the validity of these assumptions in free theories and holographic theories to all orders in 1 /N .

Modularity Induced Gating and Delays in Neuronal Networks

PubMed Central

Shein-Idelson, Mark; Cohen, Gilad; Hanein, Yael

2016-01-01

Neural networks, despite their highly interconnected nature, exhibit distinctly localized and gated activation. Modularity, a distinctive feature of neural networks, has been recently proposed as an important parameter determining the manner by which networks support activity propagation. Here we use an engineered biological model, consisting of engineered rat cortical neurons, to study the role of modular topology in gating the activity between cell populations. We show that pairs of connected modules support conditional propagation (transmitting stronger bursts with higher probability), long delays and propagation asymmetry. Moreover, large modular networks manifest diverse patterns of both local and global activation. Blocking inhibition decreased activity diversity and replaced it with highly consistent transmission patterns. By independently controlling modularity and disinhibition, experimentally and in a model, we pose that modular topology is an important parameter affecting activation localization and is instrumental for population-level gating by disinhibition. PMID:27104350

Measuring, Enabling and Comparing Modularity, Regularity and Hierarchy in Evolutionary Design

NASA Technical Reports Server (NTRS)

Hornby, Gregory S.

2005-01-01

For computer-automated design systems to scale to complex designs they must be able to produce designs that exhibit the characteristics of modularity, regularity and hierarchy - characteristics that are found both in man-made and natural designs. Here we claim that these characteristics are enabled by implementing the attributes of combination, control-flow and abstraction in the representation. To support this claim we use an evolutionary algorithm to evolve solutions to different sizes of a table design problem using five different representations, each with different combinations of modularity, regularity and hierarchy enabled and show that the best performance happens when all three of these attributes are enabled. We also define metrics for modularity, regularity and hierarchy in design encodings and demonstrate that high fitness values are achieved with high values of modularity, regularity and hierarchy and that there is a positive correlation between increases in fitness and increases in modularity. regularity and hierarchy.

Directed evolution of GH43 ß-xylosidase XylBH43 thermal stability and L186 saturation

USDA-ARS?s Scientific Manuscript database

Directed evolution of ß-xylosidase XylBH43 using DNA family shuffling identified three mutations R45K, M69P, and L186Y that affect thermal stability parameter Kt0.5 by -1.8±0.1 º C, 1.7±0.3 º C, and 3.2±0.4 º C, respectively. In addition, a cluster of four mutations near hairpin loop-D83 improved K...

The cutoff phenomenon in finite Markov chains.

PubMed Central

Diaconis, P

1996-01-01

Natural mixing processes modeled by Markov chains often show a sharp cutoff in their convergence to long-time behavior. This paper presents problems where the cutoff can be proved (card shuffling, the Ehrenfests' urn). It shows that chains with polynomial growth (drunkard's walk) do not show cutoffs. The best general understanding of such cutoffs (high multiplicity of second eigenvalues due to symmetry) is explored. Examples are given where the symmetry is broken but the cutoff phenomenon persists. PMID:11607633

KSC-2011-1020

NASA Image and Video Library

2011-01-05

CAPE CANAVERAL, Fla. -- A snowy egret wades through brackish water just north of the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. This type of bird often stalks its prey in shallow water by running or shuffling its feet, flushing small fish, shrimp, frogs or crabs into view. Kennedy coexists with the Merritt Island National Wildlife Refuge, habitat to more than 310 species of birds, 25 mammals, 117 fish and 65 amphibians and reptiles. Photo credit: NASA/Frankie Martin

The Effects of Frontal- and Sagittal-Plane Plyometrics on Change-of-Direction Speed and Power in Adolescent Female Basketball Players.

PubMed

McCormick, Brian T; Hannon, James C; Newton, Maria; Shultz, Barry; Detling, Nicole; Young, Warren B

2016-01-01

Plyometrics is a popular training modality for basketball players to improve power and change-of-direction speed. Most plyometric training has used sagittal-plane exercises, but improvements in change-of-direction speed have been greater in multi-direction programs. To determine the benefits of a 6-wk frontal-plane plyometric (FPP) training program compared with a 6-wk sagittal-plane plyometric (SPP) training program with regard to power and change-of-direction speed. Fourteen female varsity high school basketball players participated in the study. Multiple 2 × 2 repeated-measures ANOVAs were used to determine differences for the FPP and SPP groups from preintervention to postintervention on 4 tests of power and 2 tests of change-of-direction speed. There was a group main effect for time in all 6 tests. There was a significant group × time interaction effect in 3 of the 6 tests. The SPP improved performance of the countermovement vertical jump more than the FPP, whereas the FPP improved performance of the lateral hop (left) and lateral-shuffle test (left) more than the SPP. The standing long jump, lateral hop (right), and lateral-shuffle test (right) did not show a significant interaction effect. These results suggest that basketball players should incorporate plyometric training in all planes to improve power and change-of-direction speed.

Entangled time in flocking: Multi-time-scale interaction reveals emergence of inherent noise

PubMed Central

Murakami, Hisashi

2018-01-01

Collective behaviors that seem highly ordered and result in collective alignment, such as schooling by fish and flocking by birds, arise from seamless shuffling (such as super-diffusion) and bustling inside groups (such as Lévy walks). However, such noisy behavior inside groups appears to preclude the collective behavior: intuitively, we expect that noisy behavior would lead to the group being destabilized and broken into small sub groups, and high alignment seems to preclude shuffling of neighbors. Although statistical modeling approaches with extrinsic noise, such as the maximum entropy approach, have provided some reasonable descriptions, they ignore the cognitive perspective of the individuals. In this paper, we try to explain how the group tendency, that is, high alignment, and highly noisy individual behavior can coexist in a single framework. The key aspect of our approach is multi-time-scale interaction emerging from the existence of an interaction radius that reflects short-term and long-term predictions. This multi-time-scale interaction is a natural extension of the attraction and alignment concept in many flocking models. When we apply this method in a two-dimensional model, various flocking behaviors, such as swarming, milling, and schooling, emerge. The approach also explains the appearance of super-diffusion, the Lévy walk in groups, and local equilibria. At the end of this paper, we discuss future developments, including extending our model to three dimensions. PMID:29689074

Furfural-tolerant Zymomonas mobilis derived from error-prone PCR-based whole genome shuffling and their tolerant mechanism.

PubMed

Huang, Suzhen; Xue, Tingli; Wang, Zhiquan; Ma, Yuanyuan; He, Xueting; Hong, Jiefang; Zou, Shaolan; Song, Hao; Zhang, Minhua

2018-04-01

Furfural-tolerant strain is essential for the fermentative production of biofuels or chemicals from lignocellulosic biomass. In this study, Zymomonas mobilis CP4 was for the first time subjected to error-prone PCR-based whole genome shuffling, and the resulting mutants F211 and F27 that could tolerate 3 g/L furfural were obtained. The mutant F211 under various furfural stress conditions could rapidly grow when the furfural concentration reduced to 1 g/L. Meanwhile, the two mutants also showed higher tolerance to high concentration of glucose than the control strain CP4. Genome resequencing revealed that the F211 and F27 had 12 and 13 single-nucleotide polymorphisms. The activity assay demonstrated that the activity of NADH-dependent furfural reductase in mutant F211 and CP4 was all increased under furfural stress, and the activity peaked earlier in mutant than in control. Also, furfural level in the culture of F211 was also more rapidly decreased. These indicate that the increase in furfural tolerance of the mutants may be resulted from the enhanced NADH-dependent furfural reductase activity during early log phase, which could lead to an accelerated furfural detoxification process in mutants. In all, we obtained Z. mobilis mutants with enhanced furfural and high concentration of glucose tolerance, and provided valuable clues for the mechanism of furfural tolerance and strain development.

Employing in vitro directed molecular evolution for the selection of α-amylase variant inhibitors with activity toward cotton boll weevil enzyme.

PubMed

da Silva, Maria Cristina Mattar; Del Sarto, Rafael Perseghini; Lucena, Wagner Alexandre; Rigden, Daniel John; Teixeira, Fabíola Rodrigues; Bezerra, Caroline de Andrade; Albuquerque, Erika Valéria Saliba; Grossi-de-Sa, Maria Fatima

2013-09-20

Numerous species of insect pests attack cotton plants, out of which the cotton boll weevil (Anthonomus grandis) is the main insect in Brazil and must be controlled to avert large economic losses. Like other insect pests, A. grandis secretes a high level of α-amylases in the midgut lumen, which are required for digestion of carbohydrates. Thus, α-amylase inhibitors (α-AIs) represent a powerful tool to apply in the control of insect pests. Here, we applied DNA shuffling and phage display techniques and obtained a combinatorial library containing 10⁸ α-AI variant forms. From this library, variants were selected exhibiting in vitro affinity for cotton boll weevil α-amylases. Twenty-six variant sequences were cloned into plant expression vectors and expressed in Arabidopsis thaliana. Transformed plant extracts were assayed in vitro to select specific and potent α-amylase inhibitors against boll weevil amylases. While the wild type inhibitors, used to create the shuffled library, did not inhibit the A. grandis α-amylases, three α-AI mutants, named α-AIC3, α-AIA11 and α-AIG4 revealed high inhibitory activities against A. grandis α-amylases in an in vitro assay. In summary, data reported here shown the potential biotechnology of new α-AI variant genes for cotton boll weevil control. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Quality of life in Parkinson's disease: the relative importance of the symptoms.

PubMed

Rahman, Shibley; Griffin, Harry J; Quinn, Niall P; Jahanshahi, Marjan

2008-07-30

A body of literature now exists, which demonstrates that idiopathic Parkinson's disease (PD) has a major negative impact on quality of life (QoL), and that depression and cognitive impairment are among the main predictors of poor QoL in this disorder. Relatively little work has been done to assess the differential contribution of the specific symptoms of PD to QoL, which was the aim of this study. One hundred thirty patients with PD completed a booklet of questionnaires, which included the PDQ39 as a disease-specific measure of QoL, a symptom checklist, a mobility checklist, as well as patient ratings of disease stage and disability. The results indicated that the contribution of physical, medication-related, and cognitive/psychiatric symptoms to QoL can be significant. Sudden unpredictable on/off states, difficulty in dressing, difficulty in walking, falls, depression, and confusion were PD symptoms, which significantly influenced QoL scores. Among the mobility problems associated with PD, start hesitation, shuffling gait, freezing, festination, propulsion, and difficulty in turning had a significant effect on QoL scores. In addition to depression and anxiety, the major predictors of QoL were shuffling, difficulty turning, falls, difficulty in dressing, fatigue, confusion, autonomic disturbance particularly urinary incontinence, unpredictable on/off fluctuations, and sensory symptoms such as pain. The implications of these results for the medical management of PD are discussed. Copyright 2007 Movement Disorder Society.

Update schemes of multi-velocity floor field cellular automaton for pedestrian dynamics

NASA Astrophysics Data System (ADS)

Luo, Lin; Fu, Zhijian; Cheng, Han; Yang, Lizhong

2018-02-01

Modeling pedestrian movement is an interesting problem both in statistical physics and in computational physics. Update schemes of cellular automaton (CA) models for pedestrian dynamics govern the schedule of pedestrian movement. Usually, different update schemes make the models behave in different ways, which should be carefully recalibrated. Thus, in this paper, we investigated the influence of four different update schemes, namely parallel/synchronous scheme, random scheme, order-sequential scheme and shuffled scheme, on pedestrian dynamics. The multi-velocity floor field cellular automaton (FFCA) considering the changes of pedestrians' moving properties along walking paths and heterogeneity of pedestrians' walking abilities was used. As for parallel scheme only, the collisions detection and resolution should be considered, resulting in a great difference from any other update schemes. For pedestrian evacuation, the evacuation time is enlarged, and the difference in pedestrians' walking abilities is better reflected, under parallel scheme. In face of a bottleneck, for example a exit, using a parallel scheme leads to a longer congestion period and a more dispersive density distribution. The exit flow and the space-time distribution of density and velocity have significant discrepancies under four different update schemes when we simulate pedestrian flow with high desired velocity. Update schemes may have no influence on pedestrians in simulation to create tendency to follow others, but sequential and shuffled update scheme may enhance the effect of pedestrians' familiarity with environments.

A New Color Image Encryption Scheme Using CML and a Fractional-Order Chaotic System

PubMed Central

Wu, Xiangjun; Li, Yang; Kurths, Jürgen

2015-01-01

The chaos-based image cryptosystems have been widely investigated in recent years to provide real-time encryption and transmission. In this paper, a novel color image encryption algorithm by using coupled-map lattices (CML) and a fractional-order chaotic system is proposed to enhance the security and robustness of the encryption algorithms with a permutation-diffusion structure. To make the encryption procedure more confusing and complex, an image division-shuffling process is put forward, where the plain-image is first divided into four sub-images, and then the position of the pixels in the whole image is shuffled. In order to generate initial conditions and parameters of two chaotic systems, a 280-bit long external secret key is employed. The key space analysis, various statistical analysis, information entropy analysis, differential analysis and key sensitivity analysis are introduced to test the security of the new image encryption algorithm. The cryptosystem speed is analyzed and tested as well. Experimental results confirm that, in comparison to other image encryption schemes, the new algorithm has higher security and is fast for practical image encryption. Moreover, an extensive tolerance analysis of some common image processing operations such as noise adding, cropping, JPEG compression, rotation, brightening and darkening, has been performed on the proposed image encryption technique. Corresponding results reveal that the proposed image encryption method has good robustness against some image processing operations and geometric attacks. PMID:25826602

PAXIP1 potentiates the combination of WEE1 inhibitor AZD1775 and platinum agents in lung cancer

PubMed Central

Jhuraney, Ankita; Woods, Nicholas T.; Wright, Gabriela; Rix, Lily; Kinose, Fumi; Kroeger, Jodi L.; Remily-Wood, Elizabeth; Cress, W. Douglas; Koomen, John M.; Brantley, Stephen G.; Gray, Jhanelle E.; Haura, Eric B.; Rix, Uwe; Monteiro, Alvaro N.

2016-01-01

The DNA damage response (DDR) involves a complex network of signaling events mediated by modular protein domains such as the BRCT (BRCA1 C-terminal) domain. Thus, proteins that interact with BRCT domains and are a part of the DDR constitute potential targets for sensitization to DNA damaging chemotherapy agents. We performed a pharmacological screen to evaluate seventeen kinases, identified in a BRCT-mediated interaction network as targets to enhance platinum-based chemotherapy in lung cancer. Inhibition of mitotic kinase WEE1 was found to have the most effective response in combination with platinum compounds in lung cancer cell lines. In the BRCT-mediated interaction network, WEE1 was found in complex with PAXIP1, a protein containing six BRCT domains involved in transcription and in the cellular response to DNA damage. We show that PAXIP1 BRCT domains regulate WEE1-mediated phosphorylation of CDK1. Further, ectopic expression of PAXIP1 promotes enhanced caspase 3-mediated apoptosis in cells treated with WEE1 inhibitor AZD1775 (formerly, MK-1775) and cisplatin compared with cells treated with AZD1775 alone. Cell lines and patient-derived xenograft models expressing both PAXIP1 and WEE1 exhibited synergistic effects of AZD1775 and cisplatin. In summary, PAXIP1 is involved in sensitizing lung cancer cells to the WEE1 inhibitor AZD1775 in combination with platinum-based treatment. We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA damaging agents. PMID:27196765

A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells

PubMed Central

Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A.; Schmid, Michael C.; Schröder, Gunnar; Vergunst, Annette C.; Carena, Ilaria; Dehio, Christoph

2005-01-01

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells. PMID:15642951

Division Artillery: Linking Strategy to Tactics

DTIC Science & Technology

2017-05-25

operational artist, while within modularity , there is no advocate for ensuring that subordinate field artillery units are getting the manning...adaptability, and synchronization. The division artillery is the operational artist, while within modularity , there is no advocate for ensuring...30 Modularization

Modular thought in the circuit analysis

NASA Astrophysics Data System (ADS)

Wang, Feng

2018-04-01

Applied to solve the problem of modular thought, provides a whole for simplification's method, the complex problems have become of, and the study of circuit is similar to the above problems: the complex connection between components, make the whole circuit topic solution seems to be more complex, and actually components the connection between the have rules to follow, this article mainly tells the story of study on the application of the circuit modular thought. First of all, this paper introduces the definition of two-terminal network and the concept of two-terminal network equivalent conversion, then summarizes the common source resistance hybrid network modular approach, containing controlled source network modular processing method, lists the common module, typical examples analysis.

Modular entanglement.

PubMed

Gualdi, Giulia; Giampaolo, Salvatore M; Illuminati, Fabrizio

2011-02-04

We introduce and discuss the concept of modular entanglement. This is the entanglement that is established between the end points of modular systems composed by sets of interacting moduli of arbitrarily fixed size. We show that end-to-end modular entanglement scales in the thermodynamic limit and rapidly saturates with the number of constituent moduli. We clarify the mechanisms underlying the onset of entanglement between distant and noninteracting quantum systems and its optimization for applications to quantum repeaters and entanglement distribution and sharing.

Defense Acquisition Research Journal. Volume 23, Number 1, Issue 76, January 2016

DTIC Science & Technology

2016-04-21

January 2016 Vol. 23 No. 1 | ISSUE 76 The Method MATTERS Article List ARJ Extra Survey of Modular Military Vehicles: Benefits and Burdens Jean M...15 years. p. 2 Survey of Modular Military Vehicles: Benefits and Burdens Jean M. Dasch and David J. Gorsich Military vehicles can be designed from a... modular standpoint to maximize cost savings and/or adapt- ability. This article surveys vehicle modularity from a historical viewpoint and considers

Modular, Hierarchical Learning By Artificial Neural Networks

NASA Technical Reports Server (NTRS)

Baldi, Pierre F.; Toomarian, Nikzad

1996-01-01

Modular and hierarchical approach to supervised learning by artificial neural networks leads to neural networks more structured than neural networks in which all neurons fully interconnected. These networks utilize general feedforward flow of information and sparse recurrent connections to achieve dynamical effects. The modular organization, sparsity of modular units and connections, and fact that learning is much more circumscribed are all attractive features for designing neural-network hardware. Learning streamlined by imitating some aspects of biological neural networks.

Modular health services: a single case study approach to the applicability of modularity to residential mental healthcare.

PubMed

Soffers, Rutger; Meijboom, Bert; van Zaanen, Jos; van der Feltz-Cornelis, Christina

2014-05-09

The Dutch mental healthcare sector has to decrease costs by reducing intramural capacity with one third by 2020 and treating more patients in outpatient care. This transition necessitates enabling patients to become as self-supporting as possible, by customising the residential care they receive to their needs for self-development. Theoretically, modularity might help mental healthcare institutions with this. Modularity entails the decomposition of a healthcare service in parts that can be mixed-and-matched in a variety of ways, and combined form a functional whole. It brings about easier and better configuration, increased transparency and more variety without increasing costs. this study aims to explore the applicability of the modularity concept to the residential care provided in Assisted Living Facilities (ALFs) of Dutch mental healthcare institutions. A single case study is carried out at the centre for psychosis in Etten-Leur, part of the GGz Breburg IMPACT care group. The design enables in-depth analysis of a case in a specific context. This is considered appropriate since theory concerning healthcare modularity is in an early stage of development. The present study can be considered a pilot case. Data were gathered by means of interviews, observations and documentary analysis. At the centre for psychosis, the majority of the residential care can be decomposed in modules, which can be grouped in service bundles and sub-bundles; the service customisation process is sufficiently fit to apply modular thinking; and interfaces for most of the categories are present. Hence, the prerequisites for modular residential care offerings are already largely fulfilled. For not yet fulfilled aspects of these prerequisites, remedies are available. The modularity concept seems applicable to the residential care offered by the ALF of the mental healthcare institution under study. For a successful implementation of modularity however, some steps should be taken by the ALF, such as developing a catalogue of modules and a method for the personnel to work with this catalogue in application of the modules. Whether implementation of modular residential care might facilitate the transition from intramural residential care to outpatient care should be the subject of future research.

Modular health services: a single case study approach to the applicability of modularity to residential mental healthcare

PubMed Central

2014-01-01

Background The Dutch mental healthcare sector has to decrease costs by reducing intramural capacity with one third by 2020 and treating more patients in outpatient care. This transition necessitates enabling patients to become as self-supporting as possible, by customising the residential care they receive to their needs for self-development. Theoretically, modularity might help mental healthcare institutions with this. Modularity entails the decomposition of a healthcare service in parts that can be mixed-and-matched in a variety of ways, and combined form a functional whole. It brings about easier and better configuration, increased transparency and more variety without increasing costs. Aim: this study aims to explore the applicability of the modularity concept to the residential care provided in Assisted Living Facilities (ALFs) of Dutch mental healthcare institutions. Methods A single case study is carried out at the centre for psychosis in Etten-Leur, part of the GGz Breburg IMPACT care group. The design enables in-depth analysis of a case in a specific context. This is considered appropriate since theory concerning healthcare modularity is in an early stage of development. The present study can be considered a pilot case. Data were gathered by means of interviews, observations and documentary analysis. Results At the centre for psychosis, the majority of the residential care can be decomposed in modules, which can be grouped in service bundles and sub-bundles; the service customisation process is sufficiently fit to apply modular thinking; and interfaces for most of the categories are present. Hence, the prerequisites for modular residential care offerings are already largely fulfilled. For not yet fulfilled aspects of these prerequisites, remedies are available. Conclusion The modularity concept seems applicable to the residential care offered by the ALF of the mental healthcare institution under study. For a successful implementation of modularity however, some steps should be taken by the ALF, such as developing a catalogue of modules and a method for the personnel to work with this catalogue in application of the modules. Whether implementation of modular residential care might facilitate the transition from intramural residential care to outpatient care should be the subject of future research. PMID:24886367

In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.

PubMed

Moreno, Ana M; Fu, Xin; Zhu, Jie; Katrekar, Dhruva; Shih, Yu-Ru V; Marlett, John; Cabotaje, Jessica; Tat, Jasmine; Naughton, John; Lisowski, Leszek; Varghese, Shyni; Zhang, Kang; Mali, Prashant

2018-04-25

Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to develop a modular adeno-associated viral (AAV) vector platform for CRISPR-Cas9 delivery to enable the full spectrum of targeted in situ gene regulation functionalities, demonstrating robust transcriptional repression (up to 80%) and activation (up to 6-fold) of target genes in cell culture and mice. We also applied our platform for targeted in vivo gene-repression-mediated gene therapy for retinitis pigmentosa. Specifically, we engineered targeted repression of Nrl, a master regulator of rod photoreceptor determination, and demonstrated Nrl knockdown mediates in situ reprogramming of rod cells into cone-like cells that are resistant to retinitis pigmentosa-specific mutations, with concomitant prevention of secondary cone loss. Furthermore, we benchmarked our results from Nrl knockdown with those from in vivo Nrl knockout via gene editing. Taken together, our AAV-CRISPR-Cas9 platform for in vivo epigenome engineering enables a robust approach to target disease in a genomically scarless and potentially reversible manner. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

A Modular Vaccine Development Platform Based on Sortase-Mediated Site-Specific Tagging of Antigens onto Virus-Like Particles

PubMed Central

Tang, Shubing; Xuan, Baoqin; Ye, Xiaohua; Huang, Zhong; Qian, Zhikang

2016-01-01

Virus-like particles (VLPs) can be used as powerful nanoscale weapons to fight against virus infection. In addition to direct use as vaccines, VLPs have been extensively exploited as platforms on which to display foreign antigens for prophylactic vaccination and immunotherapeutic treatment. Unfortunately, fabrication of new chimeric VLP vaccines in a versatile, site-specific and highly efficient manner is beyond the capability of traditional VLP vaccine design approaches, genetic insertion and chemical conjugation. In this study, we described a greatly improved VLP display strategy by chemoenzymatic site-specific tailoring antigens on VLPs surface with high efficiency. Through the transpeptidation mediated by sortase A, one protein and two epitopes containing N-terminal oligoglycine were conjugated to the LPET motif on the surface of hepatitis B virus core protein (HBc) VLPs with high density. All of the new chimeric VLPs induced strong specific IgG responses. Furthermore, the chimeric VLPs with sortase A tagged enterovirus 71 (EV71) SP70 epitope could elicit effective antibodies against EV71 lethal challenging as well as the genetic insertion chimeric VLPs. The sortase A mediated chemoenzymatic site-specific tailoring of the HBc VLP approach shows great potential in new VLP vaccine design for its simplicity, site specificity, high efficiency, and versatility. PMID:27170066

DNA-HMGB1 interaction: The nuclear aggregates of polyamine mediation.

PubMed

Iacomino, Giuseppe; Picariello, Gianluca; Sbrana, Francesca; Raiteri, Roberto; D'Agostino, Luciano

2016-10-01

Nuclear aggregates of polyamines (NAPs) are supramolecular compounds generated by the self-assembly of protonated nuclear polyamines (spermine, spermidine and putrescine) and phosphate ions. In the presence of genomic DNA, the hierarchical process of self-structuring ultimately produces nanotube-like polymers that envelop the double helix. Because of their modular nature and their aggregation-disaggregation dynamics, NAPs confer plasticity and flexibility to DNA. Through the disposition of charges, NAPs also enable a bidirectional stream of information between the genome and interacting moieties. High mobility group (HMG) B1 is a non-histone chromosomal protein that binds to DNA and that influences multiple nuclear processes. Because genomic DNA binds to either NAPs or HMGB1 protein, we explored the ability of in vitro self-assembled NAPs (ivNAPs) to mediate the DNA-HMGB1 interaction. To this end, we structured DNA-NAPs-HMGB1 and DNA-HMGB1-NAPs ternary complexes in vitro through opportune sequential incubations. Mobility shift electrophoresis and atomic force microscopy showed that the DNA-ivNAPs-HGMB1 complex had conformational assets supposedly more suitable those of the DNA-HGMB1-ivNAPs to comply with the physiological and functional requirements of DNA. Our findings indicated that ivNAPs act as mediators of the DNA-HMGB1 interaction. Copyright © 2016 Elsevier B.V. All rights reserved.

A Native Threonine Coordinates Ordered Water to Tune Light-Oxygen-Voltage (LOV) Domain Photocycle Kinetics and Osmotic Stress Signaling in Trichoderma reesei ENVOY.

PubMed

Lokhandwala, Jameela; Silverman Y de la Vega, Rafael I; Hopkins, Hilary C; Britton, Collin W; Rodriguez-Iglesias, Aroa; Bogomolni, Roberto; Schmoll, Monika; Zoltowski, Brian D

2016-07-08

Light-oxygen-voltage (LOV) domain-containing proteins function as small light-activated modules capable of imparting blue light control of biological processes. Their small modular nature has made them model proteins for allosteric signal transduction and optogenetic devices. Despite intense research, key aspects of their signal transduction mechanisms and photochemistry remain poorly understood. In particular, ordered water has been identified as a possible key mediator of photocycle kinetics, despite the lack of ordered water in the LOV active site. Herein, we use recent crystal structures of a fungal LOV protein ENVOY to interrogate the role of Thr(101) in recruiting water to the flavin active site where it can function as an intrinsic base to accelerate photocycle kinetics. Kinetic and molecular dynamic simulations confirm a role in solvent recruitment to the active site and identify structural changes that correlate with solvent recruitment. In vivo analysis of T101I indicates a direct role of the Thr(101) position in mediating adaptation to osmotic stress, thereby verifying biological relevance of ordered water in LOV signaling. The combined studies identify position 101 as a mediator of both allostery and photocycle catalysis that can impact organism physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Modularization and Flexibilization.

ERIC Educational Resources Information Center

Van Meel, R. M.

Publications in the fields of educational science, organization theory, and project management were analyzed to identify the possibilities that modularization offers to institutions of higher professional education and to obtain background information for use in developing a method for modularization in higher professional education. It was…

Brain Network Modularity Predicts Exercise-Related Executive Function Gains in Older Adults

PubMed Central

Baniqued, Pauline L.; Gallen, Courtney L.; Voss, Michelle W.; Burzynska, Agnieszka Z.; Wong, Chelsea N.; Cooke, Gillian E.; Duffy, Kristin; Fanning, Jason; Ehlers, Diane K.; Salerno, Elizabeth A.; Aguiñaga, Susan; McAuley, Edward; Kramer, Arthur F.; D'Esposito, Mark

2018-01-01

Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that, especially in low-performing individuals, global network properties can capture individual differences in neuroplasticity. PMID:29354050

Functional modularity in lake-dwelling characin fishes of Mexico

PubMed Central

Bautista, Amando; Herder, Fabian; Doadrio, Ignacio

2017-01-01

Modular evolution promotes evolutionary change, allowing independent variation across morphological units. Recent studies have shown that under contrasting ecological pressures, patterns of modularity could be related to divergent evolution. The main goal of the present study was to evaluate the presence of modular evolution in two sister lacustrine species, Astyanax aeneus and A. caballeroi, which are differentiated by their trophic habits. Two different datasets were analyzed: (1) skull X-rays from 73 specimens (35 A. aeneus and 38 A. caballeroi) to characterize skull variation patterns, considering both species and sex effects. For this dataset, three different modularity hypotheses were tested, previously supported in other lacustrine divergent species; (2) a complete body shape dataset was also tested for four modularity hypotheses, which included a total of 196 individuals (110 Astyanax aeneus and 86 A. caballeroi). Skull shape showed significant differences among species and sex (P < 0.001), where Astyanax caballeroi species showed an upwardly projected mandible and larger preorbital region. For the skull dataset, the modularity hypothesis ranked first included three partitioning modules. While for the complete body dataset the best ranked hypothesis included two modules (head vs the rest of the body), being significant only for A. caballeroi. PMID:28951817

Functional modularity in lake-dwelling characin fishes of Mexico.

PubMed

Ornelas-García, Claudia Patricia; Bautista, Amando; Herder, Fabian; Doadrio, Ignacio

2017-01-01

Modular evolution promotes evolutionary change, allowing independent variation across morphological units. Recent studies have shown that under contrasting ecological pressures, patterns of modularity could be related to divergent evolution. The main goal of the present study was to evaluate the presence of modular evolution in two sister lacustrine species, Astyanax aeneus and A. caballeroi , which are differentiated by their trophic habits. Two different datasets were analyzed: (1) skull X-rays from 73 specimens (35 A. aeneus and 38 A. caballeroi ) to characterize skull variation patterns, considering both species and sex effects. For this dataset, three different modularity hypotheses were tested, previously supported in other lacustrine divergent species; (2) a complete body shape dataset was also tested for four modularity hypotheses, which included a total of 196 individuals (110 Astyanax aeneus and 86 A. caballeroi ). Skull shape showed significant differences among species and sex ( P  < 0.001), where Astyanax caballeroi species showed an upwardly projected mandible and larger preorbital region. For the skull dataset, the modularity hypothesis ranked first included three partitioning modules. While for the complete body dataset the best ranked hypothesis included two modules (head vs the rest of the body), being significant only for A. caballeroi .

Numerical simulations of human tibia osteosynthesis using modular plates based on Nitinol staples.

PubMed

Tarniţă, Daniela; Tarniţă, D N; Popa, D; Grecu, D; Tarniţă, Roxana; Niculescu, D; Cismaru, F

2010-01-01

The shape memory alloys exhibit a number of remarkable properties, which open new possibilities in engineering and more specifically in biomedical engineering. The most important alloy used in biomedical applications is NiTi. This alloy combines the characteristics of the shape memory effect and superelasticity with excellent corrosion resistance, wear characteristics, mechanical properties and a good biocompatibility. These properties make it an ideal biological engineering material, especially in orthopedic surgery and orthodontics. In this work, modular plates for the osteosynthesis of the long bones fractures are presented. The proposed modular plates are realized from identical modules, completely interchangeable, made of titanium or stainless steel having as connecting elements U-shaped staples made of Nitinol. Using computed tomography (CT) images to provide three-dimensional geometric details and SolidWorks software package, the three dimensional virtual models of the tibia bone and of the modular plates are obtained. The finite element models of the tibia bone and of the modular plate are generated. For numerical simulation, VisualNastran software is used. Finally, displacements diagram, von Misses strain diagram, for the modular plate and for the fractured tibia and modular plate ensemble are obtained.

Combining stable insect cell lines with baculovirus-mediated expression for multi-HA influenza VLP production.

PubMed

Sequeira, Daniela P; Correia, Ricardo; Carrondo, Manuel J T; Roldão, António; Teixeira, Ana P; Alves, Paula M

2018-05-24

Safer and broadly protective vaccines are needed to cope with the continuous evolution of circulating influenza virus strains and promising approaches based on the expression of multiple hemagglutinins (HA) in a virus-like particle (VLP) have been proposed. However, expression of multiple genes in the same vector can lead to its instability due to tandem repetition of similar sequences. By combining stable with transient expression systems we can rationally distribute the number of genes to be expressed per platform and thus mitigate this risk. In this work, we developed a modular system comprising stable and baculovirus-mediated expression in insect cells for production of multi-HA influenza enveloped VLPs. First, a stable insect High Five cell population expressing two different HA proteins from subtype H3 was established. Infection of this cell population with a baculovirus vector encoding three other HA proteins from H3 subtype proved to be as competitive as traditional co-infection approaches in producing a pentavalent H3 VLP. Aiming at increasing HA expression, the stable insect cell population was infected at increasingly higher cell concentrations (CCI). However, cultures infected at CCI of 3×10 6 cells/mL showed lower HA titers per cell in comparison to standard CCI of 2×10 6 cells/mL, a phenomenon named "cell density effect". To lessen the negative impact of this phenomenon, a tailor-made refeed strategy was designed based on the exhaustion of key nutrients during cell growth. Noteworthy, cultures supplemented and infected at a CCI of 4×10 6 cells/mL showed comparable HA titers per cell to those of CCI of 2×10 6 cells/mL, thus leading to an increase of up to 4-fold in HA titers per mL. Scalability of the modular strategy herein proposed was successfully demonstrated in 2L stirred tank bioreactors with comparable HA protein levels observed between bioreactor and shake flasks cultures. Overall, this work demonstrates the suitability of combining stable with baculovirus-mediated expression in insect cells as an efficient platform for production of multi-HA influenza VLPs, surpassing the drawbacks of traditional co-infection strategies and/or the use of larger, unstable vectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and analysis of a modular approach to payload specialist training. [training of spacecrews for Spacelab

NASA Technical Reports Server (NTRS)

Watters, H.; Steadman, J.

1976-01-01

A modular training approach for Spacelab payload crews is described. Representative missions are defined for training requirements analysis, training hardware, and simulations. Training times are projected for each experiment of each representative flight. A parametric analysis of the various flights defines resource requirements for a modular training facility at different flight frequencies. The modular approach is believed to be more flexible, time saving, and economical than previous single high fidelity trainer concepts. Block diagrams of training programs are shown.

A Modular Set of Mixed Reality Simulators for Blind and Guided Procedures

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-14-1-0113 TITLE: A Modular Set of Mixed Reality Simulators for “blind” and Guided Procedures PRINCIPAL INVESTIGATOR...2015 – 07/31/2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Modular Set of Mixed Reality Simulators for “Blind” and Guided Procedures 5b...editor developed to facilitate creation by non-technical educators of ITs for the set of modular simulators, (c) a curriculum for self-study and self

Compositions and methods for adoptive and active immunotherapy

DOEpatents

Fahmy, Tarek; Steenblock, Erin

2014-01-14

Modular aAPCs and methods of their manufacture and use are provided. The modular aAPCs are constructed from polymeric microparticles. The aAPCs include encapsulated cytokines and coupling agents which modularly couple functional elements including T cell receptor activators, co-stimulatory molecules and adhesion molecules to the particle. The ability of these aAPCs to release cytokines in a controlled manner, coupled with their modular nature and ease of ligand attachment, results in an ideal, tunable APC capable of stimulating and expanding primary T cells.

Nuclear Energy Policy

DTIC Science & Technology

2009-12-10

Small Modular Reactors Rising cost estimates for large conventional nuclear power plants—widely projected to be $6 billion or more—have contributed to growing interest in proposals for smaller, modular reactors. Ranging from about 40 to 350 megawatts of electrical capacity, such reactors would be only a fraction of the size of current commercial reactors. Several modular reactors would be installed together to make up a power block with a single control room, under most concepts. Modular reactor concepts would use a variety of technologies,

Investigation on changes of modularity and robustness by edge-removal mutations in signaling networks.

PubMed

Truong, Cong-Doan; Kwon, Yung-Keun

2017-12-21

Biological networks consisting of molecular components and interactions are represented by a graph model. There have been some studies based on that model to analyze a relationship between structural characteristics and dynamical behaviors in signaling network. However, little attention has been paid to changes of modularity and robustness in mutant networks. In this paper, we investigated the changes of modularity and robustness by edge-removal mutations in three signaling networks. We first observed that both the modularity and robustness increased on average in the mutant network by the edge-removal mutations. However, the modularity change was negatively correlated with the robustness change. This implies that it is unlikely that both the modularity and the robustness values simultaneously increase by the edge-removal mutations. Another interesting finding is that the modularity change was positively correlated with the degree, the number of feedback loops, and the edge betweenness of the removed edges whereas the robustness change was negatively correlated with them. We note that these results were consistently observed in randomly structure networks. Additionally, we identified two groups of genes which are incident to the highly-modularity-increasing and the highly-robustness-decreasing edges with respect to the edge-removal mutations, respectively, and observed that they are likely to be central by forming a connected component of a considerably large size. The gene-ontology enrichment of each of these gene groups was significantly different from the rest of genes. Finally, we showed that the highly-robustness-decreasing edges can be promising edgetic drug-targets, which validates the usefulness of our analysis. Taken together, the analysis of changes of robustness and modularity against edge-removal mutations can be useful to unravel novel dynamical characteristics underlying in signaling networks.

Finding modules and hierarchy in weighted financial network using transfer entropy

NASA Astrophysics Data System (ADS)

Yook, Soon-Hyung; Chae, Huiseung; Kim, Jinho; Kim, Yup

2016-04-01

We study the modular structure of financial network based on the transfer entropy (TE). From the comparison with the obtained modular structure using the cross-correlation (CC), we find that TE and CC both provide well organized modular structure and the hierarchical relationship between each industrial group when the time scale of the measurement is less than one month. However, when the time scale of the measurement becomes larger than one month, we find that the modular structure from CC cannot correctly reflect the known industrial classification and their hierarchy. In addition the measured maximum modularity, Qmax, for TE is always larger than that for CC, which indicates that TE is a better weight measure than CC for the system with asymmetric relationship.

Automatic Modeling and Simulation of Modular Robots

NASA Astrophysics Data System (ADS)

Jiang, C.; Wei, H.; Zhang, Y.

2018-03-01

The ability of reconfiguration makes modular robots have the ability of adaptable, low-cost, self-healing and fault-tolerant. It can also be applied to a variety of mission situations. In this manuscript, a robot platform which relied on the module library was designed, based on the screw theory and module theory. Then, the configuration design method of the modular robot was proposed. And the different configurations of modular robot system have been built, including industrial mechanical arms, the mobile platform, six-legged robot and 3D exoskeleton manipulator. Finally, the simulation and verification of one system among them have been made, using the analyses of screw kinematics and polynomial planning. The results of experiments demonstrate the feasibility and superiority of this modular system.

Curriculum Development through YTS Modular Credit Accumulation.

ERIC Educational Resources Information Center

Further Education Unit, London (England).

This document reports the evaluation of the collaborately developed Modular Training Framework (MainFrame), a British curriculum development project, built around a commitment to a competency-based, modular credit accumulation program. The collaborators were three local education authorities (LEAs), those of Bedfordshire, Haringey, and Sheffield,…

Modular support blocks for fluid lines

NASA Technical Reports Server (NTRS)

Dimino, J. M.; Deskin, R. D.

1974-01-01

Modular line block comprises matched modular elements machined to accept fluid lines of different diameters. Modules can support different fluid-line configurations. Top and bottom surfaces are machined to accept dovetail strip used for holding modules together. End modules have holes drilled through to accept fastening screws.

Scalable detection of statistically significant communities and hierarchies, using message passing for modularity

PubMed Central

Zhang, Pan; Moore, Cristopher

2014-01-01

Modularity is a popular measure of community structure. However, maximizing the modularity can lead to many competing partitions, with almost the same modularity, that are poorly correlated with each other. It can also produce illusory ‘‘communities’’ in random graphs where none exist. We address this problem by using the modularity as a Hamiltonian at finite temperature and using an efficient belief propagation algorithm to obtain the consensus of many partitions with high modularity, rather than looking for a single partition that maximizes it. We show analytically and numerically that the proposed algorithm works all of the way down to the detectability transition in networks generated by the stochastic block model. It also performs well on real-world networks, revealing large communities in some networks where previous work has claimed no communities exist. Finally we show that by applying our algorithm recursively, subdividing communities until no statistically significant subcommunities can be found, we can detect hierarchical structure in real-world networks more efficiently than previous methods. PMID:25489096

Multiple D3-Instantons and Mock Modular Forms II

NASA Astrophysics Data System (ADS)

Alexandrov, Sergei; Banerjee, Sibasish; Manschot, Jan; Pioline, Boris

2018-03-01

We analyze the modular properties of D3-brane instanton corrections to the hypermultiplet moduli space in type IIB string theory compactified on a Calabi-Yau threefold. In Part I, we found a necessary condition for the existence of an isometric action of S-duality on this moduli space: the generating function of DT invariants in the large volume attractor chamber must be a vector-valued mock modular form with specified modular properties. In this work, we prove that this condition is also sufficient at two-instanton order. This is achieved by producing a holomorphic action of {SL(2,Z)} on the twistor space which preserves the holomorphic contact structure. The key step is to cancel the anomalous modular variation of the Darboux coordinates by a local holomorphic contact transformation, which is generated by a suitable indefinite theta series. For this purpose we introduce a new family of theta series of signature (2, n - 2), find their modular completion, and conjecture sufficient conditions for their convergence, which may be of independent mathematical interest.

Domain organizations of modular extracellular matrix proteins and their evolution.

PubMed

Engel, J

1996-11-01

Multidomain proteins which are composed of modular units are a rather recent invention of evolution. Domains are defined as autonomously folding regions of a protein, and many of them are similar in sequence and structure, indicating common ancestry. Their modular nature is emphasized by frequent repetitions in identical or in different proteins and by a large number of different combinations with other domains. The extracellular matrix is perhaps the largest biological system composed of modular mosaic proteins, and its astonishing complexity and diversity are based on them. A cluster of minireviews on modular proteins is being published in Matrix Biology. These deal with the evolution of modular proteins, the three-dimensional structure of domains and the ways in which these interact in a multidomain protein. They discuss structure-function relationships in calcium binding domains, collagen helices, alpha-helical coiled-coil domains and C-lectins. The present minireview is focused on some general aspects and serves as an introduction to the cluster.

Prophinder: a computational tool for prophage prediction in prokaryotic genomes.

PubMed

Lima-Mendez, Gipsi; Van Helden, Jacques; Toussaint, Ariane; Leplae, Raphaël

2008-03-15

Prophinder is a prophage prediction tool coupled with a prediction database, a web server and web service. Predicted prophages will help to fill the gaps in the current sparse phage sequence space, which should cover an estimated 100 million species. Systematic and reliable predictions will enable further studies of prophages contribution to the bacteriophage gene pool and to better understand gene shuffling between prophages and phages infecting the same host. Softare is available at http://aclame.ulb.ac.be/prophinder

Machine Learning Techniques for Persuasion Detection in Conversation

DTIC Science & Technology

2010-06-01

files maintained the original post and tile ordering within each transcript. These files were each internally shuffled prior to creating test and...of the number of post or tiles. The other 90% was used for training data. Each post and each tile appeared in only one of the 10 test sets. Each post ...concatenating 5 test sets and pairing it with the 6th test set. This process was conducted for both posts and tiles. The shortest transcript (19 posts , 0 tiles

Origins of DNA Replication and Amplification in the Breast Cancer Genome

DTIC Science & Technology

2013-09-01

three peaks from the uncorrected data set remain in the corrected set. As shown in Figure 6, the peak on the left disappears as it was caused by Lexo...distribution (p. 14) Shuffled Inter‐peak distance distribution (p. 15) Peak length distribution (p. 16) Number of features per chromosome (p. 17) Correlation...with G4 ( Chromosomes 1, 3, 6, 7, 11, 19 and genome‐wide)(pp. 18-24 Proximity distribution of peaks near Delino ORC sites (p. 25) GC content of

The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

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

Fransen, E.; Vits, L.; Van Camp, G.

1996-07-12

Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. 22 refs., 3 figs., 4 tabs.

Cryptanalysis of "an improvement over an image encryption method based on total shuffling"

NASA Astrophysics Data System (ADS)

Akhavan, A.; Samsudin, A.; Akhshani, A.

2015-09-01

In the past two decades, several image encryption algorithms based on chaotic systems had been proposed. Many of the proposed algorithms are meant to improve other chaos based and conventional cryptographic algorithms. Whereas, many of the proposed improvement methods suffer from serious security problems. In this paper, the security of the recently proposed improvement method for a chaos-based image encryption algorithm is analyzed. The results indicate the weakness of the analyzed algorithm against chosen plain-text.

Correlation structures in short-term variabilities of stock indices and exchange rates

NASA Astrophysics Data System (ADS)

Nakamura, Tomomichi; Small, Michael

2007-09-01

Financial data usually show irregular fluctuations and some trends. We investigate whether there are correlation structures in short-term variabilities (irregular fluctuations) among financial data from the viewpoint of deterministic dynamical systems. Our method is based on the small-shuffle surrogate method. The data we use are daily closing price of Standard & Poor's 500 and the volume, and daily foreign exchange rates, Euro/US Dollar (USD), British Pound/USD and Japanese Yen/USD. We found that these data are not independent.

Advanced Modular Power Approach to Affordable, Supportable Space Systems

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Kimnach, Greg L.; Fincannon, James; Mckissock,, Barbara I.; Loyselle, Patricia L.; Wong, Edmond

2013-01-01

Recent studies of missions to the Moon, Mars and Near Earth Asteroids (NEA) indicate that these missions often involve several distinct separately launched vehicles that must ultimately be integrated together in-flight and operate as one unit. Therefore, it is important to see these vehicles as elements of a larger segmented spacecraft rather than separate spacecraft flying in formation. The evolution of large multi-vehicle exploration architecture creates the need (and opportunity) to establish a global power architecture that is common across all vehicles. The Advanced Exploration Systems (AES) Modular Power System (AMPS) project managed by NASA Glenn Research Center (GRC) is aimed at establishing the modular power system architecture that will enable power systems to be built from a common set of modular building blocks. The project is developing, demonstrating and evaluating key modular power technologies that are expected to minimize non-recurring development costs, reduce recurring integration costs, as well as, mission operational and support costs. Further, modular power is expected to enhance mission flexibility, vehicle reliability, scalability and overall mission supportability. The AMPS project not only supports multi-vehicle architectures but should enable multi-mission capability as well. The AMPS technology development involves near term demonstrations involving developmental prototype vehicles and field demonstrations. These operational demonstrations not only serve as a means of evaluating modular technology but also provide feedback to developers that assure that they progress toward truly flexible and operationally supportable modular power architecture.

Proteomics links the redox state to calcium signaling during bleaching of the scleractinian coral Acropora microphthalma on exposure to high solar irradiance and thermal stress.

PubMed

Weston, Andrew J; Dunlap, Walter C; Beltran, Victor H; Starcevic, Antonio; Hranueli, Daslav; Ward, Malcolm; Long, Paul F

2015-03-01

Shipboard experiments were each performed over a 2 day period to examine the proteomic response of the symbiotic coral Acropora microphthalma exposed to acute conditions of high temperature/low light or high light/low temperature stress. During these treatments, corals had noticeably bleached. The photosynthetic performance of residual algal endosymbionts was severely impaired but showed signs of recovery in both treatments by the end of the second day. Changes in the coral proteome were determined daily and, using recently available annotated genome sequences, the individual contributions of the coral host and algal endosymbionts could be extracted from these data. Quantitative changes in proteins relevant to redox state and calcium metabolism are presented. Notably, expression of common antioxidant proteins was not detected from the coral host but present in the algal endosymbiont proteome. Possible roles for elevated carbonic anhydrase in the coral host are considered: to restore intracellular pH diminished by loss of photosynthetic activity, to indirectly limit intracellular calcium influx linked with enhanced calmodulin expression to impede late-stage symbiont exocytosis, or to enhance inorganic carbon transport to improve the photosynthetic performance of algal symbionts that remain in hospite. Protein effectors of calcium-dependent exocytosis were present in both symbiotic partners. No caspase-family proteins associated with host cell apoptosis, with exception of the autophagy chaperone HSP70, were detected, suggesting that algal loss and photosynthetic dysfunction under these experimental conditions were not due to host-mediated phytosymbiont destruction. Instead, bleaching occurred by symbiont exocytosis and loss of light-harvesting pigments of algae that remain in hospite. These proteomic data are, therefore, consistent with our premise that coral endosymbionts can mediate their own retention or departure from the coral host, which may manifest as "symbiont shuffling" of Symbiodinium clades in response to environmental stress. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Implementing Modular A Levels.

ERIC Educational Resources Information Center

Holding, Gordon

This document, which is designed for curriculum managers at British further education (FE) colleges, presents basic information on the implementation and perceived benefits of the General Certificate of Education (GCE) modular A (Advanced) levels. The information was synthesized from a survey of 12 FE colleges that introduced the modular A levels…

24 CFR 3282.12 - Excluded structures-modular homes.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Excluded structures-modular homes... HOUSING AND URBAN DEVELOPMENT MANUFACTURED HOME PROCEDURAL AND ENFORCEMENT REGULATIONS General § 3282.12 Excluded structures—modular homes. (a) The purpose of this section is to provide the certification...

24 CFR 3282.12 - Excluded structures-modular homes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Excluded structures-modular homes... HOUSING AND URBAN DEVELOPMENT MANUFACTURED HOME PROCEDURAL AND ENFORCEMENT REGULATIONS General § 3282.12 Excluded structures—modular homes. (a) The purpose of this section is to provide the certification...

Novel 11β-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV.

PubMed

Boudon, Stéphanie M; Vuorinen, Anna; Geotti-Bianchini, Piero; Wandeler, Eliane; Kratschmar, Denise V; Heidl, Marc; Campiche, Remo; Jackson, Eileen; Odermatt, Alex

2017-01-01

Activity and selectivity assessment of new bi-aryl amide 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11β-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11β-HSD1 over 11β-HSD2, 17β-HSD1 and 17β-HSD2. These inhibitors also potently inhibited 11β-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme and in intact primary human keratinocytes expressing endogenous 11β-HSD1. Moreover, compounds 2b, 3e and 12e were tested for their activity in human skin biopsies. They were able to prevent, at least in part, both the cortisone- and the UV-mediated decreases in collagen content. Thus, inhibition of 11β-HSD1 by these compounds can be further investigated to delay or prevent UV-mediated skin damage and skin aging.

Targeted intracellular delivery of proteins with spatial and temporal control.

PubMed

Morales, Demosthenes P; Braun, Gary B; Pallaoro, Alessia; Chen, Renwei; Huang, Xiao; Zasadzinski, Joseph A; Reich, Norbert O

2015-02-02

While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.

A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery.

PubMed

Hung, Michelle E; Leonard, Joshua N

2016-01-01

Extracellular vesicles (EVs) mediate intercellular communication through transfer of RNA and protein between cells. Thus, understanding how cargo molecules are loaded and delivered by EVs is of central importance for elucidating the biological roles of EVs and developing EV-based therapeutics. While some motifs modulating the loading of biomolecular cargo into EVs have been elucidated, the general rules governing cargo loading and delivery remain poorly understood. To investigate how general biophysical properties impact loading and delivery of RNA by EVs, we developed a platform for actively loading engineered cargo RNAs into EVs. In our system, the MS2 bacteriophage coat protein was fused to EV-associated proteins, and the cognate MS2 stem loop was engineered into cargo RNAs. Using this Targeted and Modular EV Loading (TAMEL) approach, we identified a configuration that substantially enhanced cargo RNA loading (up to 6-fold) into EVs. When applied to vesicles expressing the vesicular stomatitis virus glycoprotein (VSVG) - gesicles - we observed a 40-fold enrichment in cargo RNA loading. While active loading of mRNA-length (>1.5 kb) cargo molecules was possible, active loading was much more efficient for smaller (~0.5 kb) RNA molecules. We next leveraged the TAMEL platform to elucidate the limiting steps in EV-mediated delivery of mRNA and protein to prostate cancer cells, as a model system. Overall, most cargo was rapidly degraded in recipient cells, despite high EV-loading efficiencies and substantial EV uptake by recipient cells. While gesicles were efficiently internalized via a VSVG-mediated mechanism, most cargo molecules were rapidly degraded. Thus, in this model system, inefficient endosomal fusion or escape likely represents a limiting barrier to EV-mediated transfer. Altogether, the TAMEL platform enabled a comparative analysis elucidating a key opportunity for enhancing EV-mediated delivery to prostate cancer cells, and this technology should be of general utility for investigations and applications of EV-mediated transfer in other systems.

Connective tissue growth factor (CTGF) and cancer progression.

PubMed

Chu, Chia-Yu; Chang, Cheng-Chi; Prakash, Ekambaranellore; Kuo, Min-Liang

2008-11-01

Connective tissue growth factor (CTGF) is a member of the CCN family of secreted, matrix-associated proteins encoded by immediate early genes that play various roles in angiogenesis and tumor growth. CCN family proteins share uniform modular structure which mediates various cellular functions such as regulation of cell division, chemotaxis, apoptosis, adhesion, motility, angiogenesis, neoplastic transformation, and ion transport. Recently, CTGF expression has been shown to be associated with tumor development and progression. There is growing body of evidence that CTGF may regulate cancer cell migration, invasion, angiogenesis, and anoikis. In this review, we will highlight the influence of CTGF expression on the biological behavior and progression of various cancer cells, as well as its regulation on various types of protein signals and their mechanisms.

Enhanced sampling of glutamate receptor ligand-binding domains.

PubMed

Lau, Albert Y

2018-04-14

The majority of excitatory synaptic transmission in the central nervous system is mediated by ionotropic glutamate receptors (iGluRs). These membrane-bound protein assemblies consist of modular domains that can be genetically isolated and expressed, which has resulted in a plethora of crystal structures of individual domains in different conformations bound to different ligands. These structures have presented opportunities for molecular dynamics (MD) simulation studies. To examine the free energies that govern molecular behavior, simulation strategies and algorithms have been developed, collectively called enhanced sampling methods This review focuses on the use of enhanced sampling MD simulations of isolated iGluR ligand-binding domains to characterize thermodynamic properties important to receptor function. Copyright © 2018 Elsevier B.V. All rights reserved.

Multisubunit tethering complexes in higher plants.

PubMed

Ravikumar, Raksha; Steiner, Alexander; Assaad, Farhah F

2017-12-01

Tethering complexes mediate the initial, specific contact between donor and acceptor membranes. This review focuses on the modularity and function of multisubunit tethering complexes (MTCs) in higher plants. One emphasis is on molecular interactions of plant MTCs. Here, a number of insights have been gained concerning interactions between different tethering complexes, and between tethers and microtubule-associated proteins. The roles of tethering complexes in abiotic stress responses appear indirect, but in the context of biotic stress responses it has been suggested that some tethers are direct targets of pathogen effectors or virulence factors. In light of the central roles tethering complexes play in plant development, an emerging concept is that tethers may be co-opted for plant adaptive responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Conserved interdomain linker promotes phase separation of the multivalent adaptor protein Nck

PubMed Central

Banjade, Sudeep; Wu, Qiong; Mittal, Anuradha; Peeples, William B.; Pappu, Rohit V.; Rosen, Michael K.

2015-01-01

The organization of membranes, the cytosol, and the nucleus of eukaryotic cells can be controlled through phase separation of lipids, proteins, and nucleic acids. Collective interactions of multivalent molecules mediated by modular binding domains can induce gelation and phase separation in several cytosolic and membrane-associated systems. The adaptor protein Nck has three SRC-homology 3 (SH3) domains that bind multiple proline-rich segments in the actin regulatory protein neuronal Wiskott-Aldrich syndrome protein (N-WASP) and an SH2 domain that binds to multiple phosphotyrosine sites in the adhesion protein nephrin, leading to phase separation. Here, we show that the 50-residue linker between the first two SH3 domains of Nck enhances phase separation of Nck/N-WASP/nephrin assemblies. Two linear motifs within this element, as well as its overall positively charged character, are important for this effect. The linker increases the driving force for self-assembly of Nck, likely through weak interactions with the second SH3 domain, and this effect appears to promote phase separation. The linker sequence is highly conserved, suggesting that the sequence determinants of the driving forces for phase separation may be generally important to Nck functions. Our studies demonstrate that linker regions between modular domains can contribute to the driving forces for self-assembly and phase separation of multivalent proteins. PMID:26553976

Knowing your friends and foes--plant receptor-like kinases as initiators of symbiosis or defence.

PubMed

Antolín-Llovera, Meritxell; Petutsching, Elena Kristin; Ried, Martina Katharina; Lipka, Volker; Nürnberger, Thorsten; Robatzek, Silke; Parniske, Martin

2014-12-01

The decision between defence and symbiosis signalling in plants involves alternative and modular plasma membrane-localized receptor complexes. A critical step in their activation is ligand-induced homo- or hetero-oligomerization of leucine-rich repeat (LRR)- and/or lysin motif (LysM) receptor-like kinases (RLKs). In defence signalling, receptor complexes form upon binding of pathogen-associated molecular patterns (PAMPs), including the bacterial flagellin-derived peptide flg22, or chitin. Similar mechanisms are likely to operate during the perception of microbial symbiont-derived (lipo)-chitooligosaccharides. The structurally related chitin-oligomer ligands chitooctaose and chitotetraose trigger defence and symbiosis signalling, respectively, and their discrimination involves closely related, if not identical, LysM-RLKs. This illustrates the demand for and the challenges imposed on decision mechanisms that ensure appropriate signal initiation. Appropriate signalling critically depends on abundance and localization of RLKs at the cell surface. This is regulated by internalization, which also provides a mechanism for the removal of activated signalling RLKs. Abundance of the malectin-like domain (MLD)-LRR-RLK Symbiosis Receptor-like Kinase (SYMRK) is additionally controlled by cleavage of its modular ectodomain, which generates a truncated and rapidly degraded RLK fragment. This review explores LRR- and LysM-mediated signalling, the involvement of MLD-LRR-RLKs in symbiosis and defence, and the role of endocytosis in RLK function. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

77 FR 28861 - Secretary of Energy Advisory Board, Small Modular Reactor Subcommittee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-16

... DEPARTMENT OF ENERGY Secretary of Energy Advisory Board, Small Modular Reactor Subcommittee AGENCY: Department of Energy. ACTION: Notice of Open Meeting. SUMMARY: This notice announces an open meeting of the Secretary of Energy Advisory Board (SEAB), Small Modular Reactor Subcommittee (SMR). The Federal Advisory...

Modular Access and Progression Routes: Support Issues and Student Directed Learning.

ERIC Educational Resources Information Center

Ward, Jill

1995-01-01

The effects of modularizing Access Courses provided by the University of Derby were examined for 299 adult students. No significant differences appeared in retention, but the modular approach had increased recruitment/retention of unskilled and lower achieving students. Students with lower entry qualifications had higher achievement than similar…

Modular Building Supplement: A Quick, Quality Solution for Schools.

ERIC Educational Resources Information Center

Goodmiller, Brian D.; Schendell, Derek G.

2003-01-01

This supplement presents three articles on modular construction that look at: "Fast Track Expansion for a New Jersey School" (involving a modular addition); "Precast Construction Helps Schools Meet Attendance Boom" (precast concrete components are quick, durable, and flexible); and "Airing HVAC Concerns" (poor indoor air quality in prefabricated…

Manufactured Housing--The Modular Home in Texas.

ERIC Educational Resources Information Center

Sindt, Roger P.

This report deals principally with modular homes (permanently sited structures) although it also presents some recent information on mobile homes. In 1976, modular home construction companies were surveyed in Texas and across the United States to assess the extent of their construction activity and market penetration and to gather some insight…

Modular standards for emerging avionics technologies

NASA Astrophysics Data System (ADS)

Radcliffe, B.; Boaz, J.

The present investigation is concerned with modular standards for the integration of new avionics technologies into production aircraft, taking into account also major retrofit programs. It is pointed out that avionics systems are about to undergo drastic changes in the partitioning of functions and judicious sharing of resources. These changes have the potential to significantly improve reliability and maintainability, and to reduce costs. Attention is given to a definition of the modular avionics concept, the existing module program, the development approach, development progress on the modular avionics standard, and the future of avionics installation standards.

Modularity in developmental biology and artificial organs: a missing concept in tissue engineering.

PubMed

Lenas, Petros; Luyten, Frank P; Doblare, Manuel; Nicodemou-Lena, Eleni; Lanzara, Andreina Elena

2011-06-01

Tissue engineering is reviving itself, adopting the concept of biomimetics of in vivo tissue development. A basic concept of developmental biology is the modularity of the tissue architecture according to which intermediates in tissue development constitute semiautonomous entities. Both engineering and nature have chosen the modular architecture to optimize the product or organism development and evolution. Bioartificial tissues do not have a modular architecture. On the contrary, artificial organs of modular architecture have been already developed in the field of artificial organs. Therefore the conceptual support of tissue engineering by the field of artificial organs becomes critical in its new endeavor of recapitulating in vitro the in vivo tissue development. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Fretting-corrosion at the modular tapers interface: Inspection of standard ASTM F1875-98.

PubMed

Bingley, Rachel; Martin, Alan; Manfredi, Olivia; Nejadhamzeeigilani, Mahdiyar; Oladokun, Abimbola; Beadling, Andrew Robert; Siddiqui, Sohail; Anderson, James; Thompson, Jonathan; Neville, Anne; Bryant, Michael

2018-05-01

Interest in the degradation mechanisms at the modular tapers interfaces has been renewed due to increased reported cases of adverse reactions to metal debris and the appearance of wear and corrosion at the modular tapers interfaces at revision. Over the past two decades, a lot of research has been expended to understand the degradation mechanisms, with two primary implant loading procedures and orientations used consistently across the literature. ASTM F1875-98 is often used as a guide to understand and benchmark the tribocorrosion processes occurring within the modular tapers interface. This article presents a comparison of the two methods outlined in ASTM F1875-98 as well as a critique of the standard considering the current paradigm in pre-clinical assessment of modular tapers.

Spacecraft Modularity for Serviceable Satellites

NASA Technical Reports Server (NTRS)

Rossetti, Dino; Keer, Beth; Panek, John; Reed, Benjamin; Cepollina, Frank; Ritter, Robert

2015-01-01

Satellite servicing has been a proven capability of NASA since the first servicing missions in the 1980s with astronauts on the space shuttle. This capability enabled the on-orbit assembly of the International Space Station (ISS) and saved the Hubble Space Telescope (HST) mission following the discovery of the flawed primary mirror. The effectiveness and scope of servicing opportunities, especially using robotic servicers, is a function of how cooperative a spacecraft is. In this paper, modularity will be presented as a critical design aspect for a spacecraft that is cooperative from a servicing perspective. Different features of modularity are discussed using examples from HST and the Multimission Modular Spacecraft (MMS) program from the 1980s and 1990s. The benefits of modularity will be presented including those directly related to servicing and those outside of servicing including reduced costs and increased flexibility. The new Reconfigurable Operational spacecraft for Science and Exploration (ROSE) concept is introduced as an affordable implementation of modularity that provides cost savings and flexibility. Key aspects of the ROSE architecture are discussed such as the module design and the distributed avionics architecture. The ROSE concept builds on the experience from MMS and due to its modularity, would be highly suitable as a future client for on-orbit servicing.

Pressurized bellows flat contact heat exchanger interface

NASA Technical Reports Server (NTRS)

Voss, Fred E. (Inventor); Howell, Harold R. (Inventor); Winkler, Roger V. (Inventor)

1990-01-01

Disclosed is an interdigitated plate-type heat exchanger interface. The interface includes a modular interconnect to thermally connect a pair or pairs of plate-type heat exchangers to a second single or multiple plate-type heat exchanger. The modular interconnect comprises a series of parallel, plate-type heat exchangers arranged in pairs to form a slot therebetween. The plate-type heat exchangers of the second heat exchanger insert into the slots of the modular interconnect. Bellows are provided between the pairs of fins of the modular interconnect so that when the bellows are pressurized, they drive the plate-type heat exchangers of the modular interconnect toward one another, thus closing upon the second heat exchanger plates. Each end of the bellows has a part thereof a thin, membrane diaphragm which readily conforms to the contours of the heat exchanger plates of the modular interconnect when the bellows is pressurized. This ensures an even distribution of pressure on the heat exchangers of the modular interconnect thus creating substantially planar contact between the two heat exchangers. The effect of the interface of the present invention is to provide a dry connection between two heat exchangers whereby the rate of heat transfer can be varied by varying the pressure within the bellows.

Comparison of the PHISICS/RELAP5-3D ring and block model results for phase I of the OECD/NEA MHTGR-350 benchmark

DOE PAGES

Strydom, G.; Epiney, A. S.; Alfonsi, Andrea; ...

2015-12-02

The PHISICS code system has been under development at INL since 2010. It consists of several modules providing improved coupled core simulation capability: INSTANT (3D nodal transport core calculations), MRTAU (depletion and decay heat generation) and modules performing criticality searches, fuel shuffling and generalized perturbation. Coupling of the PHISICS code suite to the thermal hydraulics system code RELAP5-3D was finalized in 2013, and as part of the verification and validation effort the first phase of the OECD/NEA MHTGR-350 Benchmark has now been completed. The theoretical basis and latest development status of the coupled PHISICS/RELAP5-3D tool are described in more detailmore » in a concurrent paper. This paper provides an overview of the OECD/NEA MHTGR-350 Benchmark and presents the results of Exercises 2 and 3 defined for Phase I. Exercise 2 required the modelling of a stand-alone thermal fluids solution at End of Equilibrium Cycle for the Modular High Temperature Reactor (MHTGR). The RELAP5-3D results of four sub-cases are discussed, consisting of various combinations of coolant bypass flows and material thermophysical properties. Exercise 3 required a coupled neutronics and thermal fluids solution, and the PHISICS/RELAP5-3D code suite was used to calculate the results of two sub-cases. The main focus of the paper is a comparison of results obtained with the traditional RELAP5-3D “ring” model approach against a much more detailed model that include kinetics feedback on individual block level and thermal feedbacks on a triangular sub-mesh. The higher fidelity that can be obtained by this “block” model is illustrated with comparison results on the temperature, power density and flux distributions. Furthermore, it is shown that the ring model leads to significantly lower fuel temperatures (up to 10%) when compared with the higher fidelity block model, and that the additional model development and run-time efforts are worth the gains obtained in the improved spatial temperature and flux distributions.« less

MODULAR ANALYTICS: A New Approach to Automation in the Clinical Laboratory.

PubMed

Horowitz, Gary L; Zaman, Zahur; Blanckaert, Norbert J C; Chan, Daniel W; Dubois, Jeffrey A; Golaz, Olivier; Mensi, Noury; Keller, Franz; Stolz, Herbert; Klingler, Karl; Marocchi, Alessandro; Prencipe, Lorenzo; McLawhon, Ronald W; Nilsen, Olaug L; Oellerich, Michael; Luthe, Hilmar; Orsonneau, Jean-Luc; Richeux, Gérard; Recio, Fernando; Roldan, Esther; Rymo, Lars; Wicktorsson, Anne-Charlotte; Welch, Shirley L; Wieland, Heinrich; Grawitz, Andrea Busse; Mitsumaki, Hiroshi; McGovern, Margaret; Ng, Katherine; Stockmann, Wolfgang

2005-01-01

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality.

MODULAR ANALYTICS: A New Approach to Automation in the Clinical Laboratory

PubMed Central

Zaman, Zahur; Blanckaert, Norbert J. C.; Chan, Daniel W.; Dubois, Jeffrey A.; Golaz, Olivier; Mensi, Noury; Keller, Franz; Stolz, Herbert; Klingler, Karl; Marocchi, Alessandro; Prencipe, Lorenzo; McLawhon, Ronald W.; Nilsen, Olaug L.; Oellerich, Michael; Luthe, Hilmar; Orsonneau, Jean-Luc; Richeux, Gérard; Recio, Fernando; Roldan, Esther; Rymo, Lars; Wicktorsson, Anne-Charlotte; Welch, Shirley L.; Wieland, Heinrich; Grawitz, Andrea Busse; Mitsumaki, Hiroshi; McGovern, Margaret; Ng, Katherine; Stockmann, Wolfgang

2005-01-01

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality. PMID:18924721

Preliminary development of an advanced modular pressure relief cushion: Testing and user evaluation.

PubMed

Freeto, Tyler; Mitchell, Steven J; Bogie, Kath M

2018-02-01

Effective pressure relief cushions are identified as a core assistive technology need by the World Health Organization Global Cooperation on Assistive Technology. High quality affordable wheelchair cushions could provide effective pressure relief for many individuals with limited access to advanced assistive technology. Value driven engineering (VdE) principles were employed to develop a prototype modular cushion. Low cost dynamically responsive gel balls were arranged in a close packed array and seated in bilayer foam for containment and support. Two modular cushions, one with high compliance balls and one with moderate compliance balls were compared with High Profile and Low Profile Roho ® and Jay ® Medical 2 cushions. ISO 16480-2 biomechanical standardized tests were applied to assess cushion performance. A preliminary materials cost analysis was carried out. A prototype modular cushion was evaluated by 12 participants who reported satisfaction using a questionnaire based on the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST 2.0) instrument. Overall the modular cushions performed better than, or on par with, the most widely prescribed commercially available cushions under ISO 16480-2 testing. Users rated the modular cushion highly for overall appearance, size and dimensions, comfort, safety, stability, ease of adjustment and general ease of use. Cost-analysis indicated that every modular cushion component a could be replaced several times and still maintain cost-efficacy over the complete cushion lifecycle. A VdE modular cushion has the potential provide effective pressure relief for many users at a low lifetime cost. Copyright © 2017. Published by Elsevier Ltd.

Fractures above and below a modular nail for knee arthrodesis. A case report.

PubMed

Hinarejos, Pedro; Ginés, Alberto; Monllau, Juan C; Puig, Lluis; Cáceres, Enric

2005-06-01

Several techniques have been advocated for knee arthrodesis, and there has been an increasing interest in modular intramedullary nails in the recent last years. We report a case of femoral and tibial fractures at each end of a modular nail in a solidly fused knee 8 months after an arthrodesis.

Modularized and Outcomes-Led Planning of Higher Education in Post-Apartheid South Africa.

ERIC Educational Resources Information Center

Ntshoe, I. M.

1999-01-01

Examines modularization and outcomes-based planning of higher education in South Africa as part of transforming higher education in a post-apartheid society. Discusses principles and assumptions of modularization and outcomes-based planning, identifies intended and unintended outcomes, and notes such issues as the origins of outcome-based…

Going Modular--For Better or Worse? AIR 1994 Annual Forum Paper.

ERIC Educational Resources Information Center

McLachlan, Jeffrey E.; Wood, Vivienne

A modular system for undergraduate programs was implemented in three degree programs at Napier University in Scotland. This paper describes the degree course structure prior to 1992-93 and factors leading to change, including university response to government policy encouraging wider access to higher education. A rationale for modularization is…

Modular Vocational Education and Training in Scotland and the Netherlands: Between Specificity and Coherence.

ERIC Educational Resources Information Center

de Bruijn, E.; Howieson, C.

1995-01-01

Draws on sociological and learning theory perspectives to compare Scottish and Dutch initiatives in the modularization of initial (postcompulsory) vocational education and training. Features of the modular system in both countries seem closely related to strategies chosen to offer customized vocational training for various client groups while not…

Modular Training Systems and Strategies: An International Meeting (Washington, D.C., May 11-12, 1992).

ERIC Educational Resources Information Center

American Society for Training and Development, Alexandria, VA.

This publication contains materials from a conference to discuss modular approaches to curriculum design. The materials from the United States and five other countries address both national skills standards and modular systems of training delivery. An introduction provides brief summaries of the conference materials and the agenda. "National…

Model of brain activation predicts the neural collective influence map of the brain

PubMed Central

Morone, Flaviano; Roth, Kevin; Min, Byungjoon; Makse, Hernán A.

2017-01-01

Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a longstanding challenge that has concerned many scientists. Current models of dependencies in NoN inspired by the power grid express interactions among modules with fragile couplings that amplify even small shocks, thus preventing functionality. Therefore, we introduce a model of NoN to shape the pattern of brain activations to form a modular environment that is robust. The model predicts the map of neural collective influencers (NCIs) in the brain, through the optimization of the influence of the minimal set of essential nodes responsible for broadcasting information to the whole-brain NoN. Our results suggest intervention protocols to control brain activity by targeting influential neural nodes predicted by network theory. PMID:28351973

Human Impacts and Climate Change Influence Nestedness and Modularity in Food-Web and Mutualistic Networks.

PubMed

Takemoto, Kazuhiro; Kajihara, Kosuke

2016-01-01

Theoretical studies have indicated that nestedness and modularity-non-random structural patterns of ecological networks-influence the stability of ecosystems against perturbations; as such, climate change and human activity, as well as other sources of environmental perturbations, affect the nestedness and modularity of ecological networks. However, the effects of climate change and human activities on ecological networks are poorly understood. Here, we used a spatial analysis approach to examine the effects of climate change and human activities on the structural patterns of food webs and mutualistic networks, and found that ecological network structure is globally affected by climate change and human impacts, in addition to current climate. In pollination networks, for instance, nestedness increased and modularity decreased in response to increased human impacts. Modularity in seed-dispersal networks decreased with temperature change (i.e., warming), whereas food web nestedness increased and modularity declined in response to global warming. Although our findings are preliminary owing to data-analysis limitations, they enhance our understanding of the effects of environmental change on ecological communities.

Statistical mechanics of two-dimensional shuffled foams: Geometry-topology correlation in small or large disorder limits

NASA Astrophysics Data System (ADS)

Durand, Marc; Kraynik, Andrew M.; van Swol, Frank; Käfer, Jos; Quilliet, Catherine; Cox, Simon; Ataei Talebi, Shirin; Graner, François

2014-06-01

Bubble monolayers are model systems for experiments and simulations of two-dimensional packing problems of deformable objects. We explore the relation between the distributions of the number of bubble sides (topology) and the bubble areas (geometry) in the low liquid fraction limit. We use a statistical model [M. Durand, Europhys. Lett. 90, 60002 (2010), 10.1209/0295-5075/90/60002] which takes into account Plateau laws. We predict the correlation between geometrical disorder (bubble size dispersity) and topological disorder (width of bubble side number distribution) over an extended range of bubble size dispersities. Extensive data sets arising from shuffled foam experiments, surface evolver simulations, and cellular Potts model simulations all collapse surprisingly well and coincide with the model predictions, even at extremely high size dispersity. At moderate size dispersity, we recover our earlier approximate predictions [M. Durand, J. Kafer, C. Quilliet, S. Cox, S. A. Talebi, and F. Graner, Phys. Rev. Lett. 107, 168304 (2011), 10.1103/PhysRevLett.107.168304]. At extremely low dispersity, when approaching the perfectly regular honeycomb pattern, we study how both geometrical and topological disorders vanish. We identify a crystallization mechanism and explore it quantitatively in the case of bidisperse foams. Due to the deformability of the bubbles, foams can crystallize over a larger range of size dispersities than hard disks. The model predicts that the crystallization transition occurs when the ratio of largest to smallest bubble radii is 1.4.

Psychophysiological Synchrony During Verbal Interaction in Romantic Relationships.

PubMed

Coutinho, Joana; Oliveira-Silva, Patrícia; Fernandes, Eugénia; Gonçalves, Oscar F; Correia, Diogo; Perrone Mc-Govern, Kristin; Tschacher, Wolfgang

2018-06-10

Previous studies about romantic relationships have shown that the reciprocal influence between partners occurs not only at the behavioral and socio-emotional levels, but also at the psychophysiological level. This reciprocal influence is expressed in a pattern of physiological synchrony between partners (i.e., coordinated dynamics of the physiological time series). The main aim of the present study was to explore the presence of a pattern of physiological synchrony in electrodermal activity (EDA) during a couple interaction task. A second objective was to compare the synchrony levels during a negative interaction condition versus a positive interaction condition. Finally, we analyzed the association between synchrony and self-perception of empathy, dyadic empathy, and relationship satisfaction. Thirty-two couples (64 individuals) participated in this study. Each couple performed a structured interaction task while the EDA of both partners was being registered. The quantification of synchrony was based on the cross-correlation of both members' EDA time-series. In order to control for coincidental synchrony, surrogate datasets were created by repeatedly shuffling the original data of spouses X and Y of a dyad and computing synchronies on the basis of the shuffled data (pseudosynchrony values). Our results confirmed the presence of significant EDA synchrony during the interaction. We also found that synchrony was higher during the negative interactions relative to the positive interactions. Additionally, physiological synchrony during positive interaction was higher for those couples in which males scored higher in dyadic empathy. The clinical implications of these findings are discussed. © 2018 Family Process Institute.

Do rotational shear-cushioning shoes influence horizontal ground reaction forces and perceived comfort during basketball cutting maneuvers?

PubMed

Lam, Wing-Kai; Qu, Yi; Yang, Fan; Cheung, Roy T H

2017-01-01

Court shoe designs predominantly focus on reducing excessive vertical ground reaction force, but shear force cushioning has received little attention in the basketball population. We aimed to examine the effect of a novel shoe-cushioning design on both resultant horizontal ground reaction forces and comfort perception during two basketball-specific cutting movements. Fifteen university team basketball players performed lateral shuffling and 45-degree sidestep cutting at maximum effort in basketball shoes with and without the shear-cushioning system (SCS). Paired t -tests were used to examine the differences in kinetics and comfort perception between two shoes. SCS shoe allowed for larger rotational material deformation compared with control shoes, but no significant shoe differences were found in braking phase kinetics during both cutting movements ( P  = 0.35). Interestingly, a greater horizontal propulsion impulse was found with the SCS during 45-degree cutting ( P  < 0.05), when compared with the control. In addition, players wearing SCS shoes perceived better forefoot comfort ( P  = 0.012). During lateral shuffling, there were no significant differences in horizontal GRF and comfort perception between shoe conditions ( P  > 0.05). The application of a rotational shear-cushioning structure allowed for better forefoot comfort and enhanced propulsion performance in cutting, but did not influence the shear impact. Understanding horizontal ground reaction force information may be useful in designing footwear to prevent shear-related injuries in sport populations.

3-base periodicity in coding DNA is affected by intercodon dinucleotides

PubMed Central

Sánchez, Joaquín

2011-01-01

All coding DNAs exhibit 3-base periodicity (TBP), which may be defined as the tendency of nucleotides and higher order n-tuples, e.g. trinucleotides (triplets), to be preferentially spaced by 3, 6, 9 etc, bases, and we have proposed an association between TBP and clustering of same-phase triplets. We here investigated if TBP was affected by intercodon dinucleotide tendencies and whether clustering of same-phase triplets was involved. Under constant protein sequence intercodon dinucleotide frequencies depend on the distribution of synonymous codons. So, possible effects were revealed by randomly exchanging synonymous codons without altering protein sequences to subsequently document changes in TBP via frequency distribution of distances (FDD) of DNA triplets. A tripartite positive correlation was found between intercodon dinucleotide frequencies, clustering of same-phase triplets and TBP. So, intercodon C|A (where “|” indicates the boundary between codons) was more frequent in native human DNA than in the codon-shuffled sequences; higher C|A frequency occurred along with more frequent clustering of C|AN triplets (where N jointly represents A, C, G and T) and with intense CAN TBP. The opposite was found for C|G, which was less frequent in native than in shuffled sequences; lower C|G frequency occurred together with reduced clustering of C|GN triplets and with less intense CGN TBP. We hence propose that intercodon dinucleotides affect TBP via same-phase triplet clustering. A possible biological relevance of our findings is briefly discussed. PMID:21814388

Do the shuffle: Changes in Symbiodinium consortia throughout juvenile coral development

PubMed Central

Reich, Hannah G.; Robertson, Deborah L.; Goodbody-Gringley, Gretchen

2017-01-01

Previous studies of symbiotic associations between scleractinians corals and Symbiodinium have demonstrated that the consortium of symbionts can change in response to environmental conditions. However, less is known about symbiont shuffling during early coral development, particularly in brooding species. This study examined whether Symbiodinium consortia (1) varied in Porites astreoides on shallow (10m) and upper mesophotic (30m) reefs, (2) changed during coral development, and (3) influenced growth of juveniles in different environments. Symbiodinium ITS2 sequences were amplified using universal primers and analyzed using phylotype-specific primers designed for phylotypes A, B, and C. Adults from both depths were found to host only phylotype A, phylotypes A and B, or phylotypes A, B, and C and the frequency of the phylotype composition did not vary with depth. However, phylotype A was the dominant symbiont that was vertically transmitted to the planulae. The presence of phylotypes B and C was detected in the majority of juveniles when transplanted onto the shallow and upper mesophotic reefs whereas only phylotype A was detected in the majority of juveniles reared in outdoor aquaria. In addition, growth of juvenile P. astreoides harboring different combinations of Symbiodinium phylotypes did not vary when transplanted to different reef zones. However, juveniles reared in in situ reef environments grew faster than those reared in ex situ outdoor aquaria. These results show that Symbiodinium consortia change during development of P. astreoides and are influenced by environmental conditions. PMID:28182684

A simplified computational memory model from information processing.

PubMed

Zhang, Lanhua; Zhang, Dongsheng; Deng, Yuqin; Ding, Xiaoqian; Wang, Yan; Tang, Yiyuan; Sun, Baoliang

2016-11-23

This paper is intended to propose a computational model for memory from the view of information processing. The model, called simplified memory information retrieval network (SMIRN), is a bi-modular hierarchical functional memory network by abstracting memory function and simulating memory information processing. At first meta-memory is defined to express the neuron or brain cortices based on the biology and graph theories, and we develop an intra-modular network with the modeling algorithm by mapping the node and edge, and then the bi-modular network is delineated with intra-modular and inter-modular. At last a polynomial retrieval algorithm is introduced. In this paper we simulate the memory phenomena and functions of memorization and strengthening by information processing algorithms. The theoretical analysis and the simulation results show that the model is in accordance with the memory phenomena from information processing view.

Neural Modularity Helps Organisms Evolve to Learn New Skills without Forgetting Old Skills

PubMed Central

Ellefsen, Kai Olav; Mouret, Jean-Baptiste; Clune, Jeff

2015-01-01

A long-standing goal in artificial intelligence is creating agents that can learn a variety of different skills for different problems. In the artificial intelligence subfield of neural networks, a barrier to that goal is that when agents learn a new skill they typically do so by losing previously acquired skills, a problem called catastrophic forgetting. That occurs because, to learn the new task, neural learning algorithms change connections that encode previously acquired skills. How networks are organized critically affects their learning dynamics. In this paper, we test whether catastrophic forgetting can be reduced by evolving modular neural networks. Modularity intuitively should reduce learning interference between tasks by separating functionality into physically distinct modules in which learning can be selectively turned on or off. Modularity can further improve learning by having a reinforcement learning module separate from sensory processing modules, allowing learning to happen only in response to a positive or negative reward. In this paper, learning takes place via neuromodulation, which allows agents to selectively change the rate of learning for each neural connection based on environmental stimuli (e.g. to alter learning in specific locations based on the task at hand). To produce modularity, we evolve neural networks with a cost for neural connections. We show that this connection cost technique causes modularity, confirming a previous result, and that such sparsely connected, modular networks have higher overall performance because they learn new skills faster while retaining old skills more and because they have a separate reinforcement learning module. Our results suggest (1) that encouraging modularity in neural networks may help us overcome the long-standing barrier of networks that cannot learn new skills without forgetting old ones, and (2) that one benefit of the modularity ubiquitous in the brains of natural animals might be to alleviate the problem of catastrophic forgetting. PMID:25837826

Neural modularity helps organisms evolve to learn new skills without forgetting old skills.

PubMed

Ellefsen, Kai Olav; Mouret, Jean-Baptiste; Clune, Jeff

2015-04-01

A long-standing goal in artificial intelligence is creating agents that can learn a variety of different skills for different problems. In the artificial intelligence subfield of neural networks, a barrier to that goal is that when agents learn a new skill they typically do so by losing previously acquired skills, a problem called catastrophic forgetting. That occurs because, to learn the new task, neural learning algorithms change connections that encode previously acquired skills. How networks are organized critically affects their learning dynamics. In this paper, we test whether catastrophic forgetting can be reduced by evolving modular neural networks. Modularity intuitively should reduce learning interference between tasks by separating functionality into physically distinct modules in which learning can be selectively turned on or off. Modularity can further improve learning by having a reinforcement learning module separate from sensory processing modules, allowing learning to happen only in response to a positive or negative reward. In this paper, learning takes place via neuromodulation, which allows agents to selectively change the rate of learning for each neural connection based on environmental stimuli (e.g. to alter learning in specific locations based on the task at hand). To produce modularity, we evolve neural networks with a cost for neural connections. We show that this connection cost technique causes modularity, confirming a previous result, and that such sparsely connected, modular networks have higher overall performance because they learn new skills faster while retaining old skills more and because they have a separate reinforcement learning module. Our results suggest (1) that encouraging modularity in neural networks may help us overcome the long-standing barrier of networks that cannot learn new skills without forgetting old ones, and (2) that one benefit of the modularity ubiquitous in the brains of natural animals might be to alleviate the problem of catastrophic forgetting.

Standardized Modular Power Interfaces for Future Space Explorations Missions

NASA Technical Reports Server (NTRS)

Oeftering, Richard

2015-01-01

Earlier studies show that future human explorations missions are composed of multi-vehicle assemblies with interconnected electric power systems. Some vehicles are often intended to serve as flexible multi-purpose or multi-mission platforms. This drives the need for power architectures that can be reconfigured to support this level of flexibility. Power system developmental costs can be reduced, program wide, by utilizing a common set of modular building blocks. Further, there are mission operational and logistics cost benefits of using a common set of modular spares. These benefits are the goals of the Advanced Exploration Systems (AES) Modular Power System (AMPS) project. A common set of modular blocks requires a substantial level of standardization in terms of the Electrical, Data System, and Mechanical interfaces. The AMPS project is developing a set of proposed interface standards that will provide useful guidance for modular hardware developers but not needlessly constrain technology options, or limit future growth in capability. In 2015 the AMPS project focused on standardizing the interfaces between the elements of spacecraft power distribution and energy storage. The development of the modular power standard starts with establishing mission assumptions and ground rules to define design application space. The standards are defined in terms of AMPS objectives including Commonality, Reliability-Availability, Flexibility-Configurability and Supportability-Reusability. The proposed standards are aimed at assembly and sub-assembly level building blocks. AMPS plans to adopt existing standards for spacecraft command and data, software, network interfaces, and electrical power interfaces where applicable. Other standards including structural encapsulation, heat transfer, and fluid transfer, are governed by launch and spacecraft environments and bound by practical limitations of weight and volume. Developing these mechanical interface standards is more difficult but an essential part of defining physical building blocks of modular power. This presentation describes the AMPS projects progress towards standardized modular power interfaces.

Episodic Memory Retrieval Benefits from a Less Modular Brain Network Organization.

PubMed

Westphal, Andrew J; Wang, Siliang; Rissman, Jesse

2017-03-29

Most complex cognitive tasks require the coordinated interplay of multiple brain networks, but the act of retrieving an episodic memory may place especially heavy demands for communication between the frontoparietal control network (FPCN) and the default mode network (DMN), two networks that do not strongly interact with one another in many task contexts. We applied graph theoretical analysis to task-related fMRI functional connectivity data from 20 human participants and found that global brain modularity-a measure of network segregation-is markedly reduced during episodic memory retrieval relative to closely matched analogical reasoning and visuospatial perception tasks. Individual differences in modularity were correlated with memory task performance, such that lower modularity levels were associated with a lower false alarm rate. Moreover, the FPCN and DMN showed significantly elevated coupling with each other during the memory task, which correlated with the global reduction in brain modularity. Both networks also strengthened their functional connectivity with the hippocampus during the memory task. Together, these results provide a novel demonstration that reduced modularity is conducive to effective episodic retrieval, which requires close collaboration between goal-directed control processes supported by the FPCN and internally oriented self-referential processing supported by the DMN. SIGNIFICANCE STATEMENT Modularity, an index of the degree to which nodes of a complex system are organized into discrete communities, has emerged as an important construct in the characterization of brain connectivity dynamics. We provide novel evidence that the modularity of the human brain is reduced when individuals engage in episodic memory retrieval, relative to other cognitive tasks, and that this state of lower modularity is associated with improved memory performance. We propose a neural systems mechanism for this finding where the nodes of the frontoparietal control network and default mode network strengthen their interaction with one another during episodic retrieval. Such across-network communication likely facilitates effective access to internally generated representations of past event knowledge. Copyright © 2017 the authors 0270-6474/17/373523-09$15.00/0.

Generalized epidemic process on modular networks.

PubMed

Chung, Kihong; Baek, Yongjoo; Kim, Daniel; Ha, Meesoon; Jeong, Hawoong

2014-05-01

Social reinforcement and modular structure are two salient features observed in the spreading of behavior through social contacts. In order to investigate the interplay between these two features, we study the generalized epidemic process on modular networks with equal-sized finite communities and adjustable modularity. Using the analytical approach originally applied to clique-based random networks, we show that the system exhibits a bond-percolation type continuous phase transition for weak social reinforcement, whereas a discontinuous phase transition occurs for sufficiently strong social reinforcement. Our findings are numerically verified using the finite-size scaling analysis and the crossings of the bimodality coefficient.

Multi-kilowatt modularized spacecraft power processing system development

NASA Technical Reports Server (NTRS)

Andrews, R. E.; Hayden, J. H.; Hedges, R. T.; Rehmann, D. W.

1975-01-01

A review of existing information pertaining to spacecraft power processing systems and equipment was accomplished with a view towards applicability to the modularization of multi-kilowatt power processors. Power requirements for future spacecraft were determined from the NASA mission model-shuttle systems payload data study which provided the limits for modular power equipment capabilities. Three power processing systems were compared to evaluation criteria to select the system best suited for modularity. The shunt regulated direct energy transfer system was selected by this analysis for a conceptual design effort which produced equipment specifications, schematics, envelope drawings, and power module configurations.

A Modular Robotic System with Applications to Space Exploration

NASA Technical Reports Server (NTRS)

Hancher, Matthew D.; Hornby, Gregory S.

2006-01-01

Modular robotic systems offer potential advantages as versatile, fault-tolerant, cost-effective platforms for space exploration, but a sufficiently mature system is not yet available. We describe the possible applications of such a system, and present prototype hardware intended as a step in the right direction. We also present elements of an automated design and optimization framework aimed at making modular robots easier to design and use, and discuss the results of applying the system to a gait optimization problem. Finally, we discuss the potential near-term applications of modular robotics to terrestrial robotics research.

Multiple D3-Instantons and Mock Modular Forms I

NASA Astrophysics Data System (ADS)

Alexandrov, Sergei; Banerjee, Sibasish; Manschot, Jan; Pioline, Boris

2017-07-01

We study D3-instanton corrections to the hypermultiplet moduli space in type IIB string theory compactified on a Calabi-Yau threefold. In a previous work, consistency of D3-instantons with S-duality was established at first order in the instanton expansion, using the modular properties of the M5-brane elliptic genus. We extend this analysis to the two-instanton level, where wall-crossing phenomena start playing a role. We focus on the contact potential, an analogue of the Kähler potential which must transform as a modular form under S-duality. We show that it can be expressed in terms of a suitable modification of the partition function of D4-D2-D0 BPS black holes, constructed out of the generating function of MSW invariants (the latter coincide with Donaldson-Thomas invariants in a particular chamber). Modular invariance of the contact potential then requires that, in the case where the D3-brane wraps a reducible divisor, the generating function of MSW invariants must transform as a vector-valued mock modular form, with a specific modular completion built from the MSW invariants of the constituents. Physically, this gives a powerful constraint on the degeneracies of BPS black holes. Mathematically, our result gives a universal prediction for the modular properties of Donaldson-Thomas invariants of pure two-dimensional sheaves.

Potential Applications of Modularity to Enable a Deep Space Habitation Capability for Future Human Exploration Beyond Low-Earth Orbit

NASA Technical Reports Server (NTRS)

Simon, Matthew A.; Toups, Larry; Smitherman, David

2012-01-01

Evaluating preliminary concepts of a Deep Space Habitat (DSH) enabling long duration crewed exploration of asteroids, the Moon, and Mars is a technically challenging problem. Sufficient habitat volumes and equipment, necessary to ensure crew health and functionality, increase propellant requirements and decrease launch flexibility to deliver multiple elements on a single launch vehicle; both of which increase overall mission cost. Applying modularity in the design of the habitat structures and subsystems can alleviate these difficulties by spreading the build-up of the overall habitation capability across several smaller parts. This allows for a more flexible habitation approach that accommodates various crew mission durations and levels of functionality. This paper provides a technical analysis of how various modular habitation approaches can impact the parametric design of a DSH with potential benefits in mass, packaging volume, and architectural flexibility. This includes a description of the desired long duration habitation capability, the definition of a baseline model for comparison, a small trade study to investigate alternatives, and commentary on potentially advantageous configurations to enable different levels of habitability. The approaches investigated include modular pressure vessel strategies, modular subsystems, and modular manufacturing approaches to habitat structure. The paper also comments upon the possibility of an integrated habitation strategy using modular components to create all short and long duration habitation elements required in the current exploration architectures.

Structure and composition of the courtship phenotype in the bird of paradise Parotia lawesii (Aves: Paradisaeidae).

PubMed

Scholes, Edwin

2008-01-01

Ethology is rooted in the idea that behavior is composed of discrete units and sub-units that can be compared among taxa in a phylogenetic framework. This means that behavior, like morphology and genes, is inherently modular. Yet, the concept of modularity is not well integrated into how we envision the behavioral components of phenotype. Understanding ethological modularity, and its implications for animal phenotype organization and evolution, requires that we construct interpretive schemes that permit us to examine it. In this study, I describe the structure and composition of a complex part of the behavioral phenotype of Parotia lawesii Ramsay, 1885--a bird of paradise (Aves: Paradisaeidae) from the forests of eastern New Guinea. I use archived voucher video clips, photographic ethograms, and phenotype ontology diagrams to describe the modular units comprising courtship at various levels of integration. Results show P. lawesii to have 15 courtship and mating behaviors (11 males, 4 females) hierarchically arranged within a complex seven-level structure. At the finest level examined, male displays are comprised of 49 modular sub-units (elements) differentially employed to form more complex modular units (phases and versions) at higher-levels of integration. With its emphasis on hierarchical modularity, this study provides an important conceptual framework for understanding courtship-related phenotypic complexity and provides a solid basis for comparative study of the genus Parotia.

A Modular Laser Graphics Projection System

NASA Astrophysics Data System (ADS)

Newswanger, Craig D.

1984-05-01

WED Enterprises has designed and built a modular projection system for the presentation of animated laser shows. This system was designed specifically for use in Disney theme shows. Its modular design allows it to be adapted to many show situations with simple hardware and software adjustments. The primary goals were superior animation, long life, low maintenance and stand alone operation.

Design of a modular digital computer system, DRL 4. [for meeting future requirements of spaceborne computers

NASA Technical Reports Server (NTRS)

1972-01-01

The design is reported of an advanced modular computer system designated the Automatically Reconfigurable Modular Multiprocessor System, which anticipates requirements for higher computing capacity and reliability for future spaceborne computers. Subjects discussed include: an overview of the architecture, mission analysis, synchronous and nonsynchronous scheduling control, reliability, and data transmission.

Current Issues in Art and Design Education: Modularization and Course Ethos: The Case of Art and Design Higher Education.

ERIC Educational Resources Information Center

Wayte, Gillian; Wayte, Nick

1990-01-01

Examines why art and design educators resist the modularization of degree-level courses. Identifies key characteristics of art education in England through an ethnographic study. Discusses government policy and rationales for modular and integrated courses. Concludes that the holistic approach to education allows students to expound and develop…

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-30

efforts—the Expedited, Non-Developmental Item (NDI) APS effort and the Modular Active Protection System (MAPS) effort. The Marines describe their...17 Modular Active Protection System (MAPS) Effort .......................................................... 18 The Marine Corps APS...Merkava Mark 4 tank was designed around the Trophy APS. 32 The Army’s Modular Active Protection System (MAPS) effort, described below, is intended to

Proteolytic Processing of Turnip Yellow Mosaic Virus Replication Proteins and Functional Impact on Infectivity▿

PubMed Central

Jakubiec, Anna; Drugeon, Gabrièle; Camborde, Laurent; Jupin, Isabelle

2007-01-01

Turnip yellow mosaic virus (TYMV), a positive-strand RNA virus belonging to the alphavirus-like supergroup, encodes its nonstructural replication proteins as a 206K precursor with domains indicative of methyltransferase (MT), proteinase (PRO), NTPase/helicase (HEL), and polymerase (POL) activities. Subsequent processing of 206K generates a 66K protein encompassing the POL domain and uncharacterized 115K and 85K proteins. Here, we demonstrate that TYMV proteinase mediates an additional cleavage between the PRO and HEL domains of the polyprotein, generating the 115K protein and a 42K protein encompassing the HEL domain that can be detected in plant cells using a specific antiserum. Deletion and substitution mutagenesis experiments and sequence comparisons indicate that the scissile bond is located between residues Ser879 and Gln880. The 85K protein is generated by a host proteinase and is likely to result from nonspecific proteolytic degradation occurring during protein sample extraction or analysis. We also report that TYMV proteinase has the ability to process substrates in trans in vivo. Finally, we examined the processing of the 206K protein containing native, mutated, or shuffled cleavage sites and analyzed the effects of cleavage mutations on viral infectivity and RNA synthesis by performing reverse-genetics experiments. We present evidence that PRO/HEL cleavage is critical for productive virus infection and that the impaired infectivity of PRO/HEL cleavage mutants is due mainly to defective synthesis of positive-strand RNA. PMID:17686855

A conserved genetic module that encodes the major virion components in both the coliphage T4 and the marine cyanophage S-PM2

PubMed Central

Hambly, Emma; Tétart, Francoise; Desplats, Carine; Wilson, William H.; Krisch, Henry M.; Mann, Nicholas H.

2001-01-01

Sequence analysis of a 10-kb region of the genome of the marine cyanomyovirus S-PM2 reveals a homology to coliphage T4 that extends as a contiguous block from gene (g)18 to g23. The order of the S-PM2 genes in this region is similar to that of T4, but there are insertions and deletions of small ORFs of unknown function. In T4, g18 codes for the tail sheath, g19, the tail tube, g20, the head portal protein, g21, the prohead core protein, g22, a scaffolding protein, and g23, the major capsid protein. Thus, the entire module that determines the structural components of the phage head and contractile tail is conserved between T4 and this cyanophage. The significant differences in the morphology of these phages must reflect the considerable divergence of the amino acid sequence of their homologous virion proteins, which uniformly exceeds 50%. We suggest that their enormous diversity in the sea could be a result of genetic shuffling between disparate phages mediated by such commonly shared modules. These conserved sequences could facilitate genetic exchange by providing partially homologous substrates for recombination between otherwise divergent phage genomes. Such a mechanism would thus expand the pool of phage genes accessible by recombination to all those phages that share common modules. PMID:11553768

Modular-extramodular organization in developing multisensory shell regions of the mouse inferior colliculus.

PubMed

Dillingham, Christopher H; Gay, Sean M; Behrooz, Roxana; Gabriele, Mark L

2017-12-01

The complex neuroanatomical connections of the inferior colliculus (IC) and its major subdivisions offer a juxtaposition of segregated processing streams with distinct organizational features. While the tonotopically layered central nucleus is well-documented, less is known about functional compartments in the neighboring lateral cortex (LCIC). In addition to a laminar framework, LCIC afferent-efferent patterns suggest a multimodal mosaic, consisting of a patchy modular network with surrounding extramodular domains. This study utilizes several neurochemical markers that reveal an emerging LCIC modular-extramodular microarchitecture. In newborn and post-hearing C57BL/6J and CBA/CaJ mice, histochemical and immunocytochemical stains were performed for acetylcholinesterase (AChE), nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), glutamic acid decarboxylase (GAD), cytochrome oxidase (CO), and calretinin (CR). Discontinuous layer 2 modules are positive for AChE, NADPH-d, GAD, and CO throughout the rostrocaudal LCIC. While not readily apparent at birth, discrete cell clusters emerge over the first postnatal week, yielding an identifiable modular network prior to hearing onset. Modular boundaries continue to become increasingly distinct with age, as surrounding extramodular fields remain largely negative for each marker. Alignment of modular markers in serial sections suggests each highlight the same periodic patchy network throughout the nascent LCIC. In contrast, CR patterns appear complementary, preferentially staining extramodular LCIC zones. Double-labeling experiments confirm that NADPH-d, the most consistent developmental modular marker, and CR label separate, nonoverlapping LCIC compartments. Determining how this emerging modularity may align with similar LCIC patch-matrix-like Eph/ephrin guidance patterns, and how each interface with, and potentially influence developing multimodal LCIC projection configurations is discussed. © 2017 Wiley Periodicals, Inc.

General software design for multisensor data fusion

NASA Astrophysics Data System (ADS)

Zhang, Junliang; Zhao, Yuming

1999-03-01

In this paper a general method of software design for multisensor data fusion is discussed in detail, which adopts object-oriented technology under UNIX operation system. The software for multisensor data fusion is divided into six functional modules: data collection, database management, GIS, target display and alarming data simulation etc. Furthermore, the primary function, the components and some realization methods of each modular is given. The interfaces among these functional modular relations are discussed. The data exchange among each functional modular is performed by interprocess communication IPC, including message queue, semaphore and shared memory. Thus, each functional modular is executed independently, which reduces the dependence among functional modules and helps software programing and testing. This software for multisensor data fusion is designed as hierarchical structure by the inheritance character of classes. Each functional modular is abstracted and encapsulated through class structure, which avoids software redundancy and enhances readability.

Large-scale modular biofiltration system for effective odor removal in a composting facility.

PubMed

Lin, Yueh-Hsien; Chen, Yu-Pei; Ho, Kuo-Ling; Lee, Tsung-Yih; Tseng, Ching-Ping

2013-01-01

Several different foul odors such as nitrogen-containing groups, sulfur-containing groups, and short-chain fatty-acids commonly emitted from composting facilities. In this study, an experimental laboratory-scale bioreactor was scaled up to build a large-scale modular biofiltration system that can process 34 m(3)min(-1)waste gases. This modular reactor system was proven effective in eliminating odors, with a 97% removal efficiency for 96 ppm ammonia, a 98% removal efficiency for 220 ppm amines, and a 100% removal efficiency of other odorous substances. The results of operational parameters indicate that this modular biofiltration system offers long-term operational stability. Specifically, a low pressure drop (<45 mmH2O m(-1)) was observed, indicating that the packing carrier in bioreactor units does not require frequent replacement. Thus, this modular biofiltration system can be used in field applications to eliminate various odors with compact working volume.

Development of a Commercially Viable, Modular Autonomous Robotic Systems for Converting any Vehicle to Autonomous Control

NASA Technical Reports Server (NTRS)

Parish, David W.; Grabbe, Robert D.; Marzwell, Neville I.

1994-01-01

A Modular Autonomous Robotic System (MARS), consisting of a modular autonomous vehicle control system that can be retrofit on to any vehicle to convert it to autonomous control and support a modular payload for multiple applications is being developed. The MARS design is scalable, reconfigurable, and cost effective due to the use of modern open system architecture design methodologies, including serial control bus technology to simplify system wiring and enhance scalability. The design is augmented with modular, object oriented (C++) software implementing a hierarchy of five levels of control including teleoperated, continuous guidepath following, periodic guidepath following, absolute position autonomous navigation, and relative position autonomous navigation. The present effort is focused on producing a system that is commercially viable for routine autonomous patrolling of known, semistructured environments, like environmental monitoring of chemical and petroleum refineries, exterior physical security and surveillance, perimeter patrolling, and intrafacility transport applications.

Network modularity reveals critical scales for connectivity in ecology and evolution

USGS Publications Warehouse

Fletcher, Robert J.; Revell, Andre; Reichert, Brian E.; Kitchens, Wiley M.; Dixon, J.; Austin, James D.

2013-01-01

For nearly a century, biologists have emphasized the profound importance of spatial scale for ecology, evolution and conservation. Nonetheless, objectively identifying critical scales has proven incredibly challenging. Here we extend new techniques from physics and social sciences that estimate modularity on networks to identify critical scales for movement and gene flow in animals. Using four species that vary widely in dispersal ability and include both mark-recapture and population genetic data, we identify significant modularity in three species, two of which cannot be explained by geographic distance alone. Importantly, the inclusion of modularity in connectivity and population viability assessments alters conclusions regarding patch importance to connectivity and suggests higher metapopulation viability than when ignoring this hidden spatial scale. We argue that network modularity reveals critical meso-scales that are probably common in populations, providing a powerful means of identifying fundamental scales for biology and for conservation strategies aimed at recovering imperilled species.

A simplified computational memory model from information processing

PubMed Central

Zhang, Lanhua; Zhang, Dongsheng; Deng, Yuqin; Ding, Xiaoqian; Wang, Yan; Tang, Yiyuan; Sun, Baoliang

2016-01-01

This paper is intended to propose a computational model for memory from the view of information processing. The model, called simplified memory information retrieval network (SMIRN), is a bi-modular hierarchical functional memory network by abstracting memory function and simulating memory information processing. At first meta-memory is defined to express the neuron or brain cortices based on the biology and graph theories, and we develop an intra-modular network with the modeling algorithm by mapping the node and edge, and then the bi-modular network is delineated with intra-modular and inter-modular. At last a polynomial retrieval algorithm is introduced. In this paper we simulate the memory phenomena and functions of memorization and strengthening by information processing algorithms. The theoretical analysis and the simulation results show that the model is in accordance with the memory phenomena from information processing view. PMID:27876847

Antibody-mediated targeting of replication-competent retroviral vectors.

PubMed

Tai, Chien-Kuo; Logg, Christopher R; Park, Jinha M; Anderson, W French; Press, Michael F; Kasahara, Noriyuki

2003-05-20

Replication-competent murine leukemia virus (MLV) vectors can be engineered to achieve high efficiency gene transfer to solid tumors in vivo and tumor-restricted replication, however their safety can be further enhanced by redirecting tropism of the virus envelope. We have therefore tested the targeting capability and replicative stability of ecotropic and amphotropic replication-competent retrovirus (RCR) vectors containing two tandem repeats from the immunoglobulin G-binding domain of Staphylococcal protein A inserted into the proline-rich "hinge" region of the envelope, which enables modular use of antibodies of various specificities for vector targeting. The modified envelopes were efficiently expressed and incorporated into virions, were capable of capturing monoclonal anti-HER2 antibodies, and mediated efficient binding of the virus-antibody complex to HER2-positive target cells. While infectivity was markedly reduced by pseudotyping with targeted envelopes alone, coexpression of wild-type envelope rescued efficient cellular entry. Both ecotropic and amphotropic RCR vector/anti-HER2 antibody complexes achieved significant enhancement of transduction on murine target cells overexpressing HER2, which could be competed by preincubation with excess free antibodies. Interestingly, HER2-expressing human breast cancer cells did not show enhancement of transduction despite efficient antibody-mediated cell surface binding, suggesting that target cell-specific parameters markedly affect the efficiency of post-binding entry processes. Serial replication of targeted vectors resulted in selection of Z domain deletion variants, but reduction of the overall size of the vector genome enhanced its stability. Application of antibody-mediated targeting to the initial localization of replication-competent virus vectors to tumor sites will thus require optimized target selection and vector design.

Src binds cortactin through an SH2 domain cystine-mediated linkage.

PubMed

Evans, Jason V; Ammer, Amanda G; Jett, John E; Bolcato, Chris A; Breaux, Jason C; Martin, Karen H; Culp, Mark V; Gannett, Peter M; Weed, Scott A

2012-12-15

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions.

Src binds cortactin through an SH2 domain cystine-mediated linkage

PubMed Central

Evans, Jason V.; Ammer, Amanda G.; Jett, John E.; Bolcato, Chris A.; Breaux, Jason C.; Martin, Karen H.; Culp, Mark V.; Gannett, Peter M.; Weed, Scott A.

2012-01-01

Summary Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions. PMID:23097045