Enrichment assessment of multiple virtual screening strategies for Toll-like receptor 8 agonists based on a maximal unbiased benchmarking data set.

PubMed

Pei, Fen; Jin, Hongwei; Zhou, Xin; Xia, Jie; Sun, Lidan; Liu, Zhenming; Zhang, Liangren

2015-11-01

Toll-like receptor 8 agonists, which activate adaptive immune responses by inducing robust production of T-helper 1-polarizing cytokines, are promising candidates for vaccine adjuvants. As the binding site of toll-like receptor 8 is large and highly flexible, virtual screening by individual method has inevitable limitations; thus, a comprehensive comparison of different methods may provide insights into seeking effective strategy for the discovery of novel toll-like receptor 8 agonists. In this study, the performance of knowledge-based pharmacophore, shape-based 3D screening, and combined strategies was assessed against a maximum unbiased benchmarking data set containing 13 actives and 1302 decoys specialized for toll-like receptor 8 agonists. Prior structure-activity relationship knowledge was involved in knowledge-based pharmacophore generation, and a set of antagonists was innovatively used to verify the selectivity of the selected knowledge-based pharmacophore. The benchmarking data set was generated from our recently developed 'mubd-decoymaker' protocol. The enrichment assessment demonstrated a considerable performance through our selected three-layer virtual screening strategy: knowledge-based pharmacophore (Phar1) screening, shape-based 3D similarity search (Q4_combo), and then a Gold docking screening. This virtual screening strategy could be further employed to perform large-scale database screening and to discover novel toll-like receptor 8 agonists. © 2015 John Wiley & Sons A/S.

Long-term selection strategies for complex traits using high-density genetic markers.

PubMed

Kemper, K E; Bowman, P J; Pryce, J E; Hayes, B J; Goddard, M E

2012-08-01

Selection of animals for breeding ranked on estimated breeding value maximizes genetic gain in the next generation but does not necessarily maximize long-term response. An alternative method, as practiced by plant breeders, is to build a desired genotype by selection on specific loci. Maximal long-term response in animal breeding requires selection on estimated breeding values with constraints on coancestry. In this paper, we compared long-term genetic response using either a genotype building or a genomic estimated breeding value (GEBV) strategy for the Australian Selection Index (ASI), a measure of profit. First, we used real marker effects from the Australian Dairy Herd Improvement Scheme to estimate breeding values for chromosome segments (approximately 25 cM long) for 2,650 Holstein bulls. Second, we selected 16 animals to be founders for a simulated breeding program where, between them, founders contain the best possible combination of 2 segments from 2 animals at each position in the genome. Third, we mated founder animals and their descendants over 30 generations with 2 breeding objectives: (1) to create a population with the "ideal genotype," where the best 2 segments from the founders segregate at each position, or (2) obtain the highest possible response in ASI with coancestry lower than that achieved under breeding objective 1. Results show that genotype building achieved the ideal genotype for breeding objective 1 and obtained a large gain in ASI over the current population (+A$864.99). However, selection on overall GEBV had greater short-term response and almost as much long-term gain (+A$820.42). When coancestry was lowered under breeding objective 2, selection on overall GEBV achieved a higher response in ASI than the genotype building strategy. Selection on overall GEBV seems more flexible in its selection decisions and was therefore better able to precisely control coancestry while maximizing ASI. We conclude that selection on overall GEBV while minimizing average coancestry is the more practical strategy for dairy cattle where selection is for highly polygenic traits, the reproductive rate is relatively low, and there is low tolerance of coancestry. The outcome may be different for traits controlled by few loci of relatively large effects or for different species. In contrast to other simulations, our results indicate that response to selection on overall GEBV may continue for several generations. This is because long-term genetic change in complex traits requires favorable changes to allele frequencies for many loci located throughout the genome. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Microbiome studies in the biological control of plant pathogens

USDA-ARS?s Scientific Manuscript database

Biological control of plant pathogens, although it has been a successful alternative that has allowed to select microorganisms for the generation of bioproducts and to understand multiple biological mechanisms, cannot be considered as a strategy defined only from the selection of a range of cultiva...

Next-Generation Sequencing of Antibody Display Repertoires

PubMed Central

Rouet, Romain; Jackson, Katherine J. L.; Langley, David B.; Christ, Daniel

2018-01-01

In vitro selection technology has transformed the development of therapeutic monoclonal antibodies. Using methods such as phage, ribosome, and yeast display, high affinity binders can be selected from diverse repertoires. Here, we review strategies for the next-generation sequencing (NGS) of phage- and other antibody-display libraries, as well as NGS platforms and analysis tools. Moreover, we discuss recent examples relating to the use of NGS to assess library diversity, clonal enrichment, and affinity maturation. PMID:29472918

Dosimetric advantages of a clinical daily adaptive plan selection strategy compared with a non-adaptive strategy in cervical cancer radiation therapy.

PubMed

van de Schoot, Agustinus J A J; de Boer, Peter; Visser, Jorrit; Stalpers, Lukas J A; Rasch, Coen R N; Bel, Arjan

2017-05-01

Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer. Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included. Non-adaptive plans were generated based on the PTV defined using the full bladder planning CT. For the adaptive strategy, multiple PTVs were created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV, cervix, corpus-uterus and upper part of the vagina) and corresponding library plans were generated. Daily CBCTs were rigidly aligned to the full bladder planning CT for plan selection. For daily plan recalculation, selected CTs based on initial similarity were deformably registered to CBCTs. Differences in daily target coverage (D 98%  > 95%) and in V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% for rectum, bladder and bowel were assessed. Non-adaptive RT showed inadequate primary CTV coverage in 17% of the daily fractions. Plan selection compensated for anatomical changes and improved primary CTV coverage significantly (p < 0.01) to 98%. Compared with non-adaptive RT, plan selection decreased the fraction dose to rectum and bowel indicated by significant (p < 0.01) improvements for daily V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% . However, daily plan selection significantly increased the bladder V 1.5Gy , V 2Gy , D 50% and D 2% . In cervical cancer RT, a non-adaptive strategy led to inadequate target coverage for individual patients. Daily plan selection corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to bowel and rectum was decreased significantly when applying adaptive RT.

BEAT: A Web-Based Boolean Expression Fault-Based Test Case Generation Tool

ERIC Educational Resources Information Center

Chen, T. Y.; Grant, D. D.; Lau, M. F.; Ng, S. P.; Vasa, V. R.

2006-01-01

BEAT is a Web-based system that generates fault-based test cases from Boolean expressions. It is based on the integration of our several fault-based test case selection strategies. The generated test cases are considered to be fault-based, because they are aiming at the detection of particular faults. For example, when the Boolean expression is in…

Impact of agriculture on the selection of insecticide resistance in the malaria vector Anopheles gambiae: a multigenerational study in controlled conditions.

PubMed

Nkya, Theresia Estomih; Poupardin, Rodolphe; Laporte, Frederic; Akhouayri, Idir; Mosha, Franklin; Magesa, Stephen; Kisinza, William; David, Jean-Philippe

2014-10-16

Resistance of mosquitoes to insecticides is mainly attributed to their adaptation to vector control interventions. Although pesticides used in agriculture have been frequently mentioned as an additional force driving the selection of resistance, only a few studies were dedicated to validate this hypothesis and characterise the underlying mechanisms. While insecticide resistance is rising dramatically in Africa, deciphering how agriculture affects resistance is crucial for improving resistance management strategies. In this context, the multigenerational effect of agricultural pollutants on the selection of insecticide resistance was examined in Anopheles gambiae. An urban Tanzanian An. gambiae population displaying a low resistance level was used as a parental strain for a selection experiment across 20 generations. At each generation larvae were selected with a mixture containing pesticides and herbicides classically used in agriculture in Africa. The resistance levels of adults to deltamethrin, DDT and bendiocarb were compared between the selected and non-selected strains across the selection process together with the frequency of kdr mutations. A microarray approach was used for pinpointing transcription level variations selected by the agricultural pesticide mixture at the adult stage. A gradual increase of adult resistance to all insecticides was observed across the selection process. The frequency of the L1014S kdr mutation rose from 1.6% to 12.5% after 20 generations of selection. Microarray analysis identified 90 transcripts over-transcribed in the selected strain as compared to the parental and the non-selected strains. Genes encoding cuticle proteins, detoxification enzymes, proteins linked to neurotransmitter activity and transcription regulators were mainly affected. RT-qPCR transcription profiling of candidate genes across multiple generations supported their link with insecticide resistance. This study confirms the potency of agriculture in selecting for insecticide resistance in malaria vectors. We demonstrated that the recurrent exposure of larvae to agricultural pollutants can select for resistance mechanisms to vector control insecticides at the adult stage. Our data suggest that in addition to selected target-site resistance mutations, agricultural pollutants may also favor cuticle, metabolic and synaptic transmission-based resistance mechanisms. These results emphasize the need for integrated resistance management strategies taking into account agriculture activities.

An automatic fuzzy-based multi-temporal brain digital subtraction angiography image fusion algorithm using curvelet transform and content selection strategy.

PubMed

Momeni, Saba; Pourghassem, Hossein

2014-08-01

Recently image fusion has prominent role in medical image processing and is useful to diagnose and treat many diseases. Digital subtraction angiography is one of the most applicable imaging to diagnose brain vascular diseases and radiosurgery of brain. This paper proposes an automatic fuzzy-based multi-temporal fusion algorithm for 2-D digital subtraction angiography images. In this algorithm, for blood vessel map extraction, the valuable frames of brain angiography video are automatically determined to form the digital subtraction angiography images based on a novel definition of vessel dispersion generated by injected contrast material. Our proposed fusion scheme contains different fusion methods for high and low frequency contents based on the coefficient characteristic of wrapping second generation of curvelet transform and a novel content selection strategy. Our proposed content selection strategy is defined based on sample correlation of the curvelet transform coefficients. In our proposed fuzzy-based fusion scheme, the selection of curvelet coefficients are optimized by applying weighted averaging and maximum selection rules for the high frequency coefficients. For low frequency coefficients, the maximum selection rule based on local energy criterion is applied to better visual perception. Our proposed fusion algorithm is evaluated on a perfect brain angiography image dataset consisting of one hundred 2-D internal carotid rotational angiography videos. The obtained results demonstrate the effectiveness and efficiency of our proposed fusion algorithm in comparison with common and basic fusion algorithms.

First macrocyclic 3rd-generation ALK inhibitor for treatment of ALK/ROS1 cancer: Clinical and designing strategy update of lorlatinib.

PubMed

Basit, Sulman; Ashraf, Zaman; Lee, Kwangho; Latif, Muhammad

2017-07-07

Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to 2 nd -generation ALK inhibitors. Lorlatinib (PF-06463922) (6) is a 3 rd -generation macrocyclic ALK-TKI that demonstrates many advantages over 2 nd -generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Real-world datasets for portfolio selection and solutions of some stochastic dominance portfolio models.

PubMed

Bruni, Renato; Cesarone, Francesco; Scozzari, Andrea; Tardella, Fabio

2016-09-01

A large number of portfolio selection models have appeared in the literature since the pioneering work of Markowitz. However, even when computational and empirical results are described, they are often hard to replicate and compare due to the unavailability of the datasets used in the experiments. We provide here several datasets for portfolio selection generated using real-world price values from several major stock markets. The datasets contain weekly return values, adjusted for dividends and for stock splits, which are cleaned from errors as much as possible. The datasets are available in different formats, and can be used as benchmarks for testing the performances of portfolio selection models and for comparing the efficiency of the algorithms used to solve them. We also provide, for these datasets, the portfolios obtained by several selection strategies based on Stochastic Dominance models (see "On Exact and Approximate Stochastic Dominance Strategies for Portfolio Selection" (Bruni et al. [2])). We believe that testing portfolio models on publicly available datasets greatly simplifies the comparison of the different portfolio selection strategies.

When does a strategy intervention overcome a failure of inhibition? Evidence from two left frontal brain tumour cases.

PubMed

Robinson, Gail A; Walker, David G; Biggs, Vivien; Shallice, Tim

2016-06-01

Initiation and inhibition of responses are crucial for appropriate behaviour across different settings. Initiation and inhibition difficulties are well documented following frontal damage, although task differences have limited our understanding. The Hayling Sentence Completion Test was designed to assess verbal initiation and inhibition within the same task. This study investigates the ability of two patients with left frontal tumours (KI: high grade glioma; PM: meningioma) to use a strategy to overcome profound suppression failures on the Hayling Test. KI and PM completed the Hayling Test and two experimental tasks. The Selection Investigation assessed verbal initiation on a sentence completion task that varied selection demands (high/low). The Suppression and Strategy Investigation assessed ability to implement four strategies aimed to override a suppression failure and facilitate production of an unconnected word. On the Hayling Test, KI and PM initiated responses to complete high constraint sentences, in contrast to impaired suppression. KI benefitted minimally from strategies to overcome suppression failure although one strategy (object naming) was partially successful. KI's errors revealed fast suppression errors, in contrast to slow no responses, and selection ability was also impaired for verbal initiation. PM, however, implemented each strategy 100% to overcome a suppression failure and had no difficulty completing sentences meaningfully, regardless of selection demands. This first investigation of strategy implementation to overcome profound suppression impairments provides insights into verbal initiation, inhibition, selection and strategy mechanisms, which has implications for neurorehabilitation. Specifically, both patients had profound inhibition deficits but KI also presented with a selection deficit and was unable to implement a strategy. By contrast, PM's selection ability was intact but she was unable to generate, rather than implement, a strategy. We suggest that KI has both fast, uncontrolled semantic output and response inhibition difficulty, whereas PM's difficulty is underpinned by motivational factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neanderthal hunting strategies inferred from mortality profiles within the Abric Romaní sequence

PubMed Central

Carbonell, Eudald

2017-01-01

Ungulate mortality profiles are commonly used to study Neanderthal subsistence strategies. To assess the hunting strategies used by Neanderthals, we studied the ages at death of the cervids and equids found in levels E, H, I, Ja, Jb, K, L and M of the Abric Romaní sequence. These levels date between 43.2 ± 1.1 ka BP (14C AMS) and 54.5 ± 1.7 ka BP (U-series). The degree of eruption and development of the teeth and their wear stages were used to determine the ages of these animals at death, and mortality profiles were constructed using these data. The equids display prime dominated profiles in all of the analyzed levels, whereas the cervids display variable profiles. These results suggest that the Neanderthals of Abric Romaní employed both selective and non-selective hunting strategies. The selective strategy focused on the hunting of prime adults and generated prime dominated profiles. On the other hand, non-selective strategies, involved the consumption of animals of variable ages, resulting in catastrophic profiles. It is likely that in the selective hunting events were conducted using selective ambushes in which it was possible to select specific prey animals. On the other hand, encounter hunting or non-selective ambush hunting may have also been used at times, based on the abundances of prey animals and encounter rates. Specific hunting strategies would have been developed accordance with the taxa and the age of the individual to be hunted. The hunting groups most likely employed cooperative hunting techniques, especially in the capture of large animals. Thus, it is not possible to uniquely associate a single mortality profile with the predation tactics of Neanderthals at Abric Romaní. PMID:29166384

Neanderthal hunting strategies inferred from mortality profiles within the Abric Romaní sequence.

PubMed

Marín, Juan; Saladié, Palmira; Rodríguez-Hidalgo, Antonio; Carbonell, Eudald

2017-01-01

Ungulate mortality profiles are commonly used to study Neanderthal subsistence strategies. To assess the hunting strategies used by Neanderthals, we studied the ages at death of the cervids and equids found in levels E, H, I, Ja, Jb, K, L and M of the Abric Romaní sequence. These levels date between 43.2 ± 1.1 ka BP (14C AMS) and 54.5 ± 1.7 ka BP (U-series). The degree of eruption and development of the teeth and their wear stages were used to determine the ages of these animals at death, and mortality profiles were constructed using these data. The equids display prime dominated profiles in all of the analyzed levels, whereas the cervids display variable profiles. These results suggest that the Neanderthals of Abric Romaní employed both selective and non-selective hunting strategies. The selective strategy focused on the hunting of prime adults and generated prime dominated profiles. On the other hand, non-selective strategies, involved the consumption of animals of variable ages, resulting in catastrophic profiles. It is likely that in the selective hunting events were conducted using selective ambushes in which it was possible to select specific prey animals. On the other hand, encounter hunting or non-selective ambush hunting may have also been used at times, based on the abundances of prey animals and encounter rates. Specific hunting strategies would have been developed accordance with the taxa and the age of the individual to be hunted. The hunting groups most likely employed cooperative hunting techniques, especially in the capture of large animals. Thus, it is not possible to uniquely associate a single mortality profile with the predation tactics of Neanderthals at Abric Romaní.

High-Speed Lateral Flow Strategy for a Fast Biosensing with an Improved Selectivity and Binding Affinity.

PubMed

Cho, Dong Guk; Yoo, Haneul; Lee, Haein; Choi, Yeol Kyo; Lee, Minju; Ahn, Dong June; Hong, Seunghun

2018-05-10

We report a high-speed lateral flow strategy for a fast biosensing with an improved selectivity and binding affinity even under harsh conditions. In this strategy, biosensors were fixed at a location away from the center of a round shape disk, and the disk was rotated to create the lateral flow of a target solution on the biosensors during the sensing measurements. Experimental results using the strategy showed high reaction speeds, high binding affinity, and low nonspecific adsorptions of target molecules to biosensors. Furthermore, binding affinity between target molecules and sensing molecules was enhanced even in harsh conditions such as low pH and low ionic strength conditions. These results show that the strategy can improve the performance of conventional biosensors by generating high-speed lateral flows on a biosensor surface. Therefore, our strategy can be utilized as a simple but powerful tool for versatile bio and medical applications.

Generation of Stable Knockout Mammalian Cells by TALEN-Mediated Locus-Specific Gene Editing.

PubMed

Mahata, Barun; Biswas, Kaushik

2017-01-01

Precise and targeted genome editing using Transcription Activator-Like Effector Endonucleases (TALENs) has been widely used and proven to be an extremely effective and specific knockout strategy in both cultured cells and animal models. The current chapter describes a protocol for the construction and generation of TALENs using serial and hierarchical digestion and ligation steps, and using the synthesized TALEN pairs to achieve locus-specific targeted gene editing in mammalian cell lines using a modified clonal selection strategy in an easy and cost-efficient manner.

Cottowood Breeding Strategies for the Future

Treesearch

D. T. Cooper

1976-01-01

A large number of genotypes of eastern cottonwood of diverse parentage should be evaluated followed by multiple-stage selection for the most important characters to obtain substantial gains per sexual cycle while retaining genetic diversity. More intensive testing should be practiced in selecting clones tor commercial use than for use as parents of the next generation...

Microbiome Selection Could Spur Next-Generation Plant Breeding Strategies.

PubMed

Gopal, Murali; Gupta, Alka

2016-01-01

" No plant is an island too …" Plants, though sessile, have developed a unique strategy to counter biotic and abiotic stresses by symbiotically co-evolving with microorganisms and tapping into their genome for this purpose. Soil is the bank of microbial diversity from which a plant selectively sources its microbiome to suit its needs. Besides soil, seeds, which carry the genetic blueprint of plants during trans-generational propagation, are home to diverse microbiota that acts as the principal source of microbial inoculum in crop cultivation. Overall, a plant is ensconced both on the outside and inside with a diverse assemblage of microbiota. Together, the plant genome and the genes of the microbiota that the plant harbors in different plant tissues, i.e., the 'plant microbiome,' form the holobiome which is now considered as unit of selection: 'the holobiont.' The 'plant microbiome' not only helps plants to remain fit but also offers critical genetic variability, hitherto, not employed in the breeding strategy by plant breeders, who traditionally have exploited the genetic variability of the host for developing high yielding or disease tolerant or drought resistant varieties. This fresh knowledge of the microbiome, particularly of the rhizosphere, offering genetic variability to plants, opens up new horizons for breeding that could usher in cultivation of next-generation crops depending less on inorganic inputs, resistant to insect pest and diseases and resilient to climatic perturbations. We surmise, from ever increasing evidences, that plants and their microbial symbionts need to be co-propagated as life-long partners in future strategies for plant breeding. In this perspective, we propose bottom-up approach to co-propagate the co-evolved, the plant along with the target microbiome, through - (i) reciprocal soil transplantation method, or (ii) artificial ecosystem selection method of synthetic microbiome inocula, or (iii) by exploration of microRNA transfer method - for realizing this next-generation plant breeding approach. Our aim, thus, is to bring closer the information accrued through the advanced nucleotide sequencing and bioinformatics in conjunction with conventional culture-dependent isolation method for practical application in plant breeding and overall agriculture.

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

PubMed

Del Prete, Gregory Q; Ailers, Braiden; Moldt, Brian; Keele, Brandon F; Estes, Jacob D; Rodriguez, Anthony; Sampias, Marissa; Oswald, Kelli; Fast, Randy; Trubey, Charles M; Chertova, Elena; Smedley, Jeremy; LaBranche, Celia C; Montefiori, David C; Burton, Dennis R; Shaw, George M; Markowitz, Marty; Piatak, Michael; KewalRamani, Vineet N; Bieniasz, Paul D; Lifson, Jeffrey D; Hatziioannou, Theodora

2014-09-10

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevention of surgical resident attrition by a novel selection strategy.

PubMed

Kelz, Rachel R; Mullen, James L; Kaiser, Larry R; Pray, Lori A; Shea, Gregory P; Drebin, Jeff A; Wirtalla, Chris J; Morris, Jon B

2010-09-01

We modified the resident selection strategy in an attempt to reduce resident attrition (RA). Despite implementation of the Accreditation Council for Graduate Medical Education work rules, lifestyle and generational priorities have fostered a persistent and relatively high attrition rate for surgical trainees. An independent external review of residents who left the training program and a detailed analysis of the resident selection strategy were performed by an organizational management expert. Modifications implemented in 2005 (the intervention) included standardization of the screening and interview format. Applicants were required to submit a 500 words essay related to stress management, organizational skills, future aspirations, and prioritization abilities. Their responses formed the basis of an extended, personalized, and structured interview script. Candidate characteristics and RA were compared for the 5 years before and after the intervention, using Fisher exact test or chi2. Age, sex, birthplace, medical school ranking, step 1 score, and American Board of Surgey In-Training Examination performance were not significantly different between the selection strategy groups. Risk factors for RA included ABSITE performance and gender. Resident performance and subsequent RA were significantly affected by the resident selection strategy. RA was dramatically reduced following the intervention. A custom designed process to identify candidates most likely to succeed substantially improved resident retention in a demanding academic training program.

Controlling selective stimulations below a spinal cord hemisection using brain recordings with a neural interface system approach

NASA Astrophysics Data System (ADS)

Panetsos, Fivos; Sanchez-Jimenez, Abel; Torets, Carlos; Largo, Carla; Micera, Silvestro

2011-08-01

In this work we address the use of realtime cortical recordings for the generation of coherent, reliable and robust motor activity in spinal-lesioned animals through selective intraspinal microstimulation (ISMS). The spinal cord of adult rats was hemisectioned and groups of multielectrodes were implanted in both the central nervous system (CNS) and the spinal cord below the lesion level to establish a neural system interface (NSI). To test the reliability of this new NSI connection, highly repeatable neural responses recorded from the CNS were used as a pattern generator of an open-loop control strategy for selective ISMS of the spinal motoneurons. Our experimental procedure avoided the spontaneous non-controlled and non-repeatable neural activity that could have generated spurious ISMS and the consequent undesired muscle contractions. Combinations of complex CNS patterns generated precisely coordinated, reliable and robust motor actions.

Generation of radio vortex beams with designable polarization using anisotropic frequency selective surface

NASA Astrophysics Data System (ADS)

Yang, Jin; Zhang, Cheng; Ma, Hui Feng; Zhao, Jie; Dai, Jun Yan; Yuan, Wei; Yang, Liu Xi; Cheng, Qiang; Cui, Tie Jun

2018-05-01

We propose a strategy to convert a linearly polarized wave from a single point source to an orbital angular momentum (OAM) wave by arbitrary polarization via an anisotropic frequency selective surface (FSS) in the microwave frequency. By tailoring the geometries of FSS elements, reflection-phases in x and y polarizations are engineered and encoded independently, which allows us to design the eventual polarization state of the generated OAM vortex beam by elaborately selecting individual coding sequences for each polarization. Two types of FSSs are designed and experimentally characterized to demonstrate the capability of OAM generation with circular and linear polarizations, respectively, showing excellent performance in a wide bandwidth from 14 to 16 GHz. This method provides opportunities for polarization multiplexing in microwave OAM communication systems.

Role of the neostriatal dopaminergic activity in sequencing and selecting behavioural strategies: facilitation of processes involved in selecting the best strategy in a stressful situation.

PubMed

Cools, A R

1980-10-01

The purpose of this study was to detect the behavioural effect of drug-induced changes in the neostriatal dopaminergic activity upon the degree of intrinsic (self-generated) and extrinsic (externally produced) constraints on the selection of behavioural patterns in rats. Both systemic and neostriatal injections of extremely low doses of apomorphine and haloperidol were used to change the neostriatal dopaminergic activity. Behavioural changes were observed in (a) an open-field test, (b) a so-called 'swimming without escape' test, (c) a so-called 'swimming with escape' test, and (d) a test to detect deficiencies in sensory, motor and sensorimotor capacities required to perform both swimming tests. Evidence is found that the neostriatum, especially the neostriatal, dopaminergic activity determines the animal's ability to select the best strategy in a stressful situation by modifying the process of switching strategies under pressure of factors intrinsic to the organism: neither sensory neglect nor inability to initiate voluntary movements underlay the observed phenomena. It is suggested that the neostriatum determines the individual flexibility to cope with available sensory information.

Comparison of three coding strategies for a low cost structure light scanner

NASA Astrophysics Data System (ADS)

Xiong, Hanwei; Xu, Jun; Xu, Chenxi; Pan, Ming

2014-12-01

Coded structure light is widely used for 3D scanning, and different coding strategies are adopted to suit for different goals. In this paper, three coding strategies are compared, and one of them is selected to implement a low cost structure light scanner under the cost of €100. To reach this goal, the projector and the video camera must be the cheapest, which will lead to some problems related to light coding. For a cheapest projector, complex intensity pattern can't be generated; even if it can be generated, it can't be captured by a cheapest camera. Based on Gray code, three different strategies are implemented and compared, called phase-shift, line-shift, and bit-shift, respectively. The bit-shift Gray code is the contribution of this paper, in which a simple, stable light pattern is used to generate dense(mean points distance<0.4mm) and accurate(mean error<0.1mm) results. The whole algorithm details and some example are presented in the papers.

Efficient Iris Recognition Based on Optimal Subfeature Selection and Weighted Subregion Fusion

PubMed Central

Deng, Ning

2014-01-01

In this paper, we propose three discriminative feature selection strategies and weighted subregion matching method to improve the performance of iris recognition system. Firstly, we introduce the process of feature extraction and representation based on scale invariant feature transformation (SIFT) in detail. Secondly, three strategies are described, which are orientation probability distribution function (OPDF) based strategy to delete some redundant feature keypoints, magnitude probability distribution function (MPDF) based strategy to reduce dimensionality of feature element, and compounded strategy combined OPDF and MPDF to further select optimal subfeature. Thirdly, to make matching more effective, this paper proposes a novel matching method based on weighted sub-region matching fusion. Particle swarm optimization is utilized to accelerate achieve different sub-region's weights and then weighted different subregions' matching scores to generate the final decision. The experimental results, on three public and renowned iris databases (CASIA-V3 Interval, Lamp, andMMU-V1), demonstrate that our proposed methods outperform some of the existing methods in terms of correct recognition rate, equal error rate, and computation complexity. PMID:24683317

Efficient iris recognition based on optimal subfeature selection and weighted subregion fusion.

PubMed

Chen, Ying; Liu, Yuanning; Zhu, Xiaodong; He, Fei; Wang, Hongye; Deng, Ning

2014-01-01

In this paper, we propose three discriminative feature selection strategies and weighted subregion matching method to improve the performance of iris recognition system. Firstly, we introduce the process of feature extraction and representation based on scale invariant feature transformation (SIFT) in detail. Secondly, three strategies are described, which are orientation probability distribution function (OPDF) based strategy to delete some redundant feature keypoints, magnitude probability distribution function (MPDF) based strategy to reduce dimensionality of feature element, and compounded strategy combined OPDF and MPDF to further select optimal subfeature. Thirdly, to make matching more effective, this paper proposes a novel matching method based on weighted sub-region matching fusion. Particle swarm optimization is utilized to accelerate achieve different sub-region's weights and then weighted different subregions' matching scores to generate the final decision. The experimental results, on three public and renowned iris databases (CASIA-V3 Interval, Lamp, and MMU-V1), demonstrate that our proposed methods outperform some of the existing methods in terms of correct recognition rate, equal error rate, and computation complexity.

Distribution patterns of haplotypes for symbionts from Umbilicaria esculenta and U. muehlenbergii reflect the importance of reproductive strategy in shaping population genetic structure.

PubMed

Cao, Shunan; Zhang, Fang; Liu, Chuanpeng; Hao, Zhihua; Tian, Yuan; Zhu, Lingxiang; Zhou, Qiming

2015-10-15

The diversity of lichen fungal components and their photosynthetic partners reflects both ecological and evolutionary factors. In present study, molecular investigations of the internal transcribed spacer of the nuclear ribosomal DNA (ITS nrDNA) region were conducted to analyze the genetic diversity of Umbilicaria esculenta and U. muehlenbergii together with their associated green algae. It was here demonstrated that the reproductive strategy is a principal reason for fungal selectivity to algae. U. muehlenbergii, which disperses via sexual spores, exhibits lower selectivity to its photosynthetic partners than U. esculenta, which has a vegetative reproductive strategy. The difference of genotypic diversity (both fungal and algal) between these two Umbilicaria species is low, although their nucleotide diversity can vary greatly. The present study illustrates that lichen-forming fungi with sexual reproductive strategies are less selective with respect to their photobionts; and reveals that both sexual and vegetative reproduction allow lichens to generate similar amounts of diversity to adapt to the environments. The current study will be helpful for elucidating how lichens with different reproductive strategies adapt to changing environments.

A novel strategy for selection of allosteric ribozymes yields RiboReporter™ sensors for caffeine and aspartame

PubMed Central

Ferguson, Alicia; Boomer, Ryan M.; Kurz, Markus; Keene, Sara C.; Diener, John L.; Keefe, Anthony D.; Wilson, Charles; Cload, Sharon T.

2004-01-01

We have utilized in vitro selection technology to develop allosteric ribozyme sensors that are specific for the small molecule analytes caffeine or aspartame. Caffeine- or aspartame-responsive ribozymes were converted into fluorescence-based RiboReporter™ sensor systems that were able to detect caffeine or aspartame in solution over a concentration range from 0.5 to 5 mM. With read-times as short as 5 min, these caffeine- or aspartame-dependent ribozymes function as highly specific and facile molecular sensors. Interestingly, successful isolation of allosteric ribozymes for the analytes described here was enabled by a novel selection strategy that incorporated elements of both modular design and activity-based selection methods typically used for generation of catalytic nucleic acids. PMID:15026535

Automatic Evolution of Molecular Nanotechnology Designs

NASA Technical Reports Server (NTRS)

Globus, Al; Lawton, John; Wipke, Todd; Saini, Subhash (Technical Monitor)

1998-01-01

This paper describes strategies for automatically generating designs for analog circuits at the molecular level. Software maps out the edges and vertices of potential nanotechnology systems on graphs, then selects appropriate ones through evolutionary or genetic paradigms.

Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs.

PubMed

Jenko, Janez; Gorjanc, Gregor; Cleveland, Matthew A; Varshney, Rajeev K; Whitelaw, C Bruce A; Woolliams, John A; Hickey, John M

2015-07-02

Genome editing (GE) is a method that enables specific nucleotides in the genome of an individual to be changed. To date, use of GE in livestock has focussed on simple traits that are controlled by a few quantitative trait nucleotides (QTN) with large effects. The aim of this study was to evaluate the potential of GE to improve quantitative traits that are controlled by many QTN, referred to here as promotion of alleles by genome editing (PAGE). Multiple scenarios were simulated to test alternative PAGE strategies for a quantitative trait. They differed in (i) the number of edits per sire (0 to 100), (ii) the number of edits per generation (0 to 500), and (iii) the extent of use of PAGE (i.e. editing all sires or only a proportion of them). The base line scenario involved selecting individuals on true breeding values (i.e., genomic selection only (GS only)-genomic selection with perfect accuracy) for several generations. Alternative scenarios complemented this base line scenario with PAGE (GS + PAGE). The effect of different PAGE strategies was quantified by comparing response to selection, changes in allele frequencies, the number of distinct QTN edited, the sum of absolute effects of the edited QTN per generation, and inbreeding. Response to selection after 20 generations was between 1.08 and 4.12 times higher with GS + PAGE than with GS only. Increases in response to selection were larger with more edits per sire and more sires edited. When the total resources for PAGE were limited, editing a few sires for many QTN resulted in greater response to selection and inbreeding compared to editing many sires for a few QTN. Between the scenarios GS only and GS + PAGE, there was little difference in the average change in QTN allele frequencies, but there was a major difference for the QTN with the largest effects. The sum of the effects of the edited QTN decreased across generations. This study showed that PAGE has great potential for application in livestock breeding programs, but inbreeding needs to be managed.

Optimization of a CRISPR/Cas9-mediated Knock-in Strategy at the Porcine Rosa26 Locus in Porcine Foetal Fibroblasts.

PubMed

Xie, Zicong; Pang, Daxin; Wang, Kankan; Li, Mengjing; Guo, Nannan; Yuan, Hongming; Li, Jianing; Zou, Xiaodong; Jiao, Huping; Ouyang, Hongsheng; Li, Zhanjun; Tang, Xiaochun

2017-06-08

Genetically modified pigs have important roles in agriculture and biomedicine. However, genome-specific knock-in techniques in pigs are still in their infancy and optimal strategies have not been extensively investigated. In this study, we performed electroporation to introduce a targeting donor vector (a non-linearized vector that did not contain a promoter or selectable marker) into Porcine Foetal Fibroblasts (PFFs) along with a CRISPR/Cas9 vector. After optimization, the efficiency of the EGFP site-specific knock-in could reach up to 29.6% at the pRosa26 locus in PFFs. Next, we used the EGFP reporter PFFs to address two key conditions in the process of achieving transgenic pigs, the limiting dilution method and the strategy to evaluate the safety and feasibility of the knock-in locus. This study demonstrates that we establish an efficient procedures for the exogenous gene knock-in technique and creates a platform to efficiently generate promoter-less and selectable marker-free transgenic PFFs through the CRISPR/Cas9 system. This study should contribute to the generation of promoter-less and selectable marker-free transgenic pigs and it may provide insights into sophisticated site-specific genome engineering techniques for additional species.

Therapeutic Antibodies by Phage Display.

PubMed

Shim, Hyunbo

2016-01-01

Antibody phage display is a major technological platform for the generation of fully human antibodies for therapeutic purposes. The in vitro binder selection by phage display allows researchers to have more extensive control over binding parameters and facilitates the isolation of clinical candidate antibodies with desired binding and/or functional profiles. Since the invention of antibody phage display in late 1980s, significant technological advancements in the design, construction, and selection of the antibody libraries have been made, and several fully human antibodies generated by phage display are currently approved or in various clinical development stages. In this review, the background and details of antibody phage display technology, and representative antibody libraries with natural or synthetic sequence diversity and different construction strategies are described. The generation, optimization, functional and biophysical properties, and preclinical and clinical developments of some of the phage display-derived therapeutic antibodies approved for use in patients or in late-stage clinical trials are also discussed. With evolving novel disease targets and therapeutic strategies, antibody phage display is expected to continue to play a central role in the development of the next generation of therapeutic antibodies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Specialization of the DNA-Cleaving Activity of a Group I Ribozyme Through In Vitro Evolution

NASA Technical Reports Server (NTRS)

Tsang, Joyce; Joyce, Gerald F.

1996-01-01

In an earlier study, an in vitro evolution procedure was applied to a large population of variants of the Tetrahymena group 1 ribozyme to obtain individuals with a 10(exp 5)-fold improved ability to cleave a target single-stranded DNA substrate under simulated physiological conditions. The evolved ribozymes also showed a twofold improvement, compared to the wild-type, in their ability to cleave a single-stranded RNA substrate. Here, we report continuation of the in vitro evolution process using a new selection strategy to achieve both enhanced DNA and diminished RNA-cleavage activity. Our strategy combines a positive selection for DNA cleavage with a negative selection against RNA binding. After 36 "generations" of in vitro evolution, the evolved population showed an approx. 100-fold increase in the ratio of DNA to RNA-cleavage activity. Site-directed mutagenesis experiment confirmed the selective advantage of two covarying mutations within the catalytic core of ribozyme that are largely responsible for this modified behavior. The population of ribozymes has now undergone a total of 63 successive generations of evolution, resulting in an average 28 mutations relative to the wild-type that are responsible for the altered phenotype.

Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape.

PubMed

Leitman, Ellen M; Thobakgale, Christina F; Adland, Emily; Ansari, M Azim; Raghwani, Jayna; Prendergast, Andrew J; Tudor-Williams, Gareth; Kiepiela, Photini; Hemelaar, Joris; Brener, Jacqui; Tsai, Ming-Han; Mori, Masahiko; Riddell, Lynn; Luzzi, Graz; Jooste, Pieter; Ndung'u, Thumbi; Walker, Bruce D; Pybus, Oliver G; Kellam, Paul; Naranbhai, Vivek; Matthews, Philippa C; Gall, Astrid; Goulder, Philip J R

2017-11-06

Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. © 2017 Leitman et al.

Biomimetic Strategies for Sensing Biological Species

PubMed Central

Hussain, Munawar; Wackerlig, Judith; Lieberzeit, Peter A.

2013-01-01

The starting point of modern biosensing was the application of actual biological species for recognition. Increasing understanding of the principles underlying such recognition (and biofunctionality in general), however, has triggered a dynamic field in chemistry and materials sciences that aims at joining the best of two worlds by combining concepts derived from nature with the processability of manmade materials, e.g., sensitivity and ruggedness. This review covers different biomimetic strategies leading to highly selective (bio)chemical sensors: the first section covers molecularly imprinted polymers (MIP) that attempt to generate a fully artificial, macromolecular mold of a species in order to detect it selectively. A different strategy comprises of devising polymer coatings to change the biocompatibility of surfaces that can also be used to immobilized natural receptors/ligands and thus stabilize them. Rationally speaking, this leads to self-assembled monolayers closely resembling cell membranes, sometimes also including bioreceptors. Finally, this review will highlight some approaches to generate artificial analogs of natural recognition materials and biomimetic approaches in nanotechnology. It mainly focuses on the literature published since 2005. PMID:25587400

Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): metabolically stable γ-secretase Inhibitors that selectively inhibit the production of amyloid-β over Notch.

PubMed

Probst, Gary; Aubele, Danielle L; Bowers, Simeon; Dressen, Darren; Garofalo, Albert W; Hom, Roy K; Konradi, Andrei W; Marugg, Jennifer L; Mattson, Matthew N; Neitzel, Martin L; Semko, Chris M; Sham, Hing L; Smith, Jenifer; Sun, Minghua; Truong, Anh P; Ye, Xiaocong M; Xu, Ying-Zi; Dappen, Michael S; Jagodzinski, Jacek J; Keim, Pamela S; Peterson, Brian; Latimer, Lee H; Quincy, David; Wu, Jing; Goldbach, Erich; Ness, Daniel K; Quinn, Kevin P; Sauer, John-Michael; Wong, Karina; Zhang, Hongbin; Zmolek, Wes; Brigham, Elizabeth F; Kholodenko, Dora; Hu, Kang; Kwong, Grace T; Lee, Michael; Liao, Anna; Motter, Ruth N; Sacayon, Patricia; Santiago, Pamela; Willits, Christopher; Bard, Frédérique; Bova, Michael P; Hemphill, Susanna S; Nguyen, Lam; Ruslim, Lany; Tanaka, Kevin; Tanaka, Pearl; Wallace, William; Yednock, Ted A; Basi, Guriqbal S

2013-07-11

Herein, we describe our strategy to design metabolically stable γ-secretase inhibitors which are selective for inhibition of Aβ generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of Aβ generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered Aβ in the CSF of healthy human volunteers.

In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

PubMed

Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

2013-11-26

Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

Optimization of selection for growth in Menz Sheep while minimizing inbreeding depression in fitness traits

PubMed Central

2013-01-01

The genetic trends in fitness (inbreeding, fertility and survival) of a closed nucleus flock of Menz sheep under selection during ten years for increased body weight were investigated to evaluate the consequences of selection for body weight on fitness. A mate selection tool was used to optimize in retrospect the actual selection and matings conducted over the project period to assess if the observed genetic gains in body weight could have been achieved with a reduced level of inbreeding. In the actual selection, the genetic trends for yearling weight, fertility of ewes and survival of lambs were 0.81 kg, –0.00026% and 0.016% per generation. The average inbreeding coefficient remained zero for the first few generations and then tended to increase over generations. The genetic gains achieved with the optimized retrospective selection and matings were highly comparable with the observed values, the correlation between the average breeding values of lambs born from the actual and optimized matings over the years being 0.99. However, the level of inbreeding with the optimized mate selections remained zero until late in the years of selection. Our results suggest that an optimal selection strategy that considers both genetic merits and coancestry of mates should be adopted to sustain the Menz sheep breeding program. PMID:23783076

Gene-targeted Random Mutagenesis to Select Heterochromatin-destabilizing Proteasome Mutants in Fission Yeast.

PubMed

Seo, Hogyu David; Lee, Daeyoup

2018-05-15

Random mutagenesis of a target gene is commonly used to identify mutations that yield the desired phenotype. Of the methods that may be used to achieve random mutagenesis, error-prone PCR is a convenient and efficient strategy for generating a diverse pool of mutants (i.e., a mutant library). Error-prone PCR is the method of choice when a researcher seeks to mutate a pre-defined region, such as the coding region of a gene while leaving other genomic regions unaffected. After the mutant library is amplified by error-prone PCR, it must be cloned into a suitable plasmid. The size of the library generated by error-prone PCR is constrained by the efficiency of the cloning step. However, in the fission yeast, Schizosaccharomyces pombe, the cloning step can be replaced by the use of a highly efficient one-step fusion PCR to generate constructs for transformation. Mutants of desired phenotypes may then be selected using appropriate reporters. Here, we describe this strategy in detail, taking as an example, a reporter inserted at centromeric heterochromatin.

Electrically heated DPF start-up strategy

DOEpatents

Gonze, Eugene V [Pinckney, MI; Ament, Frank [Troy, MI

2012-04-10

An exhaust system that processes exhaust generated by an engine has a diesel particulate filter (DPF) that is disposed downstream of the engine and that filters particulates in the exhaust. An electrical heater is disposed upstream of the DPF and selectively heats the exhaust to initiate combustion of the particulates. Heat generated by combustion of particulates in the heater induces combustion of particulates within the DPF. A control module selectively enables current flow to the electrical heater for an initial period of a DPF regeneration cycle, and limits exhaust flow while the electrical heater is heating to a predetermined soot combustion temperature.

Experimental comparison of residual stresses for a thermomechanical model for the simulation of selective laser melting

DOE PAGES

Hodge, N. E.; Ferencz, R. M.; Vignes, R. M.

2016-05-30

Selective laser melting (SLM) is an additive manufacturing process in which multiple, successive layers of metal powders are heated via laser in order to build a part. Modeling of SLM requires consideration of the complex interaction between heat transfer and solid mechanics. Here, the present work describes the authors initial efforts to validate their first generation model. In particular, the comparison of model-generated solid mechanics results, including both deformation and stresses, is presented. Additionally, results of various perturbations of the process parameters and modeling strategies are discussed.

Discriminative dictionary learning for abdominal multi-organ segmentation.

PubMed

Tong, Tong; Wolz, Robin; Wang, Zehan; Gao, Qinquan; Misawa, Kazunari; Fujiwara, Michitaka; Mori, Kensaku; Hajnal, Joseph V; Rueckert, Daniel

2015-07-01

An automated segmentation method is presented for multi-organ segmentation in abdominal CT images. Dictionary learning and sparse coding techniques are used in the proposed method to generate target specific priors for segmentation. The method simultaneously learns dictionaries which have reconstructive power and classifiers which have discriminative ability from a set of selected atlases. Based on the learnt dictionaries and classifiers, probabilistic atlases are then generated to provide priors for the segmentation of unseen target images. The final segmentation is obtained by applying a post-processing step based on a graph-cuts method. In addition, this paper proposes a voxel-wise local atlas selection strategy to deal with high inter-subject variation in abdominal CT images. The segmentation performance of the proposed method with different atlas selection strategies are also compared. Our proposed method has been evaluated on a database of 150 abdominal CT images and achieves a promising segmentation performance with Dice overlap values of 94.9%, 93.6%, 71.1%, and 92.5% for liver, kidneys, pancreas, and spleen, respectively. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

More efficient evolutionary strategies for model calibration with watershed model for demonstration

NASA Astrophysics Data System (ADS)

Baggett, J. S.; Skahill, B. E.

2008-12-01

Evolutionary strategies allow automatic calibration of more complex models than traditional gradient based approaches, but they are more computationally intensive. We present several efficiency enhancements for evolution strategies, many of which are not new, but when combined have been shown to dramatically decrease the number of model runs required for calibration of synthetic problems. To reduce the number of expensive model runs we employ a surrogate objective function for an adaptively determined fraction of the population at each generation (Kern et al., 2006). We demonstrate improvements to the adaptive ranking strategy that increase its efficiency while sacrificing little reliability and further reduce the number of model runs required in densely sampled parts of parameter space. Furthermore, we include a gradient individual in each generation that is usually not selected when the search is in a global phase or when the derivatives are poorly approximated, but when selected near a smooth local minimum can dramatically increase convergence speed (Tahk et al., 2007). Finally, the selection of the gradient individual is used to adapt the size of the population near local minima. We show, by incorporating these enhancements into the Covariance Matrix Adaption Evolution Strategy (CMAES; Hansen, 2006), that their synergetic effect is greater than their individual parts. This hybrid evolutionary strategy exploits smooth structure when it is present but degrades to an ordinary evolutionary strategy, at worst, if smoothness is not present. Calibration of 2D-3D synthetic models with the modified CMAES requires approximately 10%-25% of the model runs of ordinary CMAES. Preliminary demonstration of this hybrid strategy will be shown for watershed model calibration problems. Hansen, N. (2006). The CMA Evolution Strategy: A Comparing Review. In J.A. Lozano, P. Larrañga, I. Inza and E. Bengoetxea (Eds.). Towards a new evolutionary computation. Advances in estimation of distribution algorithms. pp. 75-102, Springer Kern, S., N. Hansen and P. Koumoutsakos (2006). Local Meta-Models for Optimization Using Evolution Strategies. In Ninth International Conference on Parallel Problem Solving from Nature PPSN IX, Proceedings, pp.939-948, Berlin: Springer. Tahk, M., Woo, H., and Park. M, (2007). A hybrid optimization of evolutionary and gradient search. Engineering Optimization, (39), 87-104.

Cooperation and charity in spatial public goods game under different strategy update rules

NASA Astrophysics Data System (ADS)

Li, Yixiao; Jin, Xiaogang; Su, Xianchuang; Kong, Fansheng; Peng, Chengbin

2010-03-01

Human cooperation can be influenced by other human behaviors and recent years have witnessed the flourishing of studying the coevolution of cooperation and punishment, yet the common behavior of charity is seldom considered in game-theoretical models. In this article, we investigate the coevolution of altruistic cooperation and egalitarian charity in spatial public goods game, by considering charity as the behavior of reducing inter-individual payoff differences. Our model is that, in each generation of the evolution, individuals play games first and accumulate payoff benefits, and then each egalitarian makes a charity donation by payoff transfer in its neighborhood. To study the individual-level evolutionary dynamics, we adopt different strategy update rules and investigate their effects on charity and cooperation. These rules can be classified into two global rules: random selection rule in which individuals randomly update strategies, and threshold selection rule where only those with payoffs below a threshold update strategies. Simulation results show that random selection enhances the cooperation level, while threshold selection lowers the threshold of the multiplication factor to maintain cooperation. When charity is considered, it is incapable in promoting cooperation under random selection, whereas it promotes cooperation under threshold selection. Interestingly, the evolution of charity strongly depends on the dispersion of payoff acquisitions of the population, which agrees with previous results. Our work may shed light on understanding human egalitarianism.

The Impact of Selection with Diflubenzuron, a Chitin Synthesis Inhibitor, on the Fitness of Two Brazilian Aedes aegypti Field Populations.

PubMed

Belinato, Thiago Affonso; Valle, Denise

2015-01-01

Several Aedes aegypti field populations are resistant to neurotoxic insecticides, mainly organophoshates and pyrethroids, which are extensively used as larvicides and adulticides, respectively. Diflubenzuron (DFB), a chitin synthesis inhibitor (CSI), was recently approved for use in drinking water, and is presently employed in Brazil for Ae. aegypti control, against populations resistant to the organophosphate temephos. However, tests of DFB efficacy against field Ae. aegypti populations are lacking. In addition, information regarding the dynamics of CSI resistance, and characterization of any potential fitness effects that may arise in conjunction with resistance are essential for new Ae. aegypti control strategies. Here, the efficacy of DFB was evaluated for two Brazilian Ae. aegypti populations known to be resistant to both temephos and the pyrethroid deltamethrin. Laboratory selection for DFB resistance was then performed over six or seven generations, using a fixed dose of insecticide that inhibited 80% of adult emergence in the first generation. The selection process was stopped when adult emergence in the diflubenzuron-treated groups was equivalent to that of the control groups, kept without insecticide. Diflubenzuron was effective against the two Ae. aegypti field populations evaluated, regardless of their resistance level to neurotoxic insecticides. However, only a few generations of DFB selection were sufficient to change the susceptible status of both populations to this compound. Several aspects of mosquito biology were affected in both selected populations, indicating that diflubenzuron resistance acquisition is associated with a fitness cost. We believe that these results can significantly contribute to the design of control strategies involving the use of insect growth regulators.

Integration of genomic information into sport horse breeding programs for optimization of accuracy of selection.

PubMed

Haberland, A M; König von Borstel, U; Simianer, H; König, S

2012-09-01

Reliable selection criteria are required for young riding horses to increase genetic gain by increasing accuracy of selection and decreasing generation intervals. In this study, selection strategies incorporating genomic breeding values (GEBVs) were evaluated. Relevant stages of selection in sport horse breeding programs were analyzed by applying selection index theory. Results in terms of accuracies of indices (r(TI) ) and relative selection response indicated that information on single nucleotide polymorphism (SNP) genotypes considerably increases the accuracy of breeding values estimated for young horses without own or progeny performance. In a first scenario, the correlation between the breeding value estimated from the SNP genotype and the true breeding value (= accuracy of GEBV) was fixed to a relatively low value of r(mg) = 0.5. For a low heritability trait (h(2) = 0.15), and an index for a young horse based only on information from both parents, additional genomic information doubles r(TI) from 0.27 to 0.54. Including the conventional information source 'own performance' into the before mentioned index, additional SNP information increases r(TI) by 40%. Thus, particularly with regard to traits of low heritability, genomic information can provide a tool for well-founded selection decisions early in life. In a further approach, different sources of breeding values (e.g. GEBV and estimated breeding values (EBVs) from different countries) were combined into an overall index when altering accuracies of EBVs and correlations between traits. In summary, we showed that genomic selection strategies have the potential to contribute to a substantial reduction in generation intervals in horse breeding programs.

Notification of real-time clinical alerts generated by pharmacy expert systems.

PubMed Central

Miller, J. E.; Reichley, R. M.; McNamee, L. A.; Steib, S. A.; Bailey, T. C.

1999-01-01

We developed and implemented a strategy for notifying clinical pharmacists of alerts generated in real-time by two pharmacy expert systems: one for drug dosing and the other for adverse drug event prevention. Display pagers were selected as the preferred notification method and a concise, yet readable, format for displaying alert data was developed. This combination of real-time alert generation and notification via display pagers was shown to be efficient and effective in a 30-day trial. PMID:10566374

Employee resourcing strategies and universities' corporate image: A survey dataset.

PubMed

Falola, Hezekiah Olubusayo; Oludayo, Olumuyiwa Akinrole; Olokundun, Maxwell Ayodele; Salau, Odunayo Paul; Ibidunni, Ayodotun Stephen; Igbinoba, Ebe

2018-06-01

The data examined the effect of employee resourcing strategies on corporate image. The data were generated from a total of 500 copies of questionnaire administered to the academic staff of the six (6) selected private Universities in Southwest, Nigeria, out of which four hundred and forty-three (443) were retrieved. Stratified and simple random sampling techniques were used to select the respondents for this study. Descriptive and Linear Regression, were used for the presentation of the data. Mean score was used as statistical tool of analysis. Therefore, the data presented in this article is made available to facilitate further and more comprehensive investigation on the subject matter.

A methodology for generating a tailored implementation blueprint: an exemplar from a youth residential setting.

PubMed

Lewis, Cara C; Scott, Kelli; Marriott, Brigid R

2018-05-16

Tailored implementation approaches are touted as more likely to support the integration of evidence-based practices. However, to our knowledge, few methodologies for tailoring implementations exist. This manuscript will apply a model-driven, mixed methods approach to a needs assessment to identify the determinants of practice, and pilot a modified conjoint analysis method to generate an implementation blueprint using a case example of a cognitive behavioral therapy (CBT) implementation in a youth residential center. Our proposed methodology contains five steps to address two goals: (1) identify the determinants of practice and (2) select and match implementation strategies to address the identified determinants (focusing on barriers). Participants in the case example included mental health therapists and operations staff in two programs of Wolverine Human Services. For step 1, the needs assessment, they completed surveys (clinician N = 10; operations staff N = 58; other N = 7) and participated in focus groups (clinician N = 15; operations staff N = 38) guided by the domains of the Framework for Diffusion [1]. For step 2, the research team conducted mixed methods analyses following the QUAN + QUAL structure for the purpose of convergence and expansion in a connecting process, revealing 76 unique barriers. Step 3 consisted of a modified conjoint analysis. For step 3a, agency administrators prioritized the identified barriers according to feasibility and importance. For step 3b, strategies were selected from a published compilation and rated for feasibility and likelihood of impacting CBT fidelity. For step 4, sociometric surveys informed implementation team member selection and a meeting was held to identify officers and clarify goals and responsibilities. For step 5, blueprints for each of pre-implementation, implementation, and sustainment phases were generated. Forty-five unique strategies were prioritized across the 5 years and three phases representing all nine categories. Our novel methodology offers a relatively low burden collaborative approach to generating a plan for implementation that leverages advances in implementation science including measurement, models, strategy compilations, and methods from other fields.

Pharmacological characterization of the selective 11β-hydroxysteroid dehydrogenase 1 inhibitor, BI 135585, a clinical candidate for the treatment of type 2 diabetes.

PubMed

Hamilton, Bradford S; Himmelsbach, Frank; Nar, Herbert; Schuler-Metz, Annette; Krosky, Paula; Guo, Joan; Guo, Rong; Meng, Shi; Zhao, Yi; Lala, Deepak S; Zhuang, Linghang; Claremon, David A; McGeehan, Gerard M

2015-01-05

To combat the increased morbidity and mortality associated with the developing diabetes epidemic new therapeutic interventions are desirable. Inhibition of intracellular cortisol generation from cortisone by blocking 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been shown to ameliorate the risk factors associated with the metabolic syndrome. A challenge in developing 11β-HSD1 inhibitors has been the species selectivity of small molecules, as many compounds are primate specific. Here we describe our strategy to identify potent selective 11β-HSD1 inhibitors while ensuring target engagement in key metabolic tissues, liver and fat. This strategy enabled the identification of the clinical candidate, BI 135585. Copyright © 2014 Elsevier B.V. All rights reserved.

Threshold-selecting strategy for best possible ground state detection with genetic algorithms

NASA Astrophysics Data System (ADS)

Lässig, Jörg; Hoffmann, Karl Heinz

2009-04-01

Genetic algorithms are a standard heuristic to find states of low energy in complex state spaces as given by physical systems such as spin glasses but also in combinatorial optimization. The paper considers the problem of selecting individuals in the current population in genetic algorithms for crossover. Many schemes have been considered in literature as possible crossover selection strategies. We show for a large class of quality measures that the best possible probability distribution for selecting individuals in each generation of the algorithm execution is a rectangular distribution over the individuals sorted by their energy values. This means uniform probabilities have to be assigned to a group of the individuals with lowest energy in the population but probabilities equal to zero to individuals which are corresponding to energy values higher than a fixed cutoff, which is equal to a certain rank in the vector sorted by the energy of the states in the current population. The considered strategy is dubbed threshold selecting. The proof applies basic arguments of Markov chains and linear optimization and makes only a few assumptions on the underlying principles and hence applies to a large class of algorithms.

Self-locked aptamer probe mediated cascade amplification strategy for highly sensitive and selective detection of protein and small molecule.

PubMed

Li, Wei; Jiang, Wei; Wang, Lei

2016-10-12

In this work, a novel self-locked aptamer probe mediated cascade amplification strategy has been constructed for highly sensitive and specific detection of protein. First, the self-locked aptamer probe was designed with three functions: one was specific molecular recognition attributed to the aptamer sequence, the second was signal transduction owing to the transduction sequence, and the third was self-locking through the hybridization of the transduction sequence and part of the aptamer sequence. Then, the aptamer sequence specific recognized the target and folded into a three-way helix junction, leading to the release of the transduction sequence. Next, the 3'-end of this three-way junction acted as primer to trigger the strand displacement amplification (SDA), yielding a large amount of primers. Finally, the primers initiated the dual-exponential rolling circle amplification (DE-RCA) and generated numerous G-quadruples sequences. By inserting the fluorescent dye N-methyl mesoporphyrin IX (NMM), enhanced fluorescence signal was achieved. In this strategy, the self-locked aptamer probe was more stable to reduce the interference signals generated by the uncontrollable folding in unbounded state. Through the cascade amplification of SDA and DE-RCA, the sensitivity was further improved with a detection limit of 3.8 × 10(-16) mol/L for protein detection. Furthermore, by changing the aptamer sequence of the probe, sensitive and selective detection of adenosine has been also achieved, suggesting that the proposed strategy has good versatility and can be widely used in sensitive and selective detection of biomolecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Planning and Design: A Systems Approach.

ERIC Educational Resources Information Center

Bozeman, William C.; Clements, Mary A.

1981-01-01

Explains "purpose design," a planning and problem-solving strategy involving determination of planning purposes, generation and selection of solutions, specification of solution details, implementation, and evaluation. Describes the application of purpose design to the planning of an alumni association at Black Hawk College, a community…

General chemoselective and redox-responsive ligation and release strategy.

PubMed

Park, Sungjin; Westcott, Nathan P; Luo, Wei; Dutta, Debjit; Yousaf, Muhammad N

2014-03-19

We report a switchable redox click and cleave reaction strategy for conjugating and releasing a range of molecules on demand. This chemoselective redox-responsive ligation (CRRL) and release strategy is based on a redox switchable oxime linkage that is controlled by mild chemical or electrochemical redox signals and can be performed at physiological conditions without the use of a catalyst. Both conjugation and release reactions are kinetically well behaved and quantitative. The CRRL strategy is synthetically modular and easily monitored and characterized by routine analytical techniques. We demonstrate how the CRRL strategy can be used for the dynamic generation of cyclic peptides and the ligation of two different peptides that are stable but can be selectively cleaved upon changes in the redox environment. We also demonstrate a new redox based delivery of cargoes to live cells strategy via the CRRL methodology by synthesizing a FRET redox-responsive probe that is selectively activated within a cellular environment. We believe the ease of the CRRL strategy should find wide use in a range of applications in biology, tissue engineering, nanoscience, synthetic chemistry, and material science and will expand the suite of current conjugation and release strategies.

Performance of Seven Tree Breeding Strategies Under Conditions of Inbreeding Depression.

PubMed

Wu, Harry X; Hallingbäck, Henrik R; Sánchez, Leopoldo

2016-01-06

In the domestication and breeding of tree species that suffer from inbreeding depression (ID), the long-term performance of different breeding strategies is poorly known. Therefore, seven tree breeding strategies including single population, subline, selfing, and nucleus breeding were simulated using a multi-locus model with additive, partial, and complete dominance allele effects, and with intermediate, U-shaped, and major allele distributions. The strategies were compared for genetic gain, inbreeding accumulation, capacity to show ID, the frequencies and fixations of unfavorable alleles, and genetic variances in breeding and production populations. Measured by genetic gain of production population, the nucleus breeding and the single breeding population with mass selection strategies were equal or superior to subline and single breeding population with within-family selection strategies in all simulated scenarios, in spite of their higher inbreeding coefficients. Inbreeding and cross-breeding effectively decreased ID and could in some scenarios produce genetic gains during the first few generations. However, in all scenarios, considerable fixation of unfavorable alleles rendered the purging performance of selfing and cross-breeding strategies ineffective, and resulted in substantial inferiority in comparison to the other strategies in the long-term. Copyright © 2016 Wu et al.

Performance of Seven Tree Breeding Strategies Under Conditions of Inbreeding Depression

PubMed Central

Wu, Harry X.; Hallingbäck, Henrik R.; Sánchez, Leopoldo

2016-01-01

In the domestication and breeding of tree species that suffer from inbreeding depression (ID), the long-term performance of different breeding strategies is poorly known. Therefore, seven tree breeding strategies including single population, subline, selfing, and nucleus breeding were simulated using a multi-locus model with additive, partial, and complete dominance allele effects, and with intermediate, U-shaped, and major allele distributions. The strategies were compared for genetic gain, inbreeding accumulation, capacity to show ID, the frequencies and fixations of unfavorable alleles, and genetic variances in breeding and production populations. Measured by genetic gain of production population, the nucleus breeding and the single breeding population with mass selection strategies were equal or superior to subline and single breeding population with within-family selection strategies in all simulated scenarios, in spite of their higher inbreeding coefficients. Inbreeding and cross-breeding effectively decreased ID and could in some scenarios produce genetic gains during the first few generations. However, in all scenarios, considerable fixation of unfavorable alleles rendered the purging performance of selfing and cross-breeding strategies ineffective, and resulted in substantial inferiority in comparison to the other strategies in the long-term. PMID:26739644

[Functional selectivity of opioid receptors ligands].

PubMed

Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

2010-01-01

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction.

PubMed

Akhter, Nasrin; Shehu, Amarda

2018-01-19

Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

Feature selection in feature network models: finding predictive subsets of features with the Positive Lasso.

PubMed

Frank, Laurence E; Heiser, Willem J

2008-05-01

A set of features is the basis for the network representation of proximity data achieved by feature network models (FNMs). Features are binary variables that characterize the objects in an experiment, with some measure of proximity as response variable. Sometimes features are provided by theory and play an important role in the construction of the experimental conditions. In some research settings, the features are not known a priori. This paper shows how to generate features in this situation and how to select an adequate subset of features that takes into account a good compromise between model fit and model complexity, using a new version of least angle regression that restricts coefficients to be non-negative, called the Positive Lasso. It will be shown that features can be generated efficiently with Gray codes that are naturally linked to the FNMs. The model selection strategy makes use of the fact that FNM can be considered as univariate multiple regression model. A simulation study shows that the proposed strategy leads to satisfactory results if the number of objects is less than or equal to 22. If the number of objects is larger than 22, the number of features selected by our method exceeds the true number of features in some conditions.

Maximizing Selective Cleavages at Aspartic Acid and Proline Residues for the Identification of Intact Proteins

NASA Astrophysics Data System (ADS)

Foreman, David J.; Dziekonski, Eric T.; McLuckey, Scott A.

2018-04-01

A new approach for the identification of intact proteins has been developed that relies on the generation of relatively few abundant products from specific cleavage sites. This strategy is intended to complement standard approaches that seek to generate many fragments relatively non-selectively. Specifically, this strategy seeks to maximize selective cleavage at aspartic acid and proline residues via collisional activation of precursor ions formed via electrospray ionization (ESI) under denaturing conditions. A statistical analysis of the SWISS-PROT database was used to predict the number of arginine residues for a given intact protein mass and predict a m/z range where the protein carries a similar charge to the number of arginine residues thereby enhancing cleavage at aspartic acid residues by limiting proton mobility. Cleavage at aspartic acid residues is predicted to be most favorable in the m/z range of 1500-2500, a range higher than that normally generated by ESI at low pH. Gas-phase proton transfer ion/ion reactions are therefore used for precursor ion concentration from relatively high charge states followed by ion isolation and subsequent generation of precursor ions within the optimal m/z range via a second proton transfer reaction step. It is shown that the majority of product ion abundance is concentrated into cleavages C-terminal to aspartic acid residues and N-terminal to proline residues for ions generated by this process. Implementation of a scoring system that weights both ion fragment type and ion fragment area demonstrated identification of standard proteins, ranging in mass from 8.5 to 29.0 kDa. [Figure not available: see fulltext.

Maximizing Selective Cleavages at Aspartic Acid and Proline Residues for the Identification of Intact Proteins.

PubMed

Foreman, David J; Dziekonski, Eric T; McLuckey, Scott A

2018-04-30

A new approach for the identification of intact proteins has been developed that relies on the generation of relatively few abundant products from specific cleavage sites. This strategy is intended to complement standard approaches that seek to generate many fragments relatively non-selectively. Specifically, this strategy seeks to maximize selective cleavage at aspartic acid and proline residues via collisional activation of precursor ions formed via electrospray ionization (ESI) under denaturing conditions. A statistical analysis of the SWISS-PROT database was used to predict the number of arginine residues for a given intact protein mass and predict a m/z range where the protein carries a similar charge to the number of arginine residues thereby enhancing cleavage at aspartic acid residues by limiting proton mobility. Cleavage at aspartic acid residues is predicted to be most favorable in the m/z range of 1500-2500, a range higher than that normally generated by ESI at low pH. Gas-phase proton transfer ion/ion reactions are therefore used for precursor ion concentration from relatively high charge states followed by ion isolation and subsequent generation of precursor ions within the optimal m/z range via a second proton transfer reaction step. It is shown that the majority of product ion abundance is concentrated into cleavages C-terminal to aspartic acid residues and N-terminal to proline residues for ions generated by this process. Implementation of a scoring system that weights both ion fragment type and ion fragment area demonstrated identification of standard proteins, ranging in mass from 8.5 to 29.0 kDa. Graphical Abstract ᅟ.

Genetic progress estimation strategy for upright common bean plants using recurrent selection.

PubMed

Pereira, L A; Abreu, A F B; Júnior, I C Vieira; Pires, L P M; Ramalho, M A P

2017-03-22

Common bean producers in Brazil tend to grow plants as upright as possible. Because the control of this trait involves a large number of genes, recurrent selection (RS) is the best approach for successful plant improvement. Because plant architecture (PA) is evaluated using scores and usually has high heritability, RS for PA is performed through visual selection in generation S 0 . The aim of the present study was to evaluate selection progress and investigate whether this progress varies with the number of selected progenies or the generation evaluated. In addition, the effect of RS for the upright (PA) trait on progeny grain yield (GY) was investigated. Data of progenies S 0:3 and S 0:4 of the fifth, eighth, and twelfth cycles were used. A combined analysis of variance was performed using the adjusted means of the 47 best progenies from each generation and cycle, using two control cultivars as reference. A joint analysis of the two generations used during the evaluation of progenies for the different cycles was also performed. The genetic progress (GP) was estimated by fitting a linear regression equation to the relationship between the adjusted mean of each cycle and the number of cycles. We found that RS was efficient and the estimated GP of the evaluated progenies was 4.5%. Based on the GY heritability estimates, in more advanced generation selection for GY can be successfully performed on progenies. Thus, the selection already done for PA in F 2 could be associated to the most productive progenies.

The Impact of Selection with Diflubenzuron, a Chitin Synthesis Inhibitor, on the Fitness of Two Brazilian Aedes aegypti Field Populations

PubMed Central

Belinato, Thiago Affonso; Valle, Denise

2015-01-01

Several Aedes aegypti field populations are resistant to neurotoxic insecticides, mainly organophoshates and pyrethroids, which are extensively used as larvicides and adulticides, respectively. Diflubenzuron (DFB), a chitin synthesis inhibitor (CSI), was recently approved for use in drinking water, and is presently employed in Brazil for Ae. aegypti control, against populations resistant to the organophosphate temephos. However, tests of DFB efficacy against field Ae. aegypti populations are lacking. In addition, information regarding the dynamics of CSI resistance, and characterization of any potential fitness effects that may arise in conjunction with resistance are essential for new Ae. aegypti control strategies. Here, the efficacy of DFB was evaluated for two Brazilian Ae. aegypti populations known to be resistant to both temephos and the pyrethroid deltamethrin. Laboratory selection for DFB resistance was then performed over six or seven generations, using a fixed dose of insecticide that inhibited 80% of adult emergence in the first generation. The selection process was stopped when adult emergence in the diflubenzuron-treated groups was equivalent to that of the control groups, kept without insecticide. Diflubenzuron was effective against the two Ae. aegypti field populations evaluated, regardless of their resistance level to neurotoxic insecticides. However, only a few generations of DFB selection were sufficient to change the susceptible status of both populations to this compound. Several aspects of mosquito biology were affected in both selected populations, indicating that diflubenzuron resistance acquisition is associated with a fitness cost. We believe that these results can significantly contribute to the design of control strategies involving the use of insect growth regulators. PMID:26107715

Context Aware Programmable Trackers for the Next Generation Internet

NASA Astrophysics Data System (ADS)

Sousa, Pedro

This work introduces and proposes the concept of context aware programmable trackers for the next generation Internet. The proposed solution gives ground for the development of advanced applications based on the P2P paradigm and will foster collaborative efforts among several network entities (e.g. P2P applications and ISPs). The proposed concept of context aware programmable trackers allows that several peer selection strategies might be supported by a P2P tracker entity able to improve the peer selection decisions according with pre-defined objectives and external inputs provided by specific services. The flexible, adaptive and enhanced peer selection semantics that might be achieved by the proposed solution will contribute for devising novel P2P based services and business models for the future Internet.

Improving industrial yeast strains: exploiting natural and artificial diversity

PubMed Central

Steensels, Jan; Snoek, Tim; Meersman, Esther; Nicolino, Martina Picca; Voordeckers, Karin; Verstrepen, Kevin J

2014-01-01

Yeasts have been used for thousands of years to make fermented foods and beverages, such as beer, wine, sake, and bread. However, the choice for a particular yeast strain or species for a specific industrial application is often based on historical, rather than scientific grounds. Moreover, new biotechnological yeast applications, such as the production of second-generation biofuels, confront yeast with environments and challenges that differ from those encountered in traditional food fermentations. Together, this implies that there are interesting opportunities to isolate or generate yeast variants that perform better than the currently used strains. Here, we discuss the different strategies of strain selection and improvement available for both conventional and nonconventional yeasts. Exploiting the existing natural diversity and using techniques such as mutagenesis, protoplast fusion, breeding, genome shuffling and directed evolution to generate artificial diversity, or the use of genetic modification strategies to alter traits in a more targeted way, have led to the selection of superior industrial yeasts. Furthermore, recent technological advances allowed the development of high-throughput techniques, such as ‘global transcription machinery engineering’ (gTME), to induce genetic variation, providing a new source of yeast genetic diversity. PMID:24724938

Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound ALK Mutations in ALK-Positive Lung Cancer.

PubMed

Yoda, Satoshi; Lin, Jessica J; Lawrence, Michael S; Burke, Benjamin J; Friboulet, Luc; Langenbucher, Adam; Dardaei, Leila; Prutisto-Chang, Kylie; Dagogo-Jack, Ibiayi; Timofeevski, Sergei; Hubbeling, Harper; Gainor, Justin F; Ferris, Lorin A; Riley, Amanda K; Kattermann, Krystina E; Timonina, Daria; Heist, Rebecca S; Iafrate, A John; Benes, Cyril H; Lennerz, Jochen K; Mino-Kenudson, Mari; Engelman, Jeffrey A; Johnson, Ted W; Hata, Aaron N; Shaw, Alice T

2018-06-01

The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy with increasingly potent and selective ALK inhibitors. The third-generation ALK inhibitor lorlatinib has demonstrated clinical activity in patients who failed previous ALK inhibitors. To define the spectrum of ALK mutations that confer lorlatinib resistance, we performed accelerated mutagenesis screening of Ba/F3 cells expressing EML4-ALK. Under comparable conditions, N -ethyl- N -nitrosourea (ENU) mutagenesis generated numerous crizotinib-resistant but no lorlatinib-resistant clones harboring single ALK mutations. In similar screens with EML4-ALK containing single ALK resistance mutations, numerous lorlatinib-resistant clones emerged harboring compound ALK mutations. To determine the clinical relevance of these mutations, we analyzed repeat biopsies from lorlatinib-resistant patients. Seven of 20 samples (35%) harbored compound ALK mutations, including two identified in the ENU screen. Whole-exome sequencing in three cases confirmed the stepwise accumulation of ALK mutations during sequential treatment. These results suggest that sequential ALK inhibitors can foster the emergence of compound ALK mutations, identification of which is critical to informing drug design and developing effective therapeutic strategies. Significance: Treatment with sequential first-, second-, and third-generation ALK inhibitors can select for compound ALK mutations that confer high-level resistance to ALK-targeted therapies. A more efficacious long-term strategy may be up-front treatment with a third-generation ALK inhibitor to prevent the emergence of on-target resistance. Cancer Discov; 8(6); 714-29. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663 . ©2018 American Association for Cancer Research.

On the Structure of a Best Possible Crossover Selection Strategy in Genetic Algorithms

NASA Astrophysics Data System (ADS)

Lässig, Jörg; Hoffmann, Karl Heinz

The paper considers the problem of selecting individuals in the current population in genetic algorithms for crossover to find a solution with high fitness for a given optimization problem. Many different schemes have been described in the literature as possible strategies for this task but so far comparisons have been predominantly empirical. It is shown that if one wishes to maximize any linear function of the final state probabilities, e.g. the fitness of the best individual in the final population of the algorithm, then a best probability distribution for selecting an individual in each generation is a rectangular distribution over the individuals sorted in descending sequence by their fitness values. This means uniform probabilities have to be assigned to a group of the best individuals of the population but probabilities equal to zero to individuals with lower fitness, assuming that the probability distribution to choose individuals from the current population can be chosen independently for each iteration and each individual. This result is then generalized also to typical practically applied performance measures, such as maximizing the expected fitness value of the best individual seen in any generation.

Assessing directed evolution methods for the generation of biosynthetic enzymes with potential in drug biosynthesis

PubMed Central

Nannemann, David P; Birmingham, William R; Scism, Robert A; Bachmann, Brian O

2011-01-01

To address the synthesis of increasingly structurally diverse small-molecule drugs, methods for the generation of efficient and selective biological catalysts are becoming increasingly important. ‘Directed evolution’ is an umbrella term referring to a variety of methods for improving or altering the function of enzymes using a nature-inspired twofold strategy of mutagenesis followed by selection. This article provides an objective assessment of the effectiveness of directed evolution campaigns in generating enzymes with improved catalytic parameters for new substrates from the last decade, excluding studies that aimed to select for only improved physical properties and those that lack kinetic characterization. An analysis of the trends of methodologies and their success rates from 81 qualifying examples in the literature reveals the average fold improvement for kcat (or Vmax), Km and kcat/Km to be 366-, 12- and 2548-fold, respectively, whereas the median fold improvements are 5.4, 3 and 15.6. Further analysis by enzyme class, library-generation methodology and screening methodology explores relationships between successful campaigns and the methodologies employed. PMID:21644826

A PET study of word generation in Huntington's disease: effects of lexical competition and verb/noun category.

PubMed

Lepron, Evelyne; Péran, Patrice; Cardebat, Dominique; Démonet, Jean-François

2009-08-01

Huntington's disease (HD) patients show language production deficits that have been conceptualized as a consequence of executive disorders, e.g. selection deficit between candidate words or switching between word categories. More recently, a deficit of word generation specific to verbs has been reported, which might relate to impaired action representations in HD. We studied the brain correlates of language impairment in HD using H(2)O(15) positron emission tomography (PET). The activation task consisted of generation of semantically appropriate nouns and verbs in dominant (low lexical selection) and selective conditions (high lexical selection). Reaction times were longer and number of errors was higher in 12 non-demented HD than in 17 age-matched controls in all conditions. In both groups, the selective condition yielded longer reaction time and a greater number of errors than the dominant one. PET data revealed that, in control subjects, the left inferior temporal gyrus was involved in the selective condition whereas it was not in HD. Moreover, activity in the anterior cingulate and the inferior frontal gyri was correlated with behavioral performance in control subjects only. In HD, the lack of implication of these regions, already shown to be crucial in lexical selection, might have been partly compensated by the activation in the left supramarginal gyrus (phonological loop activity) and the right inferior frontal gyrus (effortful retrieval processes), which might support accessory language strategies allowing patients to achieve word generation.

Power systems for future missions

NASA Technical Reports Server (NTRS)

Gill, S. P.; Frye, P. E.; Littman, Franklin D.; Meisl, C. J.

1994-01-01

A comprehensive scenario of future missions was developed and applicability of different power technologies to these missions was assessed. Detailed technology development roadmaps for selected power technologies were generated. A simple methodology to evaluate economic benefits of current and future power system technologies by comparing Life Cycle Costs of potential missions was developed. The methodology was demonstrated by comparing Life Cycle Costs for different implementation strategies of DIPS/CBC technology to a selected set of missions.

Automatic detection of regions of interest in mammographic images

NASA Astrophysics Data System (ADS)

Cheng, Erkang; Ling, Haibin; Bakic, Predrag R.; Maidment, Andrew D. A.; Megalooikonomou, Vasileios

2011-03-01

This work is a part of our ongoing study aimed at comparing the topology of anatomical branching structures with the underlying image texture. Detection of regions of interest (ROIs) in clinical breast images serves as the first step in development of an automated system for image analysis and breast cancer diagnosis. In this paper, we have investigated machine learning approaches for the task of identifying ROIs with visible breast ductal trees in a given galactographic image. Specifically, we have developed boosting based framework using the AdaBoost algorithm in combination with Haar wavelet features for the ROI detection. Twenty-eight clinical galactograms with expert annotated ROIs were used for training. Positive samples were generated by resampling near the annotated ROIs, and negative samples were generated randomly by image decomposition. Each detected ROI candidate was given a confidences core. Candidate ROIs with spatial overlap were merged and their confidence scores combined. We have compared three strategies for elimination of false positives. The strategies differed in their approach to combining confidence scores by summation, averaging, or selecting the maximum score.. The strategies were compared based upon the spatial overlap with annotated ROIs. Using a 4-fold cross-validation with the annotated clinical galactographic images, the summation strategy showed the best performance with 75% detection rate. When combining the top two candidates, the selection of maximum score showed the best performance with 96% detection rate.

A strategy for male sterility facilitated recurrent selection in peach

USDA-ARS?s Scientific Manuscript database

Commercial peach is a highly homozygous self-compatible species with limited diversity. The incorporation of exotic germplasm and breeding of new varieties is hindered by the labor required to generate large segregating populations. Hand pollinations are characterized by a high failure rate with onl...

Bingo! Select Games for Mathematical Thinking

ERIC Educational Resources Information Center

Jackson, Christa; Taylor, Cynthia; Buchheister, Kelley

2013-01-01

Games can both generate excitement among students and motivate them to participate in mathematics. Although games have been used primarily to "review" mathematical concepts at the middle school level, games should, and often do, have other instructional purposes. When teachers use mathematical games as an instructional strategy, they are…

Contrasting adaptive strategies to terminal drought-stress gradients in Mediterranean legumes: phenology, productivity, and water relations in wild and domesticated Lupinus luteus L.

PubMed

Berger, J D; Ludwig, C

2014-11-01

Our understanding of within-species annual plant adaptation to rainfall gradients is fragmented. Broad-scale ecological applications of Grime's C-S-R triangle are often superficial, while detailed drought physiology tends to be narrow, focusing on elite cultivars. The former lack the detail to explain how plants respond, while the latter provide little context to investigate trade-offs among traits, to explain where/why these might be adaptive. Ecophysiology, combining the breadth of the former with the detail of the latter, can resolve this disconnect and is applied here to describe adaptive strategies in the Mediterranean legume Lupinus luteus. Wild and domesticated material from low- and high-rainfall environments was evaluated under contrasting terminal drought. These opposing environments have selected for contrasting, integrated, adaptive strategies. Long-season, high-rainfall habitats select for competitive (C) traits: delayed phenology, high above- and below-ground biomass, productivity, and fecundity, leading to high water-use and early stress onset. Terminal drought-prone environments select for the opposite: ruderal (R) traits that facilitate drought escape/avoidance but limit reproductive potential. Surprisingly, high-rainfall ecotypes generate lower critical leaf water potentials under water deficit, maintaining higher relative water content than the latter. Given that L. luteus evolved in sandy, low-water-holding capacity soils, this represents a bet-hedging response to intermittent self-imposed water-deficits associated with a strongly C-selected adaptive strategy that is therefore redundant in R-selected low-rainfall ecotypes. Domesticated L. luteus is even more R-selected, reflecting ongoing selection for early maturity. Introgression of appropriate C-selected adaptive traits from wild germplasm may widen the crop production range. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Contrasting adaptive strategies to terminal drought-stress gradients in Mediterranean legumes: phenology, productivity, and water relations in wild and domesticated Lupinus luteus L.

PubMed Central

Berger, J. D.; Ludwig, C.

2014-01-01

Our understanding of within-species annual plant adaptation to rainfall gradients is fragmented. Broad-scale ecological applications of Grime’s C-S-R triangle are often superficial, while detailed drought physiology tends to be narrow, focusing on elite cultivars. The former lack the detail to explain how plants respond, while the latter provide little context to investigate trade-offs among traits, to explain where/why these might be adaptive. Ecophysiology, combining the breadth of the former with the detail of the latter, can resolve this disconnect and is applied here to describe adaptive strategies in the Mediterranean legume Lupinus luteus. Wild and domesticated material from low- and high-rainfall environments was evaluated under contrasting terminal drought. These opposing environments have selected for contrasting, integrated, adaptive strategies. Long-season, high-rainfall habitats select for competitive (C) traits: delayed phenology, high above- and below-ground biomass, productivity, and fecundity, leading to high water-use and early stress onset. Terminal drought-prone environments select for the opposite: ruderal (R) traits that facilitate drought escape/avoidance but limit reproductive potential. Surprisingly, high-rainfall ecotypes generate lower critical leaf water potentials under water deficit, maintaining higher relative water content than the latter. Given that L. luteus evolved in sandy, low-water-holding capacity soils, this represents a bet-hedging response to intermittent self-imposed water-deficits associated with a strongly C-selected adaptive strategy that is therefore redundant in R-selected low-rainfall ecotypes. Domesticated L. luteus is even more R-selected, reflecting ongoing selection for early maturity. Introgression of appropriate C-selected adaptive traits from wild germplasm may widen the crop production range. PMID:24591050

Multiprocessor sparse L/U decomposition with controlled fill-in

NASA Technical Reports Server (NTRS)

Alaghband, G.; Jordan, H. F.

1985-01-01

Generation of the maximal compatibles of pivot elements for a class of small sparse matrices is studied. The algorithm involves a binary tree search and has a complexity exponential in the order of the matrix. Different strategies for selection of a set of compatible pivots based on the Markowitz criterion are investigated. The competing issues of parallelism and fill-in generation are studied and results are provided. A technque for obtaining an ordered compatible set directly from the ordered incompatible table is given. This technique generates a set of compatible pivots with the property of generating few fills. A new hueristic algorithm is then proposed that combines the idea of an ordered compatible set with a limited binary tree search to generate several sets of compatible pivots in linear time. Finally, an elimination set to reduce the matrix is selected. Parameters are suggested to obtain a balance between parallelism and fill-ins. Results of applying the proposed algorithms on several large application matrices are presented and analyzed.

Introgression of heat shock protein (Hsp70 and sHsp) genes into the Malaysian elite chilli variety Kulai (Capsicum annuum L.) through the application of marker-assisted backcrossing (MAB).

PubMed

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

2018-03-01

Backcrossing together with simple sequence repeat marker strategy was adopted to improve popular Malaysian chilli Kulai (Capsicum annuum L.) for heat tolerance. The use of molecular markers in backcross breeding and selection contributes significantly to overcoming the main drawbacks such as increase linkage drag and time consumption, in the ancient manual breeding approach (conventional), and speeds up the genome recovery of the recurrent parent. The strategy was adopted to introgress heat shock protein gene(s) from AVPP0702 (C. annuum L.), which are heat-tolerant, into the genetic profile of Kulai, a popular high-yielding chilli but which is heat sensitive. The parents were grown on seed trays, and parental screening was carried out with 252 simple sequence repeat markers. The selected parents were crossed and backcrossed to generate F 1 hybrids and backcross generations. Sixty-eight markers appeared to be polymorphic and were used to assess the backcross generation; BC 1 F 1 , BC 2 F 1 and BC 3 F 1 . The average recipient allele of the selected four BC 1 F 1 plants was 80.75% which were used to produce the BC 2 F 1 generation. BC 1 -P 7 was the best BC 1 F 1 plant because it had the highest recovery at 83.40% and was positive to Hsp-linked markers (Hsp70-u2 and AGi42). After three successive generations of backcrossing, the average genome recovery of the recurrent parent in the selected plants in BC 3 F 1 was 95.37%. Hsp gene expression analysis was carried out on BC 1 F 1 , BC 2 F 1 and BC 3 F 1 selected lines. The Hsp genes were found to be up-regulated when exposed to heat treatment. The pattern of Hsp expression in the backcross generations was similar to that of the donor parent. This confirms the successful introgression of a stress-responsive gene (Hsp) into a Kulai chilli pepper variety. Furthermore, the yield performance viz. plant height, number of fruits, fruit length and weight and total yield of the improved plant were similar with the recurrent parent except that the plant height was significantly lower than the Kulai (recurrent) parent.

Automatic parameter selection for feature-based multi-sensor image registration

NASA Astrophysics Data System (ADS)

DelMarco, Stephen; Tom, Victor; Webb, Helen; Chao, Alan

2006-05-01

Accurate image registration is critical for applications such as precision targeting, geo-location, change-detection, surveillance, and remote sensing. However, the increasing volume of image data is exceeding the current capacity of human analysts to perform manual registration. This image data glut necessitates the development of automated approaches to image registration, including algorithm parameter value selection. Proper parameter value selection is crucial to the success of registration techniques. The appropriate algorithm parameters can be highly scene and sensor dependent. Therefore, robust algorithm parameter value selection approaches are a critical component of an end-to-end image registration algorithm. In previous work, we developed a general framework for multisensor image registration which includes feature-based registration approaches. In this work we examine the problem of automated parameter selection. We apply the automated parameter selection approach of Yitzhaky and Peli to select parameters for feature-based registration of multisensor image data. The approach consists of generating multiple feature-detected images by sweeping over parameter combinations and using these images to generate estimated ground truth. The feature-detected images are compared to the estimated ground truth images to generate ROC points associated with each parameter combination. We develop a strategy for selecting the optimal parameter set by choosing the parameter combination corresponding to the optimal ROC point. We present numerical results showing the effectiveness of the approach using registration of collected SAR data to reference EO data.

Strategies in identifying individuals in a segregant population of common bean and implications of genotype x environment interaction in the success of selection.

PubMed

Mendes, M P; Ramalho, M A P; Abreu, A F B

2012-04-10

The objective of this study was to compare the BLUP selection method with different selection strategies in F(2:4) and assess the efficiency of this method on the early choice of the best common bean (Phaseolus vulgaris) lines. Fifty-one F(2:4) progenies were produced from a cross between the CVIII8511 x RP-26 lines. A randomized block design was used with 20 replications and one-plant field plots. Character data on plant architecture and grain yield were obtained and then the sum of the standardized variables was estimated for simultaneous selection of both traits. Analysis was carried out by mixed models (BLUP) and the least squares method to compare different selection strategies, like mass selection, stratified mass selection and between and within progeny selection. The progenies selected by BLUP were assessed in advanced generations, always selecting the greatest and smallest sum of the standardized variables. Analyses by the least squares method and BLUP procedure ranked the progenies in the same way. The coincidence of the individuals identified by BLUP and between and within progeny selection was high and of the greatest magnitude when BLUP was compared with mass selection. Although BLUP is the best estimator of genotypic value, its efficiency in the response to long term selection is not different from any of the other methods, because it is also unable to predict the future effect of the progenies x environments interaction. It was inferred that selection success will always depend on the most accurate possible progeny assessment and using alternatives to reduce the progenies x environments interaction effect.

Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity.

PubMed

Fawcett, Tim W; Kuijper, Bram; Weissing, Franz J; Pen, Ido

2011-09-20

Female choice is a powerful selective force, driving the elaboration of conspicuous male ornaments. This process of sexual selection has profound implications for many life-history decisions, including sex allocation. For example, females with attractive partners should produce more sons, because these sons will inherit their father's attractiveness and enjoy high mating success, thereby yielding greater fitness returns than daughters. However, previous research has overlooked the fact that there is a reciprocal feedback from life-history strategies to sexual selection. Here, using a simple mathematical model, we show that if mothers adaptively control offspring sex in relation to their partner's attractiveness, sexual selection is weakened and male ornamentation declines. This weakening occurs because the ability to determine offspring sex reduces the fitness difference between females with attractive and unattractive partners. We use individual-based, evolutionary simulations to show that this result holds under more biologically realistic conditions. Sexual selection and sex allocation thus interact in a dynamic fashion: The evolution of conspicuous male ornaments favors sex-ratio adjustment, but this conditional strategy then undermines the very same process that generated it, eroding sexual selection. We predict that, all else being equal, the most elaborate sexual displays should be seen in species with little or no control over offspring sex. The feedback process we have described points to a more general evolutionary principle, in which a conditional strategy weakens directional selection on another trait by reducing fitness differences.

[Costly drugs: analysis and proposals for the Mercosur countries].

PubMed

Marín, Gustavo H; Polach, María Andrea

2011-08-01

Determine how the Mercosur countries access, regulate, and finance costly drugs and propose joint selection and financing strategies at the subregional level. Qualitative design, using content analyses of primary and secondary sources, document reviews, interviews, focus groups, and case studies. The variables selected included: selection criteria, access, financing, and regulations in the various countries. Costly drugs were divided into those that do not alter the natural course of the disease and those with demonstrated efficacy, using the defined daily dose to compare the costs of classical treatments and those involving costly drugs. The Mercosur countries generally lack formal strategies for dealing with the demand for costly drugs, and governments and insurers wind up financing them by court order. The case studies show that there are costly drugs whose efficacy has not been established but that nonetheless generate demand. The fragmentation of procurement, international commitments with regard to intellectual property, and low negotiating power exponentially increase the price of costly drugs, putting health system finances in jeopardy. Costly drugs must be regulated and rationally selected so that only those that substantively benefit people are accepted. To finance the drugs so selected, common country strategies are needed that include such options as flexible in trade agreements, the creation of national resource funds, or joint procurement by countries to enhance their negotiating power.

The Management of the Radioactive Waste Generated by Cernavoda NPP, Romania, an Example of International Cooperation - 13449

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

Barariu, Gheorghe

2013-07-01

The design criteria and constraints for the development of the management strategy for radioactive waste generated from operating and decommissioning of CANDU Nuclear Units from Cernavoda NPP in Romania, present many specific aspects. The main characteristics of CANDU type waste are its high concentrations of tritium and radiocarbon. Also, the existing management strategy for radioactive waste at Cernavoda NPP provides no treatment or conditioning for radioactive waste disposal. These characteristics embodied a challenging effort, in order to select a proper strategy for radioactive waste management at present, when Romania is an EU member and a signatory country of the Jointmore » Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management. The helping of advanced countries in radioactive waste management, directly or into the frame of the international organizations, like IAEA, become solve the aforementioned challenges at adequate level. (authors)« less

Realized gain from breeding Eucalyptus grandis in Florida

Treesearch

George Meskimen

1983-01-01

E. grandis is in the fourth generation of selection in southwest Florida. The breeding strategy combines a provenance trial, genetic base population, seedling seed orchard, and progeny test in a single plantation where all families are completely randomized in single-tree plots. That planting configuration closely predicted the magnitude of genetic...

Efficient Generation of Marker-Free Transgenic Rice Plants Using an Improved Transposon-Mediated Transgene Reintegration Strategy1

PubMed Central

Gao, Xiaoqing; Zhou, Jie; Li, Jun; Zou, Xiaowei; Zhao, Jianhua; Li, Qingliang; Xia, Ran; Yang, Ruifang; Wang, Dekai; Zuo, Zhaoxue; Tu, Jumin; Tao, Yuezhi; Chen, Xiaoyun; Xie, Qi; Zhu, Zengrong

2015-01-01

Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize (Zea mays) Activator/Dissociation (Ds) transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest was linked to green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent protein-aided counterselection against T-DNA was used together with polymerase chain reaction (PCR)-based positive selection for the gene of interest to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) δ-endotoxin gene into the Ds elements and transformed transposon vectors into rice (Oryza sativa) cultivars via Agrobacterium tumefaciens. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis. Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops. PMID:25371551

Efficient generation of marker-free transgenic rice plants using an improved transposon-mediated transgene reintegration strategy.

PubMed

Gao, Xiaoqing; Zhou, Jie; Li, Jun; Zou, Xiaowei; Zhao, Jianhua; Li, Qingliang; Xia, Ran; Yang, Ruifang; Wang, Dekai; Zuo, Zhaoxue; Tu, Jumin; Tao, Yuezhi; Chen, Xiaoyun; Xie, Qi; Zhu, Zengrong; Qu, Shaohong

2015-01-01

Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize (Zea mays) Activator/Dissociation (Ds) transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest was linked to green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent protein-aided counterselection against T-DNA was used together with polymerase chain reaction (PCR)-based positive selection for the gene of interest to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) δ-endotoxin gene into the Ds elements and transformed transposon vectors into rice (Oryza sativa) cultivars via Agrobacterium tumefaciens. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis. Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops. © 2015 American Society of Plant Biologists. All Rights Reserved.

Tests of selection in pooled case-control data: an empirical study.

PubMed

Udpa, Nitin; Zhou, Dan; Haddad, Gabriel G; Bafna, Vineet

2011-01-01

For smaller organisms with faster breeding cycles, artificial selection can be used to create sub-populations with different phenotypic traits. Genetic tests can be employed to identify the causal markers for the phenotypes, as a precursor to engineering strains with a combination of traits. Traditional approaches involve analyzing crosses of inbred strains to test for co-segregation with genetic markers. Here we take advantage of cheaper next generation sequencing techniques to identify genetic signatures of adaptation to the selection constraints. Obtaining individual sequencing data is often unrealistic due to cost and sample issues, so we focus on pooled genomic data. We explore a series of statistical tests for selection using pooled case (under selection) and control populations. The tests generally capture skews in the scaled frequency spectrum of alleles in a region, which are indicative of a selective sweep. Extensive simulations are used to show that these approaches work well for a wide range of population divergence times and strong selective pressures. Control vs control simulations are used to determine an empirical False Positive Rate, and regions under selection are determined using a 1% FPR level. We show that pooling does not have a significant impact on statistical power. The tests are also robust to reasonable variations in several different parameters, including window size, base-calling error rate, and sequencing coverage. We then demonstrate the viability (and the challenges) of one of these methods in two independent Drosophila populations (Drosophila melanogaster) bred under selection for hypoxia and accelerated development, respectively. Testing for extreme hypoxia tolerance showed clear signals of selection, pointing to loci that are important for hypoxia adaptation. Overall, we outline a strategy for finding regions under selection using pooled sequences, then devise optimal tests for that strategy. The approaches show promise for detecting selection, even several generations after fixation of the beneficial allele has occurred.

Replication Strategy for Spatiotemporal Data Based on Distributed Caching System

PubMed Central

Xiong, Lian; Tao, Yang; Xu, Juan; Zhao, Lun

2018-01-01

The replica strategy in distributed cache can effectively reduce user access delay and improve system performance. However, developing a replica strategy suitable for varied application scenarios is still quite challenging, owing to differences in user access behavior and preferences. In this paper, a replication strategy for spatiotemporal data (RSSD) based on a distributed caching system is proposed. By taking advantage of the spatiotemporal locality and correlation of user access, RSSD mines high popularity and associated files from historical user access information, and then generates replicas and selects appropriate cache node for placement. Experimental results show that the RSSD algorithm is simple and efficient, and succeeds in significantly reducing user access delay. PMID:29342897

Strategy Developed for Selecting Optimal Sensors for Monitoring Engine Health

NASA Technical Reports Server (NTRS)

2004-01-01

Sensor indications during rocket engine operation are the primary means of assessing engine performance and health. Effective selection and location of sensors in the operating engine environment enables accurate real-time condition monitoring and rapid engine controller response to mitigate critical fault conditions. These capabilities are crucial to ensure crew safety and mission success. Effective sensor selection also facilitates postflight condition assessment, which contributes to efficient engine maintenance and reduced operating costs. Under the Next Generation Launch Technology program, the NASA Glenn Research Center, in partnership with Rocketdyne Propulsion and Power, has developed a model-based procedure for systematically selecting an optimal sensor suite for assessing rocket engine system health. This optimization process is termed the systematic sensor selection strategy. Engine health management (EHM) systems generally employ multiple diagnostic procedures including data validation, anomaly detection, fault-isolation, and information fusion. The effectiveness of each diagnostic component is affected by the quality, availability, and compatibility of sensor data. Therefore systematic sensor selection is an enabling technology for EHM. Information in three categories is required by the systematic sensor selection strategy. The first category consists of targeted engine fault information; including the description and estimated risk-reduction factor for each identified fault. Risk-reduction factors are used to define and rank the potential merit of timely fault diagnoses. The second category is composed of candidate sensor information; including type, location, and estimated variance in normal operation. The final category includes the definition of fault scenarios characteristic of each targeted engine fault. These scenarios are defined in terms of engine model hardware parameters. Values of these parameters define engine simulations that generate expected sensor values for targeted fault scenarios. Taken together, this information provides an efficient condensation of the engineering experience and engine flow physics needed for sensor selection. The systematic sensor selection strategy is composed of three primary algorithms. The core of the selection process is a genetic algorithm that iteratively improves a defined quality measure of selected sensor suites. A merit algorithm is employed to compute the quality measure for each test sensor suite presented by the selection process. The quality measure is based on the fidelity of fault detection and the level of fault source discrimination provided by the test sensor suite. An inverse engine model, whose function is to derive hardware performance parameters from sensor data, is an integral part of the merit algorithm. The final component is a statistical evaluation algorithm that characterizes the impact of interference effects, such as control-induced sensor variation and sensor noise, on the probability of fault detection and isolation for optimal and near-optimal sensor suites.

Forward and reverse mutagenesis in C. elegans

PubMed Central

Kutscher, Lena M.; Shaham, Shai

2014-01-01

Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

Generative Topographic Mapping of Conformational Space.

PubMed

Horvath, Dragos; Baskin, Igor; Marcou, Gilles; Varnek, Alexandre

2017-10-01

Herein, Generative Topographic Mapping (GTM) was challenged to produce planar projections of the high-dimensional conformational space of complex molecules (the 1LE1 peptide). GTM is a probability-based mapping strategy, and its capacity to support property prediction models serves to objectively assess map quality (in terms of regression statistics). The properties to predict were total, non-bonded and contact energies, surface area and fingerprint darkness. Map building and selection was controlled by a previously introduced evolutionary strategy allowed to choose the best-suited conformational descriptors, options including classical terms and novel atom-centric autocorrellograms. The latter condensate interatomic distance patterns into descriptors of rather low dimensionality, yet precise enough to differentiate between close favorable contacts and atom clashes. A subset of 20 K conformers of the 1LE1 peptide, randomly selected from a pool of 2 M geometries (generated by the S4MPLE tool) was employed for map building and cross-validation of property regression models. The GTM build-up challenge reached robust three-fold cross-validated determination coefficients of Q 2 =0.7…0.8, for all modeled properties. Mapping of the full 2 M conformer set produced intuitive and information-rich property landscapes. Functional and folding subspaces appear as well-separated zones, even though RMSD with respect to the PDB structure was never used as a selection criterion of the maps. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detecting math problem solving strategies: an investigation into the use of retrospective self-reports, latency and fMRI data.

PubMed

Tenison, Caitlin; Fincham, Jon M; Anderson, John R

2014-02-01

This research explores how to determine when mathematical problems are solved by retrieval versus computation strategies. Past research has indicated that verbal reports, solution latencies, and neural imaging all provide imperfect indicators of this distinction. Participants in the current study solved mathematical problems involving two distinct problem types, called 'Pyramid' and 'Formula' problems. Participants were given extensive training solving 3 select Pyramid and 3 select Formula problems. Trained problems were highly practiced, whereas untrained problems were not. The distinction between untrained and trained problems was observed in the data. Untrained problems took longer to solve, more often used procedural strategies and showed a greater activation in the horizontal intraparietal sulcus (HIPS) when compared to trained problems. A classifier fit to the neural distinction between trained-untrained problems successfully predicted training within and between the two problem types. We employed this classifier to generate a prediction of strategy use. By combining evidence from the classifier, problem solving latencies, and retrospective reports, we predicted the strategy used to solve each problem in the scanner and gained unexpected insight into the distinction between different strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

A computational approach to compare regression modelling strategies in prediction research.

PubMed

Pajouheshnia, Romin; Pestman, Wiebe R; Teerenstra, Steven; Groenwold, Rolf H H

2016-08-25

It is often unclear which approach to fit, assess and adjust a model will yield the most accurate prediction model. We present an extension of an approach for comparing modelling strategies in linear regression to the setting of logistic regression and demonstrate its application in clinical prediction research. A framework for comparing logistic regression modelling strategies by their likelihoods was formulated using a wrapper approach. Five different strategies for modelling, including simple shrinkage methods, were compared in four empirical data sets to illustrate the concept of a priori strategy comparison. Simulations were performed in both randomly generated data and empirical data to investigate the influence of data characteristics on strategy performance. We applied the comparison framework in a case study setting. Optimal strategies were selected based on the results of a priori comparisons in a clinical data set and the performance of models built according to each strategy was assessed using the Brier score and calibration plots. The performance of modelling strategies was highly dependent on the characteristics of the development data in both linear and logistic regression settings. A priori comparisons in four empirical data sets found that no strategy consistently outperformed the others. The percentage of times that a model adjustment strategy outperformed a logistic model ranged from 3.9 to 94.9 %, depending on the strategy and data set. However, in our case study setting the a priori selection of optimal methods did not result in detectable improvement in model performance when assessed in an external data set. The performance of prediction modelling strategies is a data-dependent process and can be highly variable between data sets within the same clinical domain. A priori strategy comparison can be used to determine an optimal logistic regression modelling strategy for a given data set before selecting a final modelling approach.

Role of income in intergenerational co-residence: Evidence from selected African and Asian countries.

PubMed

Aziz, Nusrate; Hossain, Belayet; Emran, Masum

2018-06-01

The study investigates the macroeconomic determinants of co-residing arrangement between generations in selected developing countries with a focus on examining the effect of changing income level of the working generation. A reduced form model is specified for co-residence between the older generation and altruistic working generation. The fixed- and random-effects models are applied in two waves of data for 22 countries. Estimated results indicate that the income of the altruistic working generation has a negative effect on co-residence, suggesting that if the income of the working generation increases, co-residence decreases. This decrease is greater for older men compared with their female counterparts. Life expectancy, literacy and culture also have significant influences on co-residence. Co-residence is expected to fall in developing countries with economic growth over time. Consequently, a higher proportion of older citizens will be vulnerable in the future. Hence, governments of developing countries will face increasing pressure from their older people to provide appropriate planning and strategy to face this challenge. © 2018 AJA Inc.

A fast inverse treatment planning strategy facilitating optimized catheter selection in image-guided high-dose-rate interstitial gynecologic brachytherapy.

PubMed

Guthier, Christian V; Damato, Antonio L; Hesser, Juergen W; Viswanathan, Akila N; Cormack, Robert A

2017-12-01

Interstitial high-dose rate (HDR) brachytherapy is an important therapeutic strategy for the treatment of locally advanced gynecologic (GYN) cancers. The outcome of this therapy is determined by the quality of dose distribution achieved. This paper focuses on a novel yet simple heuristic for catheter selection for GYN HDR brachytherapy and their comparison against state of the art optimization strategies. The proposed technique is intended to act as a decision-supporting tool to select a favorable needle configuration. The presented heuristic for catheter optimization is based on a shrinkage-type algorithm (SACO). It is compared against state of the art planning in a retrospective study of 20 patients who previously received image-guided interstitial HDR brachytherapy using a Syed Neblett template. From those plans, template orientation and position are estimated via a rigid registration of the template with the actual catheter trajectories. All potential straight trajectories intersecting the contoured clinical target volume (CTV) are considered for catheter optimization. Retrospectively generated plans and clinical plans are compared with respect to dosimetric performance and optimization time. All plans were generated with one single run of the optimizer lasting 0.6-97.4 s. Compared to manual optimization, SACO yields a statistically significant (P ≤ 0.05) improved target coverage while at the same time fulfilling all dosimetric constraints for organs at risk (OARs). Comparing inverse planning strategies, dosimetric evaluation for SACO and "hybrid inverse planning and optimization" (HIPO), as gold standard, shows no statistically significant difference (P > 0.05). However, SACO provides the potential to reduce the number of used catheters without compromising plan quality. The proposed heuristic for needle selection provides fast catheter selection with optimization times suited for intraoperative treatment planning. Compared to manual optimization, the proposed methodology results in fewer catheters without a clinically significant loss in plan quality. The proposed approach can be used as a decision support tool that guides the user to find the ideal number and configuration of catheters. © 2017 American Association of Physicists in Medicine.

Practice makes proficient: pigeons (Columba livia) learn efficient routes on full-circuit navigational traveling salesperson problems.

PubMed

Baron, Danielle M; Ramirez, Alejandro J; Bulitko, Vadim; Madan, Christopher R; Greiner, Ariel; Hurd, Peter L; Spetch, Marcia L

2015-01-01

Visiting multiple locations and returning to the start via the shortest route, referred to as the traveling salesman (or salesperson) problem (TSP), is a valuable skill for both humans and non-humans. In the current study, pigeons were trained with increasing set sizes of up to six goals, with each set size presented in three distinct configurations, until consistency in route selection emerged. After training at each set size, the pigeons were tested with two novel configurations. All pigeons acquired routes that were significantly more efficient (i.e., shorter in length) than expected by chance selection of the goals. On average, the pigeons also selected routes that were more efficient than expected based on a local nearest-neighbor strategy and were as efficient as the average route generated by a crossing-avoidance strategy. Analysis of the routes taken indicated that they conformed to both a nearest-neighbor and a crossing-avoidance strategy significantly more often than expected by chance. Both the time taken to visit all goals and the actual distance traveled decreased from the first to the last trials of training in each set size. On the first trial with novel configurations, average efficiency was higher than chance, but was not higher than expected from a nearest-neighbor or crossing-avoidance strategy. These results indicate that pigeons can learn to select efficient routes on a TSP problem.

An adaptive model order reduction by proper snapshot selection for nonlinear dynamical problems

NASA Astrophysics Data System (ADS)

Nigro, P. S. B.; Anndif, M.; Teixeira, Y.; Pimenta, P. M.; Wriggers, P.

2016-04-01

Model Order Reduction (MOR) methods are employed in many fields of Engineering in order to reduce the processing time of complex computational simulations. A usual approach to achieve this is the application of Galerkin projection to generate representative subspaces (reduced spaces). However, when strong nonlinearities in a dynamical system are present and this technique is employed several times along the simulation, it can be very inefficient. This work proposes a new adaptive strategy, which ensures low computational cost and small error to deal with this problem. This work also presents a new method to select snapshots named Proper Snapshot Selection (PSS). The objective of the PSS is to obtain a good balance between accuracy and computational cost by improving the adaptive strategy through a better snapshot selection in real time (online analysis). With this method, it is possible a substantial reduction of the subspace, keeping the quality of the model without the use of the Proper Orthogonal Decomposition (POD).

Evolutionary Agroecology: the potential for cooperative, high density, weed-suppressing cereals.

PubMed

Weiner, Jacob; Andersen, Sven B; Wille, Wibke K-M; Griepentrog, Hans W; Olsen, Jannie M

2010-09-01

Evolutionary theory can be applied to improve agricultural yields and/or sustainability, an approach we call Evolutionary Agroecology. The basic idea is that plant breeding is unlikely to improve attributes already favored by millions of years of natural selection, whereas there may be unutilized potential in selecting for attributes that increase total crop yield but reduce plants' individual fitness. In other words, plant breeding should be based on group selection. We explore this approach in relation to crop-weed competition, and argue that it should be possible to develop high density cereals that can utilize their initial size advantage over weeds to suppress them much better than under current practices, thus reducing or eliminating the need for chemical or mechanical weed control. We emphasize the role of density in applying group selection to crops: it is competition among individuals that generates the 'Tragedy of the Commons', providing opportunities to improve plant production by selecting for attributes that natural selection would not favor. When there is competition for light, natural selection of individuals favors a defensive strategy of 'shade avoidance', but a collective, offensive 'shading' strategy could increase weed suppression and yield in the high density, high uniformity cropping systems we envision.

Managing the rate of increase in average co-ancestry in a rolling front tree breeding strategy.

PubMed

Kerr, R J; McRae, T A; Dutkowski, G W; Tier, B

2015-04-01

In breeding forest trees, as for livestock, the goal is to capture as much genetic gain as possible for the breeding objective, while limiting long- and short-term inbreeding. The Southern Tree Breeding Association (STBA) is responsible for breeding Australia's two main commercial forest tree species and has adopted algorithms and methods commonly used in animal breeding to achieve this balance. Discrete generation breeding is the norm for most tree breeding programmes. However, the STBA uses an overlapping generation strategy, with a new stream of breeding initiated each year. A feature of the species bred by the STBA (Pinus radiata and Eucalyptus globulus) is the long interval (up to 7 years) between when an individual is mated and when its progeny is first assessed in field trials and performance data included in the national performance database. Mate selection methods must therefore recognize the large pool of unmeasured progeny generated over recent years of crossing. In addition, the substantial delay between when an individual is selected in a field trial and when it is clonally copied into a mating facility (breeding arboretum) means that selection and mating must occur as a two-step process. In this article, we describe modifications to preselection and mate selection algorithms that allow unmeasured progeny (juveniles) to be recognized. We also demonstrate that the addition of hypothetical new progeny to the juvenile pool is important for computing the increase in average co-ancestry in the population. Methods outlined in this article may have relevance to animal breeding programmes where between mating and progeny measurement, new rounds of mating are initiated. © 2015 Blackwell Verlag GmbH.

Selection for Cry3Bb1 resistance in a genetically diverse population of nondiapausing western corn rootworm (Coleoptera: Chrysomelidae).

PubMed

Oswald, Kenneth J; French, B Wade; Nielson, Chad; Bagley, Mark

2011-06-01

Five short-diapause laboratory lines of western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), were selected for resistance to MON863, a variety of corn genetically modified with the Bacillus thuringiensis Berliner (Bt) transgene that expresses the Cry3Bb1 delta-endotoxin. Three of the selected lines were developed by incremental increase in the duration of exposure to MON863 over 11 generations (moderate selected lines). Two selected lines were developed from a control group by constant exposure to MON863 for at least 14 d posthatch over seven generations (intense selected lines). At the end of the experiment, survivorship, as measured by adult emergence, was approximately 4 times higher in each of the selected lines reared on MON863 compared with control lines. Estimates of realized heritabilities (h2) were 0.16 and 0.15 for the moderate and intense selected lines, respectively, and are consistent with h2 estimates reported previously from a variety of pest insects. These lines provide data necessary for evaluating the potential for Bt resistance within diabroticite beetles and will be useful for developing improved insect resistance management strategies.

Biomechanical Diversity of Mating Structures among Harvestmen Species Is Consistent with a Spectrum of Precopulatory Strategies

PubMed Central

Burns, Mercedes; Shultz, Jeffrey W.

2015-01-01

Diversity in reproductive structures is frequently explained by selection acting at individual to generational timescales, but interspecific differences predicted by such models (e.g., female choice or sexual conflict) are often untestable in a phylogenetic framework. An alternative approach focuses on clade- or function-specific hypotheses that predict evolutionary patterns in terms neutral to specific modes of sexual selection. Here we test a hypothesis that diversity of reproductive structures in leiobunine harvestmen (daddy longlegs) of eastern North America reflects two sexually coevolved but non-overlapping precopulatory strategies, a primitive solicitous strategy (females enticed by penis-associated nuptial gifts), and a multiply derived antagonistic strategy (penis exerts mechanical force against armature of the female pregenital opening). Predictions of sexual coevolution and fidelity to precopulatory categories were tested using 10 continuously varying functional traits from 28 species. Multivariate analyses corroborated sexual coevolution but failed to partition species by precopulatory strategy, with multiple methods placing species along a spectrum of mechanical antagonistic potential. These findings suggest that precopulatory features within species reflect different co-occurring levels of solicitation and antagonism, and that gradualistic evolutionary pathways exist between extreme strategies. The ability to quantify antagonistic potential of precopulatory structures invites comparison with ecological variables that may promote evolutionary shifts in precopulatory strategies. PMID:26352413

Biomechanical Diversity of Mating Structures among Harvestmen Species Is Consistent with a Spectrum of Precopulatory Strategies.

PubMed

Burns, Mercedes; Shultz, Jeffrey W

2015-01-01

Diversity in reproductive structures is frequently explained by selection acting at individual to generational timescales, but interspecific differences predicted by such models (e.g., female choice or sexual conflict) are often untestable in a phylogenetic framework. An alternative approach focuses on clade- or function-specific hypotheses that predict evolutionary patterns in terms neutral to specific modes of sexual selection. Here we test a hypothesis that diversity of reproductive structures in leiobunine harvestmen (daddy longlegs) of eastern North America reflects two sexually coevolved but non-overlapping precopulatory strategies, a primitive solicitous strategy (females enticed by penis-associated nuptial gifts), and a multiply derived antagonistic strategy (penis exerts mechanical force against armature of the female pregenital opening). Predictions of sexual coevolution and fidelity to precopulatory categories were tested using 10 continuously varying functional traits from 28 species. Multivariate analyses corroborated sexual coevolution but failed to partition species by precopulatory strategy, with multiple methods placing species along a spectrum of mechanical antagonistic potential. These findings suggest that precopulatory features within species reflect different co-occurring levels of solicitation and antagonism, and that gradualistic evolutionary pathways exist between extreme strategies. The ability to quantify antagonistic potential of precopulatory structures invites comparison with ecological variables that may promote evolutionary shifts in precopulatory strategies.

The 'retro-design' concept for novel kinase inhibitors.

PubMed

Müller, Gerhard; Sennhenn, Peter C; Woodcock, Timothy; Neumann, Lars

2010-07-01

Protein kinases are among the most attractive therapeutic targets for a broad range of diseases. This feature review highlights and classifies the main design principles employed to generate active and selective kinase inhibitors. In particular, emphasis is focused on a fragment-based lead-generation approach, which constitutes a novel design method for developing type II kinase inhibitors with distinct binding kinetic attributes. This 'retro-design' strategy relies on a customized fragment library, and contrasts the traditional approach used in the design of type II inhibitors.

Improving industrial yeast strains: exploiting natural and artificial diversity.

PubMed

Steensels, Jan; Snoek, Tim; Meersman, Esther; Picca Nicolino, Martina; Voordeckers, Karin; Verstrepen, Kevin J

2014-09-01

Yeasts have been used for thousands of years to make fermented foods and beverages, such as beer, wine, sake, and bread. However, the choice for a particular yeast strain or species for a specific industrial application is often based on historical, rather than scientific grounds. Moreover, new biotechnological yeast applications, such as the production of second-generation biofuels, confront yeast with environments and challenges that differ from those encountered in traditional food fermentations. Together, this implies that there are interesting opportunities to isolate or generate yeast variants that perform better than the currently used strains. Here, we discuss the different strategies of strain selection and improvement available for both conventional and nonconventional yeasts. Exploiting the existing natural diversity and using techniques such as mutagenesis, protoplast fusion, breeding, genome shuffling and directed evolution to generate artificial diversity, or the use of genetic modification strategies to alter traits in a more targeted way, have led to the selection of superior industrial yeasts. Furthermore, recent technological advances allowed the development of high-throughput techniques, such as 'global transcription machinery engineering' (gTME), to induce genetic variation, providing a new source of yeast genetic diversity. © 2014 The Authors. FEMS Microbiology Reviews published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

Choosing experiments to accelerate collective discovery

PubMed Central

Rzhetsky, Andrey; Foster, Jacob G.; Foster, Ian T.

2015-01-01

A scientist’s choice of research problem affects his or her personal career trajectory. Scientists’ combined choices affect the direction and efficiency of scientific discovery as a whole. In this paper, we infer preferences that shape problem selection from patterns of published findings and then quantify their efficiency. We represent research problems as links between scientific entities in a knowledge network. We then build a generative model of discovery informed by qualitative research on scientific problem selection. We map salient features from this literature to key network properties: an entity’s importance corresponds to its degree centrality, and a problem’s difficulty corresponds to the network distance it spans. Drawing on millions of papers and patents published over 30 years, we use this model to infer the typical research strategy used to explore chemical relationships in biomedicine. This strategy generates conservative research choices focused on building up knowledge around important molecules. These choices become more conservative over time. The observed strategy is efficient for initial exploration of the network and supports scientific careers that require steady output, but is inefficient for science as a whole. Through supercomputer experiments on a sample of the network, we study thousands of alternatives and identify strategies much more efficient at exploring mature knowledge networks. We find that increased risk-taking and the publication of experimental failures would substantially improve the speed of discovery. We consider institutional shifts in grant making, evaluation, and publication that would help realize these efficiencies. PMID:26554009

Selection is more intelligent than design: improving the affinity of a bivalent ligand through directed evolution.

PubMed

Ahmad, Kareem M; Xiao, Yi; Soh, H Tom

2012-12-01

Multivalent molecular interactions can be exploited to dramatically enhance the performance of an affinity reagent. The enhancement in affinity and specificity achieved with a multivalent construct depends critically on the effectiveness of the scaffold that joins the ligands, as this determines their positions and orientations with respect to the target molecule. Currently, no generalizable design rules exist for construction of an optimal multivalent ligand for targets with known structures, and the design challenge remains an insurmountable obstacle for the large number of proteins whose structures are not known. As an alternative to such design-based strategies, we report here a directed evolution-based method for generating optimal bivalent aptamers. To demonstrate this approach, we fused two thrombin aptamers with a randomized DNA sequence and used a microfluidic in vitro selection strategy to isolate scaffolds with exceptionally high affinities. Within five rounds of selection, we generated a bivalent aptamer that binds thrombin with an apparent dissociation constant (K(d)) <10 pM, representing a ∼200-fold improvement in binding affinity over the monomeric aptamers and a ∼15-fold improvement over the best designed bivalent construct. The process described here can be used to produce high-affinity multivalent aptamers and could potentially be adapted to other classes of biomolecules.

Enabling Catalytic Strategies for Biomass Conversion

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

Waymouth, Robert

This research program employed a mix of fundamental investigations of catalytic reactivity with targeted approaches for the catalytic synthesis of monomers and renewable polymers. We investigated the mechanisms of selective aerobic oxidation of polyols and carbohydrates with Pd catalysts with a special focus on the role of hydrogen peroxide and peroxy intermediates in an effort to increase catalyst lifetime. We also extended our studies on the selective oxidation of sugars to ketoses and the oxidative lactonization of 1,5-diols to generate new families of lactone monomers.

Site selective generation of sol-gel deposits in layered bimetallic macroporous electrode architectures.

PubMed

Lalo, Hélène; Bon-Saint-Côme, Yémima; Plano, Bernard; Etienne, Mathieu; Walcarius, Alain; Kuhn, Alexander

2012-02-07

The elaboration of an original composite bimetallic macroporous electrode containing a site-selective sol-gel deposit is reported. Regular colloidal crystals, obtained by a modified Langmuir-Blodgett approach, are used as templates for the electrogeneration of the desired metals in the form of a well-defined layered bimetallic porous electrode. This porous matrix shows a spatially modulated electroactivity which is subsequently used as a strategy for targeted electrogeneration of a sol-gel deposit, exclusively in one predefined part of the porous electrode.

Applications of Participatory Action Research with Students Who Have Disabilities. ERIC/OSEP Digest.

ERIC Educational Resources Information Center

Warger, Cynthia; Burnette, Jane

This brief paper defines participatory action research, reviews the literature on its use, and offers examples of how researchers and practitioners are applying principles of participatory action research data to select effective practices and support change and innovation in schools. Generation of data-based strategies in natural environments is…

UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small molecule natural product libraries

USDA-ARS?s Scientific Manuscript database

Generation of natural product libraries containing column fractions, each with only a few small molecules, by a high throughput, automated fractionation system has made it possible to implement an improved dereplication strategy for selection and prioritization of hits in a natural product discovery...

The Role of the Librarian in Developing Leadership Capabilities in Staff

ERIC Educational Resources Information Center

Hough, Michael

2010-01-01

This session will focus on the dilemmas and challenges of providing effective leadership skills for modern schools with digital information and communication technology (ICT) capabilities. It will review the selected challenges of engaging different generations of staff in ICT based learning and recommend strategies for effective leadership of ICT…

Limited fitness costs of herbicide-resistance traits in Amaranthus tuberculatus facilitate resistance evolution.

PubMed

Wu, Chenxi; Davis, Adam S; Tranel, Patrick J

2018-02-01

The fitness cost of herbicide resistance (HR) in the absence of herbicide selection plays a key role in HR evolution. Quantifying the fitness cost of resistance, however, is challenging, and there exists a knowledge gap in this area. A synthetic (artificially generated) Amaranthus tuberculatus population segregating for five types of HR was subjected to competitive growth conditions in the absence of herbicide selection for six generations. Fitness costs were quantified by using a combination of phenotyping and genotyping to monitor HR frequency changes over generations. In the absence of herbicide selection, a significant fitness cost was observed for resistance to acetolactate synthase-inhibiting herbicides, but not for resistances to atrazine (non-target-site resistance mechanism), protoporphyrinogen oxidase inhibitors, 4-hydroxyphenylpryuvate dioxygenase inhibitors or glyphosate. Glyphosate resistance was conferred by multiple mechanisms in the synthetic population, and further analysis revealed that one mechanism, amplification of the 5-enolypyruvylshikimate-3-phosphate synthase gene, did decrease in frequency. Our results indicate that herbicide-resistance mitigation strategies (e.g. herbicide rotation) that rely on the existence of fitness costs in the absence of herbicide selection likely will be largely ineffective in many cases. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Male-biased sex ratio does not promote increased sperm competitiveness in the seed beetle, Callosobruchus maculatus.

PubMed

McNamara, Kathryn B; Robinson, Stephen P; Rosa, Márta E; Sloan, Nadia S; van Lieshout, Emile; Simmons, Leigh W

2016-06-16

Sperm competition risk and intensity can select for adaptations that increase male fertilisation success. Evolutionary responses are examined typically by generating increased strength of sexual selection via direct manipulation of female mating rates (by enforcing monandry or polyandry) or by alteration of adult sex ratios. Despite being a model species for sexual selection research, the effect of sexual selection intensity via adult sex-ratio manipulation on male investment strategies has not been investigated in the seed beetle, Callosobruchus maculatus. We imposed 32 generations of experimental evolution on 10 populations of beetles by manipulating adult sex ratio. Contrary to predictions, males evolving in male-biased populations did not increase their testes and accessory gland size. This absence of divergence in ejaculate investment was also reflected in the fact that males from male-biased populations were not more successful in either preventing females from remating, or in competing directly for fertilisations. These populations already demonstrate divergence in mating behaviour and immunity, suggesting sufficient generations have passed to allow divergence in physiological and behavioural traits. We propose several explanations for the absence of divergence in sperm competitiveness among our populations and the pitfalls of using sex ratio manipulation to assess evolutionary responses to sexual selection intensity.

Male-biased sex ratio does not promote increased sperm competitiveness in the seed beetle, Callosobruchus maculatus

PubMed Central

McNamara, Kathryn B.; Robinson, Stephen P.; Rosa, Márta E.; Sloan, Nadia S.; van Lieshout, Emile; Simmons, Leigh W.

2016-01-01

Sperm competition risk and intensity can select for adaptations that increase male fertilisation success. Evolutionary responses are examined typically by generating increased strength of sexual selection via direct manipulation of female mating rates (by enforcing monandry or polyandry) or by alteration of adult sex ratios. Despite being a model species for sexual selection research, the effect of sexual selection intensity via adult sex-ratio manipulation on male investment strategies has not been investigated in the seed beetle, Callosobruchus maculatus. We imposed 32 generations of experimental evolution on 10 populations of beetles by manipulating adult sex ratio. Contrary to predictions, males evolving in male-biased populations did not increase their testes and accessory gland size. This absence of divergence in ejaculate investment was also reflected in the fact that males from male-biased populations were not more successful in either preventing females from remating, or in competing directly for fertilisations. These populations already demonstrate divergence in mating behaviour and immunity, suggesting sufficient generations have passed to allow divergence in physiological and behavioural traits. We propose several explanations for the absence of divergence in sperm competitiveness among our populations and the pitfalls of using sex ratio manipulation to assess evolutionary responses to sexual selection intensity. PMID:27306351

Genomic and environmental selection patterns in two distinct lettuce crop–wild hybrid crosses

PubMed Central

Hartman, Yorike; Uwimana, Brigitte; Hooftman, Danny A P; Schranz, Michael E; van de Wiel, Clemens C M; Smulders, Marinus J M; Visser, Richard G F; van Tienderen, Peter H

2013-01-01

Genomic selection patterns and hybrid performance influence the chance that crop (trans)genes can spread to wild relatives. We measured fitness(-related) traits in two different field environments employing two different crop–wild crosses of lettuce. We performed quantitative trait loci (QTL) analyses and estimated the fitness distribution of early- and late-generation hybrids. We detected consistent results across field sites and crosses for a fitness QTL at linkage group 7, where a selective advantage was conferred by the wild allele. Two fitness QTL were detected on linkage group 5 and 6, which were unique to one of the crop–wild crosses. Average hybrid fitness was lower than the fitness of the wild parent, but several hybrid lineages outperformed the wild parent, especially in a novel habitat for the wild type. In early-generation hybrids, this may partly be due to heterosis effects, whereas in late-generation hybrids transgressive segregation played a major role. The study of genomic selection patterns can identify crop genomic regions under negative selection across multiple environments and cultivar–wild crosses that might be applicable in transgene mitigation strategies. At the same time, results were cultivar-specific, so that a case-by-case environmental risk assessment is still necessary, decreasing its general applicability. PMID:23789025

Genomic and environmental selection patterns in two distinct lettuce crop-wild hybrid crosses.

PubMed

Hartman, Yorike; Uwimana, Brigitte; Hooftman, Danny A P; Schranz, Michael E; van de Wiel, Clemens C M; Smulders, Marinus J M; Visser, Richard G F; van Tienderen, Peter H

2013-06-01

Genomic selection patterns and hybrid performance influence the chance that crop (trans)genes can spread to wild relatives. We measured fitness(-related) traits in two different field environments employing two different crop-wild crosses of lettuce. We performed quantitative trait loci (QTL) analyses and estimated the fitness distribution of early- and late-generation hybrids. We detected consistent results across field sites and crosses for a fitness QTL at linkage group 7, where a selective advantage was conferred by the wild allele. Two fitness QTL were detected on linkage group 5 and 6, which were unique to one of the crop-wild crosses. Average hybrid fitness was lower than the fitness of the wild parent, but several hybrid lineages outperformed the wild parent, especially in a novel habitat for the wild type. In early-generation hybrids, this may partly be due to heterosis effects, whereas in late-generation hybrids transgressive segregation played a major role. The study of genomic selection patterns can identify crop genomic regions under negative selection across multiple environments and cultivar-wild crosses that might be applicable in transgene mitigation strategies. At the same time, results were cultivar-specific, so that a case-by-case environmental risk assessment is still necessary, decreasing its general applicability.

PHASTpep: Analysis Software for Discovery of Cell-Selective Peptides via Phage Display and Next-Generation Sequencing

PubMed Central

Dasa, Siva Sai Krishna; Kelly, Kimberly A.

2016-01-01

Next-generation sequencing has enhanced the phage display process, allowing for the quantification of millions of sequences resulting from the biopanning process. In response, many valuable analysis programs focused on specificity and finding targeted motifs or consensus sequences were developed. For targeted drug delivery and molecular imaging, it is also necessary to find peptides that are selective—targeting only the cell type or tissue of interest. We present a new analysis strategy and accompanying software, PHage Analysis for Selective Targeted PEPtides (PHASTpep), which identifies highly specific and selective peptides. Using this process, we discovered and validated, both in vitro and in vivo in mice, two sequences (HTTIPKV and APPIMSV) targeted to pancreatic cancer-associated fibroblasts that escaped identification using previously existing software. Our selectivity analysis makes it possible to discover peptides that target a specific cell type and avoid other cell types, enhancing clinical translatability by circumventing complications with systemic use. PMID:27186887

Maximizing power generation from dark fermentation effluents in microbial fuel cell by selective enrichment of exoelectrogens and optimization of anodic operational parameters.

PubMed

Varanasi, Jhansi L; Sinha, Pallavi; Das, Debabrata

2017-05-01

To selectively enrich an electrogenic mixed consortium capable of utilizing dark fermentative effluents as substrates in microbial fuel cells and to further enhance the power outputs by optimization of influential anodic operational parameters. A maximum power density of 1.4 W/m 3 was obtained by an enriched mixed electrogenic consortium in microbial fuel cells using acetate as substrate. This was further increased to 5.43 W/m 3 by optimization of influential anodic parameters. By utilizing dark fermentative effluents as substrates, the maximum power densities ranged from 5.2 to 6.2 W/m 3 with an average COD removal efficiency of 75% and a columbic efficiency of 10.6%. A simple strategy is provided for selective enrichment of electrogenic bacteria that can be used in microbial fuel cells for generating power from various dark fermentative effluents.

Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

PubMed

Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

2014-01-01

High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

Evaluation of breeding strategies for polledness in dairy cattle using a newly developed simulation framework for quantitative and Mendelian traits.

PubMed

Scheper, Carsten; Wensch-Dorendorf, Monika; Yin, Tong; Dressel, Holger; Swalve, Herrmann; König, Sven

2016-06-29

Intensified selection of polled individuals has recently gained importance in predominantly horned dairy cattle breeds as an alternative to routine dehorning. The status quo of the current polled breeding pool of genetically-closely related artificial insemination sires with lower breeding values for performance traits raises questions regarding the effects of intensified selection based on this founder pool. We developed a stochastic simulation framework that combines the stochastic simulation software QMSim and a self-designed R program named QUALsim that acts as an external extension. Two traits were simulated in a dairy cattle population for 25 generations: one quantitative (QMSim) and one qualitative trait with Mendelian inheritance (i.e. polledness, QUALsim). The assignment scheme for qualitative trait genotypes initiated realistic initial breeding situations regarding allele frequencies, true breeding values for the quantitative trait and genetic relatedness. Intensified selection for polled cattle was achieved using an approach that weights estimated breeding values in the animal best linear unbiased prediction model for the quantitative trait depending on genotypes or phenotypes for the polled trait with a user-defined weighting factor. Selection response for the polled trait was highest in the selection scheme based on genotypes. Selection based on phenotypes led to significantly lower allele frequencies for polled. The male selection path played a significantly greater role for a fast dissemination of polled alleles compared to female selection strategies. Fixation of the polled allele implies selection based on polled genotypes among males. In comparison to a base breeding scenario that does not take polledness into account, intensive selection for polled substantially reduced genetic gain for this quantitative trait after 25 generations. Reducing selection intensity for polled males while maintaining strong selection intensity among females, simultaneously decreased losses in genetic gain and achieved a final allele frequency of 0.93 for polled. A fast transition to a completely polled population through intensified selection for polled was in contradiction to the preservation of high genetic gain for the quantitative trait. Selection on male polled genotypes with moderate weighting, and selection on female polled phenotypes with high weighting, could be a suitable compromise regarding all important breeding aspects.

Trait-specific long-term consequences of genomic selection in beef cattle.

PubMed

de Rezende Neves, Haroldo Henrique; Carvalheiro, Roberto; de Queiroz, Sandra Aidar

2018-02-01

Simulation studies allow addressing consequences of selection schemes, helping to identify effective strategies to enable genetic gain and maintain genetic diversity. The aim of this study was to evaluate the long-term impact of genomic selection (GS) in genetic progress and genetic diversity of beef cattle. Forward-in-time simulation generated a population with pattern of linkage disequilibrium close to that previously reported for real beef cattle populations. Different scenarios of GS and traditional pedigree-based BLUP (PBLUP) selection were simulated for 15 generations, mimicking selection for female reproduction and meat quality. For GS scenarios, an alternative selection criterion was simulated (wGBLUP), intended to enhance long-term gains by attributing more weight to favorable alleles with low frequency. GS allowed genetic progress up to 40% greater than PBLUP, for female reproduction and meat quality. The alternative criterion wGBLUP did not increase long-term response, although allowed reducing inbreeding rates and loss of favorable alleles. The results suggest that GS outperforms PBLUP when the selected trait is under less polygenic background and that attributing more weight to low-frequency favorable alleles can reduce inbreeding rates and loss of favorable alleles in GS.

Use of Phage Display to Generate Conformation-Sensor Recombinant Antibodies

PubMed Central

Haque, Aftabul; Tonks, Nicholas K.

2013-01-01

We describe a phage display approach that we have previously used to generate conformation-sensor antibodies that recognize specifically and stabilize the oxidized, inactive conformation of protein tyrosine phosphatase 1B (PTP1B). We use a solution-based panning and screening strategy conducted in the presence of reduced active PTP1B, which enriches antibodies to epitopes unique to the oxidized form, while excluding antibodies that recognize epitopes common to oxidized and reduced forms of PTP1B. This strategy avoids conventional solid-phase immobilization, with its inherent potential for denaturation of the antigen. In addition, a functional screening strategy selects scFvs directly for their capacity for both specific binding and stabilization of the target enzyme in its inactive conformation. These conformation-specific scFvs illustrate that stabilization of oxidized PTP1B is an effective strategy to inhibit PTP1B function; it is possible that this approach may be applicable to the PTP family as a whole. Using this protocol, isolation and characterization of specific scFvs from immune responsive animals should take ~6 weeks. PMID:23154784

Templated and template-free fabrication strategies for zero-dimensional hollow MOF superstructures.

PubMed

Kim, Hyehyun; Lah, Myoung Soo

2017-05-16

Various fabrication strategies for hollow metal-organic framework (MOF) superstructures are reviewed and classified using various types of external templates and their properties. Hollow MOF superstructures have also been prepared without external templates, wherein unstable intermediates obtained during reactions convert to the final hollow MOF superstructures. Many hollow MOF superstructures have been fabricated using hard templates. After the core-shell core@MOF structure was prepared using a hard template, the core was selectively etched to generate a hollow MOF superstructure. Another approach for generating hollow superstructures is to use a solid reactant as a sacrificial template; this method requires no additional etching process. Soft templates such as discontinuous liquid/emulsion droplets and gas bubbles in a continuous soft phase have also been employed to prepare hollow MOF superstructures.

Bayesian inference for the genetic control of water deficit tolerance in spring wheat by stochastic search variable selection.

PubMed

Safari, Parviz; Danyali, Syyedeh Fatemeh; Rahimi, Mehdi

2018-06-02

Drought is the main abiotic stress seriously influencing wheat production. Information about the inheritance of drought tolerance is necessary to determine the most appropriate strategy to develop tolerant cultivars and populations. In this study, generation means analysis to identify the genetic effects controlling grain yield inheritance in water deficit and normal conditions was considered as a model selection problem in a Bayesian framework. Stochastic search variable selection (SSVS) was applied to identify the most important genetic effects and the best fitted models using different generations obtained from two crosses applying two water regimes in two growing seasons. The SSVS is used to evaluate the effect of each variable on the dependent variable via posterior variable inclusion probabilities. The model with the highest posterior probability is selected as the best model. In this study, the grain yield was controlled by the main effects (additive and non-additive effects) and epistatic. The results demonstrate that breeding methods such as recurrent selection and subsequent pedigree method and hybrid production can be useful to improve grain yield.

Skin lesion computational diagnosis of dermoscopic images: Ensemble models based on input feature manipulation.

PubMed

Oliveira, Roberta B; Pereira, Aledir S; Tavares, João Manuel R S

2017-10-01

The number of deaths worldwide due to melanoma has risen in recent times, in part because melanoma is the most aggressive type of skin cancer. Computational systems have been developed to assist dermatologists in early diagnosis of skin cancer, or even to monitor skin lesions. However, there still remains a challenge to improve classifiers for the diagnosis of such skin lesions. The main objective of this article is to evaluate different ensemble classification models based on input feature manipulation to diagnose skin lesions. Input feature manipulation processes are based on feature subset selections from shape properties, colour variation and texture analysis to generate diversity for the ensemble models. Three subset selection models are presented here: (1) a subset selection model based on specific feature groups, (2) a correlation-based subset selection model, and (3) a subset selection model based on feature selection algorithms. Each ensemble classification model is generated using an optimum-path forest classifier and integrated with a majority voting strategy. The proposed models were applied on a set of 1104 dermoscopic images using a cross-validation procedure. The best results were obtained by the first ensemble classification model that generates a feature subset ensemble based on specific feature groups. The skin lesion diagnosis computational system achieved 94.3% accuracy, 91.8% sensitivity and 96.7% specificity. The input feature manipulation process based on specific feature subsets generated the greatest diversity for the ensemble classification model with very promising results. Copyright © 2017 Elsevier B.V. All rights reserved.

Strategies to enhance waste minimization and energy conservation within organizations: a case study from the UK construction sector.

PubMed

Jones, Jo; Jackson, Janet; Tudor, Terry; Bates, Margaret

2012-09-01

Strategies for enhancing environmental management are a key focus for the government in the UK. Using a manufacturing company from the construction sector as a case study, this paper evaluates selected interventionist techniques, including environmental teams, awareness raising and staff training to improve environmental performance. The study employed a range of methods including questionnaire surveys and audits of energy consumption and generation of waste to examine the outcomes of the selected techniques. The results suggest that initially environmental management was not a focus for either the employees or the company. However, as a result of employing the techniques, the company was able to reduce energy consumption, increase recycling rates and achieve costs savings in excess of £132,000.

Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy.

PubMed

Ortiz, Adrian; Soumeillant, Maxime; Savage, Scott A; Strotman, Neil A; Haley, Matthew; Benkovics, Tamas; Nye, Jeffrey; Xu, Zhongmin; Tan, Yichen; Ayers, Sloan; Gao, Qi; Kiau, Susanne

2017-05-05

A concise and scalable second generation synthesis of HIV maturation inhibitor BMS-955176 is described. The synthesis is framed by an oxidation strategy highlighted by a Cu I mediated aerobic oxidation of betulin, a highly selective PIFA mediated dehydrogenation of an oxime, and a subsequent Lossen rearrangement which occurs through a unique reaction mechanism for the installation of the C17 amino functionality. The synthetic route proceeds in 7 steps with 47% overall yield and begins from the abundant and inexpensive natural product betulin.

Analysis of optoelectronic strategic planning in Taiwan by artificial intelligence portfolio tool

NASA Astrophysics Data System (ADS)

Chang, Rang-Seng

1992-05-01

Taiwan ROC has achieved significant advances in the optoelectronic industry with some Taiwan products ranked high in the world market and technology. Six segmentations of optoelectronic were planned. Each one was divided into several strategic items, design artificial intelligent portfolio tool (AIPT) to analyze the optoelectronic strategic planning in Taiwan. The portfolio is designed to provoke strategic thinking intelligently. This computer- generated strategy should be selected and modified by the individual. Some strategies for the development of the Taiwan optoelectronic industry also are discussed in this paper.

Selection for Improved Energy Use Efficiency and Drought Tolerance in Canola Results in Distinct Transcriptome and Epigenome Changes.

PubMed

Verkest, Aurine; Byzova, Marina; Martens, Cindy; Willems, Patrick; Verwulgen, Tom; Slabbinck, Bram; Rombaut, Debbie; Van de Velde, Jan; Vandepoele, Klaas; Standaert, Evi; Peeters, Marrit; Van Lijsebettens, Mieke; Van Breusegem, Frank; De Block, Marc

2015-08-01

To increase both the yield potential and stability of crops, integrated breeding strategies are used that have mostly a direct genetic basis, but the utility of epigenetics to improve complex traits is unclear. A better understanding of the status of the epigenome and its contribution to agronomic performance would help in developing approaches to incorporate the epigenetic component of complex traits into breeding programs. Starting from isogenic canola (Brassica napus) lines, epilines were generated by selecting, repeatedly for three generations, for increased energy use efficiency and drought tolerance. These epilines had an enhanced energy use efficiency, drought tolerance, and nitrogen use efficiency. Transcriptome analysis of the epilines and a line selected for its energy use efficiency solely revealed common differentially expressed genes related to the onset of stress tolerance-regulating signaling events. Genes related to responses to salt, osmotic, abscisic acid, and drought treatments were specifically differentially expressed in the drought-tolerant epilines. The status of the epigenome, scored as differential trimethylation of lysine-4 of histone 3, further supported the phenotype by targeting drought-responsive genes and facilitating the transcription of the differentially expressed genes. From these results, we conclude that the canola epigenome can be shaped by selection to increase energy use efficiency and stress tolerance. Hence, these findings warrant the further development of strategies to incorporate epigenetics into breeding. © 2015 American Society of Plant Biologists. All Rights Reserved.

Investing in Youth: A Compilation of Recommended Policies and Practices. National Conference (New Orleans, Louisiana, December 9-11, 1992).

ERIC Educational Resources Information Center

National Governors' Association, Washington, DC.

These proceedings include 13 "perspectives from the field" and 9 selected papers (with abstracts) from a national conference on recommended policies and practices for investing in youth. The 13 perspectives papers are as follows: "Saving the Next Generation" (Berlin); "Effective Strategies for Investing in Youth"…

Robustness analysis of complex networks with power decentralization strategy via flow-sensitive centrality against cascading failures

NASA Astrophysics Data System (ADS)

Guo, Wenzhang; Wang, Hao; Wu, Zhengping

2018-03-01

Most existing cascading failure mitigation strategy of power grids based on complex network ignores the impact of electrical characteristics on dynamic performance. In this paper, the robustness of the power grid under a power decentralization strategy is analysed through cascading failure simulation based on AC flow theory. The flow-sensitive (FS) centrality is introduced by integrating topological features and electrical properties to help determine the siting of the generation nodes. The simulation results of the IEEE-bus systems show that the flow-sensitive centrality method is a more stable and accurate approach and can enhance the robustness of the network remarkably. Through the study of the optimal flow-sensitive centrality selection for different networks, we find that the robustness of the network with obvious small-world effect depends more on contribution of the generation nodes detected by community structure, otherwise, contribution of the generation nodes with important influence on power flow is more critical. In addition, community structure plays a significant role in balancing the power flow distribution and further slowing the propagation of failures. These results are useful in power grid planning and cascading failure prevention.

Operationally optimal maneuver strategy for spacecraft injected into sub-geosynchronous transfer orbit

NASA Astrophysics Data System (ADS)

Kiran, B. S.; Singh, Satyendra; Negi, Kuldeep

The GSAT-12 spacecraft is providing Communication services from the INSAT/GSAT system in the Indian region. The spacecraft carries 12 extended C-band transponders. GSAT-12 was launched by ISRO’s PSLV from Sriharikota, into a sub-geosynchronous Transfer Orbit (sub-GTO) of 284 x 21000 km with inclination 18 deg. This Mission successfully accomplished combined optimization of launch vehicle and satellite capabilities to maximize operational life of the s/c. This paper describes mission analysis carried out for GSAT-12 comprising launch window, orbital events study and orbit raising maneuver strategies considering various Mission operational constraints. GSAT-12 is equipped with two earth sensors (ES), three gyroscopes and digital sun sensor. The launch window was generated considering mission requirement of minimum 45 minutes of ES data for calibration of gyros with Roll-sun-pointing orientation in T.O. Since the T.O. period was a rather short 6.1 hr, required pitch biases were worked out to meet the gyro-calibration requirement. A 440 N Liquid Apogee Motor (LAM) is used for orbit raising. The objective of the maneuver strategy is to achieve desired drift orbit satisfying mission constraints and minimizing propellant expenditure. In case of sub-GTO, the optimal strategy is to first perform an in-plane maneuver at perigee to raise the apogee to synchronous level and then perform combined maneuvers at the synchronous apogee to achieve desired drift orbit. The perigee burn opportunities were examined considering ground station visibility requirement for monitoring the burn. Two maneuver strategies were proposed: an optimal five-burn strategy with two perigee burns centered around perigee#5 and perigee#8 with partial ground station visibility and three apogee burns with dual station visibility, a near-optimal five-burn strategy with two off-perigee burns at perigee#5 and perigee#8 with single ground station visibility and three apogee burns with dual station visibility. The range vector profiles were studied in the s/c frame during LAM burn phases and accurate polarization predictions were provided to supporting ground stations. The near optimal strategy was selected for implementation in order to ensure full visibility during each LAM burn. Contingency maneuver plans were generated in preparation for specified Propulsion system related contingencies. Maneuver plans were generated considering 3-sigma dispersions in T.O. GSAT-12 is positioned at 83 deg East longitude. The estimated operational life is about 11 years which was realized through operationally optimal maneuver strategy selected from the detailed mission analysis.

Size principle and information theory.

PubMed

Senn, W; Wyler, K; Clamann, H P; Kleinle, J; Lüscher, H R; Müller, L

1997-01-01

The motor units of a skeletal muscle may be recruited according to different strategies. From all possible recruitment strategies nature selected the simplest one: in most actions of vertebrate skeletal muscles the recruitment of its motor units is by increasing size. This so-called size principle permits a high precision in muscle force generation since small muscle forces are produced exclusively by small motor units. Larger motor units are activated only if the total muscle force has already reached certain critical levels. We show that this recruitment by size is not only optimal in precision but also optimal in an information theoretical sense. We consider the motoneuron pool as an encoder generating a parallel binary code from a common input to that pool. The generated motoneuron code is sent down through the motoneuron axons to the muscle. We establish that an optimization of this motoneuron code with respect to its information content is equivalent to the recruitment of motor units by size. Moreover, maximal information content of the motoneuron code is equivalent to a minimal expected error in muscle force generation.

A general strategy for synthesis of cyclophane-braced peptide macrocycles via palladium-catalysed intramolecular sp3 C-H arylation

NASA Astrophysics Data System (ADS)

Zhang, Xuekai; Lu, Gang; Sun, Meng; Mahankali, Madhu; Ma, Yanfei; Zhang, Mingming; Hua, Wangde; Hu, Yuting; Wang, Qingbing; Chen, Jinghuo; He, Gang; Qi, Xiangbing; Shen, Weijun; Liu, Peng; Chen, Gong

2018-05-01

New methods capable of effecting cyclization, and forming novel three-dimensional structures while maintaining favourable physicochemical properties are needed to facilitate the development of cyclic peptide-based drugs that can engage challenging biological targets, such as protein-protein interactions. Here, we report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalysed intramolecular C(sp3)-H arylation reactions. Easily accessible linear peptide precursors of simple and versatile design can be selectively cyclized at the side chains of either aromatic or modified non-aromatic amino acid units to form various cyclophane-braced peptide cycles. This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures. Preliminary cell proliferation screening of the pilot library revealed a potent lead compound with selective cytotoxicity toward proliferative Myc-dependent cancer cell lines.

On the way to the creation of next generation photoactive materials.

PubMed

Emeline, A V; Kuznetsov, V N; Ryabchuk, V K; Serpone, N

2012-11-01

Transition from first- to second-generation photocatalysts has followed the notion that greater absorption of light in the visible region would yield greater spectral sensitivity and greater photoactivity. Though a promising strategy, in practice, it did not meet expectation because of various side issues, which in many cases has led to loss of photoactivity and chemical reactivity. This article examines some earlier notions that arose from applications of different metal oxides (e.g., TiO(2), ZnO, MgO among others) that made these oxides good photocatalysts in many processes. Phenomena that proved relevant in developing next generation photoactive materials are considered: the dependence of the activity of photocatalysts on the band gap energy, the spectral variations of the activity of photoactive materials, and the spectral variations of selectivity of photoactive materials. The tendency to decrease the energy of actinic photons through doping in forming second-generation photocatalysts is completely opposite the fundamental observation in first-generation photocatalysts whereby the activity increased with increasing band gap energy. Extension of spectral sensitivity of second-generation photoactive materials also caused a decrease of their photoactivity; hence, some notions are reconsidered to produce next(third) generation photoactive materials. The article proposes the following concepts to develop next generation photocatalysts: (1) multi(two)-photon excitation of photoactive materials with lower energy photons to achieve the same excited state as with higher energy photons, (2) utilization of heterojunctions to drive electronic processes in the desired direction, and (3) selective photoexcitation of localized electronic states to gain better selectivity.

Genetic and economic benefits of selection based on performance recording and genotyping in lower tiers of multi-tiered sheep breeding schemes.

PubMed

Santos, Bruno F S; van der Werf, Julius H J; Gibson, John P; Byrne, Timothy J; Amer, Peter R

2017-01-17

Performance recording and genotyping in the multiplier tier of multi-tiered sheep breeding schemes could potentially reduce the difference in the average genetic merit between nucleus and commercial flocks, and create additional economic benefits for the breeding structure. The genetic change in a multiple-trait breeding objective was predicted for various selection strategies that included performance recording, parentage testing and genomic selection. A deterministic simulation model was used to predict selection differentials and the flow of genetic superiority through the different tiers. Cumulative discounted economic benefits were calculated based on trait gains achieved in each of the tiers and considering the extra revenue and associated costs of applying recording, genotyping and selection practices in the multiplier tier of the breeding scheme. Performance recording combined with genomic or parentage information in the multiplier tier reduced the genetic lag between the nucleus and commercial flock by 2 to 3 years. The overall economic benefits of improved performance in the commercial tier offset the costs of recording the multiplier. However, it took more than 18 years before the cumulative net present value of benefits offset the costs at current test prices. Strategies in which recorded multiplier ewes were selected as replacements for the nucleus flock did modestly increase profitability when compared to a closed nucleus structure. Applying genomic selection is the most beneficial strategy if testing costs can be reduced or by genotyping only a proportion of the selection candidates. When the cost of genotyping was reduced, scenarios that combine performance recording with genomic selection were more profitable and reached breakeven point about 10 years earlier. Economic benefits can be generated in multiplier flocks by implementing performance recording in conjunction with either DNA pedigree recording or genomic technology. These recording practices reduce the long genetic lag between the nucleus and commercial flocks in multi-tiered breeding programs. Under current genotyping costs, the time to breakeven was found to be generally very long, although this varied between strategies. Strategies using either genomic selection or DNA pedigree verification were found to be economically viable provided the price paid for the tests is lower than current prices, in the long-term.

Directed evolution: tailoring biocatalysts for industrial applications.

PubMed

Kumar, Ashwani; Singh, Suren

2013-12-01

Current challenges and promises of white biotechnology encourage protein engineers to use a directed evolution approach to generate novel and useful biocatalysts for various sets of applications. Different methods of enzyme engineering have been used in the past in an attempt to produce enzymes with improved functions and properties. Recent advancement in the field of random mutagenesis, screening, selection and computational design increased the versatility and the rapid development of enzymes under strong selection pressure with directed evolution experiments. Techniques of directed evolution improve enzymes fitness without understanding them in great detail and clearly demonstrate its future role in adapting enzymes for use in industry. Despite significant advances to date regarding biocatalyst improvement, there still remains a need to improve mutagenesis strategies and development of easy screening and selection tools without significant human intervention. This review covers fundamental and major development of directed evolution techniques, and highlights the advances in mutagenesis, screening and selection methods with examples of enzymes developed by using these approaches. Several commonly used methods for creating molecular diversity with their advantages and disadvantages including some recently used strategies are also discussed.

Selection for predation, not female fecundity, explains sexual size dimorphism in the orchid mantises.

PubMed

Svenson, Gavin J; Brannoch, Sydney K; Rodrigues, Henrique M; O'Hanlon, James C; Wieland, Frank

2016-12-01

Here we reconstruct the evolutionary shift towards floral simulation in orchid mantises and suggest female predatory selection as the likely driving force behind the development of extreme sexual size dimorphism. Through analysis of body size data and phylogenetic modelling of trait evolution, we recovered an ancestral shift towards sexual dimorphisms in both size and appearance in a lineage of flower-associated praying mantises. Sedentary female flower mantises dramatically increased in size prior to a transition from camouflaged, ambush predation to a floral simulation strategy, gaining access to, and visually attracting, a novel resource: large pollinating insects. Male flower mantises, however, remained small and mobile to facilitate mate-finding and reproductive success, consistent with ancestral male life strategy. Although moderate sexual size dimorphisms are common in many arthropod lineages, the predominant explanation is female size increase for increased fecundity. However, sex-dependent selective pressures acting outside of female fecundity have been suggested as mechanisms behind niche dimorphisms. Our hypothesised role of predatory selection acting on females to generate both extreme sexual size dimorphism coupled with niche dimorphism is novel among arthropods.

Selection for predation, not female fecundity, explains sexual size dimorphism in the orchid mantises

PubMed Central

Svenson, Gavin J.; Brannoch, Sydney K.; Rodrigues, Henrique M.; O’Hanlon, James C.; Wieland, Frank

2016-01-01

Here we reconstruct the evolutionary shift towards floral simulation in orchid mantises and suggest female predatory selection as the likely driving force behind the development of extreme sexual size dimorphism. Through analysis of body size data and phylogenetic modelling of trait evolution, we recovered an ancestral shift towards sexual dimorphisms in both size and appearance in a lineage of flower-associated praying mantises. Sedentary female flower mantises dramatically increased in size prior to a transition from camouflaged, ambush predation to a floral simulation strategy, gaining access to, and visually attracting, a novel resource: large pollinating insects. Male flower mantises, however, remained small and mobile to facilitate mate-finding and reproductive success, consistent with ancestral male life strategy. Although moderate sexual size dimorphisms are common in many arthropod lineages, the predominant explanation is female size increase for increased fecundity. However, sex-dependent selective pressures acting outside of female fecundity have been suggested as mechanisms behind niche dimorphisms. Our hypothesised role of predatory selection acting on females to generate both extreme sexual size dimorphism coupled with niche dimorphism is novel among arthropods. PMID:27905469

Speed congenics: accelerated genome recovery using genetic markers.

PubMed

Visscher, P M

1999-08-01

Genetic markers throughout the genome can be used to speed up 'recovery' of the recipient genome in the backcrossing phase of the construction of a congenic strain. The prediction of the genomic proportion during backcrossing depends on the assumptions regarding the distribution of chromosome segments, the population structure, the marker spacing and the selection strategy. In this study simulation was used to investigate the rate of recovery of the recipient genome for a mouse, Drosophila and Arabidopsis genome. It was shown that an incorrect assumption of a binomial distribution of chromosome segments, and failing to take account of a reduction in variance in genomic proportion due to selection, can lead to a downward bias of up to two generations in the estimation of the number of generations required for the formation of a congenic strain.

Biological trait analysis and stability of lambda-cyhalothrin resistance in the house fly, Musca domestica L. (Diptera: Muscidae).

PubMed

Abbas, Naeem; Shah, Rizwan Mustafa; Shad, Sarfraz Ali; Iqbal, Naeem; Razaq, Muhammad

2016-05-01

House flies, Musca domestica L., (Diptera: Muscidae), are pests of poultry and have the ability to develop resistance to insecticides. To design a strategy for resistance management, life history traits based on laboratory observations were established for lambda-cyhalothrin-resistant, susceptible and reciprocal crosses of M. domestica strains. Bioassay results showed that the lambda-cyhalothrin-selected strain developed a resistance ratio of 98.34 compared to its susceptible strain. The lambda-cyhalothrin-selected strain had a relative fitness of 0.26 and lower fecundity, hatchability, lower number of next generation larvae, and net reproductive rate compared with its susceptible strain. Mean population growth rates, such as intrinsic rate of population increase, and biotic potential were lower for the lambda-cyhalothrin-selected strain compared to its susceptible strain. Resistance to lambda-cyhalothrin, indoxacarb, and abamectin was unstable while resistance to bifenthrin and methomyl was stable in the lambda-cyhalothrin-selected strain of M. domestica. Development of resistance can cost considerable fitness for the lambda-cyhalothrin-selected strain. The present study provided useful information for making potential management strategies to delay resistance development in M. domestica.

Library design practices for success in lead generation with small molecule libraries.

PubMed

Goodnow, R A; Guba, W; Haap, W

2003-11-01

The generation of novel structures amenable to rapid and efficient lead optimization comprises an emerging strategy for success in modern drug discovery. Small molecule libraries of sufficient size and diversity to increase the chances of discovery of novel structures make the high throughput synthesis approach the method of choice for lead generation. Despite an industry trend for smaller, more focused libraries, the need to generate novel lead structures makes larger libraries a necessary strategy. For libraries of a several thousand or more members, solid phase synthesis approaches are the most suitable. While the technology and chemistry necessary for small molecule library synthesis continue to advance, success in lead generation requires rigorous consideration in the library design process to ensure the synthesis of molecules possessing the proper characteristics for subsequent lead optimization. Without proper selection of library templates and building blocks, solid phase synthesis methods often generate molecules which are too heavy, too lipophilic and too complex to be useful for lead optimization. The appropriate filtering of virtual library designs with multiple computational tools allows the generation of information-rich libraries within a drug-like molecular property space. An understanding of the hit-to-lead process provides a practical guide to molecular design characteristics. Examples of leads generated from library approaches also provide a benchmarking of successes as well as aspects for continued development of library design practices.

Biocatalytic site- and enantioselective oxidative dearomatization of phenols

NASA Astrophysics Data System (ADS)

Baker Dockrey, Summer A.; Lukowski, April L.; Becker, Marc R.; Narayan, Alison R. H.

2018-02-01

The biocatalytic transformations used by chemists are often restricted to simple functional-group interconversions. In contrast, nature has developed complexity-generating biocatalytic reactions within natural product pathways. These sophisticated catalysts are rarely employed by chemists, because the substrate scope, selectivity and robustness of these catalysts are unknown. Our strategy to bridge the gap between the biosynthesis and synthetic chemistry communities leverages the diversity of catalysts available within natural product pathways. Here we show that, starting from a suite of biosynthetic enzymes, catalysts with complementary substrate scope as well as selectivity can be identified. This strategy has been applied to the oxidative dearomatization of phenols, a chemical transformation that rapidly builds molecular complexity from simple starting materials and cannot be accomplished with high selectivity using existing catalytic methods. Using enzymes from biosynthetic pathways, we have successfully developed a method to produce ortho-quinol products with controlled site- and stereoselectivity. Furthermore, we have capitalized on the scalability and robustness of this method in gram-scale reactions as well as multi-enzyme and chemoenzymatic cascades.

Development of a Markerless Genetic Exchange System in Desulfovibrio vulgaris Hildenborough and Its Use in Generating a Strain with Increased Transformation Efficiency

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

Keller, Kimberly L.; Bender, Kelly S.; Wall, Judy D.

2009-07-21

In recent years, the genetic manipulation of the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough has seen enormous progress. In spite of this progress, the current marker exchange deletion method does not allow for easy selection of multiple sequential gene deletions in a single strain because of the limited number of selectable markers available in D. vulgaris. To broaden the repertoire of genetic tools for manipulation, an in-frame, markerless deletion system has been developed. The counterselectable marker that makes this deletion system possible is the pyrimidine salvage enzyme, uracil phosphoribosyltransferase, encoded by upp. In wild-type D. vulgaris, growth was shown to bemore » inhibited by the toxic pyrimidine analog 5-fluorouracil (5-FU); whereas, a mutant bearing a deletion of the upp gene was resistant to 5-FU. When a plasmid containing the wild-type upp gene expressed constitutively from the aph(3')-II promoter (promoter for the kanamycin resistance gene in Tn5) was introduced into the upp deletion strain, sensitivity to 5-FU was restored. This observation allowed us to develop a two-step integration and excision strategy for the deletion of genes of interest. Since this inframe deletion strategy does not retain an antibiotic cassette, multiple deletions can be generated in a single strain without the accumulation of genes conferring antibiotic resistances. We used this strategy to generate a deletion strain lacking the endonuclease (hsdR, DVU1703) of a type I restriction-modification system, that we designated JW7035. The transformation efficiency of the JW7035 strain was found to be 100 to 1000 times greater than that of the wild-type strain when stable plasmids were introduced via electroporation.« less

Recycling Flight Hardware Components and Systems to Reduce Next Generation Research Costs

NASA Technical Reports Server (NTRS)

Turner, Wlat

2011-01-01

With the recent 'new direction' put forth by President Obama identifying NASA's new focus in research rather than continuing on a path to return to the Moon and Mars, the focus of work at Kennedy Space Center (KSC) may be changing dramatically. Research opportunities within the micro-gravity community potentially stands at the threshold of resurgence when the new direction of the agency takes hold for the next generation of experimenters. This presentation defines a strategy for recycling flight experiment components or part numbers, in order to reduce research project costs, not just in component selection and fabrication, but in expediting qualification of hardware for flight. A key component of the strategy is effective communication of relevant flight hardware information and available flight hardware components to researchers, with the goal of 'short circuiting' the design process for flight experiments

CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors

PubMed Central

Alonso-Camino, Vanesa; Sánchez-Martín, David; Compte, Marta; Nuñez-Prado, Natalia; Diaz, Rosa M; Vile, Richard; Alvarez-Vallina, Luis

2013-01-01

A human single-chain variable fragment (scFv) antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs). The repertoire was fused to a first-generation T cell receptor ζ (TCRζ)-based chimeric antigen receptor (CAR). We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CARv2) bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CARv2 fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR) and the selection context (cell synapse), which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells. PMID:23695536

Optimal Strategy for Integrated Dynamic Inventory Control and Supplier Selection in Unknown Environment via Stochastic Dynamic Programming

NASA Astrophysics Data System (ADS)

Sutrisno; Widowati; Solikhin

2016-06-01

In this paper, we propose a mathematical model in stochastic dynamic optimization form to determine the optimal strategy for an integrated single product inventory control problem and supplier selection problem where the demand and purchasing cost parameters are random. For each time period, by using the proposed model, we decide the optimal supplier and calculate the optimal product volume purchased from the optimal supplier so that the inventory level will be located at some point as close as possible to the reference point with minimal cost. We use stochastic dynamic programming to solve this problem and give several numerical experiments to evaluate the model. From the results, for each time period, the proposed model was generated the optimal supplier and the inventory level was tracked the reference point well.

Selected Core Thinking Skills and Cognitive Strategy of an Expert and Novice Engineer

ERIC Educational Resources Information Center

Dixon, Raymond A.

2011-01-01

This exploratory study highlights certain differences in the way an expert and a novice engineer used their analyzing and generating skills while solving a fairly ill-structured design problem. The expert tends to use more inferences and elaboration when solving the design problem and the novice tend to use analysis that is focused on the…

Mutasynthesis of fluorinated pactamycin analogues and their antimalarial activity.

PubMed

Almabruk, Khaled H; Lu, Wanli; Li, Yuexin; Abugreen, Mostafa; Kelly, Jane X; Mahmud, Taifo

2013-04-05

A mutasynthetic strategy has been used to generate fluorinated TM-025 and TM-026, two biosynthetically engineered pactamycin analogues produced by Streptomyces pactum ATCC 27456. The fluorinated compounds maintain excellent activity and selectivity toward chloroquine-sensitive and multidrug-resistant strains of malarial parasites as the parent compounds. The results also provide insights into the biosynthesis of 3-aminobenzoic acid in S. pactum.

Landfill gas control at military installations. Final report

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

Shafer, R.A.; Renta-Babb, A.; Bandy, J.T.

1984-01-01

This report provides information useful to Army personnel responsible for recognizing and solving potential problems from gas generated by landfills. Information is provided on recognizing and gauging the magnitude of landfill gas problems; selecting appropriate gas control strategies, procedures, and equipment; use of computer modeling to predict gas production and migration and the success of gas control devices; and safety considerations.

Study of Strategies Used in Online Searching: 2. Positional Logic--an Example of the Importance of Selecting the Right Boolean Operator.

ERIC Educational Resources Information Center

Oldroyd, Betty K.; Schroder, J. J.

1982-01-01

Reviews the advantages and disadvantages of different types of term combination using the positional logic capability of online information retrieval systems and describes a study in which searches for material on "microwave integrated circuits" were conducted in order to find the most economical way of generating the most relevant…

Considerations for IEL Courseware Design and the Next Generation of E-Learning

ERIC Educational Resources Information Center

Sözcü, Ömer Faruk; Ipek, Ismail

2013-01-01

The purpose of this study is to discuss strategies for developing integrated e-learning (IEL) courseware based on instructional design and technology (IDT) models and approaches as well as new discussions of e-learning. For this purpose, the study begins with the selection of one or more IDT models to conduct an e-courseware design including IEL…

Using Computers in the Classroom To Promote Generative Strategies for Reading Comprehension.

ERIC Educational Resources Information Center

Brown, Carol A.

Reading management programs have become very popular in elementary schools. Students select a title from a prescribed reading list, then are tested for recall of facts and events in the story. Students are motivated to read as many titles as possible since they must achieve a certain score to win prizes. Although there have been reports that this…

Strategies to address participant misrepresentation for eligibility in Web-based research.

PubMed

Kramer, Jessica; Rubin, Amy; Coster, Wendy; Helmuth, Eric; Hermos, John; Rosenbloom, David; Moed, Rich; Dooley, Meghan; Kao, Ying-Chia; Liljenquist, Kendra; Brief, Deborah; Enggasser, Justin; Keane, Terence; Roy, Monica; Lachowicz, Mark

2014-03-01

Emerging methodological research suggests that the World Wide Web ("Web") is an appropriate venue for survey data collection, and a promising area for delivering behavioral intervention. However, the use of the Web for research raises concerns regarding sample validity, particularly when the Web is used for recruitment and enrollment. The purpose of this paper is to describe the challenges experienced in two different Web-based studies in which participant misrepresentation threatened sample validity: a survey study and an online intervention study. The lessons learned from these experiences generated three types of strategies researchers can use to reduce the likelihood of participant misrepresentation for eligibility in Web-based research. Examples of procedural/design strategies, technical/software strategies and data analytic strategies are provided along with the methodological strengths and limitations of specific strategies. The discussion includes a series of considerations to guide researchers in the selection of strategies that may be most appropriate given the aims, resources and target population of their studies. Copyright © 2014 John Wiley & Sons, Ltd.

Industrial waste recycling strategies optimization problem: mixed integer programming model and heuristics

NASA Astrophysics Data System (ADS)

Tang, Jiafu; Liu, Yang; Fung, Richard; Luo, Xinggang

2008-12-01

Manufacturers have a legal accountability to deal with industrial waste generated from their production processes in order to avoid pollution. Along with advances in waste recovery techniques, manufacturers may adopt various recycling strategies in dealing with industrial waste. With reuse strategies and technologies, byproducts or wastes will be returned to production processes in the iron and steel industry, and some waste can be recycled back to base material for reuse in other industries. This article focuses on a recovery strategies optimization problem for a typical class of industrial waste recycling process in order to maximize profit. There are multiple strategies for waste recycling available to generate multiple byproducts; these byproducts are then further transformed into several types of chemical products via different production patterns. A mixed integer programming model is developed to determine which recycling strategy and which production pattern should be selected with what quantity of chemical products corresponding to this strategy and pattern in order to yield maximum marginal profits. The sales profits of chemical products and the set-up costs of these strategies, patterns and operation costs of production are considered. A simulated annealing (SA) based heuristic algorithm is developed to solve the problem. Finally, an experiment is designed to verify the effectiveness and feasibility of the proposed method. By comparing a single strategy to multiple strategies in an example, it is shown that the total sales profit of chemical products can be increased by around 25% through the simultaneous use of multiple strategies. This illustrates the superiority of combinatorial multiple strategies. Furthermore, the effects of the model parameters on profit are discussed to help manufacturers organize their waste recycling network.

Analysing key influences over actors' use of evidence in developing policies and strategies in Nigeria: a retrospective study of the Integrated Maternal Newborn and Child Health strategy.

PubMed

Mbachu, Chinyere O; Onwujekwe, Obinna; Chikezie, Ifeanyi; Ezumah, Nkoli; Das, Mahua; Uzochukwu, Benjamin S C

2016-04-12

Evidence-informed policymaking has been promoted as a means of ensuring better outcomes. However, what counts as evidence in policymaking lies within a spectrum of expert knowledge and scientifically generated information. Since not all forms of evidence share an equal validity or weighting for policymakers, it is important to understand the key factors that influence their preferences for different types of evidence in policy and strategy development. A retrospective study was carried out at the national level in Nigeria using a case-study approach to examine the Nigerian Integrated Maternal Newborn and Child Health (IMNCH) strategy. Two frameworks were used for conceptualization and data analysis, namely (1) to analyse the role of evidence in policymaking and (2) the policy triangle. They were used to explore the key contextual and participatory influences on choice of evidence in developing the IMNCH strategy. Data was collected through review of relevant national documents and in-depth interviews of purposively selected key policy and strategic decision makers. Thematic analysis was applied to generate information from collected data. The breadth of evidence used was wide, ranging from expert opinions to systematic reviews. The choice of different types of evidence was found to overlap across actor categories. Key influences over actors' choice of evidence were: (1) perceived robustness of evidence - comprehensive, representative, recent, scientifically sound; (2) roles in evidence process, i.e. their degree and level of participation in evidence generation and dissemination, with regards to their role in the policy process; and (3) contextual factors such as global agenda and influence, timeline for strategy development, availability of resources for evidence generation, and lessons learnt from previous unsuccessful policies/plans. Actors' preferences for different types of evidence for policy are influenced not only by the characteristics of evidence itself, but on actors' roles in the evidence process, their power to influence the policy, and the context in which evidence is used.

[Immunotherapy: a therapeutic revolution against prostate cancer?].

PubMed

Pracht, Marc; Herrera, Fernanda; Tawadros, Thomas; Berthold, Dominik

2013-05-22

The interaction between the immune system and cancer was an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of sipuleucel-T and ipilimumab stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies under development are therapeutic vaccination strategies, such as sipuleucel-T and PROSTVAC-VF, or immune checkpoint blockade of CTLA-4. Improved understanding of the immune responses generated by the development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide new treatment options in prostate cancer.

B-Raf kinase inhibitors: hit enrichment through scaffold hopping.

PubMed

Gopalsamy, Ariamala; Shi, Mengxiao; Hu, Yongbo; Lee, Frederick; Feldberg, Larry; Frommer, Eileen; Kim, Steven; Collins, Karen; Wojciechowicz, Donald; Mallon, Robert

2010-04-15

In continuation of our efforts toward hit identification and optimization for a B-Raf kinase project, we have employed a scaffold hopping strategy. The original HTS hit scaffold pyrazolo[1,5-a]pyrimidine was replaced with different thienopyrimidine and thienopyridine scaffolds to append the optimal pharmacophore moieties in order to generate novel B-raf kinase inhibitors with desirable potency and properties. This strategy led to the identification of additional lead compound 11b which had good enzyme and cell potency, while maintaining selectivity over a number of kinases. Copyright 2010 Elsevier Ltd. All rights reserved.

Functionalizing carbon nitride with heavy atom-free spin converters for enhanced 1 O 2 generation

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

Wu, Wenting; Han, Congcong; Zhang, Qinhua

advanced photosensitizers for singlet oxygen (1O2) generation. However, the intersystem crossing (ISC) process is quite insufficient in carbon nitride, limiting the 1O2 generation. Here, we report a facile and general strategy to confined benzophenone as a heavy atom-free spin converter dopant in carbon nitride via the facile copolymerization. With proper energy level matching between the heavy atom-free spin converter and various ligands based on carbon nitride precursors, the proper combination can decrease the singlet-triplet energy gap (DEST) and hence generate 1O2 effectively. Due to its significant and selectivity for 1O2 generation, the as-prepared carbon nitride-based photosensitizer shows a high selectivemore » photooxidation activity for 1,5-dihydroxy-naphthalene (1,5-DHN). The product yield reached 71.8% after irradiation for 60 min, which was higher than that of cyclometalated PtII complexes (53.6%) in homogeneous photooxidation. This study can broaden the application of carbon nitride in the field of selective heterogeneous photooxidation due to simple operation, low cost, and high efficiency, making it a strong candidate for future industrialization.« less

Which Individuals To Choose To Update the Reference Population? Minimizing the Loss of Genetic Diversity in Animal Genomic Selection Programs.

PubMed

Eynard, Sonia E; Croiseau, Pascal; Laloë, Denis; Fritz, Sebastien; Calus, Mario P L; Restoux, Gwendal

2018-01-04

Genomic selection (GS) is commonly used in livestock and increasingly in plant breeding. Relying on phenotypes and genotypes of a reference population, GS allows performance prediction for young individuals having only genotypes. This is expected to achieve fast high genetic gain but with a potential loss of genetic diversity. Existing methods to conserve genetic diversity depend mostly on the choice of the breeding individuals. In this study, we propose a modification of the reference population composition to mitigate diversity loss. Since the high cost of phenotyping is the limiting factor for GS, our findings are of major economic interest. This study aims to answer the following questions: how would decisions on the reference population affect the breeding population, and how to best select individuals to update the reference population and balance maximizing genetic gain and minimizing loss of genetic diversity? We investigated three updating strategies for the reference population: random, truncation, and optimal contribution (OC) strategies. OC maximizes genetic merit for a fixed loss of genetic diversity. A French Montbéliarde dairy cattle population with 50K SNP chip genotypes and simulations over 10 generations were used to compare these different strategies using milk production as the trait of interest. Candidates were selected to update the reference population. Prediction bias and both genetic merit and diversity were measured. Changes in the reference population composition slightly affected the breeding population. Optimal contribution strategy appeared to be an acceptable compromise to maintain both genetic gain and diversity in the reference and the breeding populations. Copyright © 2018 Eynard et al.

Drought-avoiding plants with low water use can achieve high rainfall retention without jeopardising survival on green roofs.

PubMed

Szota, Christopher; Farrell, Claire; Williams, Nicholas S G; Arndt, Stefan K; Fletcher, Tim D

2017-12-15

Green roofs are increasingly being used among the suite of tools designed to reduce the volume of surface water runoff generated by cities. Plants provide the primary mechanism for restoring the rainfall retention capacity of green roofs, but selecting plants with high water use is likely to increase drought stress. Using empirically-derived plant physiological parameters, we used a water balance model to assess the trade-off between rainfall retention and plant drought stress under a 30-year climate scenario. We compared high and low water users with either drought avoidance or drought tolerance strategies. Green roofs with low water-using, drought-avoiding species achieved high rainfall retention (66-81%) without experiencing significant drought stress. Roofs planted with other strategies showed high retention (72-90%), but they also experienced >50days of drought stress per year. However, not all species with the same strategy behaved similarly, therefore selecting plants based on water use and drought strategy alone does not guarantee survival in shallow substrates where drought stress can develop quickly. Despite this, it is more likely that green roofs will achieve high rainfall retention with minimal supplementary irrigation if planted with low water users with drought avoidance strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

MSEBAG: a dynamic classifier ensemble generation based on `minimum-sufficient ensemble' and bagging

NASA Astrophysics Data System (ADS)

Chen, Lei; Kamel, Mohamed S.

2016-01-01

In this paper, we propose a dynamic classifier system, MSEBAG, which is characterised by searching for the 'minimum-sufficient ensemble' and bagging at the ensemble level. It adopts an 'over-generation and selection' strategy and aims to achieve a good bias-variance trade-off. In the training phase, MSEBAG first searches for the 'minimum-sufficient ensemble', which maximises the in-sample fitness with the minimal number of base classifiers. Then, starting from the 'minimum-sufficient ensemble', a backward stepwise algorithm is employed to generate a collection of ensembles. The objective is to create a collection of ensembles with a descending fitness on the data, as well as a descending complexity in the structure. MSEBAG dynamically selects the ensembles from the collection for the decision aggregation. The extended adaptive aggregation (EAA) approach, a bagging-style algorithm performed at the ensemble level, is employed for this task. EAA searches for the competent ensembles using a score function, which takes into consideration both the in-sample fitness and the confidence of the statistical inference, and averages the decisions of the selected ensembles to label the test pattern. The experimental results show that the proposed MSEBAG outperforms the benchmarks on average.

A systems-level approach for metabolic engineering of yeast cell factories.

PubMed

Kim, Il-Kwon; Roldão, António; Siewers, Verena; Nielsen, Jens

2012-03-01

The generation of novel yeast cell factories for production of high-value industrial biotechnological products relies on three metabolic engineering principles: design, construction, and analysis. In the last two decades, strong efforts have been put on developing faster and more efficient strategies and/or technologies for each one of these principles. For design and construction, three major strategies are described in this review: (1) rational metabolic engineering; (2) inverse metabolic engineering; and (3) evolutionary strategies. Independent of the selected strategy, the process of designing yeast strains involves five decision points: (1) choice of product, (2) choice of chassis, (3) identification of target genes, (4) regulating the expression level of target genes, and (5) network balancing of the target genes. At the construction level, several molecular biology tools have been developed through the concept of synthetic biology and applied for the generation of novel, engineered yeast strains. For comprehensive and quantitative analysis of constructed strains, systems biology tools are commonly used and using a multi-omics approach. Key information about the biological system can be revealed, for example, identification of genetic regulatory mechanisms and competitive pathways, thereby assisting the in silico design of metabolic engineering strategies for improving strain performance. Examples on how systems and synthetic biology brought yeast metabolic engineering closer to industrial biotechnology are described in this review, and these examples should demonstrate the potential of a systems-level approach for fast and efficient generation of yeast cell factories. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Cloud computing task scheduling strategy based on improved differential evolution algorithm

NASA Astrophysics Data System (ADS)

Ge, Junwei; He, Qian; Fang, Yiqiu

2017-04-01

In order to optimize the cloud computing task scheduling scheme, an improved differential evolution algorithm for cloud computing task scheduling is proposed. Firstly, the cloud computing task scheduling model, according to the model of the fitness function, and then used improved optimization calculation of the fitness function of the evolutionary algorithm, according to the evolution of generation of dynamic selection strategy through dynamic mutation strategy to ensure the global and local search ability. The performance test experiment was carried out in the CloudSim simulation platform, the experimental results show that the improved differential evolution algorithm can reduce the cloud computing task execution time and user cost saving, good implementation of the optimal scheduling of cloud computing tasks.

Environmental evaluation of alternatives for long-term management of Defense high-level radioactive wastes at the Idaho Chemical Processing Plant

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

Not Available

1982-09-01

The U.S. Department of Energy (DOE) is considering the selection of a strategy for the long-term management of the defense high-level wastes at the Idaho Chemical Processing Plant (ICPP). This report describes the environmental impacts of alternative strategies. These alternative strategies include leaving the calcine in its present form at the Idaho National Engineering Laboratory (INEL), or retrieving and modifying the calcine to a more durable waste form and disposing of it either at the INEL or in an offsite repository. This report addresses only the alternatives for a program to manage the high-level waste generated at the ICPP. 24more » figures, 60 tables.« less

A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis.

PubMed

Tran-Duy, An; Boonen, Annelies; van de Laar, Mart A F J; Franke, Angelinus C; Severens, Johan L

2011-12-01

To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Discrete event simulation paradigm was selected for model development. Drug efficacy was modelled as changes in disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis Functional Index (BASFI)), which were linked to costs and health utility using statistical models fitted based on an observational AS cohort. Published clinical data were used to estimate drug efficacy and time to events. Two strategies were compared: (1) five available non-steroidal anti-inflammatory drugs (strategy 1) and (2) same as strategy 1 plus two tumour necrosis factor α inhibitors (strategy 2). 13,000 patients were followed up individually until death. For probability sensitivity analysis, Monte Carlo simulations were performed with 1000 sets of parameters sampled from the appropriate probability distributions. The models successfully generated valid data on treatments, BASDAI, BASFI, utility, quality-adjusted life years (QALYs) and costs at time points with intervals of 1-3 months during the simulation length of 70 years. Incremental cost per QALY gained in strategy 2 compared with strategy 1 was €35,186. At a willingness-to-pay threshold of €80,000, it was 99.9% certain that strategy 2 was cost-effective. The modelling framework provides great flexibility to implement complex algorithms representing treatment selection, disease progression and changes in costs and utilities over time of patients with AS. Results obtained from the simulation are plausible.

Pharmacophore modeling, docking, and principal component analysis based clustering: combined computer-assisted approaches to identify new inhibitors of the human rhinovirus coat protein.

PubMed

Steindl, Theodora M; Crump, Carolyn E; Hayden, Frederick G; Langer, Thierry

2005-10-06

The development and application of a sophisticated virtual screening and selection protocol to identify potential, novel inhibitors of the human rhinovirus coat protein employing various computer-assisted strategies are described. A large commercially available database of compounds was screened using a highly selective, structure-based pharmacophore model generated with the program Catalyst. A docking study and a principal component analysis were carried out within the software package Cerius and served to validate and further refine the obtained results. These combined efforts led to the selection of six candidate structures, for which in vitro anti-rhinoviral activity could be shown in a biological assay.

Evolution of precopulatory and post-copulatory strategies of inbreeding avoidance and associated polyandry.

PubMed

Duthie, A B; Bocedi, G; Germain, R R; Reid, J M

2018-01-01

Inbreeding depression is widely hypothesized to drive adaptive evolution of precopulatory and post-copulatory mechanisms of inbreeding avoidance, which in turn are hypothesized to affect evolution of polyandry (i.e. female multiple mating). However, surprisingly little theory or modelling critically examines selection for precopulatory or post-copulatory inbreeding avoidance, or both strategies, given evolutionary constraints and direct costs, or examines how evolution of inbreeding avoidance strategies might feed back to affect evolution of polyandry. Selection for post-copulatory inbreeding avoidance, but not for precopulatory inbreeding avoidance, requires polyandry, whereas interactions between precopulatory and post-copulatory inbreeding avoidance might cause functional redundancy (i.e. 'degeneracy') potentially generating complex evolutionary dynamics among inbreeding strategies and polyandry. We used individual-based modelling to quantify evolution of interacting precopulatory and post-copulatory inbreeding avoidance and associated polyandry given strong inbreeding depression and different evolutionary constraints and direct costs. We found that evolution of post-copulatory inbreeding avoidance increased selection for initially rare polyandry and that evolution of a costly inbreeding avoidance strategy became negligible over time given a lower-cost alternative strategy. Further, fixed precopulatory inbreeding avoidance often completely precluded evolution of polyandry and hence post-copulatory inbreeding avoidance, but fixed post-copulatory inbreeding avoidance did not preclude evolution of precopulatory inbreeding avoidance. Evolution of inbreeding avoidance phenotypes and associated polyandry is therefore affected by evolutionary feedbacks and degeneracy. All else being equal, evolution of precopulatory inbreeding avoidance and resulting low polyandry is more likely when post-copulatory inbreeding avoidance is precluded or costly, and evolution of post-copulatory inbreeding avoidance greatly facilitates evolution of costly polyandry. © The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.

Adaptation of Decoy Fusion Strategy for Existing Multi-Stage Search Workflows

NASA Astrophysics Data System (ADS)

Ivanov, Mark V.; Levitsky, Lev I.; Gorshkov, Mikhail V.

2016-09-01

A number of proteomic database search engines implement multi-stage strategies aiming at increasing the sensitivity of proteome analysis. These approaches often employ a subset of the original database for the secondary stage of analysis. However, if target-decoy approach (TDA) is used for false discovery rate (FDR) estimation, the multi-stage strategies may violate the underlying assumption of TDA that false matches are distributed uniformly across the target and decoy databases. This violation occurs if the numbers of target and decoy proteins selected for the second search are not equal. Here, we propose a method of decoy database generation based on the previously reported decoy fusion strategy. This method allows unbiased TDA-based FDR estimation in multi-stage searches and can be easily integrated into existing workflows utilizing popular search engines and post-search algorithms.

A kinase-focused compound collection: compilation and screening strategy.

PubMed

Sun, Dongyu; Chuaqui, Claudio; Deng, Zhan; Bowes, Scott; Chin, Donovan; Singh, Juswinder; Cullen, Patrick; Hankins, Gretchen; Lee, Wen-Cherng; Donnelly, Jason; Friedman, Jessica; Josiah, Serene

2006-06-01

Lead identification by high-throughput screening of large compound libraries has been supplemented with virtual screening and focused compound libraries. To complement existing approaches for lead identification at Biogen Idec, a kinase-focused compound collection was designed, developed and validated. Two strategies were adopted to populate the compound collection: a ligand shape-based virtual screening and a receptor-based approach (structural interaction fingerprint). Compounds selected with the two approaches were cherry-picked from an existing high-throughput screening compound library, ordered from suppliers and supplemented with specific medicinal compounds from internal programs. Promising hits and leads have been generated from the kinase-focused compound collection against multiple kinase targets. The principle of the collection design and screening strategy was validated and the use of the kinase-focused compound collection for lead identification has been added to existing strategies.

Amorphization strategy affects the stability and supersaturation profile of amorphous drug nanoparticles.

PubMed

Cheow, Wean Sin; Kiew, Tie Yi; Yang, Yue; Hadinoto, Kunn

2014-05-05

Amorphous drug nanoparticles have recently emerged as a promising bioavailability enhancement strategy of poorly soluble drugs attributed to the high supersaturation solubility generated by the amorphous state and fast dissolution afforded by the nanoparticles. Herein we examine the effects of two amorphization strategies in the nanoscale, i.e., (1) molecular mobility restrictions and (2) high energy surface occupation, both by polymer excipient stabilizers, on the (i) morphology, (ii) colloidal stability, (iii) drug loading, (iv) amorphous state stability after three-month storage, and (v) in vitro supersaturation profiles, using itraconazole (ITZ) as the model drug. Drug-polyelectrolyte complexation is employed in the first strategy to prepare amorphous ITZ nanoparticles using dextran sulfate as the polyelectrolyte (ITZ nanoplex), while the second strategy employs pH-shift precipitation using hydroxypropylmethylcellulose as the surface stabilizer (nano-ITZ), with both strategies resulting in >90% ITZ utilization. Both amorphous ITZ nanoparticles share similar morphology (∼300 nm spheres) with the ITZ nanoplex exhibiting better colloidal stability, albeit at lower ITZ loading (65% versus 94%), due to the larger stabilizer amount used. The ITZ nanoplex also exhibits superior amorphous state stability, attributed to the ITZ molecular mobility restriction by electrostatic complexation with dextran sulfate. The higher stability, however, is obtained at the expense of slower supersaturation generation, which is maintained over a prolonged period, compared to the nano-ITZ. The present results signify the importance of selecting the optimal amorphization strategy, in addition to formulating the excipient stabilizers, to produce amorphous drug nanoparticles having the desired characteristics.

Variable speed generator application on the MOD-5A 7.3 mW wind turbine generator

NASA Technical Reports Server (NTRS)

Barton, Robert S.

1995-01-01

This paper describes the application of a Scherbiustat type variable speed subsystem in the MOD-5A Wind Turbine Generator. As designed by General Electric Company, Advanced Energy Programs Department, under contract DEN3-153 with NASA Lewis Research Center and DOE, the MOD-5A utilizes the subsystem for both starting assistance in a motoring mode and generation in a controlled airgap torque mode. Reactive power control is also provided. The Scherbiustat type arrangement of a wound rotor machine with a cycloconverter in the rotor circuit was selected after an evaluation of variable speed technologies that followed a system evaluation of drivetrain cost and risk. The paper describes the evaluation factors considered, the results of the evaluations and summarizes operating strategy and performance simulations.

From Physics Model to Results: An Optimizing Framework for Cross-Architecture Code Generation

DOE PAGES

Blazewicz, Marek; Hinder, Ian; Koppelman, David M.; ...

2013-01-01

Starting from a high-level problem description in terms of partial differential equations using abstract tensor notation, the Chemora framework discretizes, optimizes, and generates complete high performance codes for a wide range of compute architectures. Chemora extends the capabilities of Cactus, facilitating the usage of large-scale CPU/GPU systems in an efficient manner for complex applications, without low-level code tuning. Chemora achieves parallelism through MPI and multi-threading, combining OpenMP and CUDA. Optimizations include high-level code transformations, efficient loop traversal strategies, dynamically selected data and instruction cache usage strategies, and JIT compilation of GPU code tailored to the problem characteristics. The discretization ismore » based on higher-order finite differences on multi-block domains. Chemora's capabilities are demonstrated by simulations of black hole collisions. This problem provides an acid test of the framework, as the Einstein equations contain hundreds of variables and thousands of terms.« less

Rapid access to compound libraries through flow technology: fully automated synthesis of a 3-aminoindolizine library via orthogonal diversification.

PubMed

Lange, Paul P; James, Keith

2012-10-08

A novel methodology for the synthesis of druglike heterocycle libraries has been developed through the use of flow reactor technology. The strategy employs orthogonal modification of a heterocyclic core, which is generated in situ, and was used to construct both a 25-membered library of druglike 3-aminoindolizines, and selected examples of a 100-member virtual library. This general protocol allows a broad range of acylation, alkylation and sulfonamidation reactions to be performed in conjunction with a tandem Sonogashira coupling/cycloisomerization sequence. All three synthetic steps were conducted under full automation in the flow reactor, with no handling or isolation of intermediates, to afford the desired products in good yields. This fully automated, multistep flow approach opens the way to highly efficient generation of druglike heterocyclic systems as part of a lead discovery strategy or within a lead optimization program.

Photogeneration of singlet oxygen by the phenothiazine derivatives covalently bound to the surface-modified glassy carbon

NASA Astrophysics Data System (ADS)

Blacha-Grzechnik, Agata; Piwowar, Katarzyna; Krukiewicz, Katarzyna; Koscielniak, Piotr; Szuber, Jacek; Zak, Jerzy K.

2016-05-01

The selected group of four amine-derivatives of phenothiazine was covalently grafted to the glassy carbon surface in the four-step procedure consisting of the electrochemical reduction of the diazonium salt followed by the electrochemical and chemical post-modification steps. The proposed strategy involves the bonding of linker molecule to which the photosensitizer is attached. The synthesized organic layers were characterized by means of cyclic voltammetry, XPS and Raman Spectroscopy. It was shown that the phenothiazines immobilized via proposed strategy retain their photochemical properties and are able to generate 1O2 when activated by the laser radiation. The effectiveness of in situ singlet oxygen generation by those new solid photoactive materials was determined by means of UVVis spectroscopy. The reported, covalently modified solid surfaces may find their application as the singlet oxygen photogenerators in the fine chemicals' synthesis or in the wastewater treatment.

Assembly of barcode-like nucleic acid nanostructures.

PubMed

Wang, Pengfei; Tian, Cheng; Li, Xiang; Mao, Chengde

2014-10-15

Barcode-like (BC) nanopatterns from programmed self-assembly of nucleic acids (DNA and RNA) are reported. BC nanostructures are generated by the introduction of open spaces at selected sites to an otherwise closely packed, plain, rectangle nucleic acid nanostructure. This strategy is applied to nanostructures assembled from both origami approach and single stranded tile approach. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Direct stenting versus balloon predilation: Jury is still out.

PubMed

Belardi, Jorge A; Albertal, Mariano

2017-08-01

Compared to balloon predilation, direct stenting (DS) shortens procedural time and reduces radiation and contrast exposure. A meta-analysis that included 7 studies comparing these 2 strategies revealed lower adverse event rate with DS. Studies included in the present meta-analysis were mostly observational and utilized first generation drug-eluting stent. Patient and lesion selection may explain these positive results. © 2017 Wiley Periodicals, Inc.

Non-communicable diseases and global health governance: enhancing global processes to improve health development

PubMed Central

Magnusson, Roger S

2007-01-01

This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy. PMID:17519005

Non-communicable diseases and global health governance: enhancing global processes to improve health development.

PubMed

Magnusson, Roger S

2007-05-22

This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy.

Current advances in the generation of human iPS cells: implications in cell-based regenerative medicine.

PubMed

Revilla, Ana; González, Clara; Iriondo, Amaia; Fernández, Bárbara; Prieto, Cristina; Marín, Carlos; Liste, Isabel

2016-11-01

Over the last few years, the generation of induced pluripotent stem cells (iPSCs) from human somatic cells has proved to be one of the most potentially useful discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to study the pathology of different diseases and for drug screening. However, several limitations still affect the possibility of applying iPS cell-based technology in therapeutic prospects. Most strategies for iPSCs generation are based on gene delivery via retroviral or lentiviral vectors, which integrate into the host's cell genome, causing a remarkable risk of insertional mutagenesis and oncogenic transformation. To avoid such risks, significant advances have been made with non-integrative reprogramming strategies. On the other hand, although many different kinds of somatic cells have been employed to generate iPSCs, there is still no consensus about the ideal type of cell to be reprogrammed. In this review we present the recent advances in the generation of human iPSCs, discussing their advantages and limitations in terms of safety and efficiency. We also present a selection of somatic cell sources, considering their capability to be reprogrammed and tissue accessibility. From a translational medicine perspective, these two topics will provide evidence to elucidate the most suitable combination of reprogramming strategy and cell source to be applied in each human iPSC-based therapy. The wide variety of diseases this technology could treat opens a hopeful future for regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Catalysis Meets Nonthermal Separation for the Production of (Alkyl)phenols and Hydrocarbons from Pyrolysis Oil.

PubMed

Cao, Zhengwen; Engelhardt, Jan; Dierks, Michael; Clough, Matthew T; Wang, Guang-Hui; Heracleous, Eleni; Lappas, Angelos; Rinaldi, Roberto; Schüth, Ferdi

2017-02-20

A simple and efficient hydrodeoxygenation strategy is described to selectively generate and separate high-value alkylphenols from pyrolysis bio-oil, produced directly from lignocellulosic biomass. The overall process is efficient and only requires low pressures of hydrogen gas (5 bar). Initially, an investigation using model compounds indicates that MoC x /C is a promising catalyst for targeted hydrodeoxygenation, enabling selective retention of the desired Ar-OH substituents. By applying this procedure to pyrolysis bio-oil, the primary products (phenol/4-alkylphenols and hydrocarbons) are easily separable from each other by short-path column chromatography, serving as potential valuable feedstocks for industry. The strategy requires no prior fractionation of the lignocellulosic biomass, no further synthetic steps, and no input of additional (e.g., petrochemical) platform molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combinatorial microfluidic droplet engineering for biomimetic material synthesis

PubMed Central

Bawazer, Lukmaan A.; McNally, Ciara S.; Empson, Christopher J.; Marchant, William J.; Comyn, Tim P.; Niu, Xize; Cho, Soongwon; McPherson, Michael J.; Binks, Bernard P.; deMello, Andrew; Meldrum, Fiona C.

2016-01-01

Although droplet-based systems are used in a wide range of technologies, opportunities for systematically customizing their interface chemistries remain relatively unexplored. This article describes a new microfluidic strategy for rapidly tailoring emulsion droplet compositions and properties. The approach uses a simple platform for screening arrays of droplet-based microfluidic devices and couples this with combinatorial selection of the droplet compositions. Through the application of genetic algorithms over multiple screening rounds, droplets with target properties can be rapidly generated. The potential of this method is demonstrated by creating droplets with enhanced stability, where this is achieved by selecting carrier fluid chemistries that promote titanium dioxide formation at the droplet interfaces. The interface is a mixture of amorphous and crystalline phases, and the resulting composite droplets are biocompatible, supporting in vitro protein expression in their interiors. This general strategy will find widespread application in advancing emulsion properties for use in chemistry, biology, materials, and medicine. PMID:27730209

Field Phenotyping Strategies and Breeding for Adaptation of Rice to Drought†

PubMed Central

Fischer, Ken S.; Fukai, Shu; Kumar, Arvind; Leung, Hei; Jongdee, Boonrat

2012-01-01

This paper is a section of the book “Drought phenotyping in crops: from theory to practice” (Monneveux Philippe and Ribaut Jean-Marcel eds, published by CGIAR Generation Challenge Programme. Texcoco, Mexico). The section describes recent experience in drought phenotyping in rice which is one of the most drought-susceptible crops. The section contains genetic and genomic resources for drought adaptation and methods for selection of drought-resistant varieties in rice. In appendix, there is experience from Thailand on integration of direct selection for grain yield and physiological traits to confer drought resistance. PMID:22934036

Frontal dynamic aphasia in progressive supranuclear palsy: Distinguishing between generation and fluent sequencing of novel thoughts.

PubMed

Robinson, Gail A; Spooner, Donna; Harrison, William J

2015-10-01

Frontal dynamic aphasia is characterised by a profound reduction in spontaneous speech despite well-preserved naming, repetition and comprehension. Since Luria (1966, 1970) designated this term, two main forms of dynamic aphasia have been identified: one, a language-specific selection deficit at the level of word/sentence generation, associated with left inferior frontal lesions; and two, a domain-general impairment in generating multiple responses or connected speech, associated with more extensive bilateral frontal and/or frontostriatal damage. Both forms of dynamic aphasia have been interpreted as arising due to disturbances in early prelinguistic conceptual preparation mechanisms that are critical for language production. We investigate language-specific and domain-general accounts of dynamic aphasia and address two issues: one, whether deficits in multiple conceptual preparation mechanisms can co-occur; and two, the contribution of broader cognitive processes such as energization, the ability to initiate and sustain response generation over time, to language generation failure. Thus, we report patient WAL who presented with frontal dynamic aphasia in the context of progressive supranuclear palsy (PSP). WAL was given a series of experimental tests that showed that his dynamic aphasia was not underpinned by a language-specific deficit in selection or in microplanning. By contrast, WAL presented with a domain-general deficit in fluent sequencing of novel thoughts. The latter replicated the pattern documented in a previous PSP patient (Robinson, et al., 2006); however, unique to WAL, generating novel thoughts was impaired but there was no evidence of a sequencing deficit because perseveration was absent. Thus, WAL is the first unequivocal case to show a distinction between novel thought generation and subsequent fluent sequencing. Moreover, WAL's generation deficit encompassed verbal and non-verbal responses, showing a similar (but more profoundly reduced) pattern of performance to frontal patients with an energization deficit. In addition to impaired generation of novel thoughts, WAL presented with a concurrent strategy generation deficit, both falling within the second form of dynamic aphasia comprised of domain-general conceptual preparation mechanisms. Thus, within this second form of dynamic aphasia, concurrent deficits can co-occur. Overall, WAL presented with the second form of dynamic aphasia and was impaired in the generation of novel thoughts and internally-generated strategies, in the context of PSP and bilateral frontostriatal damage. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Peptide selection and antibody generation for the prospective immunorecognition of Cry1Ab16 protein of transgenic maize.

PubMed

Costa, Joana; Marani, Mariela M; Grazina, Liliana; Villa, Caterina; Meira, Liliana; Oliveira, M Beatriz P P; Leite, José R S A; Mafra, Isabel

2017-09-15

The introduction of genes isolated from different Bacillus thuringiensis strains to express Cry-type toxins in transgenic crops is a common strategy to confer insect resistance traits. This work intended to extensively in silico analyse Cry1A(b)16 protein for the identification of peptide markers for the biorecognition of transgenic crops. By combining two different strategies based on several bioinformatic tools for linear epitope prediction, a set of seven peptides was successfully selected as potential Cry1A(b)16 immunogens. For the prediction of conformational epitopes, Cry1A(b)16 models were built on the basis of three independent templates of homologue proteins of Cry1A(a) and Cry1A(c) using an integrated approach. PcH_736-746 and PcH_876-886 peptides were selected as the best candidates, being synthesised and used for the production of polyclonal antibodies. To the best of our knowledge, this is the first attempt of selecting and defining linear peptides as immunogenic markers of Cry1A(b)-type toxins in transgenic maize. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of genome-wide selection strategies to identify furfural tolerance genes in Escherichia coli.

PubMed

Glebes, Tirzah Y; Sandoval, Nicholas R; Gillis, Jacob H; Gill, Ryan T

2015-01-01

Engineering both feedstock and product tolerance is important for transitioning towards next-generation biofuels derived from renewable sources. Tolerance to chemical inhibitors typically results in complex phenotypes, for which multiple genetic changes must often be made to confer tolerance. Here, we performed a genome-wide search for furfural-tolerant alleles using the TRackable Multiplex Recombineering (TRMR) method (Warner et al. (2010), Nature Biotechnology), which uses chromosomally integrated mutations directed towards increased or decreased expression of virtually every gene in Escherichia coli. We employed various growth selection strategies to assess the role of selection design towards growth enrichments. We also compared genes with increased fitness from our TRMR selection to those from a previously reported genome-wide identification study of furfural tolerance genes using a plasmid-based genomic library approach (Glebes et al. (2014) PLOS ONE). In several cases, growth improvements were observed for the chromosomally integrated promoter/RBS mutations but not for the plasmid-based overexpression constructs. Through this assessment, four novel tolerance genes, ahpC, yhjH, rna, and dicA, were identified and confirmed for their effect on improving growth in the presence of furfural. © 2014 Wiley Periodicals, Inc.

Public goods games in populations with fluctuating size.

PubMed

McAvoy, Alex; Fraiman, Nicolas; Hauert, Christoph; Wakeley, John; Nowak, Martin A

2018-05-01

Many mathematical frameworks of evolutionary game dynamics assume that the total population size is constant and that selection affects only the relative frequency of strategies. Here, we consider evolutionary game dynamics in an extended Wright-Fisher process with variable population size. In such a scenario, it is possible that the entire population becomes extinct. Survival of the population may depend on which strategy prevails in the game dynamics. Studying cooperative dilemmas, it is a natural feature of such a model that cooperators enable survival, while defectors drive extinction. Although defectors are favored for any mixed population, random drift could lead to their elimination and the resulting pure-cooperator population could survive. On the other hand, if the defectors remain, then the population will quickly go extinct because the frequency of cooperators steadily declines and defectors alone cannot survive. In a mutation-selection model, we find that (i) a steady supply of cooperators can enable long-term population survival, provided selection is sufficiently strong, and (ii) selection can increase the abundance of cooperators but reduce their relative frequency. Thus, evolutionary game dynamics in populations with variable size generate a multifaceted notion of what constitutes a trait's long-term success. Copyright © 2018 Elsevier Inc. All rights reserved.

Optimizing the design of small-sized nucleus breeding programs for dairy cattle with minimal performance recording.

PubMed

Kariuki, C M; Komen, H; Kahi, A K; van Arendonk, J A M

2014-12-01

Dairy cattle breeding programs in developing countries are constrained by minimal and erratic pedigree and performance recording on cows on commercial farms. Small-sized nucleus breeding programs offer a viable alternative. Deterministic simulations using selection index theory were performed to determine the optimum design for small-sized nucleus schemes for dairy cattle. The nucleus was made up of 197 bulls and 243 cows distributed in 8 non-overlapping age classes. Each year 10 sires and 100 dams were selected to produce the next generation of male and female selection candidates. Conception rates and sex ratio were fixed at 0.90 and 0.50, respectively, translating to 45 male and 45 female candidates joining the nucleus per year. Commercial recorded dams provided information for genetic evaluation of selection candidates (bulls) in the nucleus. Five strategies were defined: nucleus records only [within-nucleus dam performance (DP)], progeny records in addition to nucleus records [progeny testing (PT)], genomic information only [genomic selection (GS)], dam performance records in addition to genomic information (GS+DP), and progeny records in addition to genomic information (GS+PT). Alternative PT, GS, GS+DP, and GS+PT schemes differed in the number of progeny per sire and size of reference population. The maximum number of progeny records per sire was 30, and the maximum size of the reference population was 5,000. Results show that GS schemes had higher responses and lower accuracies compared with other strategies, with the higher response being due to shorter generation intervals. Compared with similar sized progeny-testing schemes, genomic-selection schemes would have lower accuracies but these are offset by higher responses per year, which might provide additional incentive for farmers to participate in recording. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Use of Agrobacterium rhizogenes strain 18r12v and paromomycin selection for transformation of Brachypodium distachyon and Brachypodium sylvaticum

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

Collier, Ray; Bragg, Jennifer; Hernandez, Bryan T.

In this study, the genetic transformation of monocot grasses is a resource intensive process, the quality and efficiency of which is dependent in part upon the method of DNA introduction, as well as the ability to effectively separate transformed from wildtype tissue. Agrobacterium-mediated transformation of Brachypodium has relied mainly on Agrobacterium tumefaciens strain AGL1. Currently the antibiotic hygromycin B has been the selective agent of choice for robust identification of transgenic calli in Brachypodium distachyon and Brachypodium sylvaticum but few other chemicals have been shown to work as well for selection of transgenic Brachypodium cells in tissue culture. This studymore » demonstrates that Agrobacterium rhizogenes strain 18r12v and paromomycin selection can be successfully used for the efficient generation of transgenic B. distachyon and B. sylvaticurn. Additionally we observed that the transformation rates were similar to or higher than those obtained with A. turnefaciens strain AGL1 and hygromycin selection. The A. rhizogenes strain 18r12v harboring the pARS1 binary vector and paromomycin selection is an effective means of generating transgenic Brachypodium plants. This novel approach will facilitate the transgenic complementation of T-DNA knockout mutants of B. distachyon which were created using hygromycin selection, as well as aid the implementation of more complex genome manipulation strategies which require multiple rounds of transformation.« less

Use of Agrobacterium rhizogenes strain 18r12v and paromomycin selection for transformation of Brachypodium distachyon and Brachypodium sylvaticum

DOE PAGES

Collier, Ray; Bragg, Jennifer; Hernandez, Bryan T.; ...

2016-05-24

In this study, the genetic transformation of monocot grasses is a resource intensive process, the quality and efficiency of which is dependent in part upon the method of DNA introduction, as well as the ability to effectively separate transformed from wildtype tissue. Agrobacterium-mediated transformation of Brachypodium has relied mainly on Agrobacterium tumefaciens strain AGL1. Currently the antibiotic hygromycin B has been the selective agent of choice for robust identification of transgenic calli in Brachypodium distachyon and Brachypodium sylvaticum but few other chemicals have been shown to work as well for selection of transgenic Brachypodium cells in tissue culture. This studymore » demonstrates that Agrobacterium rhizogenes strain 18r12v and paromomycin selection can be successfully used for the efficient generation of transgenic B. distachyon and B. sylvaticurn. Additionally we observed that the transformation rates were similar to or higher than those obtained with A. turnefaciens strain AGL1 and hygromycin selection. The A. rhizogenes strain 18r12v harboring the pARS1 binary vector and paromomycin selection is an effective means of generating transgenic Brachypodium plants. This novel approach will facilitate the transgenic complementation of T-DNA knockout mutants of B. distachyon which were created using hygromycin selection, as well as aid the implementation of more complex genome manipulation strategies which require multiple rounds of transformation.« less

A Landscape Approach to Invasive Species Management.

PubMed

Lurgi, Miguel; Wells, Konstans; Kennedy, Malcolm; Campbell, Susan; Fordham, Damien A

2016-01-01

Biological invasions are not only a major threat to biodiversity, they also have major impacts on local economies and agricultural production systems. Once established, the connection of local populations into metapopulation networks facilitates dispersal at landscape scales, generating spatial dynamics that can impact the outcome of pest-management actions. Much planning goes into landscape-scale invasive species management. However, effective management requires knowledge on the interplay between metapopulation network topology and management actions. We address this knowledge gap using simulation models to explore the effectiveness of two common management strategies, applied across different extents and according to different rules for selecting target localities in metapopulations with different network topologies. These management actions are: (i) general population reduction, and (ii) reduction of an obligate resource. The reduction of an obligate resource was generally more efficient than population reduction for depleting populations at landscape scales. However, the way in which local populations are selected for management is important when the topology of the metapopulation is heterogeneous in terms of the distribution of connections among local populations. We tested these broad findings using real-world scenarios of European rabbits (Oryctolagus cuniculus) infesting agricultural landscapes in Western Australia. Although management strategies targeting central populations were more effective in simulated heterogeneous metapopulation structures, no difference was observed in real-world metapopulation structures that are highly homogeneous. In large metapopulations with high proximity and connectivity of neighbouring populations, different spatial management strategies yield similar outcomes. Directly considering spatial attributes in pest-management actions will be most important for metapopulation networks with heterogeneously distributed links. Our modelling framework provides a simple approach for identifying the best possible management strategy for invasive species based on metapopulation structure and control capacity. This information can be used by managers trying to devise efficient landscape-oriented management strategies for invasive species and can also generate insights for conservation purposes.

Aquatic plant control research

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

Pryfogle, P.A.; Rinehart, B.N.; Ghio, E.G.

The Northwest region of the United States contains extensive canal systems that transport water for hydropower generation. Nuisance plants, including algae, that grow in these systems reduce their hydraulic capacity through water displacement and increased surface friction. Most control methods are applied in an ad hoc fashion. The goal of this work is to develop cost-effective, environmentally sound, long-term management strategies to prevent and control nuisance algal growth. This paper reports on a multi-year study, performed in collaboration with the Pacific Gas & Electric Company, to investigate algal growth in their canal systems, and to evaluate various control methodologies. Threemore » types of controls, including mechanical, biological and chemical treatment, were selected for testing and evaluation. As part of this study, water quality data were collected and algal communities were sampled from numerous stations throughout the distribution system at regular intervals. This study resulted in a more comprehensive understanding of conditions leading to the development of nuisance algal growth, a better informed selection of treatment plans, and improved evaluation of the effectiveness for the control strategies selected for testing.« less

Generating gene knockout rats by homologous recombination in embryonic stem cells

PubMed Central

Tong, Chang; Huang, Guanyi; Ashton, Charles; Li, Ping; Ying, Qi-Long

2013-01-01

We describe here a detailed protocol for generating gene knockout rats by homologous recombination in embryonic stem (ES) cells. This protocol comprises the following procedures: derivation and expansion of rat ES cells, construction of gene-targeting vectors, generation of gene-targeted rat ES cells and, finally, production of gene-targeted rats. The major differences between this protocol and the classical mouse gene-targeting protocol include ES cell culture methods, drug selection scheme, colony picking and screening strategies. This ES cell–based gene-targeting technique allows sophisticated genetic modifications to be performed in the rat, as many laboratories have been doing in the mouse for the past two decades. Recently we used this protocol to generate Tp53 (also known as p53) gene knockout rats. The entire process requires ~1 year to complete, from derivation of ES cells to generation of knockout rats. PMID:21637202

Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy.

PubMed

Tan, David S P; Bedard, Philippe L; Kuruvilla, John; Siu, Lillian L; Razak, Albiruni R Abdul

2014-05-01

In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed.

Applied evolutionary theories for engineering of secondary metabolic pathways.

PubMed

Bachmann, Brian O

2016-12-01

An expanded definition of 'secondary metabolism' is emerging. Once the exclusive provenance of naturally occurring organisms, evolved over geological time scales, secondary metabolism increasingly encompasses molecules generated via human engineered biocatalysts and biosynthetic pathways. Many of the tools and strategies for enzyme and pathway engineering can find origins in evolutionary theories. This perspective presents an overview of selected proposed evolutionary strategies in the context of engineering secondary metabolism. In addition to the wealth of biocatalysts provided via secondary metabolic pathways, improving the understanding of biosynthetic pathway evolution will provide rich resources for methods to adapt to applied laboratory evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Planning strategies for the Ambler walking robot

NASA Technical Reports Server (NTRS)

Wettergreen, David; Thomas, Hans; Thorpe, Chuck

1990-01-01

A hierarchy of planning strategies is proposed and explained for a walking robot called the Ambler. The hierarchy decomposes planning into levels of trajectory, gait, and footfall. An abstraction of feasible traversability allows the Ambler's trajectory planner to identify acceptable trajectories by finding paths that guarantee footfalls without specifying exactly which footfalls. Leg and body moves that achieve this trajectory can be generated by the Ambler's gait planner, which incorporates pattern constraints and measures of utility to search for the best next move. By combining constraints from the quality and details of the terrain, the Ambler's footfall planner can select footfalls that insure stability and remain within the tolerances of the gait.

Solubility studies of inorganic-organic hybrid nanoparticle photoresists with different surface functional groups

NASA Astrophysics Data System (ADS)

Li, Li; Chakrabarty, Souvik; Jiang, Jing; Zhang, Ben; Ober, Christopher; Giannelis, Emmanuel P.

2016-01-01

The solubility behavior of Hf and Zr based hybrid nanoparticles with different surface ligands in different concentrations of photoacid generator as potential EUV photoresists was investigated in detail. The nanoparticles regardless of core or ligand chemistry have a hydrodynamic diameter of 2-3 nm and a very narrow size distribution in organic solvents. The Hansen solubility parameters for nanoparticles functionalized with IBA and 2MBA have the highest contribution from the dispersion interaction than those with tDMA and MAA, which show more polar character. The nanoparticles functionalized with unsaturated surface ligands showed more apparent solubility changes after exposure to DUV than those with saturated ones. The solubility differences after exposure are more pronounced for films containing a higher amount of photoacid generator. The work reported here provides material selection criteria and processing strategies for the design of high performance EUV photoresists.The solubility behavior of Hf and Zr based hybrid nanoparticles with different surface ligands in different concentrations of photoacid generator as potential EUV photoresists was investigated in detail. The nanoparticles regardless of core or ligand chemistry have a hydrodynamic diameter of 2-3 nm and a very narrow size distribution in organic solvents. The Hansen solubility parameters for nanoparticles functionalized with IBA and 2MBA have the highest contribution from the dispersion interaction than those with tDMA and MAA, which show more polar character. The nanoparticles functionalized with unsaturated surface ligands showed more apparent solubility changes after exposure to DUV than those with saturated ones. The solubility differences after exposure are more pronounced for films containing a higher amount of photoacid generator. The work reported here provides material selection criteria and processing strategies for the design of high performance EUV photoresists. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07334k

Role of the superior colliculus in choosing mixed-strategy saccades.

PubMed

Thevarajah, Dhushan; Mikulić, Areh; Dorris, Michael C

2009-02-18

Game theory outlines optimal response strategies during mixed-strategy competitions. The neural processes involved in choosing individual strategic actions, however, remain poorly understood. Here, we tested whether the superior colliculus (SC), a brain region critical for generating sensory-guided saccades, is also involved in choosing saccades under strategic conditions. Monkeys were free to choose either of two saccade targets as they competed against a computer opponent during the mixed-strategy game "matching pennies." The accuracy with which presaccadic SC activity predicted upcoming choice gradually increased in the time leading up to the saccade. Probing the SC with suprathreshold stimulation demonstrated that these evolving signals were functionally involved in preparing strategic saccades. Finally, subthreshold stimulation of the SC increased the likelihood that contralateral saccades were selected. Together, our results suggest that motor regions of the brain play an active role in choosing strategic actions rather than passively executing those prespecified by upstream executive regions.

Optimized breeding strategies for multiple trait integration: I. Minimizing linkage drag in single event introgression.

PubMed

Peng, Ting; Sun, Xiaochun; Mumm, Rita H

2014-01-01

From a breeding standpoint, multiple trait integration (MTI) is a four-step process of converting an elite variety/hybrid for value-added traits (e.g. transgenic events) using backcross breeding, ultimately regaining the performance attributes of the target hybrid along with reliable expression of the value-added traits. In the light of the overarching goal of recovering equivalent performance in the finished conversion, this study focuses on the first step of MTI, single event introgression, exploring the feasibility of marker-aided backcross conversion of a target maize hybrid for 15 transgenic events, incorporating eight events into the female hybrid parent and seven into the male parent. Single event introgression is conducted in parallel streams to convert the recurrent parent (RP) for individual events, with the primary objective of minimizing residual non-recurrent parent (NRP) germplasm, especially in the chromosomal proximity to the event (i.e. linkage drag). In keeping with a defined lower limit of 96.66 % overall RP germplasm recovery (i.e. ≤120 cM NRP germplasm given a genome size of 1,788 cM), a breeding goal for each of the 15 single event conversions was developed: <8 cM of residual NRP germplasm across the genome with ~1 cM in the 20 cM region flanking the event. Using computer simulation, we aimed to identify optimal breeding strategies for single event introgression to achieve this breeding goal, measuring efficiency in terms of number of backcross generations required, marker data points needed, and total population size across generations. Various selection schemes classified as three-stage, modified two-stage, and combined selection conducted from BC1 through BC3, BC4, or BC5 were compared. The breeding goal was achieved with a selection scheme involving five generations of marker-aided backcrossing, with BC1 through BC3 selected for the event of interest and minimal linkage drag at population size of 600, and BC4 and BC5 selected for the event of interest and recovery of the RP germplasm across the genome at population size of 400, with selection intensity of 0.01 for all generations. In addition, strategies for choice of donor parent to facilitate conversion efficiency and quality were evaluated. Two essential criteria for choosing an optimal donor parent for a given RP were established: introgression history showing reduction of linkage drag to ~1 cM in the 20 cM region flanking the event and genetic similarity between the RP and potential donor parents. Computer simulation demonstrated that single event conversions with <8 cM residual NRP germplasm can be accomplished by BC5 with no genetic similarity, by BC4 with 30 % genetic similarity, and by BC3 with 86 % genetic similarity using previously converted RPs as event donors. This study indicates that MTI to produce a 'quality' 15-event-stacked hybrid conversion is achievable. Furthermore, it lays the groundwork for a comprehensive approach to MTI by outlining a pathway to produce appropriate starting materials with which to proceed with event pyramiding and trait fixation before version testing.

Using pilot data to size a two-arm randomized trial to find a nearly optimal personalized treatment strategy.

PubMed

Laber, Eric B; Zhao, Ying-Qi; Regh, Todd; Davidian, Marie; Tsiatis, Anastasios; Stanford, Joseph B; Zeng, Donglin; Song, Rui; Kosorok, Michael R

2016-04-15

A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness. Copyright © 2015 John Wiley & Sons, Ltd.

Global-local feature attention network with reranking strategy for image caption generation

NASA Astrophysics Data System (ADS)

Wu, Jie; Xie, Si-ya; Shi, Xin-bao; Chen, Yao-wen

2017-11-01

In this paper, a novel framework, named as global-local feature attention network with reranking strategy (GLAN-RS), is presented for image captioning task. Rather than only adopting unitary visual information in the classical models, GLAN-RS explores the attention mechanism to capture local convolutional salient image maps. Furthermore, we adopt reranking strategy to adjust the priority of the candidate captions and select the best one. The proposed model is verified using the Microsoft Common Objects in Context (MSCOCO) benchmark dataset across seven standard evaluation metrics. Experimental results show that GLAN-RS significantly outperforms the state-of-the-art approaches, such as multimodal recurrent neural network (MRNN) and Google NIC, which gets an improvement of 20% in terms of BLEU4 score and 13 points in terms of CIDER score.

Data article on the effect of work engagement strategies on faculty staff behavioural outcomes in private universities.

PubMed

Falola, Hezekiah Olubusayo; Olokundun, Maxwell Ayodele; Salau, Odunayo Paul; Oludayo, Olumuyiwa Akinrole; Ibidunni, Ayodotun Stephen

2018-06-01

The main objective of this study was to present a data article that investigate the effect of work engagement strategies on faculty behavioural outcomes. Few studies analyse how work engagement strategies could help in driving standard work behaviour particularly in higher institutions. In an attempt to bridge this gap, this study was carried out using descriptive research method and Structural Equation Model (AMOS 22) for the analysis of four hundred and forty one (441) valid questionnaire which were completed by the faculty members of the six selected private universities in Nigeria using stratified and simple random sampling techniques. Factor model which shows high-reliability and good fit was generated, while construct validity was provided through convergent and discriminant analyses.

In search of the skeletal stem cell: isolation and separation strategies at the macro/micro scale for skeletal regeneration.

PubMed

Gothard, David; Tare, Rahul S; Mitchell, Peter D; Dawson, Jonathan I; Oreffo, Richard O C

2011-04-07

Skeletal stem cells (SSCs) show great capacity for bone and cartilage repair however, current in vitro cultures are heterogeneous displaying a hierarchy of differentiation potential. SSCs represent the diminutive true multipotent stem cell fraction of bone marrow mononuclear cell (BMMNC) populations. Endeavours to isolate SSCs have generated a multitude of separation methodologies. SSCs were first identified and isolated by their ability to adhere to culture plastic. Once isolated, further separation is achieved via culture in selective or conditioned media (CM). Indeed, preferential SSC growth has been demonstrated through selective in vitro culture conditions. Other approaches have utilised cell morphology (size and shape) as selection criteria. Studies have also targeted SSCs based on their preferential adhesion to specified compounds, individually or in combination, on both macro and microscale platforms. Nevertheless, most of these methods which represent macroscale function with relatively high throughput, yield insufficient purity. Consequently, research has sought to downsize isolation methodologies to the microscale for single cell analysis. The central approach is identification of the requisite cell populations of SSC-specific surface markers that can be targeted for isolation by either positive or negative selection. SELEX and phage display technology provide apt means to sift through substantial numbers of candidate markers. In contrast, single cell analysis is the paramount advantage of microfluidics, a relatively new field for cell biology. Here cells can be separated under continuous or discontinuous flow according to intrinsic phenotypic and physicochemical properties. The combination of macroscale quantity with microscale specificity to generate robust high-throughput (HT) technology for pure SSC sorting, isolation and enrichment offers significant implications therein for skeletal regenerative strategies as a consequence of lab on chip derived methodology.

Modulating RNA Alignment Using Directional Dynamic Kinks: Application in Determining an Atomic-Resolution Ensemble for a Hairpin using NMR Residual Dipolar Couplings.

PubMed

Salmon, Loïc; Giambaşu, George M; Nikolova, Evgenia N; Petzold, Katja; Bhattacharya, Akash; Case, David A; Al-Hashimi, Hashim M

2015-10-14

Approaches that combine experimental data and computational molecular dynamics (MD) to determine atomic resolution ensembles of biomolecules require the measurement of abundant experimental data. NMR residual dipolar couplings (RDCs) carry rich dynamics information, however, difficulties in modulating overall alignment of nucleic acids have limited the ability to fully extract this information. We present a strategy for modulating RNA alignment that is based on introducing variable dynamic kinks in terminal helices. With this strategy, we measured seven sets of RDCs in a cUUCGg apical loop and used this rich data set to test the accuracy of an 0.8 μs MD simulation computed using the Amber ff10 force field as well as to determine an atomic resolution ensemble. The MD-generated ensemble quantitatively reproduces the measured RDCs, but selection of a sub-ensemble was required to satisfy the RDCs within error. The largest discrepancies between the RDC-selected and MD-generated ensembles are observed for the most flexible loop residues and backbone angles connecting the loop to the helix, with the RDC-selected ensemble resulting in more uniform dynamics. Comparison of the RDC-selected ensemble with NMR spin relaxation data suggests that the dynamics occurs on the ps-ns time scales as verified by measurements of R(1ρ) relaxation-dispersion data. The RDC-satisfying ensemble samples many conformations adopted by the hairpin in crystal structures indicating that intrinsic plasticity may play important roles in conformational adaptation. The approach presented here can be applied to test nucleic acid force fields and to characterize dynamics in diverse RNA motifs at atomic resolution.

Focal cryotherapy for prostate cancer.

PubMed

Tsivian, Matvey; Polascik, Thomas J

2010-05-01

Focal therapy for prostate cancer has emerged an interesting concept as a less morbid option for the treatment of localized low-risk disease. Despite the growing interest in focal therapy, this approach has not yet gained sufficient popularity nor provided enough data to be discussed outside the experimental application. Herein we summarize the available data on focal cryotherapy and focus on the targets to be achieved in order to increase the applicability of focal cryotherapy to clinical practice. A cautious approach to candidate selection and generation of solid scientific data that would result in wide consensus on patient selection strategies and follow-up schemes would provide the tools necessary to take the path of focal therapy. Currently available focal cryotherapy data demonstrate excellent short-term results and a favorable quality-of-life profile. Although the future role of focal treatment is debated, a growing amount of science is generated in support of this minimally invasive approach.

Generating Innovative Strategies for Healthy Infants and Children. Hearing before the Select Committee on Children, Youth, and Families. House of Representatives, One Hundred Second Congress, First Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Children, Youth, and Families.

In this report of a hearing on infants' and children's health, two factsheets present information on the lack of recent progress in reducing infant mortality rates; the accessibility of prenatal care; low birthweight; nutrition; inadequate child health care; health risks for low-income children; the lack of adequate health insurance; the health…

Maximization of Markers Linked in Coupling for Tetraploid Potatoes via Monoparental Haploids

PubMed Central

Bartkiewicz, Annette M.; Chilla, Friederike; Terefe-Ayana, Diro; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhard; Linde, Marcus; Debener, Thomas

2018-01-01

Haploid potato populations derived from a single tetraploid donor constitute an efficient strategy to analyze markers segregating from a single donor genotype. Analysis of marker segregation in populations derived from crosses between polysomic tetraploids is complicated by a maximum of eight segregating alleles, multiple dosages of the markers and problems related to linkage analysis of marker segregation in repulsion. Here, we present data on two monoparental haploid populations generated by prickle pollination of two tetraploid cultivars with Solanum phureja and genotyped with the 12.8 k SolCAP single nucleotide polymorphism (SNP) array. We show that in a population of monoparental haploids, the number of biallelic SNP markers segregating in linkage to loci from the tetraploid donor genotype is much larger than in putative crosses of this genotype to a diverse selection of 125 tetraploid cultivars. Although this strategy is more laborious than conventional breeding, the generation of haploid progeny for efficient marker analysis is straightforward if morphological markers and flow cytometry are utilized to select true haploid progeny. The level of introgressed fragments from S. phureja, the haploid inducer, is very low, supporting its suitability for genetic analysis. Mapping with single-dose markers allowed the analysis of quantitative trait loci (QTL) for four phenotypic traits. PMID:29868076

Assortative and dissortative priorities for game interaction and strategy adaptation significantly bolster network reciprocity in the prisoner’s dilemma

NASA Astrophysics Data System (ADS)

Tanimoto, Jun

2014-05-01

In 2 × 2 prisoner’s dilemma games, network reciprocity is one mechanism for adding social viscosity, which leads to cooperative equilibrium. Here we show that combining the process for selecting a gaming partner with the process for selecting an adaptation partner significantly enhances cooperation, even though such selection processes require additional costs to collect further information concerning which neighbor should be chosen. Based on elaborate investigations of the dynamics generated by our model, we find that high levels of cooperation result from two kinds of behavior: cooperators tend to interact with cooperators to prevent being exploited by defectors and defectors tend to choose cooperators to exploit despite the possibility that some defectors convert to cooperators.

Reproductive technologies combine well with genomic selection in dairy breeding programs.

PubMed

Thomasen, J R; Willam, A; Egger-Danner, C; Sørensen, A C

2016-02-01

The objective of the present study was to examine whether genomic selection of females interacts with the use of reproductive technologies (RT) to increase annual monetary genetic gain (AMGG). This was tested using a factorial design with 3 factors: genomic selection of females (0 or 2,000 genotyped heifers per year), RT (0 or 50 donors selected at 14 mo of age for producing 10 offspring), and 2 reliabilities of genomic prediction. In addition, different strategies for use of RT and how strategies interact with the reliability of genomic prediction were investigated using stochastic simulation by varying (1) number of donors (25, 50, 100, 200), (2) number of calves born per donor (10 or 20), (3) age of donor (2 or 14 mo), and (4) number of sires (25, 50, 100, 200). In total, 72 different breeding schemes were investigated. The profitability of the different breeding strategies was evaluated by deterministic simulation by varying the costs of a born calf with reproductive technologies at levels of €500, €1,000, and €1,500. The results confirm our hypothesis that combining genomic selection of females with use of RT increases AMGG more than in a reference scheme without genomic selection in females. When the reliability of genomic prediction is high, the effect on rate of inbreeding (ΔF) is small. The study also demonstrates favorable interaction effects between the components of the breeder's equation (selection intensity, selection accuracy, generation interval) for the bull dam donor path, leading to higher AMGG. Increasing the donor program and number of born calves to achieve higher AMGG is associated with the undesirable effect of increased ΔF. This can be alleviated, however, by increasing the numbers of sires without compromising AMGG remarkably. For the major part of the investigated donor schemes, the investment in RT is profitable in dairy cattle populations, even at high levels of costs for RT. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Key Aspects of Nucleic Acid Library Design for in Vitro Selection

PubMed Central

Vorobyeva, Maria A.; Davydova, Anna S.; Vorobjev, Pavel E.; Pyshnyi, Dmitrii V.; Venyaminova, Alya G.

2018-01-01

Nucleic acid aptamers capable of selectively recognizing their target molecules have nowadays been established as powerful and tunable tools for biospecific applications, be it therapeutics, drug delivery systems or biosensors. It is now generally acknowledged that in vitro selection enables one to generate aptamers to almost any target of interest. However, the success of selection and the affinity of the resulting aptamers depend to a large extent on the nature and design of an initial random nucleic acid library. In this review, we summarize and discuss the most important features of the design of nucleic acid libraries for in vitro selection such as the nature of the library (DNA, RNA or modified nucleotides), the length of a randomized region and the presence of fixed sequences. We also compare and contrast different randomization strategies and consider computer methods of library design and some other aspects. PMID:29401748

Open innovation for phenotypic drug discovery: The PD2 assay panel.

PubMed

Lee, Jonathan A; Chu, Shaoyou; Willard, Francis S; Cox, Karen L; Sells Galvin, Rachelle J; Peery, Robert B; Oliver, Sarah E; Oler, Jennifer; Meredith, Tamika D; Heidler, Steven A; Gough, Wendy H; Husain, Saba; Palkowitz, Alan D; Moxham, Christopher M

2011-07-01

Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target "agnostic" fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD(2)), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD(2) assay panel. Analysis of PD(2) submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD(2) have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD(2), may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

Evolution of learning in fluctuating environments: when selection favors both social and exploratory individual learning.

PubMed

Borenstein, Elhanan; Feldman, Marcus W; Aoki, Kenichi

2008-03-01

Cumulative cultural change requires organisms that are capable of both exploratory individual learning and faithful social learning. In our model, an organism's phenotype is initially determined innately (by its genotypic value) or by social learning (copying a phenotype from the parental generation), and then may or may not be modified by individual learning (exploration around the initial phenotype). The environment alternates periodically between two states, each defined as a certain range of phenotypes that can survive. These states may overlap, in which case the same phenotype can survive in both states, or they may not. We find that a joint social and exploratory individual learning strategy-the strategy that supports cumulative culture-is likely to spread when the environmental states do not overlap. In particular, when the environmental states are contiguous and mutation is allowed among the genotypic values, this strategy will spread in either moderately or highly stable environments, depending on the exact nature of the individual learning applied. On the other hand, natural selection often favors a social learning strategy without exploration when the environmental states overlap. We find only partial support for the "consensus" view, which holds that individual learning, social learning, and innate determination of behavior will evolve at short, intermediate, and long environmental periodicities, respectively.

Extended Wordsearches in Chemistry

NASA Astrophysics Data System (ADS)

Cotton, Simon

1998-04-01

Students can be encouraged to develop their factual knowledge by use of puzzles. One strategy described here is the extended wordsearch, where the wordsearch element generates a number of words or phrases from which the answers to a series of questions are selected. The wordsearch can be generated with the aid of computer programs, though in order to make them suitable for students with dyslexia or other learning difficulties, a simpler form is more appropriate. These problems can be employed in a variety of contexts, for example, as topic tests and classroom end-of-lesson fillers. An example is provided in the area of calcium chemistry. Sources of suitable software are listed.

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

PubMed Central

Dennehy, Olga C; Cacheux, Valérie M Y; Deadman, Benjamin J; Lynch, Denis

2016-01-01

A continuous process strategy has been developed for the preparation of α-thio-β-chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts. PMID:28144320

Evaluation of a 3D point cloud tetrahedral tomographic reconstruction method

PubMed Central

Pereira, N F; Sitek, A

2011-01-01

Tomographic reconstruction on an irregular grid may be superior to reconstruction on a regular grid. This is achieved through an appropriate choice of the image space model, the selection of an optimal set of points and the use of any available prior information during the reconstruction process. Accordingly, a number of reconstruction-related parameters must be optimized for best performance. In this work, a 3D point cloud tetrahedral mesh reconstruction method is evaluated for quantitative tasks. A linear image model is employed to obtain the reconstruction system matrix and five point generation strategies are studied. The evaluation is performed using the recovery coefficient, as well as voxel- and template-based estimates of bias and variance measures, computed over specific regions in the reconstructed image. A similar analysis is performed for regular grid reconstructions that use voxel basis functions. The maximum likelihood expectation maximization reconstruction algorithm is used. For the tetrahedral reconstructions, of the five point generation methods that are evaluated, three use image priors. For evaluation purposes, an object consisting of overlapping spheres with varying activity is simulated. The exact parallel projection data of this object are obtained analytically using a parallel projector, and multiple Poisson noise realizations of these exact data are generated and reconstructed using the different point generation strategies. The unconstrained nature of point placement in some of the irregular mesh-based reconstruction strategies has superior activity recovery for small, low-contrast image regions. The results show that, with an appropriately generated set of mesh points, the irregular grid reconstruction methods can out-perform reconstructions on a regular grid for mathematical phantoms, in terms of the performance measures evaluated. PMID:20736496

Evaluation of a 3D point cloud tetrahedral tomographic reconstruction method

NASA Astrophysics Data System (ADS)

Pereira, N. F.; Sitek, A.

2010-09-01

Tomographic reconstruction on an irregular grid may be superior to reconstruction on a regular grid. This is achieved through an appropriate choice of the image space model, the selection of an optimal set of points and the use of any available prior information during the reconstruction process. Accordingly, a number of reconstruction-related parameters must be optimized for best performance. In this work, a 3D point cloud tetrahedral mesh reconstruction method is evaluated for quantitative tasks. A linear image model is employed to obtain the reconstruction system matrix and five point generation strategies are studied. The evaluation is performed using the recovery coefficient, as well as voxel- and template-based estimates of bias and variance measures, computed over specific regions in the reconstructed image. A similar analysis is performed for regular grid reconstructions that use voxel basis functions. The maximum likelihood expectation maximization reconstruction algorithm is used. For the tetrahedral reconstructions, of the five point generation methods that are evaluated, three use image priors. For evaluation purposes, an object consisting of overlapping spheres with varying activity is simulated. The exact parallel projection data of this object are obtained analytically using a parallel projector, and multiple Poisson noise realizations of these exact data are generated and reconstructed using the different point generation strategies. The unconstrained nature of point placement in some of the irregular mesh-based reconstruction strategies has superior activity recovery for small, low-contrast image regions. The results show that, with an appropriately generated set of mesh points, the irregular grid reconstruction methods can out-perform reconstructions on a regular grid for mathematical phantoms, in terms of the performance measures evaluated.

A strategy to accelerate protein production from a pool of clones in Chinese hamster ovary cells for toxicology studies.

PubMed

Hu, Zhilan; Hsu, Wendy; Pynn, Abby; Ng, Domingos; Quicho, Donna; Adem, Yilma; Kwong, Zephie; Mauger, Brad; Joly, John; Snedecor, Bradley; Laird, Michael W; Andersen, Dana C; Shen, Amy

2017-11-01

In the biopharmaceutical industry, a clonally derived cell line is typically used to generate material for investigational new drug (IND)-enabling toxicology studies. The same cell line is then used to generate material for clinical studies. If a pool of clones can be used to produce material for IND-enabling toxicology studies (Pool for Tox (PFT) strategy) during the time a lead clone is being selected for clinical material production, the toxicology studies can be accelerated significantly (approximately 4 months at Genentech), leading to a potential acceleration of 4 months for the IND submission. We explored the feasibility of the PFT strategy with three antibodies-mAb1, mAb2, and mAb3-at the 2 L scale. For each antibody, two lead cell lines were identified that generated material with similar product quality to the material generated from the associated pool. For two antibody molecules, mAb1 and mAb2, the material generated by the lead cell lines from 2 L bioreactors was tested in an accelerated stability study and was shown to have stability comparable to the material generated by the associated pool. Additionally, we used this approach for two antibody molecules, mAb4 and mAb5, at Tox and GMP production. The materials from the Tox batch at 400 L scale and three GMP batches at 2000 L scale have comparable product quality attributes for both molecules. Our results demonstrate the feasibility of using a pool of clonally derived cell lines to generate material of similar product quality and stability for use in IND-enabling toxicology studies as was derived from the final production clone, which enabled significant acceleration of timelines into clinical development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1449-1455, 2017. © 2017 American Institute of Chemical Engineers.

A combined strategy involving Sanger and 454 pyrosequencing increases genomic resources to aid in the management of reproduction, disease control and genetic selection in the turbot (Scophthalmus maximus).

PubMed

Ribas, Laia; Pardo, Belén G; Fernández, Carlos; Alvarez-Diós, José Antonio; Gómez-Tato, Antonio; Quiroga, María Isabel; Planas, Josep V; Sitjà-Bobadilla, Ariadna; Martínez, Paulino; Piferrer, Francesc

2013-03-15

Genomic resources for plant and animal species that are under exploitation primarily for human consumption are increasingly important, among other things, for understanding physiological processes and for establishing adequate genetic selection programs. Current available techniques for high-throughput sequencing have been implemented in a number of species, including fish, to obtain a proper description of the transcriptome. The objective of this study was to generate a comprehensive transcriptomic database in turbot, a highly priced farmed fish species in Europe, with potential expansion to other areas of the world, for which there are unsolved production bottlenecks, to understand better reproductive- and immune-related functions. This information is essential to implement marker assisted selection programs useful for the turbot industry. Expressed sequence tags were generated by Sanger sequencing of cDNA libraries from different immune-related tissues after several parasitic challenges. The resulting database ("Turbot 2 database") was enlarged with sequences generated from a 454 sequencing run of brain-hypophysis-gonadal axis-derived RNA obtained from turbot at different development stages. The assembly of Sanger and 454 sequences generated 52,427 consensus sequences ("Turbot 3 database"), of which 23,661 were successfully annotated. A total of 1,410 sequences were confirmed to be related to reproduction and key genes involved in sex differentiation and maturation were identified for the first time in turbot (AR, AMH, SRY-related genes, CYP19A, ZPGs, STAR FSHR, etc.). Similarly, 2,241 sequences were related to the immune system and several novel key immune genes were identified (BCL, TRAF, NCK, CD28 and TOLLIP, among others). The number of genes of many relevant reproduction- and immune-related pathways present in the database was 50-90% of the total gene count of each pathway. In addition, 1,237 microsatellites and 7,362 single nucleotide polymorphisms (SNPs) were also compiled. Further, 2,976 putative natural antisense transcripts (NATs) including microRNAs were also identified. The combined sequencing strategies employed here significantly increased the turbot genomic resources available, including 34,400 novel sequences. The generated database contains a larger number of genes relevant for reproduction- and immune-associated studies, with an excellent coverage of most genes present in many relevant physiological pathways. This database also allowed the identification of many microsatellites and SNP markers that will be very useful for population and genome screening and a valuable aid in marker assisted selection programs.

A combined strategy involving Sanger and 454 pyrosequencing increases genomic resources to aid in the management of reproduction, disease control and genetic selection in the turbot (Scophthalmus maximus)

PubMed Central

2013-01-01

Background Genomic resources for plant and animal species that are under exploitation primarily for human consumption are increasingly important, among other things, for understanding physiological processes and for establishing adequate genetic selection programs. Current available techniques for high-throughput sequencing have been implemented in a number of species, including fish, to obtain a proper description of the transcriptome. The objective of this study was to generate a comprehensive transcriptomic database in turbot, a highly priced farmed fish species in Europe, with potential expansion to other areas of the world, for which there are unsolved production bottlenecks, to understand better reproductive- and immune-related functions. This information is essential to implement marker assisted selection programs useful for the turbot industry. Results Expressed sequence tags were generated by Sanger sequencing of cDNA libraries from different immune-related tissues after several parasitic challenges. The resulting database (“Turbot 2 database”) was enlarged with sequences generated from a 454 sequencing run of brain-hypophysis-gonadal axis-derived RNA obtained from turbot at different development stages. The assembly of Sanger and 454 sequences generated 52,427 consensus sequences (“Turbot 3 database”), of which 23,661 were successfully annotated. A total of 1,410 sequences were confirmed to be related to reproduction and key genes involved in sex differentiation and maturation were identified for the first time in turbot (AR, AMH, SRY-related genes, CYP19A, ZPGs, STAR FSHR, etc.). Similarly, 2,241 sequences were related to the immune system and several novel key immune genes were identified (BCL, TRAF, NCK, CD28 and TOLLIP, among others). The number of genes of many relevant reproduction- and immune-related pathways present in the database was 50–90% of the total gene count of each pathway. In addition, 1,237 microsatellites and 7,362 single nucleotide polymorphisms (SNPs) were also compiled. Further, 2,976 putative natural antisense transcripts (NATs) including microRNAs were also identified. Conclusions The combined sequencing strategies employed here significantly increased the turbot genomic resources available, including 34,400 novel sequences. The generated database contains a larger number of genes relevant for reproduction- and immune-associated studies, with an excellent coverage of most genes present in many relevant physiological pathways. This database also allowed the identification of many microsatellites and SNP markers that will be very useful for population and genome screening and a valuable aid in marker assisted selection programs. PMID:23497389

PSMA-targeted bispecific Fab conjugates that engage T cells.

PubMed

Patterson, James T; Isaacson, Jason; Kerwin, Lisa; Atassi, Ghazi; Duggal, Rohit; Bresson, Damien; Zhu, Tong; Zhou, Heyue; Fu, Yanwen; Kaufmann, Gunnar F

2017-12-15

Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity. Copyright © 2017. Published by Elsevier Ltd.

SSL: A Theory of How People Learn to Select Strategies

ERIC Educational Resources Information Center

Rieskamp, Jorg; Otto, Philipp E.

2006-01-01

The assumption that people possess a repertoire of strategies to solve the inference problems they face has been raised repeatedly. However, a computational model specifying how people select strategies from their repertoire is still lacking. The proposed strategy selection learning (SSL) theory predicts a strategy selection process on the basis…

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

PubMed

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

2017-01-01

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

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

PubMed Central

Lou, Xin Yuan; Sun, Lin Fu

2017-01-01

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

Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification

PubMed Central

Garg, Himanshu; Joshi, Anjali

2016-01-01

Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV-infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy. PMID:26800572

Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification.

PubMed

Garg, Himanshu; Joshi, Anjali

2016-05-01

Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV-infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy.

Novel Biomarker Discovery for Diagnostic and Therapeutic Strategies in Prostate Cancer

DTIC Science & Technology

2015-06-01

PURPOSE: to identify high affinity aptamers that distinguish between prostate cancers that are likely to remain organ- confined and those with potential to...metastasize. SCOPE: This was a pilot project to generate RNA aptamers that selectively react with a prostate cancer cell line that remains confined... Aptamer -Facilitated Biomarker Discovery (AptaBiD) technology. TASKS AND PROGRESS: (1) Non-metastatic LNCaP-Pro-5 cells, metastasis-prone LNCaP-LN3

Novel Biomarker Discovery for Diagnostic and Therapeutic Strategies in Prostate Cancer

DTIC Science & Technology

2014-03-01

aptamers that distinguish between prostate cancers that are likely to remain organ-confined and those with potential to metastasize, The scope of this...pilot is to generate DNA aptamers that selectively react with a prostate cancer cell line that remains confined to the prostate (LNCaP) vs. a...subpopulation of this cell line that has acquired the ability to metastasize aggressively, employing Cell-Selex and Aptamer -Facilitated Biomarker Discovery

General Approach to the Synthesis of the Chlorosulfolipids Danicalipin A, Mytilipin A, and Malhamensilipin A in Enantioenriched Form

PubMed Central

2015-01-01

A second-generation synthesis of three structurally related chlorosulfolipids has been developed. Key advances include highly stereocontrolled additions to α,β-dichloroaldehydes, kinetic resolutions of complex chlorinated vinyl epoxide intermediates, and Z-selective alkene cross metatheses of cis-vinyl epoxides. This strategy facilitated the synthesis of enantioenriched danicalipin A, mytilipin A, and malhamensilipin A in nine, eight, and 11 steps, respectively. PMID:24494597

Widefield Imaging: Selected Strategies for Processing Light-Contaminated Data

NASA Astrophysics Data System (ADS)

Cannistra, Stephen A.

The beauty of nebulae, galaxies, and star clusters takes on new meaning when portrayed in a widefield view, where familiar objects that are commonly seen in isolation are now shown in relation to one another. Through the use of high quality, short focal length optics combined with large, commercially available CCD chips, it is possible to capture broad regions of sky that an older generation of astrophotographers could only dream of.

The effect of parasites on sex differences in selection.

PubMed

Sharp, N P; Vincent, C M

2015-04-01

The life history strategies of males and females are often divergent, creating the potential for sex differences in selection. Deleterious mutations may be subject to stronger selection in males, owing to sexual selection, which can improve the mean fitness of females and reduce mutation load in sexual populations. However, sex differences in selection might also maintain sexually antagonistic genetic variation, creating a sexual conflict load. The overall impact of separate sexes on fitness is unclear, but the net effect is likely to be positive when there is a large sex difference in selection against deleterious mutations. Parasites can also have sex-specific effects on fitness, and there is evidence that parasites can intensify the fitness consequences of deleterious mutations. Using lines that accumulated mutations for over 60 generations, we studied the effect of the pathogenic bacterium Pseudomonas aeruginosa on sex differences in selection in the fruit fly Drosophila melanogaster. Pseudomonas infection increased the sex difference in selection, but may also have weakened the intersexual correlation for fitness. Our results suggest that parasites may increase the benefits of sexual selection.

SU-E-J-73: Extension of a Clinical OIS/EMR/R&V System to Deliver Safe and Efficient Adaptive Plan-Of-The-Day Treatments Using a Fully Customizable Plan-Library-Based Workflow

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

Akhiat, A.; Elekta, Sunnyvale, CA; Kanis, A.P.

Purpose: To extend a clinical Record and Verify (R&V) system to enable a safe and fast workflow for Plan-of-the-Day (PotD) adaptive treatments based on patient-specific plan libraries. Methods: Plan libraries for PotD adaptive treatments contain for each patient several pre-treatment generated treatment plans. They may be generated for various patient anatomies or CTV-PTV margins. For each fraction, a Cone Beam CT scan is acquired to support the selection of the plan that best fits the patient’s anatomy-of-the-day. To date, there are no commercial R&V systems that support PotD delivery strategies. Consequently, the clinical workflow requires many manual interventions. Moreover, multiplemore » scheduled plans have a high risk of excessive dose delivery. In this work we extended a commercial R&V system (MOSAIQ) to support PotD workflows using IQ-scripting. The PotD workflow was designed after extensive risk analysis of the manual procedure, and all identified risks were incorporated as logical checks. Results: All manual PotD activities were automated. The workflow first identifies if the patient is scheduled for PotD, then performs safety checks, and continues to treatment plan selection only if no issues were found. The user selects the plan to deliver from a list of candidate plans. After plan selection, the workflow makes the treatment fields of the selected plan available for delivery by adding them to the treatment calendar. Finally, control is returned to the R&V system to commence treatment. Additional logic was added to incorporate off-line changes such as updating the plan library. After extensive testing including treatment fraction interrupts and plan-library updates during the treatment course, the workflow is running successfully in a clinical pilot, in which 35 patients have been treated since October 2014. Conclusion: We have extended a commercial R&V system for improved safety and efficiency in library-based adaptive strategies enabling a wide-spread implementation of those strategies. This work was in part funded by a research grant of Elekta AB, Stockholm, Sweden.« less

Selective monitoring

NASA Astrophysics Data System (ADS)

Homem-de-Mello, Luiz S.

1992-04-01

While in NASA's earlier space missions such as Voyager the number of sensors was in the hundreds, future platforms such as the Space Station Freedom will have tens of thousands sensors. For these planned missions it will be impossible to use the comprehensive monitoring strategy that was used in the past in which human operators monitored all sensors all the time. A selective monitoring strategy must be substituted for the current comprehensive strategy. This selective monitoring strategy uses computer tools to preprocess the incoming data and direct the operators' attention to the most critical parts of the physical system at any given time. There are several techniques that can be used to preprocess the incoming information. This paper presents an approach to using diagnostic reasoning techniques to preprocess the sensor data and detect which parts of the physical system require more attention because components have failed or are most likely to have failed. Given the sensor readings and a model of the physical system, a number of assertions are generated and expressed as Boolean equations. The resulting system of Boolean equations is solved symbolically. Using a priori probabilities of component failure and Bayes' rule, revised probabilities of failure can be computed. These will indicate what components have failed or are the most likely to have failed. This approach is suitable for systems that are well understood and for which the correctness of the assertions can be guaranteed. Also, the system must be such that assertions can be made from instantaneous measurements. And the system must be such that changes are slow enough to allow the computation.

Electrochemical separation is an attractive strategy for development of radionuclide generators for medical applications.

PubMed

Chakravarty, Rubel; Dash, Ashutosh; Pillai, M R A

2012-07-01

Electrochemical separation techniques are not widely used in radionuclide generator technology and only a few studies have been reported [1-4]. Nevertheless, this strategy is useful when other parent-daughter separation techniques are not effective or not possible. Such situations are frequent when low specific activity (LSA) parent radionuclides are used for instance with adsorption chromatographic separations, which can result in lower concentration of the daughter radionuclide in the eluent. In addition, radiation instability of the column matrix in many cases can affect the performance of the generator when long lived parent radionuclides are used. Intricate knowledge of the chemistry involved in the electrochemical separation is crucial to develop a reproducible technology that ensures that the pure daughter radionuclide can be obtained in a reasonable time of operation. Crucial parameters to be critically optimized include the applied potential, choice of electrolyte, selection of electrodes, temperature of electrolyte bath and the time of electrolysis in order to ensure that the daughter radionuclide can be reproducibly recovered in high yields and high purity. The successful electrochemical generator technologies which have been developed and are discussed in this paper include the (90)Sr/(90)Y, (188)W/(188)Re and (99)Mo/(99m)Tc generators. Electrochemical separation not only acts as a separation technique but also is an effective concentration methodology which yields high radioactive concentrations of the daughter products. The lower consumption of reagents and minimal generation of radioactive wastes using such electrochemical techniques are compatible with 'green chemistry' principles.

Stability-maneuverability trade-offs during lateral steps.

PubMed

Acasio, Julian; Wu, Mengnan/Mary; Fey, Nicholas P; Gordon, Keith E

2017-02-01

Selecting a specific foot placement strategy to perform walking maneuvers requires the management of several competing factors, including: maintaining stability, positioning oneself to actively generate impulses, and minimizing mechanical energy requirements. These requirements are unlikely to be independent. Our purpose was to determine the impact of lateral foot placement on stability, maneuverability, and energetics during walking maneuvers. Ten able-bodied adults performed laterally-directed walking maneuvers. Mediolateral placement of the "Push-off" foot during the maneuvers was varied, ranging from a cross-over step to a side-step. We hypothesized that as mediolateral foot placement became wider, passive stability in the direction of the maneuver, the lateral impulse generated to create the maneuver, and mechanical energy cost would all increase. We also hypothesized that subjects would prefer an intermediate step width reflective of trade-offs between stability vs. both maneuverability and energy. In support of our first hypothesis, we found that as Push-off step width increased, lateral margin of stability, peak lateral impulse, and total joint work all increased. In support of our second hypothesis, we found that when subjects had no restrictions on their mediolateral foot placement, they chose a foot placement between the two extreme positions. We found a significant relationship (p<0.05) between lateral margin of stability and peak lateral impulse (r=0.773), indicating a trade-off between passive stability and the force input required to maneuver. These findings suggest that during anticipated maneuvers people select foot placement strategies that balance competing costs to maintain stability, actively generate impulses, and minimize mechanical energy costs. Published by Elsevier B.V.

Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection

PubMed Central

KC, R.; Srivastava, A.; Wilkowski, J. M.; Richter, C. E.; Shavit, J. A.; Burke, D. T.; Bielas, S. L.

2016-01-01

CRISPR/Cas9 genome-editing has emerged as a powerful tool to create mutant alleles in model organisms. However, the precision with which these mutations are created has introduced a new set of complications for genotyping and colony management. Traditional gene-targeting approaches in many experimental organisms incorporated exogenous DNA and/or allele specific sequence that allow for genotyping strategies based on binary readout of PCR product amplification and size selection. In contrast, alleles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by Cas9 are much less amenable to such strategies. Here we describe a novel genotyping strategy that is cost effective, sequence specific and allows for accurate and efficient multiplexing of small insertion-deletions and single-nucleotide variants characteristic of CRISPR/Cas9 edited alleles. We show that ligation detection reaction (LDR) can be used to generate products that are sequence specific and uniquely detected by product size and/or fluorescent tags. The method works independently of the model organism and will be useful for colony management as mutant alleles differing by a few nucleotides become more prevalent in experimental animal colonies. PMID:27557703

Power Management Based Current Control Technique for Photovoltaic-Battery Assisted Wind-Hydro Hybrid System

NASA Astrophysics Data System (ADS)

Ram Prabhakar, J.; Ragavan, K.

2013-07-01

This article proposes new power management based current control strategy for integrated wind-solar-hydro system equipped with battery storage mechanism. In this control technique, an indirect estimation of load current is done, through energy balance model, DC-link voltage control and droop control. This system features simpler energy management strategy and necessitates few power electronic converters, thereby minimizing the cost of the system. The generation-demand (G-D) management diagram is formulated based on the stochastic weather conditions and demand, which would likely moderate the gap between both. The features of management strategy deploying energy balance model include (1) regulating DC-link voltage within specified tolerances, (2) isolated operation without relying on external electric power transmission network, (3) indirect current control of hydro turbine driven induction generator and (4) seamless transition between grid-connected and off-grid operation modes. Furthermore, structuring of the hybrid system with appropriate selection of control variables enables power sharing among each energy conversion systems and battery storage mechanism. By addressing these intricacies, it is viable to regulate the frequency and voltage of the remote network at load end. The performance of the proposed composite scheme is demonstrated through time-domain simulation in MATLAB/Simulink environment.

An ontology model for nursing narratives with natural language generation technology.

PubMed

Min, Yul Ha; Park, Hyeoun-Ae; Jeon, Eunjoo; Lee, Joo Yun; Jo, Soo Jung

2013-01-01

The purpose of this study was to develop an ontology model to generate nursing narratives as natural as human language from the entity-attribute-value triplets of a detailed clinical model using natural language generation technology. The model was based on the types of information and documentation time of the information along the nursing process. The typesof information are data characterizing the patient status, inferences made by the nurse from the patient data, and nursing actions selected by the nurse to change the patient status. This information was linked to the nursing process based on the time of documentation. We describe a case study illustrating the application of this model in an acute-care setting. The proposed model provides a strategy for designing an electronic nursing record system.

Method of generating ploynucleotides encoding enhanced folding variants

DOEpatents

Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

2017-05-02

The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

Microbial strain improvement for enhanced polygalacturonase production by Aspergillus sojae.

PubMed

Heerd, Doreen; Tari, Canan; Fernández-Lahore, Marcelo

2014-09-01

Strain improvement is a powerful tool in commercial development of microbial fermentation processes. Strains of Aspergillus sojae which were previously identified as polygalacturonase producers were subjected to the cost-effective mutagenesis and selection method, the so-called random screening. Physical (ultraviolet irradiation at 254 nm) and chemical mutagens (N-methyl-N'-nitro-N-nitrosoguanidine) were used in the development and implementation of a classical mutation and selection strategy for the improved production of pectic acid-degrading enzymes. Three mutation cycles of both mutagenic treatments and also the combination of them were performed to generate mutants descending from A. sojae ATCC 20235 and mutants of A. sojae CBS 100928. Pectinolytic enzyme production of the mutants was compared to their wild types in submerged and solid-state fermentation. Comparing both strains, higher pectinase activity was obtained by A. sojae ATCC 20235 and mutants thereof. The highest polygalacturonase activity (1,087.2 ± 151.9 U/g) in solid-state culture was obtained by mutant M3, which was 1.7 times increased in comparison to the wild strain, A. sojae ATCC 20235. Additional, further mutation of mutant M3 for two more cycles of treatment by UV irradiation generated mutant DH56 with the highest polygalacturonase activity (98.8 ± 8.7 U/mL) in submerged culture. This corresponded to 2.4-fold enhanced polygalacturonase production in comparison to the wild strain. The results of this study indicated the development of a classical mutation and selection strategy as a promising tool to improve pectinolytic enzyme production by both fungal strains.

Support Vector Feature Selection for Early Detection of Anastomosis Leakage From Bag-of-Words in Electronic Health Records.

PubMed

Soguero-Ruiz, Cristina; Hindberg, Kristian; Rojo-Alvarez, Jose Luis; Skrovseth, Stein Olav; Godtliebsen, Fred; Mortensen, Kim; Revhaug, Arthur; Lindsetmo, Rolv-Ole; Augestad, Knut Magne; Jenssen, Robert

2016-09-01

The free text in electronic health records (EHRs) conveys a huge amount of clinical information about health state and patient history. Despite a rapidly growing literature on the use of machine learning techniques for extracting this information, little effort has been invested toward feature selection and the features' corresponding medical interpretation. In this study, we focus on the task of early detection of anastomosis leakage (AL), a severe complication after elective surgery for colorectal cancer (CRC) surgery, using free text extracted from EHRs. We use a bag-of-words model to investigate the potential for feature selection strategies. The purpose is earlier detection of AL and prediction of AL with data generated in the EHR before the actual complication occur. Due to the high dimensionality of the data, we derive feature selection strategies using the robust support vector machine linear maximum margin classifier, by investigating: 1) a simple statistical criterion (leave-one-out-based test); 2) an intensive-computation statistical criterion (Bootstrap resampling); and 3) an advanced statistical criterion (kernel entropy). Results reveal a discriminatory power for early detection of complications after CRC (sensitivity 100%; specificity 72%). These results can be used to develop prediction models, based on EHR data, that can support surgeons and patients in the preoperative decision making phase.

Harnessing dendritic cells in inflammatory skin diseases

PubMed Central

Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O.

2011-01-01

The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. PMID:21295490

Internet marketing 101.

PubMed

Miller, Ryan J

2010-11-01

In an era when social media sites like YouTube, Facebook, and Twitter dominate the popular press, many surgeons overlook the foundational tactics and strategies necessary for long-term practice development and lead generation on the Internet. This article analyzes common errors made by surgeons during the development and implementation of Web site projects, focusing on the areas of strategy development; domain name identification; site plan creation; design considerations; content development; vendor selection; and launch, promotion, and staff training. The article emphasizes that, because the Web site remains the foundation of a surgeon's branding message, minimizing errors during development and construction is critical, particularly in highly competitive or saturated markets, for today's facial plastic surgery practice. Copyright © 2010 Elsevier Inc. All rights reserved.

Wavelet-Based Visible and Infrared Image Fusion: A Comparative Study

PubMed Central

Sappa, Angel D.; Carvajal, Juan A.; Aguilera, Cristhian A.; Oliveira, Miguel; Romero, Dennis; Vintimilla, Boris X.

2016-01-01

This paper evaluates different wavelet-based cross-spectral image fusion strategies adopted to merge visible and infrared images. The objective is to find the best setup independently of the evaluation metric used to measure the performance. Quantitative performance results are obtained with state of the art approaches together with adaptations proposed in the current work. The options evaluated in the current work result from the combination of different setups in the wavelet image decomposition stage together with different fusion strategies for the final merging stage that generates the resulting representation. Most of the approaches evaluate results according to the application for which they are intended for. Sometimes a human observer is selected to judge the quality of the obtained results. In the current work, quantitative values are considered in order to find correlations between setups and performance of obtained results; these correlations can be used to define a criteria for selecting the best fusion strategy for a given pair of cross-spectral images. The whole procedure is evaluated with a large set of correctly registered visible and infrared image pairs, including both Near InfraRed (NIR) and Long Wave InfraRed (LWIR). PMID:27294938

An efficient dictionary learning algorithm and its application to 3-D medical image denoising.

PubMed

Li, Shutao; Fang, Leyuan; Yin, Haitao

2012-02-01

In this paper, we propose an efficient dictionary learning algorithm for sparse representation of given data and suggest a way to apply this algorithm to 3-D medical image denoising. Our learning approach is composed of two main parts: sparse coding and dictionary updating. On the sparse coding stage, an efficient algorithm named multiple clusters pursuit (MCP) is proposed. The MCP first applies a dictionary structuring strategy to cluster the atoms with high coherence together, and then employs a multiple-selection strategy to select several competitive atoms at each iteration. These two strategies can greatly reduce the computation complexity of the MCP and assist it to obtain better sparse solution. On the dictionary updating stage, the alternating optimization that efficiently approximates the singular value decomposition is introduced. Furthermore, in the 3-D medical image denoising application, a joint 3-D operation is proposed for taking the learning capabilities of the presented algorithm to simultaneously capture the correlations within each slice and correlations across the nearby slices, thereby obtaining better denoising results. The experiments on both synthetically generated data and real 3-D medical images demonstrate that the proposed approach has superior performance compared to some well-known methods. © 2011 IEEE

Wavelet-Based Visible and Infrared Image Fusion: A Comparative Study.

PubMed

Sappa, Angel D; Carvajal, Juan A; Aguilera, Cristhian A; Oliveira, Miguel; Romero, Dennis; Vintimilla, Boris X

2016-06-10

This paper evaluates different wavelet-based cross-spectral image fusion strategies adopted to merge visible and infrared images. The objective is to find the best setup independently of the evaluation metric used to measure the performance. Quantitative performance results are obtained with state of the art approaches together with adaptations proposed in the current work. The options evaluated in the current work result from the combination of different setups in the wavelet image decomposition stage together with different fusion strategies for the final merging stage that generates the resulting representation. Most of the approaches evaluate results according to the application for which they are intended for. Sometimes a human observer is selected to judge the quality of the obtained results. In the current work, quantitative values are considered in order to find correlations between setups and performance of obtained results; these correlations can be used to define a criteria for selecting the best fusion strategy for a given pair of cross-spectral images. The whole procedure is evaluated with a large set of correctly registered visible and infrared image pairs, including both Near InfraRed (NIR) and Long Wave InfraRed (LWIR).

Sensitive SERS detection of DNA methyltransferase by target triggering primer generation-based multiple signal amplification strategy.

PubMed

Li, Ying; Yu, Chuanfeng; Han, Huixia; Zhao, Caisheng; Zhang, Xiaoru

2016-07-15

A novel and sensitive surface-enhanced Raman scattering (SERS) method is proposed for the assay of DNA methyltransferase (MTase) activity and evaluation of inhibitors by developing a target triggering primer generation-based multiple signal amplification strategy. By using of a duplex substrate for Dam MTase, two hairpin templates and a Raman probe, multiple signal amplification mode is achieved. Once recognized by Dam MTase, the duplex substrate can be cleaved by Dpn I endonuclease and two primers are released for triggering the multiple signal amplification reaction. Consequently, a wide dynamic range and remarkably high sensitivity are obtained under isothermal conditions. The detection limit is 2.57×10(-4)UmL(-1). This assay exhibits an excellent selectivity and is successfully applied in the screening of inhibitors for Dam MTase. In addition, this novel sensing system is potentially universal as the recognition element can be conveniently designed for other target analytes by changing the substrate of DNA MTase. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic Gain and Inbreeding from Genomic Selection in a Simulated Commercial Breeding Program for Perennial Ryegrass.

PubMed

Lin, Zibei; Cogan, Noel O I; Pembleton, Luke W; Spangenberg, German C; Forster, John W; Hayes, Ben J; Daetwyler, Hans D

2016-03-01

Genomic selection (GS) provides an attractive option for accelerating genetic gain in perennial ryegrass () improvement given the long cycle times of most current breeding programs. The present study used simulation to investigate the level of genetic gain and inbreeding obtained from GS breeding strategies compared with traditional breeding strategies for key traits (persistency, yield, and flowering time). Base population genomes were simulated through random mating for 60,000 generations at an effective population size of 10,000. The degree of linkage disequilibrium (LD) in the resulting population was compared with that obtained from empirical studies. Initial parental varieties were simulated to match diversity of current commercial cultivars. Genomic selection was designed to fit into a company breeding program at two selection points in the breeding cycle (spaced plants and miniplot). Genomic estimated breeding values (GEBVs) for productivity traits were trained with phenotypes and genotypes from plots. Accuracy of GEBVs was 0.24 for persistency and 0.36 for yield for single plants, while for plots it was lower (0.17 and 0.19, respectively). Higher accuracy of GEBVs was obtained for flowering time (up to 0.7), partially as a result of the larger reference population size that was available from the clonal row stage. The availability of GEBVs permit a 4-yr reduction in cycle time, which led to at least a doubling and trebling genetic gain for persistency and yield, respectively, than the traditional program. However, a higher rate of inbreeding per cycle among varieties was also observed for the GS strategy. Copyright © 2016 Crop Science Society of America.

Learning to choose: Cognitive aging and strategy selection learning in decision making.

PubMed

Mata, Rui; von Helversen, Bettina; Rieskamp, Jörg

2010-06-01

Decision makers often have to learn from experience. In these situations, people must use the available feedback to select the appropriate decision strategy. How does the ability to select decision strategies on the basis of experience change with age? We examined younger and older adults' strategy selection learning in a probabilistic inference task using a computational model of strategy selection learning. Older adults showed poorer decision performance compared with younger adults. In particular, older adults performed poorly in an environment favoring the use of a more cognitively demanding strategy. The results suggest that the impact of cognitive aging on strategy selection learning depends on the structure of the decision environment. (c) 2010 APA, all rights reserved

Polymeric molecular sieve membranes via in situ cross-linking of non-porous polymer membrane templates.

PubMed

Qiao, Zhen-An; Chai, Song-Hai; Nelson, Kimberly; Bi, Zhonghe; Chen, Jihua; Mahurin, Shannon M; Zhu, Xiang; Dai, Sheng

2014-04-16

High-performance polymeric membranes for gas separation are attractive for molecular-level separations in industrial-scale chemical, energy and environmental processes. Molecular sieving materials are widely regarded as the next-generation membranes to simultaneously achieve high permeability and selectivity. However, most polymeric molecular sieve membranes are based on a few solution-processable polymers such as polymers of intrinsic microporosity. Here we report an in situ cross-linking strategy for the preparation of polymeric molecular sieve membranes with hierarchical and tailorable porosity. These membranes demonstrate exceptional performance as molecular sieves with high gas permeabilities and selectivities for smaller gas molecules, such as carbon dioxide and oxygen, over larger molecules such as nitrogen. Hence, these membranes have potential for large-scale gas separations of commercial and environmental relevance. Moreover, this strategy could provide a possible alternative to 'classical' methods for the preparation of porous membranes and, in some cases, the only viable synthetic route towards certain membranes.

Cognitive Niches: An Ecological Model of Strategy Selection

ERIC Educational Resources Information Center

Marewski, Julian N.; Schooler, Lael J.

2011-01-01

How do people select among different strategies to accomplish a given task? Across disciplines, the strategy selection problem represents a major challenge. We propose a quantitative model that predicts how selection emerges through the interplay among strategies, cognitive capacities, and the environment. This interplay carves out for each…

Sage-grouse habitat selection during winter in Alberta

USGS Publications Warehouse

Carpenter, Jennifer L.; Aldridge, Cameron L.; Boyce, Mark S.

2010-01-01

Greater sage-grouse (Centrocercus urophasianus) are dependent on sagebrush (Artemisia spp.) for food and shelter during winter, yet few studies have assessed winter habitat selection, particularly at scales applicable to conservation planning. Small changes to availability of winter habitats have caused drastic reductions in some sage-grouse populations. We modeled winter habitat selection by sage-grouse in Alberta, Canada, by using a resource selection function. Our purpose was to 1) generate a robust winter habitat-selection model for Alberta sage-grouse; 2) spatially depict habitat suitability in a Geographic Information System to identify areas with a high probability of selection and thus, conservation importance; and 3) assess the relative influence of human development, including oil and gas wells, in landscape models of winter habitat selection. Terrain and vegetation characteristics, sagebrush cover, anthropogenic landscape features, and energy development were important in top Akaike's Information Criterionselected models. During winter, sage-grouse selected dense sagebrush cover and homogenous less rugged areas, and avoided energy development and 2-track truck trails. Sage-grouse avoidance of energy development highlights the need for comprehensive management strategies that maintain suitable habitats across all seasons. ?? 2010 The Wildlife Society.

An effective online data monitoring and saving strategy for large-scale climate simulations

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

Xian, Xiaochen; Archibald, Rick; Mayer, Benjamin

Large-scale climate simulation models have been developed and widely used to generate historical data and study future climate scenarios. These simulation models often have to run for a couple of months to understand the changes in the global climate over the course of decades. This long-duration simulation process creates a huge amount of data with both high temporal and spatial resolution information; however, how to effectively monitor and record the climate changes based on these large-scale simulation results that are continuously produced in real time still remains to be resolved. Due to the slow process of writing data to disk,more » the current practice is to save a snapshot of the simulation results at a constant, slow rate although the data generation process runs at a very high speed. This study proposes an effective online data monitoring and saving strategy over the temporal and spatial domains with the consideration of practical storage and memory capacity constraints. Finally, our proposed method is able to intelligently select and record the most informative extreme values in the raw data generated from real-time simulations in the context of better monitoring climate changes.« less

An effective online data monitoring and saving strategy for large-scale climate simulations

DOE PAGES

Xian, Xiaochen; Archibald, Rick; Mayer, Benjamin; ...

2018-01-22

Large-scale climate simulation models have been developed and widely used to generate historical data and study future climate scenarios. These simulation models often have to run for a couple of months to understand the changes in the global climate over the course of decades. This long-duration simulation process creates a huge amount of data with both high temporal and spatial resolution information; however, how to effectively monitor and record the climate changes based on these large-scale simulation results that are continuously produced in real time still remains to be resolved. Due to the slow process of writing data to disk,more » the current practice is to save a snapshot of the simulation results at a constant, slow rate although the data generation process runs at a very high speed. This study proposes an effective online data monitoring and saving strategy over the temporal and spatial domains with the consideration of practical storage and memory capacity constraints. Finally, our proposed method is able to intelligently select and record the most informative extreme values in the raw data generated from real-time simulations in the context of better monitoring climate changes.« less

Genomic selection for the improvement of meat quality in beef.

PubMed

Pimentel, E C G; König, S

2012-10-01

Selection index theory was used to compare different selection strategies aiming at the improvement of meat quality in beef cattle. Alternative strategies were compared with a reference scenario with three basic traits in the selection index: BW at 200 d (W200) and 400 d (W400) and muscling score (MUSC). These traits resemble the combination currently used in the German national beef genetic evaluation system. Traits in the breeding goal were defined as the 3 basic traits plus marbling score (MARB), to depict a situation where an established breeding program currently selecting for growth and carcass yield intends to incorporate meat quality in its selection program. Economic weights were either the same for all 4 traits, or doubled or tripled for MARB. Two additional selection criteria for improving MARB were considered: Live animal intramuscular fat content measured by ultrasound (UIMF) as an indicator trait and a genomic breeding value (GEBV) for the target trait directly (gMARB). Results were used to estimate the required number of genotyped animals in an own calibration set for implementing genomic selection focusing on meat quality. Adding UIMF to the basic index increased the overall genetic gain per generation by 15% when the economic weight on MARB was doubled and by 44% when it was tripled. When a genomic breeding value for marbling could be estimated with an accuracy of 0.5, adding gMARB to the index provided larger genetic gain than adding UIMF. Greatest genetic gain per generation was obtained with the scenario containing GEBV for 4 traits (gW200, gW400, gMUSC, and gMARB) when the accuracies of these GEBV were ≥0.7. Adding UIMF to the index substantially improved response to selection for MARB, which switched from negative to positive when the economic weight on MARB was doubled or tripled. For all scenarios that contained gMARB in the selection index, the response to selection in MARB was positive for all relative economic weights on MARB, when the accuracy of GEBV was >0.7. Results indicated that setting up a calibration set of ∼500 genotyped animals with carcass phenotypes for MARB could suffice to obtain a larger response to selection than measuring UIMF. If the size of the calibration set is ∼2,500, adding the ultrasound trait to an index containing already the GEBV would bring little benefit, unless the relative economic weight for marbling is much larger than for the other traits.

Implementation strategies for collaborative primary care-mental health models.

PubMed

Franx, Gerdien; Dixon, Lisa; Wensing, Michel; Pincus, Harold

2013-09-01

Extensive research exists that collaborative primary care-mental health models can improve care and outcomes for patients. These programs are currently being implemented throughout the United States and beyond. The purpose of this study is to review the literature and to generate an overview of strategies currently used to implement such models in daily practice. Six overlapping strategies to implement collaborative primary care-mental health models were described in 18 selected studies. We identified interactive educational strategies, quality improvement change processes, technological support tools, stakeholder engagement in the design and execution of implementation plans, organizational changes in terms of expanding the task of nurses and financial strategies such as additional collaboration fees and pay for performance incentives. Considering the overwhelming evidence about the effectiveness of primary care-mental health models, there is a lack of good studies focusing on their implementation strategies. In practice, these strategies are multifaceted and locally defined, as a result of intensive and required stakeholder engagement. Although many barriers still exist, the implementation of collaborative models could have a chance to succeed in the United States, where new service delivery and payment models, such as the Patient-Centered Medical Home, the Health Home and the Accountable Care Organization, are being promoted.

Strategy combination during execution of memory strategies in young and older adults.

PubMed

Hinault, Thomas; Lemaire, Patrick; Touron, Dayna

2017-05-01

The present study investigated whether people can combine two memory strategies to encode pairs of words more efficiently than with a single strategy, and age-related differences in such strategy combination. Young and older adults were asked to encode pairs of words (e.g., satellite-tunnel). For each item, participants were told to use either the interactive-imagery strategy (e.g., mentally visualising the two words and making them interact), the sentence-generation strategy (i.e., generate a sentence linking the two words), or with strategy combination (i.e., generating a sentence while mentally visualising it). Participants obtained better recall performance on items encoded with strategy combination than on items encoded with interactive-imagery or sentence-generation strategies. Moreover, we found age-related decline in such strategy combination. These findings have important implications to further our understanding of execution of memory strategies, and suggest that strategy combination occurs in a variety of cognitive domains.

Active oligonucleotides incorporating alkylating an agent as potential sequence- and base selective modifier of gene expression.

PubMed

Sasaki, S

2001-04-01

A number of cross-linking (alkylating) agents have been developed and incorporated into the oligonulceotides for sequence selective control of gene expression. Recently, potential application of such active oligonucleotides has been expanding from use for improvement of inhibition efficiency to new biotechnology that may enable chemical alteration of genetic information. These interests in active oligonucleotides have encouraged the generation of new cross-linking agents that exhibit high efficiency for application of either in vitro or in vivo. This mini review summarizes structures of alkylating agents, in particular, a new basic skeleton for cross-linking, a 2'-deoxyribose derivative of 2-amino-6-vinylpurine that has been recently developed by the author's group. The 2-amino-6-vinylpurine has been shown to form a complex with cytidine under acidic conditions, and brings the vinyl and the amino reactive groups into proximity to achieve efficient alkylation. A new strategy was designed so that the reactivity of 2-amino-6-vinylpurine can be induced from the corresponding phenylsulfoxide derivative within a duplex with the complementary strand. The validity of the new strategy has been proven by achievement of cytidine-selective cross-linking with remarkably efficiency.

Immunotherapies for Targeting Ancient Retrovirus during Breast Cancer

DTIC Science & Technology

2014-03-01

collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE...in T cells. HERV-K-specific CAR+T cells were selectively propagated ex vivo on artificial antigen presenting cells (aAPC) using an approach already...demonstrate that it is feasible to generate T cells expressing a HERV-K-specific CAR using a clinically-appealing approach as a treatment strategy for HERV-K

Milestone Completion Report STCO04-1 AAPS: engagements with code teams, vendors, collaborators, developers

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

Draeger, E. W.

The Advanced Architecture and Portability Specialists team (AAPS) worked with a select set of LLNL application teams to develop and/or implement a portability strategy for next-generation architectures. The team also investigated new and updated programming models and helped develop programming abstractions targeting maintainability and performance portability. Significant progress was made on both fronts in FY17, resulting in multiple applications being significantly more prepared for the nextgeneration machines than before.

Adaptive marker-free registration using a multiple point strategy for real-time and robust endoscope electromagnetic navigation.

PubMed

Luo, Xiongbiao; Wan, Ying; He, Xiangjian; Mori, Kensaku

2015-02-01

Registration of pre-clinical images to physical space is indispensable for computer-assisted endoscopic interventions in operating rooms. Electromagnetically navigated endoscopic interventions are increasingly performed at current diagnoses and treatments. Such interventions use an electromagnetic tracker with a miniature sensor that is usually attached at an endoscope distal tip to real time track endoscope movements in a pre-clinical image space. Spatial alignment between the electromagnetic tracker (or sensor) and pre-clinical images must be performed to navigate the endoscope to target regions. This paper proposes an adaptive marker-free registration method that uses a multiple point selection strategy. This method seeks to address an assumption that the endoscope is operated along the centerline of an intraluminal organ which is easily violated during interventions. We introduce an adaptive strategy that generates multiple points in terms of sensor measurements and endoscope tip center calibration. From these generated points, we adaptively choose the optimal point, which is the closest to its assigned the centerline of the hollow organ, to perform registration. The experimental results demonstrate that our proposed adaptive strategy significantly reduced the target registration error from 5.32 to 2.59 mm in static phantoms validation, as well as from at least 7.58 mm to 4.71 mm in dynamic phantom validation compared to current available methods. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

An Improved Single-Step Cloning Strategy Simplifies the Agrobacterium tumefaciens-Mediated Transformation (ATMT)-Based Gene-Disruption Method for Verticillium dahliae.

PubMed

Wang, Sheng; Xing, Haiying; Hua, Chenlei; Guo, Hui-Shan; Zhang, Jie

2016-06-01

The soilborne fungal pathogen Verticillium dahliae infects a broad range of plant species to cause severe diseases. The availability of Verticillium genome sequences has provided opportunities for large-scale investigations of individual gene function in Verticillium strains using Agrobacterium tumefaciens-mediated transformation (ATMT)-based gene-disruption strategies. Traditional ATMT vectors require multiple cloning steps and elaborate characterization procedures to achieve successful gene replacement; thus, these vectors are not suitable for high-throughput ATMT-based gene deletion. Several advancements have been made that either involve simplification of the steps required for gene-deletion vector construction or increase the efficiency of the technique for rapid recombinant characterization. However, an ATMT binary vector that is both simple and efficient is still lacking. Here, we generated a USER-ATMT dual-selection (DS) binary vector, which combines both the advantages of the USER single-step cloning technique and the efficiency of the herpes simplex virus thymidine kinase negative-selection marker. Highly efficient deletion of three different genes in V. dahliae using the USER-ATMT-DS vector enabled verification that this newly-generated vector not only facilitates the cloning process but also simplifies the subsequent identification of fungal homologous recombinants. The results suggest that the USER-ATMT-DS vector is applicable for efficient gene deletion and suitable for large-scale gene deletion in V. dahliae.

Social cognition and social problem solving abilities in individuals with alcohol use disorder.

PubMed

Schmidt, Tobias; Roser, Patrik; Juckel, Georg; Brüne, Martin; Suchan, Boris; Thoma, Patrizia

2016-11-01

Up to now, little is known about higher order cognitive abilities like social cognition and social problem solving abilities in alcohol-dependent patients. However, impairments in these domains lead to an increased probability for relapse and are thus highly relevant in treatment contexts. This cross-sectional study assessed distinct aspects of social cognition and social problem solving in 31 hospitalized patients with alcohol use disorder (AUD) and 30 matched healthy controls (HC). Three ecologically valid scenario-based tests were used to gauge the ability to infer the mental state of story characters in complicated interpersonal situations, the capacity to select the best problem solving strategy among other less optimal alternatives, and the ability to freely generate appropriate strategies to handle difficult interpersonal conflicts. Standardized tests were used to assess executive function, attention, trait empathy, and memory, and correlations were computed between measures of executive function, attention, trait empathy, and tests of social problem solving. AUD patients generated significantly fewer socially sensitive and practically effective solutions for problematic interpersonal situations than the HC group. Furthermore, patients performed significantly worse when asked to select the best alternative among a list of presented alternatives for scenarios containing sarcastic remarks and had significantly more problems to interpret sarcastic remarks in difficult interpersonal situations. These specific patterns of impairments should be considered in treatment programs addressing impaired social skills in individuals with AUD.

Perspectives of Probabilistic Inferences: Reinforcement Learning and an Adaptive Network Compared

ERIC Educational Resources Information Center

Rieskamp, Jorg

2006-01-01

The assumption that people possess a strategy repertoire for inferences has been raised repeatedly. The strategy selection learning theory specifies how people select strategies from this repertoire. The theory assumes that individuals select strategies proportional to their subjective expectations of how well the strategies solve particular…

Effects of strategy sequences and response-stimulus intervals on children's strategy selection and strategy execution: a study in computational estimation.

PubMed

Lemaire, Patrick; Brun, Fleur

2014-07-01

The present study investigates how children's better strategy selection and strategy execution on a given problem are influenced by which strategy was used on the immediately preceding problem and by the duration between their answer to the previous problem and current problem display. These goals are pursued in the context of an arithmetic problem solving task. Third and fifth graders were asked to select the better strategy to find estimates to two-digit addition problems like 36 + 78. On each problem, children could choose rounding-down (i.e., rounding both operands down to the closest smaller decades, like doing 40 + 60 to solve 42 + 67) or rounding-up strategies (i.e., rounding both operands up to the closest larger decades, like doing 50 + 70 to solve 42 + 67). Children were tested under a short RSI condition (i.e., the next problem was displayed 900 ms after participants' answer) or under a long RSI condition (i.e., the next problem was displayed 1,900 ms after participants' answer). Results showed that both strategy selection (e.g., children selected the better strategy more often under long RSI condition and after selecting the poorer strategy on the immediately preceding problem) and strategy execution (e.g., children executed strategy more efficiently under long RSI condition and were slower when switching strategy over two consecutive problems) were influenced by RSI and which strategy was used on the immediately preceding problem. Moreover, data showed age-related changes in effects of RSI and strategy sequence on mean percent better strategy selection and on strategy performance. The present findings have important theoretical and empirical implications for our understanding of general and specific processes involved in strategy selection, strategy execution, and strategic development.

Rapid development of stable transgene CHO cell lines by CRISPR/Cas9-mediated site-specific integration into C12orf35.

PubMed

Zhao, Menglin; Wang, Jiaxian; Luo, Manyu; Luo, Han; Zhao, Meiqi; Han, Lei; Zhang, Mengxiao; Yang, Hui; Xie, Yueqing; Jiang, Hua; Feng, Lei; Lu, Huili; Zhu, Jianwei

2018-07-01

Chinese hamster ovary (CHO) cells are the most widely used mammalian hosts for recombinant protein production. However, by conventional random integration strategy, development of a high-expressing and stable recombinant CHO cell line has always been a difficult task due to the heterogenic insertion and its caused requirement of multiple rounds of selection. Site-specific integration of transgenes into CHO hot spots is an ideal strategy to overcome these challenges since it can generate isogenic cell lines with consistent productivity and stability. In this study, we investigated three sites with potential high transcriptional activities: C12orf35, HPRT, and GRIK1, to determine the possible transcriptional hot spots in CHO cells, and further construct a reliable site-specific integration strategy to develop recombinant cell lines efficiently. Genes encoding representative proteins mCherry and anti-PD1 monoclonal antibody were targeted into these three loci respectively through CRISPR/Cas9 technology. Stable cell lines were generated successfully after a single round of selection. In comparison with a random integration control, all the targeted integration cell lines showed higher productivity, among which C12orf35 locus was the most advantageous in both productivity and cell line stability. Binding affinity and N-glycan analysis of the antibody revealed that all batches of product were of similar quality independent on integrated sites. Deep sequencing demonstrated that there was low level of off-target mutations caused by CRISPR/Cas9, but none of them contributed to the development process of transgene cell lines. Our results demonstrated the feasibility of C12orf35 as the target site for exogenous gene integration, and strongly suggested that C12orf35 targeted integration mediated by CRISPR/Cas9 is a reliable strategy for the rapid development of recombinant CHO cell lines.

Strain Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against Invasive Nontyphoidal Salmonella Disease

PubMed Central

Saul, Allan; MacLennan, Calman A.; Micoli, Francesca; Rondini, Simona

2015-01-01

Nontyphoidal Salmonellae, principally S. Typhimurium and S. Enteritidis, are a major cause of invasive bloodstream infections in sub-Saharan Africa with no vaccine currently available. Conjugation of lipopolysaccharide O-antigen to a carrier protein constitutes a promising vaccination strategy. Here we describe a rational process to select the most appropriate isolates of Salmonella as source of O-antigen for developing a bivalent glycoconjugate vaccine. We screened a library of 30 S. Typhimurium and 21 S. Enteritidis in order to identify the most suitable strains for large scale O-antigen production and generation of conjugate vaccines. Initial screening was based on growth characteristics, safety profile of the isolates, O-antigen production, and O-antigen characteristics in terms of molecular size, O-acetylation and glucosylation level and position, as determined by phenol sulfuric assay, NMR, HPLC-SEC and HPAEC-PAD. Three animal isolates for each serovar were identified and used to synthesize candidate glycoconjugate vaccines, using CRM197 as carrier protein. The immunogenicity of these conjugates and the functional activity of the induced antibodies was investigated by ELISA, serum bactericidal assay and flow cytometry. S. Typhimurium O-antigen showed high structural diversity, including O-acetylation of rhamnose in a Malawian invasive strain generating a specific immunodominant epitope. S. Typhimurium conjugates provoked an anti-O-antigen response primarily against the O:5 determinant. O-antigen from S. Enteritidis was structurally more homogeneous than from S. Typhimurium, and no idiosyncratic antibody responses were detected for the S. Enteritidis conjugates. Of the three initially selected isolates, two S. Typhimurium (1418 and 2189) and two S. Enteritidis (502 and 618) strains generated glycoconjugates able to induce high specific antibody levels with high breadth of serovar-specific strain coverage, and were selected for use in vaccine production. The strain selection approach described is potentially applicable to the development of glycoconjugate vaccines against other bacterial pathogens. PMID:26445460

Adaptive suboptimal second-order sliding mode control for microgrids

NASA Astrophysics Data System (ADS)

Incremona, Gian Paolo; Cucuzzella, Michele; Ferrara, Antonella

2016-09-01

This paper deals with the design of adaptive suboptimal second-order sliding mode (ASSOSM) control laws for grid-connected microgrids. Due to the presence of the inverter, of unpredicted load changes, of switching among different renewable energy sources, and of electrical parameters variations, the microgrid model is usually affected by uncertain terms which are bounded, but with unknown upper bounds. To theoretically frame the control problem, the class of second-order systems in Brunovsky canonical form, characterised by the presence of matched uncertain terms with unknown bounds, is first considered. Four adaptive strategies are designed, analysed and compared to select the most effective ones to be applied to the microgrid case study. In the first two strategies, the control amplitude is continuously adjusted, so as to arrive at dominating the effect of the uncertainty on the controlled system. When a suitable control amplitude is attained, the origin of the state space of the auxiliary system becomes attractive. In the other two strategies, a suitable blend between two components, one mainly working during the reaching phase, the other being the predominant one in a vicinity of the sliding manifold, is generated, so as to reduce the control amplitude in steady state. The microgrid system in a grid-connected operation mode, controlled via the selected ASSOSM control strategies, exhibits appreciable stability properties, as proved theoretically and shown in simulation.

Strengths and weaknesses in the consultation skills of senior medical students: identification, enhancement and curricular change.

PubMed

Hastings, Am; McKinley, R K; Fraser, R C

2006-05-01

This paper seeks to describe the consultation strengths and weaknesses of senior medical students, the explicit and prioritised strategies for improvement utilised in student feedback, and curriculum developments informed by this work. Prospective, descriptive study of students on clinical placements in general practice. All were observed directly by 2 assessors in consultation with 5 patients in a general practice setting. Performance was judged against 5 categories of consultation competence and 35 component competences as contained in a modified version of the Leicester Assessment Package. Specific strategies for improvement were selected from a list of 69 previously formulated strategies. Data from 1116 students were included. The consultation competences identified most frequently as strengths related to interpersonal skills, while weaknesses were mainly in the domain of clinical problem-solving. The median number of key strengths identified per student was 5, with 5 additional but lesser strengths. A median of 3 key and lesser weaknesses were identified. The average number of strategies selected to address an identified weakness was 1.2. Students rated the assessment process and its impact very positively. The systematic assessment of the consultation competence of medical students by direct observation involving real patients is feasible and facilitates the 'educational diagnosis' of individuals and of their peer group. It has informed development of teaching and generated research hypotheses.

The Development of Quality Control Genotyping Approaches: A Case Study Using Elite Maize Lines.

PubMed

Chen, Jiafa; Zavala, Cristian; Ortega, Noemi; Petroli, Cesar; Franco, Jorge; Burgueño, Juan; Costich, Denise E; Hearne, Sarah J

2016-01-01

Quality control (QC) of germplasm identity and purity is a critical component of breeding and conservation activities. SNP genotyping technologies and increased availability of markers provide the opportunity to employ genotyping as a low-cost and robust component of this QC. In the public sector available low-cost SNP QC genotyping methods have been developed from a very limited panel of markers of 1,000 to 1,500 markers without broad selection of the most informative SNPs. Selection of optimal SNPs and definition of appropriate germplasm sampling in addition to platform section impact on logistical and resource-use considerations for breeding and conservation applications when mainstreaming QC. In order to address these issues, we evaluated the selection and use of SNPs for QC applications from large DArTSeq data sets generated from CIMMYT maize inbred lines (CMLs). Two QC genotyping strategies were developed, the first is a "rapid QC", employing a small number of SNPs to identify potential mislabeling of seed packages or plots, the second is a "broad QC", employing a larger number of SNP, used to identify each germplasm entry and to measure heterogeneity. The optimal marker selection strategies combined the selection of markers with high minor allele frequency, sampling of clustered SNP in proportion to marker cluster distance and selecting markers that maintain a uniform genomic distribution. The rapid and broad QC SNP panels selected using this approach were further validated using blind test assessments of related re-generation samples. The influence of sampling within each line was evaluated. Sampling 192 individuals would result in close to 100% possibility of detecting a 5% contamination in the entry, and approximately a 98% probability to detect a 2% contamination of the line. These results provide a framework for the establishment of QC genotyping. A comparison of financial and time costs for use of these approaches across different platforms is discussed providing a framework for institutions involved in maize conservation and breeding to assess the resource use effectiveness of QC genotyping. Application of these research findings, in combination with existing QC approaches, will ensure the regeneration, distribution and use in breeding of true to type inbred germplasm. These findings also provide an effective approach to optimize SNP selection for QC genotyping in other species.

New Modulation Method and Control Strategies for Power Electronics Inverters

NASA Astrophysics Data System (ADS)

Aleenejad, Mohsen

The DC to AC power Converters (so-called Inverters) are widely used in industrial applications. The MLIs are becoming increasingly popular in industrial apparatus aimed at medium to high power conversion applications. In comparison to the conventional inverters, they feature superior characteristics such as lower total harmonic distortion (THD), higher efficiency, and lower switching voltage stress. Nevertheless, the superior characteristics come at the price of a more complex topology with an increased number of power electronic switches. The increased number of power electronics switches results in more complicated control strategies for the inverter. Moreover, as the number of power electronic switches increases, the chances of fault occurrence of the switches increases, and thus the inverter's reliability decreases. Due to the extreme monetary ramifications of the interruption of operation in commercial and industrial applications, high reliability for power inverters utilized in these sectors is critical. As a result, developing simple control strategies for normal and fault-tolerant operation of MLIs has always been an interesting topic for researchers in related areas. The purpose of this dissertation is to develop new control and fault-tolerant strategies for the multilevel power inverter. For the normal operation of the inverter, a new high switching frequency technique is developed. The proposed method extends the utilization of the dc link voltage while minimizing the dv/dt of the switches. In the event of a fault, the line voltages of the faulty inverters are unbalanced and cannot be applied to the 3-phase loads. For the faulty condition of the inverter, three novel fault-tolerant techniques are developed. The proposed fault-tolerant strategies generate balanced line voltages without bypassing any healthy and operative inverter element, makes better use of the inverter capacity and generates higher output voltage. These strategies exploit the advantages of the Selective Harmonic Elimination (SHE) and Space Vector Modulation (SVM) methods in conjunction with a slightly modified Fundamental Phase Shift Compensation (FPSC) technique to generate balanced voltages and manipulate voltage harmonics at the same time. The proposed strategies are applicable to several classes of MLIs with three or more voltage levels.

Range Sensor-Based Efficient Obstacle Avoidance through Selective Decision-Making.

PubMed

Shim, Youngbo; Kim, Gon-Woo

2018-03-29

In this paper, we address a collision avoidance method for mobile robots. Many conventional obstacle avoidance methods have been focused solely on avoiding obstacles. However, this can cause instability when passing through a narrow passage, and can also generate zig-zag motions. We define two strategies for obstacle avoidance, known as Entry mode and Bypass mode. Entry mode is a pattern for passing through the gap between obstacles, while Bypass mode is a pattern for making a detour around obstacles safely. With these two modes, we propose an efficient obstacle avoidance method based on the Expanded Guide Circle (EGC) method with selective decision-making. The simulation and experiment results show the validity of the proposed method.

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

PubMed Central

Rublack, Nico

2014-01-01

Summary Over the past 20 years, the generation of functional RNAs by in vitro selection has become a standard technique. Apart from aptamers for simple binding of defined ligands, also RNAs for catalysis of chemical reactions have been selected. In the latter case, a key step often is the conjugation of one of the two reactants to the library, requiring suitable strategies for terminal or internal RNA functionalization. With the aim of selecting a ribozyme for deamination of cytidine, we have set up a selection scheme involving the attachment of the cytidine acting as deamination substrate to the 3'-terminus of the RNAs in the library, and library immobilization. Here, we report the synthesis of a bifunctional cytidine derivative suitable for conjugation to RNA and linkage of the conjugated library to a streptavidine-coated surface. Successful conjugation of the cytidine derivative to the 3'-terminus of a model RNA is demonstrated. PMID:25246949

Accuracy of genomic selection in European maize elite breeding populations.

PubMed

Zhao, Yusheng; Gowda, Manje; Liu, Wenxin; Würschum, Tobias; Maurer, Hans P; Longin, Friedrich H; Ranc, Nicolas; Reif, Jochen C

2012-03-01

Genomic selection is a promising breeding strategy for rapid improvement of complex traits. The objective of our study was to investigate the prediction accuracy of genomic breeding values through cross validation. The study was based on experimental data of six segregating populations from a half-diallel mating design with 788 testcross progenies from an elite maize breeding program. The plants were intensively phenotyped in multi-location field trials and fingerprinted with 960 SNP markers. We used random regression best linear unbiased prediction in combination with fivefold cross validation. The prediction accuracy across populations was higher for grain moisture (0.90) than for grain yield (0.58). The accuracy of genomic selection realized for grain yield corresponds to the precision of phenotyping at unreplicated field trials in 3-4 locations. As for maize up to three generations are feasible per year, selection gain per unit time is high and, consequently, genomic selection holds great promise for maize breeding programs.

Automated generation of IMRT treatment plans for prostate cancer patients with metal hip prostheses: Comparison of different planning strategies

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

Voet, Peter W. J.; Dirkx, Maarten L. P.; Breedveld, Sebastiaan

2013-07-15

Purpose: To compare IMRT planning strategies for prostate cancer patients with metal hip prostheses.Methods: All plans were generated fully automatically (i.e., no human trial-and-error interactions) using iCycle, the authors' in-house developed algorithm for multicriterial selection of beam angles and optimization of fluence profiles, allowing objective comparison of planning strategies. For 18 prostate cancer patients (eight with bilateral hip prostheses, ten with a right-sided unilateral prosthesis), two planning strategies were evaluated: (i) full exclusion of beams containing beamlets that would deliver dose to the target after passing a prosthesis (IMRT{sub remove}) and (ii) exclusion of those beamlets only (IMRT{sub cut}). Plansmore » with optimized coplanar and noncoplanar beam arrangements were generated. Differences in PTV coverage and sparing of organs at risk (OARs) were quantified. The impact of beam number on plan quality was evaluated.Results: Especially for patients with bilateral hip prostheses, IMRT{sub cut} significantly improved rectum and bladder sparing compared to IMRT{sub remove}. For 9-beam coplanar plans, rectum V{sub 60Gy} reduced by 17.5%{+-} 15.0% (maximum 37.4%, p= 0.036) and rectum D{sub mean} by 9.4%{+-} 7.8% (maximum 19.8%, p= 0.036). Further improvements in OAR sparing were achievable by using noncoplanar beam setups, reducing rectum V{sub 60Gy} by another 4.6%{+-} 4.9% (p= 0.012) for noncoplanar 9-beam IMRT{sub cut} plans. Large reductions in rectum dose delivery were also observed when increasing the number of beam directions in the plans. For bilateral implants, the rectum V{sub 60Gy} was 37.3%{+-} 12.1% for coplanar 7-beam plans and reduced on average by 13.5% (maximum 30.1%, p= 0.012) for 15 directions.Conclusions: iCycle was able to automatically generate high quality plans for prostate cancer patients with prostheses. Excluding only beamlets that passed through the prostheses (IMRT{sub cut} strategy) significantly improved OAR sparing. Noncoplanar beam arrangements and, to a larger extent, increasing the number of treatment beams further improved plan quality.« less

Target guided synthesis using DNA nano-templates for selectively assembling a G-quadruplex binding c-MYC inhibitor

NASA Astrophysics Data System (ADS)

Panda, Deepanjan; Saha, Puja; Das, Tania; Dash, Jyotirmayee

2017-07-01

The development of small molecules is essential to modulate the cellular functions of biological targets in living system. Target Guided Synthesis (TGS) approaches have been used for the identification of potent small molecules for biological targets. We herein demonstrate an innovative example of TGS using DNA nano-templates that promote Huisgen cycloaddition from an array of azide and alkyne fragments. A G-quadruplex and a control duplex DNA nano-template have been prepared by assembling the DNA structures on gold-coated magnetic nanoparticles. The DNA nano-templates facilitate the regioselective formation of 1,4-substituted triazole products, which are easily isolated by magnetic decantation. The G-quadruplex nano-template can be easily recovered and reused for five reaction cycles. The major triazole product, generated by the G-quadruplex inhibits c-MYC expression by directly targeting the c-MYC promoter G-quadruplex. This work highlights that the nano-TGS approach may serve as a valuable strategy to generate target-selective ligands for drug discovery.

Alectinib: a selective, next-generation ALK inhibitor for treatment of ALK-rearranged non-small-cell lung cancer.

PubMed

Santarpia, Mariacarmela; Altavilla, Giuseppe; Rosell, Rafael

2015-06-01

Crizotinib was the first clinically available anaplastic lymphoma kinase (ALK) inhibitor, showing remarkable activity against ALK-rearranged non-small-cell lung cancer (NSCLC). Despite initial responses, acquired resistance to crizotinib inevitably develops, with the brain being a common site of relapse. Alectinib is a highly selective, next-generation ALK inhibitor with potent inhibitory activity also against ALK mutations conferring resistance to crizotinib, including the gatekeeper L1196M substitution. In a Phase I/II study from Japan, alectinib was found to be highly active and safe in crizotinib-naïve, ALK-rearranged NSCLC patients. Alectinib also demonstrated promising antitumor activity in crizotinib-resistant patients, including those with CNS metastases. Based on these data, the drug received Breakthrough Therapy Designation by the US FDA and has been recently approved in Japan for the treatment of ALK-positive, advanced NSCLC patients. However, patients may eventually develop resistance to alectinib, highlighting the need for novel therapeutic strategies to further improve the management of ALK-rearranged NSCLC.

Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

PubMed

Bian, Yuemin; Xie, Xiang-Qun Sean

2018-04-09

Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

Evolution and stability of altruist strategies in microbial games

NASA Astrophysics Data System (ADS)

Adami, Christoph; Schossau, Jory; Hintze, Arend

2012-01-01

When microbes compete for limited resources, they often engage in chemical warfare using bacterial toxins. This competition can be understood in terms of evolutionary game theory (EGT). We study the predictions of EGT for the bacterial “suicide bomber” game in terms of the phase portraits of population dynamics, for parameter combinations that cover all interesting games for two-players, and seven of the 38 possible phase portraits of the three-player game. We compare these predictions to simulations of these competitions in finite well-mixed populations, but also allowing for probabilistic rather than pure strategies, as well as Darwinian adaptation over tens of thousands of generations. We find that Darwinian evolution of probabilistic strategies stabilizes games of the rock-paper-scissors type that emerge for parameters describing realistic bacterial populations, and point to ways in which the population fixed point can be selected by changing those parameters.

Flowering time and seed dormancy control use external coincidence to generate life history strategy.

PubMed

Springthorpe, Vicki; Penfield, Steven

2015-03-31

Climate change is accelerating plant developmental transitions coordinated with the seasons in temperate environments. To understand the importance of these timing advances for a stable life history strategy, we constructed a full life cycle model of Arabidopsis thaliana. Modelling and field data reveal that a cryptic function of flowering time control is to limit seed set of winter annuals to an ambient temperature window which coincides with a temperature-sensitive switch in seed dormancy state. This coincidence is predicted to be conserved independent of climate at the expense of flowering date, suggesting that temperature control of flowering time has evolved to constrain seed set environment and therefore frequency of dormant and non-dormant seed states. We show that late flowering can disrupt this bet-hedging germination strategy. Our analysis shows that life history modelling can reveal hidden fitness constraints and identify non-obvious selection pressures as emergent features.

Adapting Knowledge Translation Strategies for Rare Rheumatic Diseases.

PubMed

Cellucci, Tania; Lee, Shirley; Webster, Fiona

2016-08-01

Rare rheumatic diseases present unique challenges to knowledge translation (KT) researchers. There is often an urgent need to transfer knowledge from research findings into clinical practice to facilitate earlier diagnosis and better outcomes. However, existing KT frameworks have not addressed the specific considerations surrounding rare diseases for which gold standard evidence is not available. Several widely adopted models provide guidance for processes and problems associated with KT. However, they do not address issues surrounding creation or synthesis of knowledge for rare diseases. Additional problems relate to lack of awareness or experience in intended knowledge users, low motivation, and potential barriers to changing practice or policy. Strategies to address the challenges of KT for rare rheumatic diseases include considering different levels of evidence available, linking knowledge creation and transfer directly, incorporating patient and physician advocacy efforts to generate awareness of conditions, and selecting strategies to address barriers to practice or policy change.

Met gene amplification and protein hyperactivation is a mechanism of resistance to both first and third generation EGFR inhibitors in lung cancer treatment.

PubMed

Shi, Puyu; Oh, You-Take; Zhang, Guojing; Yao, Weilong; Yue, Ping; Li, Yikun; Kanteti, Rajani; Riehm, Jacob; Salgia, Ravi; Owonikoko, Taofeek K; Ramalingam, Suresh S; Chen, Mingwei; Sun, Shi-Yong

2016-10-01

The 3rd generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs; e.g., AZD9291), which selectively and irreversibly inhibit EGFR activating and T790M mutants, represent very promising therapeutic options for patients with non-small cell lung cancer (NSCLC) that has become resistant to 1st generation EGFR-TKIs due to T790M mutation. However, eventual resistance to the 3rd generation EGFR-TKIs has already been described in the clinic, resulting in disease progression. Therefore, there is a great challenge and urgent need to understand how this resistance occurs and to develop effective strategies to delay or overcome the resistance. The current study has demonstrated that Met amplification and hyperactivation is a resistance mechanism to both 1st and 3rd generation EGFR-TKIs since both erlotinib- and AZD9291-resistant HCC827 cell lines possessed amplified Met gene and hyperactivated Met, and were cross-resistant to AZD9291 or erlotinib. Met inhibition overcame the resistance of these cell lines to AZD9291 both in vitro and in vivo, including enhancement of apoptosis or G1 cell cycle arrest. Hence, we suggest that Met inhibition is also an effective strategy to overcome resistance of certain EGFR-mutated NSCLCs with Met amplification to AZD9291, warranting the further clinical validation of our findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A game-based decision support methodology for competitive systems design

NASA Astrophysics Data System (ADS)

Briceno, Simon Ignacio

This dissertation describes the development of a game-based methodology that facilitates the exploration and selection of research and development (R&D) projects under uncertain competitive scenarios. The proposed method provides an approach that analyzes competitor positioning and formulates response strategies to forecast the impact of technical design choices on a project's market performance. A critical decision in the conceptual design phase of propulsion systems is the selection of the best architecture, centerline, core size, and technology portfolio. This selection can be challenging when considering evolving requirements from both the airframe manufacturing company and the airlines in the market. Furthermore, the exceedingly high cost of core architecture development and its associated risk makes this strategic architecture decision the most important one for an engine company. Traditional conceptual design processes emphasize performance and affordability as their main objectives. These areas alone however, do not provide decision-makers with enough information as to how successful their engine will be in a competitive market. A key objective of this research is to examine how firm characteristics such as their relative differences in completing R&D projects, differences in the degree of substitutability between different project types, and first/second-mover advantages affect their product development strategies. Several quantitative methods are investigated that analyze business and engineering strategies concurrently. In particular, formulations based on the well-established mathematical field of game theory are introduced to obtain insights into the project selection problem. The use of game theory is explored in this research as a method to assist the selection process of R&D projects in the presence of imperfect market information. The proposed methodology focuses on two influential factors: the schedule uncertainty of project completion times and the uncertainty associated with competitive reactions. A normal-form matrix is created to enumerate players, their moves and payoffs, and to formulate a process by which an optimal decision can be achieved. The non-cooperative model is tested using the concept of a Nash equilibrium to identify potential strategies that are robust to uncertain market fluctuations (e.g: uncertainty in airline demand, airframe requirements and competitor positioning). A first/second-mover advantage parameter is used as a scenario dial to adjust market rewards and firms' payoffs. The methodology is applied to a commercial aircraft engine selection study where engine firms must select an optimal engine project for development. An engine modeling and simulation framework is developed to generate a broad engine project portfolio. The creation of a customer value model enables designers to incorporate airline operation characteristics into the engine modeling and simulation process to improve the accuracy of engine/customer matching. Summary. Several key findings are made that provide recommendations on project selection strategies for firms uncertain as to when they will enter the market. The proposed study demonstrates that within a technical design environment, a rational and analytical means of modeling project development strategies is beneficial in high market risk situations.

Evaluation of pyritic mine tailings as a plant growth substrate.

PubMed

Roseby, Stuart J; Kopittke, Peter M; Mulligan, David R; Menzies, Neal W

2017-10-01

At the Kidston gold mine, Australia, the direct establishment of vegetation on tailings was considered as an alternative to the use of a waste rock cover. The tailings acid/base account was used to predict plant growth limitation by acidity, and thus methods capable of identifying tailings that would acidify to pH 4.5 or lower were sought. Total S was found to be poorly correlated with acid-generating sulfide, and total C was poorly correlated with acid-neutralizing carbonate, precluding the use of readily determined total S and C as predictors of net acid generation. Therefore, the selected approach used assessment of sulfide content as a predictor of acid generation, and carbonate content as a measure of the acid-neutralizing capacity available at pH 5 and above. Using this approach, the majority of tailings (67%) were found to be non-acid generating. However, areas of potentially acid-generating tailings were randomly distributed across the dam, and could only be located by intensive sampling. The limitations imposed by the large sample numbers, and costly analysis of sulfide and carbonate, make it impractical to identify and ameliorate acid-generating areas prior to vegetation establishment. However, as only a small proportion of the tailings will acidify, a strategy of re-treating acid areas following oxidation is suggested. The findings of the present study will assist in the selection of appropriate methods for the prediction of net acid generation, particularly where more conservative measurements are required to allow vegetation to be established directly in tailings. Copyright © 2017 Elsevier Ltd. All rights reserved.

A dynamic multiarmed bandit-gene expression programming hyper-heuristic for combinatorial optimization problems.

PubMed

Sabar, Nasser R; Ayob, Masri; Kendall, Graham; Qu, Rong

2015-02-01

Hyper-heuristics are search methodologies that aim to provide high-quality solutions across a wide variety of problem domains, rather than developing tailor-made methodologies for each problem instance/domain. A traditional hyper-heuristic framework has two levels, namely, the high level strategy (heuristic selection mechanism and the acceptance criterion) and low level heuristics (a set of problem specific heuristics). Due to the different landscape structures of different problem instances, the high level strategy plays an important role in the design of a hyper-heuristic framework. In this paper, we propose a new high level strategy for a hyper-heuristic framework. The proposed high-level strategy utilizes a dynamic multiarmed bandit-extreme value-based reward as an online heuristic selection mechanism to select the appropriate heuristic to be applied at each iteration. In addition, we propose a gene expression programming framework to automatically generate the acceptance criterion for each problem instance, instead of using human-designed criteria. Two well-known, and very different, combinatorial optimization problems, one static (exam timetabling) and one dynamic (dynamic vehicle routing) are used to demonstrate the generality of the proposed framework. Compared with state-of-the-art hyper-heuristics and other bespoke methods, empirical results demonstrate that the proposed framework is able to generalize well across both domains. We obtain competitive, if not better results, when compared to the best known results obtained from other methods that have been presented in the scientific literature. We also compare our approach against the recently released hyper-heuristic competition test suite. We again demonstrate the generality of our approach when we compare against other methods that have utilized the same six benchmark datasets from this test suite.

Optimal generator bidding strategies for power and ancillary services

NASA Astrophysics Data System (ADS)

Morinec, Allen G.

As the electric power industry transitions to a deregulated market, power transactions are made upon price rather than cost. Generator companies are interested in maximizing their profits rather than overall system efficiency. A method to equitably compensate generation providers for real power, and ancillary services such as reactive power and spinning reserve, will ensure a competitive market with an adequate number of suppliers. Optimizing the generation product mix during bidding is necessary to maximize a generator company's profits. The objective of this research work is to determine and formulate appropriate optimal bidding strategies for a generation company in both the energy and ancillary services markets. These strategies should incorporate the capability curves of their generators as constraints to define the optimal product mix and price offered in the day-ahead and real time spot markets. In order to achieve such a goal, a two-player model was composed to simulate market auctions for power generation. A dynamic game methodology was developed to identify Nash Equilibria and Mixed-Strategy Nash Equilibria solutions as optimal generation bidding strategies for two-player non-cooperative variable-sum matrix games with incomplete information. These games integrated the generation product mix of real power, reactive power, and spinning reserve with the generators's capability curves as constraints. The research includes simulations of market auctions, where strategies were tested for generators with different unit constraints, costs, types of competitors, strategies, and demand levels. Studies on the capability of large hydrogen cooled synchronous generators were utilized to derive useful equations that define the exact shape of the capability curve from the intersections of the arcs defined by the centers and radial vectors of the rotor, stator, and steady-state stability limits. The available reactive reserve and spinning reserve were calculated given a generator operating point in the P-Q plane. Four computer programs were developed to automatically perform the market auction simulations using the equal incremental cost rule. The software calculates the payoffs for the two competing competitors, dispatches six generators, and allocates ancillary services for 64 combinations of bidding strategies, three levels of system demand, and three different types of competitors. Matrix Game theory was utilized to calculate Nash Equilibrium solutions and mixed-strategy Nash solutions as the optimal generator bidding strategies. A method to incorporate ancillary services into the generation bidding strategy, to assure an adequate supply of ancillary services, and to allocate these necessary resources to the on-line units was devised. The optimal generator bid strategy in a power auction was shown to be the Nash Equilibrium solution found in two-player variable-sum matrix games.

In-silico evidences for binding of Glucokinase activators to EGFR C797S to overcome EGFR resistance obstacle with mutant-selective allosteric inhibition.

PubMed

Patel, Harun; Pawara, Rahul; Surana, Sanjay

2018-03-29

The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are generally utilized as a part of patients with non-small cell lung carcinoma (NSCLC). However, EGFR T790M mutation results in resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation has been in active clinical development to triumph the resistance problem; they covalently bind with conserved Cys797 inside the EGFR active site, offering both potency and kinase-selectivity. Third generation drugs target C797, which makes the C797S resistance mutation more subtle. EGFR C797S mutation was accounted to be a main mechanism of resistance to the third-generation inhibitors. The C797S mutation gives off an impression of being an ideal target for conquering the acquired resistance to the third generation inhibitors. We have performed structure based-virtual screening strategies for binding of glucokinase activator to EGFR C797S, which can overcome EGFR resistance impediment with mutant-selective allosteric inhibition towards all kinds of mutant EGFR (T790M, L858R, TMLR) and WT EGFR. The final filter of Lipinski's Rule of Five, Jargan's Rule of Three and in silico ADME predictions gave 23 hits, which conform to Lipinski's rule and Jorgensen's rule and all their pharmacokinetic parameters are inside the appropriate range characterized for human use, in this manner demonstrating their potential as a drug-like molecule. Copyright © 2018 Elsevier Ltd. All rights reserved.

Harnessing dendritic cells in inflammatory skin diseases.

PubMed

Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

2011-02-01

The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification.

PubMed

Sahn, James J; Granger, Brett A; Martin, Stephen F

2014-10-21

A strategy for generating diverse collections of small molecules has been developed that features a multicomponent assembly process (MCAP) to efficiently construct a variety of intermediates possessing an aryl aminomethyl subunit. These key compounds are then transformed via selective ring-forming reactions into heterocyclic scaffolds, each of which possesses suitable functional handles for further derivatizations and palladium-catalyzed cross coupling reactions. The modular nature of this approach enables the facile construction of libraries of polycyclic compounds bearing a broad range of substituents and substitution patterns for biological evaluation. Screening of several compound libraries thus produced has revealed a large subset of compounds that exhibit a broad spectrum of medicinally-relevant activities.

Releasing N-glycan from peptide N-terminus by N-terminal succinylation assisted enzymatic deglycosylation.

PubMed

Weng, Yejing; Sui, Zhigang; Jiang, Hao; Shan, Yichu; Chen, Lingfan; Zhang, Shen; Zhang, Lihua; Zhang, Yukui

2015-04-22

Due to the important roles of N-glycoproteins in various biological processes, the global N-glycoproteome analysis has been paid much attention. However, by current strategies for N-glycoproteome profiling, peptides with glycosylated Asn at N-terminus (PGANs), generated by protease digestion, could hardly be identified, due to the poor deglycosylation capacity by enzymes. However, theoretically, PGANs occupy 10% of N-glycopeptides in the typical tryptic digests. Therefore, in this study, we developed a novel strategy to identify PGANs by releasing N-glycans through the N-terminal site-selective succinylation assisted enzymatic deglycosylation. The obtained PGANs information is beneficial to not only achieve the deep coverage analysis of glycoproteomes, but also discover the new biological functions of such modification.

Solving a four-destination traveling salesman problem using Escherichia coli cells as biocomputers.

PubMed

Esau, Michael; Rozema, Mark; Zhang, Tuo Huang; Zeng, Dawson; Chiu, Stephanie; Kwan, Rachel; Moorhouse, Cadence; Murray, Cameron; Tseng, Nien-Tsu; Ridgway, Doug; Sauvageau, Dominic; Ellison, Michael

2014-12-19

The Traveling Salesman Problem involves finding the shortest possible route visiting all destinations on a map only once before returning to the point of origin. The present study demonstrates a strategy for solving Traveling Salesman Problems using modified E. coli cells as processors for massively parallel computing. Sequential, combinatorial DNA assembly was used to generate routes, in the form of plasmids made up of marker genes, each representing a path between destinations, and short connecting linkers, each representing a given destination. Upon growth of the population of modified E. coli, phenotypic selection was used to eliminate invalid routes, and statistical analysis was performed to successfully identify the optimal solution. The strategy was successfully employed to solve a four-destination test problem.

A comparison of self-generated versus taught internal strategies for working memory.

PubMed

Dirette, Diane Powers

2015-01-01

Internal strategies are effective for improving working memory. These internal working memory strategies can be taught or self-generated. This study compares working memory performance using taught versus self-generated internal working memory strategies and explores the quantity, type and carry-over of the use of these strategies. An experimental cohort design with randomly assigned groups compared the performances among 120 participants on 5 memory tests given prior, immediately following and at 1 month post intervention. There were no significant differences in the number or type of internal memory strategies used by the groups with chunking, repetition and association used most commonly. The group that self-generated strategies performed significantly better on a contextual memory test and the group that was taught strategies performed better on a face/name recall test for which a specific strategy was taught. The group that was taught strategies performed significantly worse on contextual memory tests from pre-test to follow-up. Participants who generated their own strategies or used a specific strategy for a specific task did as well as participants who were taught myriad internal WM strategies. Teaching too many strategies may overwhelm participants or may distract them from using the context that is available in such tasks.

The sexual cascade and the rise of pre-ejaculatory (Darwinian) sexual selection, sex roles, and sexual conflict.

PubMed

Parker, Geoff A

2014-08-21

After brief historic overviews of sexual selection and sexual conflict, I argue that pre-ejaculatory sexual selection (the form of sexual selection discussed by Darwin) arose at a late stage in an inevitable succession of transitions flowing from the early evolution of syngamy to the evolution of copulation and sex roles. If certain conditions were met, this "sexual cascade" progressed inevitably, if not, sexual strategy remained fixed at a given stage. Prolonged evolutionary history of intense sperm competition/selection under external fertilization preceded the rise of advanced mobility, which generated pre-ejaculatory sexual selection, followed on land by internal fertilization and reduced sperm competition in the form of postcopulatory sexual selection. I develop a prospective model of the early evolution of mobility, which, as Darwin realized, was the catalyst for pre-ejaculatory sexual selection. Stages in the cascade should be regarded as consequential rather than separate phenomena and, as such, invalidate much current opposition to Darwin-Bateman sex roles. Potential for sexual conflict occurs throughout, greatly increasing later in the cascade, reaching its peak under precopulatory sexual selection when sex roles become highly differentiated. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

The Sexual Cascade and the Rise of Pre-Ejaculatory (Darwinian) Sexual Selection, Sex Roles, and Sexual Conflict

PubMed Central

Parker, Geoff A.

2014-01-01

After brief historic overviews of sexual selection and sexual conflict, I argue that pre-ejaculatory sexual selection (the form of sexual selection discussed by Darwin) arose at a late stage in an inevitable succession of transitions flowing from the early evolution of syngamy to the evolution of copulation and sex roles. If certain conditions were met, this “sexual cascade” progressed inevitably, if not, sexual strategy remained fixed at a given stage. Prolonged evolutionary history of intense sperm competition/selection under external fertilization preceded the rise of advanced mobility, which generated pre-ejaculatory sexual selection, followed on land by internal fertilization and reduced sperm competition in the form of postcopulatory sexual selection. I develop a prospective model of the early evolution of mobility, which, as Darwin realized, was the catalyst for pre-ejaculatory sexual selection. Stages in the cascade should be regarded as consequential rather than separate phenomena and, as such, invalidate much current opposition to Darwin–Bateman sex roles. Potential for sexual conflict occurs throughout, greatly increasing later in the cascade, reaching its peak under precopulatory sexual selection when sex roles become highly differentiated. PMID:25147177

Green supply chain management strategy selection using analytic network process: case study at PT XYZ

NASA Astrophysics Data System (ADS)

Adelina, W.; Kusumastuti, R. D.

2017-01-01

This study is about business strategy selection for green supply chain management (GSCM) for PT XYZ by using Analytic Network Process (ANP). GSCM is initiated as a response to reduce environmental impacts from industrial activities. The purposes of this study are identifying criteria and sub criteria in selecting GSCM Strategy, and analysing a suitable GSCM strategy for PT XYZ. This study proposes ANP network with 6 criteria and 29 sub criteria, which are obtained from the literature and experts’ judgements. One of the six criteria contains GSCM strategy options, namely risk-based strategy, efficiency-based strategy, innovation-based strategy, and closed loop strategy. ANP solves complex GSCM strategy-selection by using a more structured process and considering green perspectives from experts. The result indicates that innovation-based strategy is the most suitable green supply chain management strategy for PT XYZ.

Relative fitness of alternative male reproductive tactics in a mammal varies between years.

PubMed

Schradin, Carsten; Lindholm, Anna K

2011-09-01

1. In many species, males can use different behavioural tactics to achieve fertilization, so-called alternative reproductive tactics (ARTs). Few field studies have measured fitness consequences of ARTs under varying environmental conditions. 2. Here, we describe fitness consequences of three phenotypically plastic ARTs in the African striped mouse (Rhabdomys pumilio) and show that relative fitness of ARTs differs between years. Each year represents a different generation. 3. For the generation living under high population density, tactics differed in relative fitness in accordance with the theory of conditional strategies, with highly successful territorial breeding males having 10 times higher success than solitary roaming males and 102 times higher success than adult natally philopatric males. 4. For the generation living under intermediate population density, the territorial breeding and roaming tactics yielded similar fitness, which would be in agreement with the theory of mixed strategies. No philopatric males occurred. 5. For the generation living under low population density, roaming was the only tactic used and some roamers had very high fitness. 6. The main prediction of status-dependent selection for conditional strategies is a correlation between fitness and status, often measured as body mass, but we did not find this correlation within tactics when more than one tactic was expressed in the population. 7. Female distribution seems to have an effect on which reproductive tactics male chose: female defence polygyny when females are clumped (interference competition), but a searching tactic when females are dispersed (scramble competition). In contrast to predictions arising from theory on scramble competition, male body mass was important in determining fitness only in the year when females were dispersed, but not in other years. 8. Our results indicate that the differentiation between conditional and mixed strategies is not an absolute one. In many other species, environmental conditions might fluctuate temporally and spatially so that the normally suboptimal tactic yields similar fitness to the (usually) dominant tactic or that only a single tactic prevails. 9. We suggest the term single strategy, independent of current fitness consequences, for systems where tactics are not genetically determined, in contrast to genetically determined alternative strategies. © 2011 The Authors. Journal of Animal Ecology © 2011 British Ecological Society.

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

Dogan, N; Padgett, K; Evans, J

Purpose: Adaptive Radiotherapy (ART) with frequent CT imaging has been used to improve dosimetric accuracy by accounting for anatomical variations, such as primary tumor shrinkage and/or body weight loss, in Head and Neck (H&N) patients. In most ART strategies, the difference between the planned and the delivered dose is estimated by generating new plans on repeated CT scans using dose-volume constraints used with the initial planning CT without considering already delivered dose. The aim of this study was to assess the dosimetric gains achieved by re-planning based on prior dose by comparing them to re-planning not based-on prior dose formore » H&N patients. Methods: Ten locally-advanced H&N cancer patients were selected for this study. For each patient, six weekly CT imaging were acquired during the course of radiotherapy. PTVs, parotids, cord, brainstem, and esophagus were contoured on both planning and six weekly CT images. ART with weekly re-plans were done by two strategies: 1) Generating a new optimized IMRT plan without including prior dose from previous fractions (NoPriorDose) and 2) Generating a new optimized IMRT plan based on the prior dose given from previous fractions (PriorDose). Deformable image registration was used to accumulate the dose distributions between planning and six weekly CT scans. The differences in accumulated doses for both strategies were evaluated using the DVH constraints for all structures. Results: On average, the differences in accumulated doses for PTV1, PTV2 and PTV3 for NoPriorDose and PriorDose strategies were <2%. The differences in Dmean to the cord and brainstem were within 3%. The esophagus Dmean was reduced by 2% using PriorDose. PriorDose strategy, however, reduced the left parotid D50 and Dmean by 15% and 14% respectively. Conclusion: This study demonstrated significant parotid sparing, potentially reducing xerostomia, by using ART with IMRT optimization based on prior dose for weekly re-planning of H&N cancer patients.« less

Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical Model.

PubMed

Wichary, Szymon; Smolen, Tomasz

2016-01-01

In multi-attribute choice, decision makers use decision strategies to arrive at the final choice. What are the neural mechanisms underlying decision strategy selection? The first goal of this paper is to provide a literature review on the neural underpinnings and cognitive models of decision strategy selection and thus set the stage for a neurocognitive model of this process. The second goal is to outline such a unifying, mechanistic model that can explain the impact of noncognitive factors (e.g., affect, stress) on strategy selection. To this end, we review the evidence for the factors influencing strategy selection, the neural basis of strategy use and the cognitive models of this process. We also present the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use of the rational Weighted Additive strategy and the boundedly rational heuristic Take The Best can be explained by one unifying, neurophysiologically plausible mechanism, based on the interaction of the frontoparietal network, orbitofrontal cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus. According to BUMSS, there are three processes that form the bottom-up mechanism of decision strategy selection and lead to the final choice: (1) cue weight computation, (2) gain modulation, and (3) weighted additive evaluation of alternatives. We discuss how these processes might be implemented in the brain, and how this knowledge allows us to formulate novel predictions linking strategy use and neural signals.

Strain commonalities and differences in response-outcome decision making in mice

PubMed Central

Zimmermann, Kelsey S.; Hsu, Chia-Chun; Gourley, Shannon L.

2016-01-01

The ability to select between actions that are more vs. less likely to be reinforced is necessary for survival and navigation of a changing environment. A task termed “response-outcome contingency degradation” can be used in the laboratory to determine whether rodents behave according to such goal-directed response strategies. In one iteration of this task, rodents are trained to perform two food-reinforced behaviors, then the predictive relationship between one instrumental response and the associated outcome is modified by providing the reinforcer associated with that response non-contingently. During a subsequent probe test, animals can select between the two trained responses. Preferential engagement of the behavior most likely to be reinforced is considered goal-directed, while non-selective responding is considered a failure in response-outcome conditioning, or “habitual.” This test has largely been used with rats, and less so with mice. Here we compiled data collected from several cohorts of mice tested in our lab between 2012-2015. Mice were bred on either a C57BL/6 or predominantly BALB/c strain background. We report that both strains of mice can use information acquired as a result of instrumental contingency degradation training to select amongst multiple response options the response most likely to be reinforced. Mice differ, however, during the training sessions when the familiar response-outcome contingency is being violated. BALB/c mice readily generate perseverative or habit-like response strategies when the only available response is unlikely to be reinforced, while C57BL/6 mice more readily inhibit responding. These findings provide evidence of strain differences in response strategies when an anticipated reinforcer is unlikely to be delivered. PMID:27003118

Contract Source Selection: An Analysis of Lowest Price Technically Acceptable and Tradeoff Strategies

DTIC Science & Technology

2016-06-15

selection strategy is key to minimizing risk and ensuring best value for all stakeholders. On the basis of thorough market research , acquisition...administrative lead-time, Contractor Performance Assessment Reporting System ratings, and earned value management assessments) and source selection strategy ...Postgraduate School A. PURPOSE This research analyzes LPTA and tradeoff source selection strategies and contract outcomes to determine if a relationship

Training voluntary motor suppression with real-time feedback of motor evoked potentials.

PubMed

Majid, D S Adnan; Lewis, Christina; Aron, Adam R

2015-05-01

Training people to suppress motor representations voluntarily could improve response control. We evaluated a novel training procedure of real-time feedback of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) over motor cortex. On each trial, a cue instructed participants to use a mental strategy to suppress a particular finger representation without overt movement. A single pulse of TMS was delivered over motor cortex, and an MEP-derived measure of hand motor excitability was delivered visually to the participant within 500 ms. In experiment 1, we showed that participants learned to reduce the excitability of a particular finger beneath baseline (selective motor suppression) within 30 min of practice. In experiment 2, we performed a double-blind study with 2 training groups (1 with veridical feedback and 1 with matched sham feedback) to show that selective motor suppression depends on the veridical feedback itself. Experiment 3 further demonstrated the importance of veridical feedback by showing that selective motor suppression did not arise from mere mental imagery, even when incentivized with reward. Thus participants can use real-time feedback of TMS-induced MEPs to discover an effective mental strategy for selective motor suppression. This high-temporal-resolution, trial-by-trial-feedback training method could be used to help people better control response tendencies and may serve as a potential therapy for motor disorders such as Tourette's and dystonia. Copyright © 2015 the American Physiological Society.

A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

PubMed

Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

2012-10-05

The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

PubMed

Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

2018-01-01

Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

Processes in arithmetic strategy selection: a fMRI study.

PubMed

Taillan, Julien; Ardiale, Eléonore; Anton, Jean-Luc; Nazarian, Bruno; Félician, Olivier; Lemaire, Patrick

2015-01-01

This neuroimaging (functional magnetic resonance imaging) study investigated neural correlates of strategy selection. Young adults performed an arithmetic task in two different conditions. In both conditions, participants had to provide estimates of two-digit multiplication problems like 54 × 78. In the choice condition, participants had to select the better of two available rounding strategies, rounding-up (RU) strategy (i.e., doing 60 × 80 = 4,800) or rounding-down (RD) strategy (i.e., doing 50 × 70 = 3,500 to estimate product of 54 × 78). In the no-choice condition, participants did not have to select strategy on each problem but were told which strategy to use; they executed RU and RD strategies each on a series of problems. Participants also had a control task (i.e., providing correct products of multiplication problems like 40 × 50). Brain activations and performance were analyzed as a function of these conditions. Participants were able to frequently choose the better strategy in the choice condition; they were also slower when they executed the difficult RU than the easier RD. Neuroimaging data showed greater brain activations in right anterior cingulate cortex (ACC), dorso-lateral prefrontal cortex (DLPFC), and angular gyrus (ANG), when selecting (relative to executing) the better strategy on each problem. Moreover, RU was associated with more parietal cortex activation than RD. These results suggest an important role of fronto-parietal network in strategy selection and have important implications for our further understanding and modeling cognitive processes underlying strategy selection.

Processes in arithmetic strategy selection: a fMRI study

PubMed Central

Taillan, Julien; Ardiale, Eléonore; Anton, Jean-Luc; Nazarian, Bruno; Félician, Olivier; Lemaire, Patrick

2015-01-01

This neuroimaging (functional magnetic resonance imaging) study investigated neural correlates of strategy selection. Young adults performed an arithmetic task in two different conditions. In both conditions, participants had to provide estimates of two-digit multiplication problems like 54 × 78. In the choice condition, participants had to select the better of two available rounding strategies, rounding-up (RU) strategy (i.e., doing 60 × 80 = 4,800) or rounding-down (RD) strategy (i.e., doing 50 × 70 = 3,500 to estimate product of 54 × 78). In the no-choice condition, participants did not have to select strategy on each problem but were told which strategy to use; they executed RU and RD strategies each on a series of problems. Participants also had a control task (i.e., providing correct products of multiplication problems like 40 × 50). Brain activations and performance were analyzed as a function of these conditions. Participants were able to frequently choose the better strategy in the choice condition; they were also slower when they executed the difficult RU than the easier RD. Neuroimaging data showed greater brain activations in right anterior cingulate cortex (ACC), dorso-lateral prefrontal cortex (DLPFC), and angular gyrus (ANG), when selecting (relative to executing) the better strategy on each problem. Moreover, RU was associated with more parietal cortex activation than RD. These results suggest an important role of fronto-parietal network in strategy selection and have important implications for our further understanding and modeling cognitive processes underlying strategy selection. PMID:25698995

New self-assembly strategies for next generation lithography

NASA Astrophysics Data System (ADS)

Schwartz, Evan L.; Bosworth, Joan K.; Paik, Marvin Y.; Ober, Christopher K.

2010-04-01

Future demands of the semiconductor industry call for robust patterning strategies for critical dimensions below twenty nanometers. The self assembly of block copolymers stands out as a promising, potentially lower cost alternative to other technologies such as e-beam or nanoimprint lithography. One approach is to use block copolymers that can be lithographically patterned by incorporating a negative-tone photoresist as the majority (matrix) phase of the block copolymer, paired with photoacid generator and a crosslinker moiety. In this system, poly(α-methylstyrene-block-hydroxystyrene)(PαMS-b-PHOST), the block copolymer is spin-coated as a thin film, processed to a desired microdomain orientation with long-range order, and then photopatterned. Therefore, selfassembly of the block copolymer only occurs in select areas due to the crosslinking of the matrix phase, and the minority phase polymer can be removed to produce a nanoporous template. Using bulk TEM analysis, we demonstrate how the critical dimension of this block copolymer is shown to scale with polymer molecular weight using a simple power law relation. Enthalpic interactions such as hydrogen bonding are used to blend inorganic additives in order to enhance the etch resistance of the PHOST block. We demonstrate how lithographically patternable block copolymers might fit in to future processing strategies to produce etch-resistant self-assembled features at length scales impossible with conventional lithography.

Extrapolating Weak Selection in Evolutionary Games

PubMed Central

Wu, Bin; García, Julián; Hauert, Christoph; Traulsen, Arne

2013-01-01

In evolutionary games, reproductive success is determined by payoffs. Weak selection means that even large differences in game outcomes translate into small fitness differences. Many results have been derived using weak selection approximations, in which perturbation analysis facilitates the derivation of analytical results. Here, we ask whether results derived under weak selection are also qualitatively valid for intermediate and strong selection. By “qualitatively valid” we mean that the ranking of strategies induced by an evolutionary process does not change when the intensity of selection increases. For two-strategy games, we show that the ranking obtained under weak selection cannot be carried over to higher selection intensity if the number of players exceeds two. For games with three (or more) strategies, previous examples for multiplayer games have shown that the ranking of strategies can change with the intensity of selection. In particular, rank changes imply that the most abundant strategy at one intensity of selection can become the least abundant for another. We show that this applies already to pairwise interactions for a broad class of evolutionary processes. Even when both weak and strong selection limits lead to consistent predictions, rank changes can occur for intermediate intensities of selection. To analyze how common such games are, we show numerically that for randomly drawn two-player games with three or more strategies, rank changes frequently occur and their likelihood increases rapidly with the number of strategies . In particular, rank changes are almost certain for , which jeopardizes the predictive power of results derived for weak selection. PMID:24339769

Generation and validation of PAX7 reporter lines from human iPS cells using CRISPR/Cas9 technology.

PubMed

Wu, Jianbo; Hunt, Samuel D; Xue, Haipeng; Liu, Ying; Darabi, Radbod

2016-03-01

Directed differentiation of iPS cells toward various tissue progenitors has been the focus of recent research. Therefore, generation of tissue-specific reporter iPS cell lines provides better understanding of developmental stages in iPS cells. This technical report describes an efficient strategy for generation and validation of knock-in reporter lines in human iPS cells using the Cas9-nickase system. Here, we have generated a knock-in human iPS cell line for the early myogenic lineage specification gene of PAX7. By introduction of site-specific double-stranded breaks (DSB) in the genomic locus of PAX7 using CRISPR/Cas9 nickase pairs, a 2A-GFP reporter with selection markers has been incorporated before the stop codon of the PAX7 gene at the last exon. After positive and negative selection, single cell-derived human iPS clones have been isolated and sequenced for in-frame positioning of the reporter construct. Finally, by using a nuclease-dead Cas9 activator (dCas9-VP160) system, the promoter region of PAX7 has been targeted for transient gene induction to validate the GFP reporter activity. This was confirmed by flow cytometry analysis and immunostaining for PAX7 and GFP. This technical report provides a practical guideline for generation and validation of knock-in reporters using CRISPR/Cas9 system. Published by Elsevier B.V.

Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical Model

PubMed Central

Wichary, Szymon; Smolen, Tomasz

2016-01-01

In multi-attribute choice, decision makers use decision strategies to arrive at the final choice. What are the neural mechanisms underlying decision strategy selection? The first goal of this paper is to provide a literature review on the neural underpinnings and cognitive models of decision strategy selection and thus set the stage for a neurocognitive model of this process. The second goal is to outline such a unifying, mechanistic model that can explain the impact of noncognitive factors (e.g., affect, stress) on strategy selection. To this end, we review the evidence for the factors influencing strategy selection, the neural basis of strategy use and the cognitive models of this process. We also present the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use of the rational Weighted Additive strategy and the boundedly rational heuristic Take The Best can be explained by one unifying, neurophysiologically plausible mechanism, based on the interaction of the frontoparietal network, orbitofrontal cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus. According to BUMSS, there are three processes that form the bottom-up mechanism of decision strategy selection and lead to the final choice: (1) cue weight computation, (2) gain modulation, and (3) weighted additive evaluation of alternatives. We discuss how these processes might be implemented in the brain, and how this knowledge allows us to formulate novel predictions linking strategy use and neural signals. PMID:27877103

Cognitive niches: an ecological model of strategy selection.

PubMed

Marewski, Julian N; Schooler, Lael J

2011-07-01

How do people select among different strategies to accomplish a given task? Across disciplines, the strategy selection problem represents a major challenge. We propose a quantitative model that predicts how selection emerges through the interplay among strategies, cognitive capacities, and the environment. This interplay carves out for each strategy a cognitive niche, that is, a limited number of situations in which the strategy can be applied, simplifying strategy selection. To illustrate our proposal, we consider selection in the context of 2 theories: the simple heuristics framework and the ACT-R (adaptive control of thought-rational) architecture of cognition. From the heuristics framework, we adopt the thesis that people make decisions by selecting from a repertoire of simple decision strategies that exploit regularities in the environment and draw on cognitive capacities, such as memory and time perception. ACT-R provides a quantitative theory of how these capacities adapt to the environment. In 14 simulations and 10 experiments, we consider the choice between strategies that operate on the accessibility of memories and those that depend on elaborate knowledge about the world. Based on Internet statistics, our model quantitatively predicts people's familiarity with and knowledge of real-world objects, the distributional characteristics of the associated speed of memory retrieval, and the cognitive niches of classic decision strategies, including those of the fluency, recognition, integration, lexicographic, and sequential-sampling heuristics. In doing so, the model specifies when people will be able to apply different strategies and how accurate, fast, and effortless people's decisions will be.

"It could have been worse": Developmental change in the use of a counterfactual consoling strategy.

PubMed

Payir, Ayse; Guttentag, Robert

2016-08-01

In two experiments, we investigated developmental change in the use of a counterfactual consoling strategy: "it could have been worse." In Experiment 1, 8-year-olds, 10-year-olds, 12-year-olds, and adults were presented with two stories in which a character feels bad as the result of an event that could have turned out better or could have turned out worse. Participants were asked what they would say or do to make the characters feel better. The results revealed that the frequency with which participants mentioned a counterfactual consoling strategy increased dramatically with age. In Experiment 2, using the same stories with similar-aged participants, we tested whether providing children with several consoling strategies (rather than asking them to create one) would prompt greater use of a counterfactual consoling strategy. Under these conditions, the 10- and 12-year-olds responded in a manner very similar to that of adults, whereas the 8-year-olds selected a counterfactual consoling strategy less often than participants at any other age. The findings from the two experiments suggest that, up through at least age 12years, children are less likely than adults to spontaneously apply counterfactual thinking when generating a consoling strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

2nd Generation RLV Risk Definition Program

NASA Technical Reports Server (NTRS)

Davis, Robert M.; Stucker, Mark (Technical Monitor)

2000-01-01

The 2nd Generation RLV Risk Reduction Mid-Term Report summarizes the status of Kelly Space & Technology's activities during the first two and one half months of the program. This report was presented to the cognoscente Contracting Officer's Technical Representative (COTR) and selected Marshall Space Flight Center staff members on 26 September 2000. The report has been approved and is distributed on CD-ROM (as a PowerPoint file) in accordance with the terms of the subject contract, and contains information and data addressing the following: (1) Launch services demand and requirements; (2) Architecture, alternatives, and requirements; (3) Costs, pricing, and business cases analysis; (4) Commercial financing requirements, plans, and strategy; (5) System engineering processes and derived requirements; and (6) RLV system trade studies and design analysis.

Messenger RNA- versus retrovirus-based induced pluripotent stem cell reprogramming strategies: analysis of genomic integrity.

PubMed

Steichen, Clara; Luce, Eléanor; Maluenda, Jérôme; Tosca, Lucie; Moreno-Gimeno, Inmaculada; Desterke, Christophe; Dianat, Noushin; Goulinet-Mainot, Sylvie; Awan-Toor, Sarah; Burks, Deborah; Marie, Joëlle; Weber, Anne; Tachdjian, Gérard; Melki, Judith; Dubart-Kupperschmitt, Anne

2014-06-01

The use of synthetic messenger RNAs to generate human induced pluripotent stem cells (iPSCs) is particularly appealing for potential regenerative medicine applications, because it overcomes the common drawbacks of DNA-based or virus-based reprogramming strategies, including transgene integration in particular. We compared the genomic integrity of mRNA-derived iPSCs with that of retrovirus-derived iPSCs generated in strictly comparable conditions, by single-nucleotide polymorphism (SNP) and copy number variation (CNV) analyses. We showed that mRNA-derived iPSCs do not differ significantly from the parental fibroblasts in SNP analysis, whereas retrovirus-derived iPSCs do. We found that the number of CNVs seemed independent of the reprogramming method, instead appearing to be clone-dependent. Furthermore, differentiation studies indicated that mRNA-derived iPSCs differentiated efficiently into hepatoblasts and that these cells did not load additional CNVs during differentiation. The integration-free hepatoblasts that were generated constitute a new tool for the study of diseased hepatocytes derived from patients' iPSCs and their use in the context of stem cell-derived hepatocyte transplantation. Our findings also highlight the need to conduct careful studies on genome integrity for the selection of iPSC lines before using them for further applications. ©AlphaMed Press.

Functional Human Podocytes Generated in Organoids from Amniotic Fluid Stem Cells

PubMed Central

Benedetti, Valentina; Novelli, Rubina; Abbate, Mauro; Rizzo, Paola; Conti, Sara; Tomasoni, Susanna; Corna, Daniela; Pozzobon, Michela; Cavallotti, Daniela; Yokoo, Takashi; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe

2016-01-01

Generating kidney organoids using human stem cells could offer promising prospects for research and therapeutic purposes. However, no cell-based strategy has generated nephrons displaying an intact three-dimensional epithelial filtering barrier. Here, we generated organoids using murine embryonic kidney cells, and documented that these tissues recapitulated the complex three-dimensional filtering structure of glomerular slits in vivo and accomplished selective glomerular filtration and tubular reabsorption. Exploiting this technology, we mixed human amniotic fluid stem cells with mouse embryonic kidney cells to establish three-dimensional chimeric organoids that engrafted in vivo and grew to form vascularized glomeruli and tubular structures. Human cells contributed to the formation of glomerular structures, differentiated into podocytes with slit diaphragms, and internalized exogenously infused BSA, thus attaining in vivo degrees of specialization and function unprecedented for donor stem cells. In conclusion, human amniotic fluid stem cell chimeric organoids may offer new paths for studying renal development and human podocyte disease, and for facilitating drug discovery and translational research. PMID:26516208

Oxidase catalysis via aerobically generated hypervalent iodine intermediates

NASA Astrophysics Data System (ADS)

Maity, Asim; Hyun, Sung-Min; Powers, David C.

2018-02-01

The development of sustainable oxidation chemistry demands strategies to harness O2 as a terminal oxidant. Oxidase catalysis, in which O2 serves as a chemical oxidant without necessitating incorporation of oxygen into reaction products, would allow diverse substrate functionalization chemistry to be coupled to O2 reduction. Direct O2 utilization suffers from intrinsic challenges imposed by the triplet ground state of O2 and the disparate electron inventories of four-electron O2 reduction and two-electron substrate oxidation. Here, we generate hypervalent iodine reagents—a broadly useful class of selective two-electron oxidants—from O2. This is achieved by intercepting reactive intermediates of aldehyde autoxidation to aerobically generate hypervalent iodine reagents for a broad array of substrate oxidation reactions. The use of aryl iodides as mediators of aerobic oxidation underpins an oxidase catalysis platform that couples substrate oxidation directly to O2 reduction. We anticipate that aerobically generated hypervalent iodine reagents will expand the scope of aerobic oxidation chemistry in chemical synthesis.

Colloidal silver nanoparticles improve anti-leukemic drug efficacy via amplification of oxidative stress.

PubMed

Guo, Dawei; Zhang, Junren; Huang, Zhihai; Jiang, Shanxiang; Gu, Ning

2015-02-01

Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy. Copyright © 2015. Published by Elsevier B.V.

Autonomous self-navigating drug-delivery vehicles: from science fiction to reality.

PubMed

Petrenko, Valery A

2017-12-01

Low efficacy of targeted nanomedicines in biological experiments enforced us to challenge the traditional concept of drug targeting and suggest a paradigm of 'addressed self-navigating drug-delivery vehicles,' in which affinity selection of targeting peptides and vasculature-directed in vivo phage screening is replaced by the migration selection, which explores ability of 'promiscuous' phages and their proteins to migrate through the tumor-surrounding cellular barriers, using a 'hub and spoke' delivery strategy, and penetrate into the tumor affecting the diverse tumor cell population. The 'self-navigating' drug-delivery paradigm can be used as a theoretical and technical platform in design of a novel generation of molecular medications and imaging probes for precise and personal medicine. [Formula: see text].

Motor planning flexibly optimizes performance under uncertainty about task goals.

PubMed

Wong, Aaron L; Haith, Adrian M

2017-03-03

In an environment full of potential goals, how does the brain determine which movement to execute? Existing theories posit that the motor system prepares for all potential goals by generating several motor plans in parallel. One major line of evidence for such theories is that presenting two competing goals often results in a movement intermediate between them. These intermediate movements are thought to reflect an unintentional averaging of the competing plans. However, normative theories suggest instead that intermediate movements might actually be deliberate, generated because they improve task performance over a random guessing strategy. To test this hypothesis, we vary the benefit of making an intermediate movement by changing movement speed. We find that participants generate intermediate movements only at (slower) speeds where they measurably improve performance. Our findings support the normative view that the motor system selects only a single, flexible motor plan, optimized for uncertain goals.

High-Frequency Network Oscillations in Cerebellar Cortex

PubMed Central

Middleton, Steven J.; Racca, Claudia; Cunningham, Mark O.; Traub, Roger D.; Monyer, Hannah; Knöpfel, Thomas; Schofield, Ian S.; Jenkins, Alistair; Whittington, Miles A.

2016-01-01

SUMMARY Both cerebellum and neocortex receive input from the somatosensory system. Interaction between these regions has been proposed to underpin the correct selection and execution of motor commands, but it is not clear how such interactions occur. In neocortex, inputs give rise to population rhythms, providing a spatiotemporal coding strategy for inputs and consequent outputs. Here, we show that similar patterns of rhythm generation occur in cerebellum during nicotinic receptor subtype activation. Both gamma oscillations (30–80 Hz) and very fast oscillations (VFOs, 80–160 Hz) were generated by intrinsic cerebellar cortical circuitry in the absence of functional glutamatergic connections. As in neocortex, gamma rhythms were dependent on GABAA receptor-mediated inhibition, whereas VFOs required only nonsynaptically connected intercellular networks. The ability of cerebellar cortex to generate population rhythms within the same frequency bands as neocortex suggests that they act as a common spatiotemporal code within which corticocerebellar dialog may occur. PMID:18549787

Resuscitation of neonates at 23 weeks' gestational age: a cost-effectiveness analysis.

PubMed

Partridge, J Colin; Robertson, Kathryn R; Rogers, Elizabeth E; Landman, Geri Ottaviano; Allen, Allison J; Caughey, Aaron B

2015-01-01

Resuscitation of infants at 23 weeks' gestation remains controversial; clinical practices vary. We sought to investigate the cost effectiveness of resuscitation of infants born 23 0/7-23 6/7 weeks' gestation. Decision-analytic modeling comparing universal and selective resuscitation to non-resuscitation for 5176 live births at 23 weeks in a theoretic U.S. cohort. Estimates of death (77%) and disability (64-86%) were taken from the literature. Maternal and combined maternal-neonatal utilities were applied to discounted life expectancy to generate QALYs. Incremental cost-effectiveness ratios were calculated, discounting costs and QALYs. Main outcomes included number of survivors, their outcome status and incremental cost-effectiveness ratios for the three strategies. A cost-effectiveness threshold of $100 000/QALY was utilized. Universal resuscitation would save 1059 infants: 138 severely disabled, 413 moderately impaired and 508 without significant sequelae. Selective resuscitation would save 717 infants: 93 severely disabled, 279 moderately impaired and 343 without significant sequelae. For mothers, non-resuscitation is less expensive ($19.9 million) and more effective (127 844 mQALYs) than universal resuscitation ($1.2 billion; 126 574 mQALYs) or selective resuscitation ($845 million; 125 966 mQALYs). For neonates, both universal and selective resuscitation were cost-effective, resulting in 22 256 and 15 134 nQALYS, respectively, versus 247 nQALYs for non-resuscitation. In sensitivity analyses, universal resuscitation was cost-effective from a maternal perspective only at utilities for neonatal death <0.42. When analyzed from a maternal-neonatal perspective, universal resuscitation was cost-effective when the probability of neonatal death was <0.95. Over wide ranges of probabilities for survival and disability, universal and selective resuscitation strategies were not cost-effective from a maternal perspective. Both strategies were cost-effective from a maternal-neonatal perspective. This study offers a metric for counseling and decision-making for extreme prematurity. Our results could support a more permissive response to parental requests for aggressive intervention at 23 weeks' gestation.

High-fertility phenotypes: two outbred mouse models exhibit substantially different molecular and physiological strategies warranting improved fertility.

PubMed

Langhammer, Martina; Michaelis, Marten; Hoeflich, Andreas; Sobczak, Alexander; Schoen, Jennifer; Weitzel, Joachim M

2014-01-01

Animal models are valuable tools in fertility research. Worldwide, there are more than 400 transgenic or knockout mouse models available showing a reproductive phenotype; almost all of them exhibit an infertile or at least subfertile phenotype. By contrast, animal models revealing an improved fertility phenotype are barely described. This article summarizes data on two outbred mouse models exhibiting a 'high-fertility' phenotype. These mouse lines were generated via selection over a time period of more than 40 years and 161 generations. During this selection period, the number of offspring per litter and the total birth weight of the entire litter nearly doubled. Concomitantly with the increased fertility phenotype, several endocrine parameters (e.g. serum testosterone concentrations in male animals), physiological parameters (e.g. body weight, accelerated puberty, and life expectancy), and behavioral parameters (e.g. behavior in an open field and endurance fitness on a treadmill) were altered. We demonstrate that the two independently bred high-fertility mouse lines warranted their improved fertility phenotype using different molecular and physiological strategies. The fertility lines display female- as well as male-specific characteristics. These genetically heterogeneous mouse models provide new insights into molecular and cellular mechanisms that enhance fertility. In view of decreasing fertility in men, these models will therefore be a precious information source for human reproductive medicine. Translated abstract A German translation of abstract is freely available at http://www.reproduction-online.org/content/147/4/427/suppl/DC1.

Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development.

PubMed

Salazar-Fontana, Laura I; Desai, Dharmesh D; Khan, Tarik A; Pillutla, Renuka C; Prior, Sandra; Ramakrishnan, Radha; Schneider, Jennifer; Joseph, Alexandra

2017-03-01

All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses. This paper examines mitigation strategies currently implemented and novel under investigation approaches used by drug developers. The review describes immunomodulatory regimens used in the clinic to mitigate deleterious ADA responses to replacement therapies for deficiency syndromes, such as hemophilia A and B, and high risk classical infantile Pompe patients (e.g., cyclophosphamide, methotrexate, rituximab); novel in silico and in vitro prediction tools used to select candidates based on their immunogenicity potential (e.g., anti-CD52 antibody primary sequence and IFN beta-1a formulation); in vitro generation of tolerogenic antigen-presenting cells (APCs) to reduce ADA responses to factor VIII and IX in murine models of hemophilia; and selection of novel delivery systems to reduce in vivo ADA responses to highly immunogenic biotherapeutics (e.g., asparaginase). We conclude that mitigation strategies should be considered early in development for biotherapeutics based on our knowledge of existing clinical data for biotherapeutics and the immune response involved in the generation of these ADAs.

Application of computer assisted combinatorial chemistry in antivirial, antimalarial and anticancer agents design

NASA Astrophysics Data System (ADS)

Burello, E.; Bologa, C.; Frecer, V.; Miertus, S.

Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anticancer drugs. These illustrate library focusing strategies.

An end-to-end approach to developing biological and chemical detector requirements

NASA Astrophysics Data System (ADS)

Teclemariam, Nerayo P.; Purvis, Liston K.; Foltz, Greg W.; West, Todd; Edwards, Donna M.; Fruetel, Julia A.; Gleason, Nathaniel J.

2009-05-01

Effective defense against chemical and biological threats requires an "end-to-end" strategy that encompasses the entire problem space, from threat assessment and target hardening to response planning and recovery. A key element of the strategy is the definition of appropriate system requirements for surveillance and detection of threat agents. Our end-to-end approach to venue chem/bio defense is captured in the Facilities Weapons of Mass Destruction Decision Analysis Capability (FacDAC), an integrated system-of-systems toolset that can be used to generate requirements across all stages of detector development. For example, in the early stage of detector development the approach can be used to develop performance targets (e.g., sensitivity, selectivity, false positive rate) to provide guidance on what technologies to pursue. In the development phase, after a detector technology has been selected, the approach can aid in determining performance trade-offs and down-selection of competing technologies. During the application stage, the approach can be employed to design optimal defensive architectures that make the best use of available technology to maximize system performance. This presentation will discuss the end-to-end approach to defining detector requirements and demonstrate the capabilities of the FacDAC toolset using examples from a number of studies for the Department of Homeland Security.

Selective Induction of Tumor Cell Apoptosis by a Novel P450-mediated Reactive Oxygen Species (ROS) Inducer Methyl 3-(4-Nitrophenyl) Propiolate*

PubMed Central

Sun, Xiaoxiao; Ai, Midan; Wang, Ying; Shen, Shensi; Gu, Yuan; Jin, Yi; Zhou, Zuyu; Long, Yaqiu; Yu, Qiang

2013-01-01

Induction of tumor cell apoptosis has been recognized as a valid anticancer strategy. However, therapeutic selectivity between tumor and normal cells has always been a challenge. Here, we report a novel anti-cancer compound methyl 3-(4-nitrophenyl) propiolate (NPP) preferentially induces apoptosis in tumor cells through P450-catalyzed reactive oxygen species (ROS) production. A compound sensitivity study on multiple cell lines shows that tumor cells with high basal ROS levels, low antioxidant capacities, and p53 mutations are especially sensitive to NPP. Knockdown of p53 sensitized non-transformed cells to NPP-induced cell death. Additionally, by comparing NPP with other ROS inducers, we show that the susceptibility of tumor cells to the ROS-induced cell death is influenced by the mode, amount, duration, and perhaps location of ROS production. Our studies not only discovered a unique anticancer drug candidate but also shed new light on the understanding of ROS generation and function and the potential application of a ROS-promoting strategy in cancer treatment. PMID:23382387

Fishing diseased abalone to promote yield and conservation

PubMed Central

Ben-Horin, Tal; Bidegain, Gorka; Lenihan, Hunter S.

2016-01-01

Past theoretical models suggest fishing disease-impacted stocks can reduce parasite transmission, but this is a good management strategy only when the exploitation required to reduce transmission does not overfish the stock. We applied this concept to a red abalone fishery so impacted by an infectious disease (withering syndrome) that stock densities plummeted and managers closed the fishery. In addition to the non-selective fishing strategy considered by past disease-fishing models, we modelled targeting (culling) infected individuals, which is plausible in red abalone because modern diagnostic tools can determine infection without harming landed abalone and the diagnostic cost is minor relative to the catch value. The non-selective abalone fishing required to eradicate parasites exceeded thresholds for abalone sustainability, but targeting infected abalone allowed the fishery to generate yield and reduce parasite prevalence while maintaining stock densities at or above the densities attainable if the population was closed to fishing. The effect was strong enough that stock and yield increased even when the catch was one-third uninfected abalone. These results could apply to other fisheries as the diagnostic costs decline relative to catch value. PMID:26880843

Fishing diseased abalone to promote yield and conservation.

PubMed

Ben-Horin, Tal; Lafferty, Kevin D; Bidegain, Gorka; Lenihan, Hunter S

2016-03-05

Past theoretical models suggest fishing disease-impacted stocks can reduce parasite transmission, but this is a good management strategy only when the exploitation required to reduce transmission does not overfish the stock. We applied this concept to a red abalone fishery so impacted by an infectious disease (withering syndrome) that stock densities plummeted and managers closed the fishery. In addition to the non-selective fishing strategy considered by past disease-fishing models, we modelled targeting (culling) infected individuals, which is plausible in red abalone because modern diagnostic tools can determine infection without harming landed abalone and the diagnostic cost is minor relative to the catch value. The non-selective abalone fishing required to eradicate parasites exceeded thresholds for abalone sustainability, but targeting infected abalone allowed the fishery to generate yield and reduce parasite prevalence while maintaining stock densities at or above the densities attainable if the population was closed to fishing. The effect was strong enough that stock and yield increased even when the catch was one-third uninfected abalone. These results could apply to other fisheries as the diagnostic costs decline relative to catch value. © 2016 The Author(s).

Fishing diseased abalone to promote yield and conservation

USGS Publications Warehouse

Ben-Horin, Tal; Lafferty, Kevin D.; Bidegain, Gorka; Lenihan, Hunter S.

2016-01-01

Past theoretical models suggest fishing disease-impacted stocks can reduce parasite transmission, but this is a good management strategy only when the exploitation required to reduce transmission does not overfish the stock. We applied this concept to a red abalone fishery so impacted by an infectious disease (withering syndrome) that stock densities plummeted and managers closed the fishery. In addition to the non-selective fishing strategy considered by past disease-fishing models, we modelled targeting (culling) infected individuals, which is plausible in red abalone because modern diagnostic tools can determine infection without harming landed abalone and the diagnostic cost is minor relative to the catch value. The non-selective abalone fishing required to eradicate parasites exceeded thresholds for abalone sustainability, but targeting infected abalone allowed the fishery to generate yield and reduce parasite prevalence while maintaining stock densities at or above the densities attainable if the population was closed to fishing. The effect was strong enough that stock and yield increased even when the catch was one-third uninfected abalone. These results could apply to other fisheries as the diagnostic costs decline relative to catch value.

Rapid evolution meets invasive species control: The potential for pesticide resistance in sea lamprey

USGS Publications Warehouse

Dunlop, Erin S.; McLaughlin, Robert L.; Adams, Jean V.; Jones, Michael L.; Birceanu, Oana; Christie, Mark R.; Criger, Lori A.; Hinderer, Julia L.M.; Hollingworth, Robert M.; Johnson, Nicholas; Lantz, Stephen R.; Li, Weiming; Miller, James R.; Morrison, Bruce J.; Mota-Sanchez, David; Muir, Andrew M.; Sepulveda, Maria S.; Steeves, Todd B.; Walter, Lisa; Westman, Erin; Wirgin, Isaac; Wilkie, Michael P.

2018-01-01

Rapid evolution of pest, pathogen and wildlife populations can have undesirable effects; for example, when insects evolve resistance to pesticides or fishes evolve smaller body size in response to harvest. A destructive invasive species in the Laurentian Great Lakes, the sea lamprey (Petromyzon marinus) has been controlled with the pesticide 3-trifluoromethyl-4-nitrophenol (TFM) since the 1950s. We evaluated the likelihood of sea lamprey evolving resistance to TFM by (1) reviewing sea lamprey life history and control; (2) identifying physiological and behavioural resistance strategies; (3) estimating the strength of selection from TFM; (4) assessing the timeline for evolution; and (5) analyzing historical toxicity data for evidence of resistance. The number of sea lamprey generations exposed to TFM was within the range observed for fish populations where rapid evolution has occurred. Mortality from TFM was estimated as 82-90%, suggesting significant selective pressure. However, 57 years of toxicity data revealed no increase in lethal concentrations of TFM. Vigilance and the development of alternative controls are required to prevent this aquatic invasive species from evolving strategies to evade control.

Generation of tricyclic imidazo[1,2-a]pyrazines as novel PI3K inhibitors by application of a conformational restriction strategy.

PubMed

Martínez González, Sonia; Rodríguez-Arístegui, Sonsoles; Hernández, Ana Isabel; Varela, Carmen; González Cantalapiedra, Esther; Álvarez, Rosa María; Rodríguez Hergueta, Antonio; Bischoff, James R; Albarrán, María Isabel; Cebriá, Antonio; Cendón, Elena; Cebrián, David; Alfonso, Patricia; Pastor, Joaquín

2017-06-01

The involvement of the phosphoinositide 3-kinases (PI3Ks) in several diseases, especially in the oncology area, has singled it as one of the most explored therapeutic targets in the last two decades. Many different inhibitor classes have been developed by the industry and academia with a diverse selectivity profile within the PI3K family. In the present manuscript we report a further exploration of our lead PI3K inhibitor ETP-46321 (Martínez González et al., 2012) 1 by the application of a conformational restriction strategy. For that purpose we have successfully synthesized novel tricyclic imidazo[1,2-a]pyrazine derivatives as PI3K inhibitors. This new class of compounds had enable the exploration of the solvent-accessible region within PI3K and resulted in the identification of molecule 8q with the best selectivity PI3Kα/δ isoform profile in vitro, and promising in vivo PK data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of resistance risk to lambda-cyhalothrin and cross-resistance to four other insecticides in the house fly, Musca domestica L. (Diptera: Muscidae).

PubMed

Abbas, Naeem; Shad, Sarfraz Ali

2015-07-01

Lambda-cyhalothrin, a sodium channel modulator insecticide, has been used frequently for the control of house flies, Musca domestica L. (Diptera: Muscidae) worldwide, including Pakistan. This experiment was performed to determine the selection and assessment of lambda-cyhalothrin resistance evolution along with four other insecticides. After 26 generations of selection, the lambda-cyhalothrin-selected population developed 445-fold resistance to lambda-cyhalothrin compared to the susceptible population. There was low cross-resistance to bifenthrin and very low cross-resistance to methomyl, imidacloprid, and fipronil in the lambda-cyhalothrin-selected population compared to the field population (G1). Realized heritability (h (2)) of resistance to lambda-cyhalothrin, bifenthrin, methomyl, imidacloprid, and fipronil was 0.07, 0.05, 0.01, 0.08, and 0.08, respectively. The projected rate of resistance development revealed that if 90 % house flies were selected, then a tenfold increase in lethal concentration 50 occurred after 17, 20, 159, 13, and 14 generations for lambda-cyhalothrin (h (2) = 0.07, slope = 2.09), bifenthrin (h (2) = 0.05, slope = 1.73), methomyl (h (2) = 0.01, slope = 2.52), imidacloprid (h (2) = 0.08, slope = 1.89), and fipronil (h (2) = 0.08, slope = 2.03), respectively. The results of our study concluded that the house fly has the potential to develop multiple insecticide resistances following continued selection pressure with lambda-cyhalothrin. This study will be helpful for assisting the development of resistance management strategies.

Competitive seeds-selection in complex networks

NASA Astrophysics Data System (ADS)

Zhao, Jiuhua; Liu, Qipeng; Wang, Lin; Wang, Xiaofan

2017-02-01

This paper investigates a competitive diffusion model where two competitors simultaneously select a set of nodes (seeds) in the network to influence. We focus on the problem of how to select these seeds such that, when the diffusion process terminates, a competitor can obtain more supports than its opponent. Instead of studying this problem in the game-theoretic framework as in the existing work, in this paper we design several heuristic seed-selection strategies inspired by commonly used centrality measures-Betweenness Centrality (BC), Closeness Centrality (CC), Degree Centrality (DC), Eigenvector Centrality (EC), and K-shell Centrality (KS). We mainly compare three centrality-based strategies, which have better performances in competing with the random selection strategy, through simulations on both real and artificial networks. Even though network structure varies across different networks, we find certain common trend appearing in all of these networks. Roughly speaking, BC-based strategy and DC-based strategy are better than CC-based strategy. Moreover, if a competitor adopts CC-based strategy, then BC-based strategy is a better strategy than DC-based strategy for his opponent, and the superiority of BC-based strategy decreases as the heterogeneity of the network decreases.

From Classification to Causality: Advancing Understanding of Mechanisms of Change in Implementation Science.

PubMed

Lewis, Cara C; Klasnja, Predrag; Powell, Byron J; Lyon, Aaron R; Tuzzio, Leah; Jones, Salene; Walsh-Bailey, Callie; Weiner, Bryan

2018-01-01

The science of implementation has offered little toward understanding how different implementation strategies work. To improve outcomes of implementation efforts, the field needs precise, testable theories that describe the causal pathways through which implementation strategies function. In this perspective piece, we describe a four-step approach to developing causal pathway models for implementation strategies. First, it is important to ensure that implementation strategies are appropriately specified. Some strategies in published compilations are well defined but may not be specified in terms of its core component that can have a reliable and measureable impact. Second, linkages between strategies and mechanisms need to be generated. Existing compilations do not offer mechanisms by which strategies act, or the processes or events through which an implementation strategy operates to affect desired implementation outcomes. Third, it is critical to identify proximal and distal outcomes the strategy is theorized to impact, with the former being direct, measurable products of the strategy and the latter being one of eight implementation outcomes (1). Finally, articulating effect modifiers, like preconditions and moderators, allow for an understanding of where, when, and why strategies have an effect on outcomes of interest. We argue for greater precision in use of terms for factors implicated in implementation processes; development of guidelines for selecting research design and study plans that account for practical constructs and allow for the study of mechanisms; psychometrically strong and pragmatic measures of mechanisms; and more robust curation of evidence for knowledge transfer and use.

Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

PubMed Central

Ray, Thomas A; Roy, Suva; Kozlowski, Christopher; Wang, Jingjing; Cafaro, Jon; Hulbert, Samuel W; Wright, Christopher V; Field, Greg D

2018-01-01

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers. PMID:29611808

Optimal Sensor Selection for Health Monitoring Systems

NASA Technical Reports Server (NTRS)

Santi, L. Michael; Sowers, T. Shane; Aguilar, Robert B.

2005-01-01

Sensor data are the basis for performance and health assessment of most complex systems. Careful selection and implementation of sensors is critical to enable high fidelity system health assessment. A model-based procedure that systematically selects an optimal sensor suite for overall health assessment of a designated host system is described. This procedure, termed the Systematic Sensor Selection Strategy (S4), was developed at NASA John H. Glenn Research Center in order to enhance design phase planning and preparations for in-space propulsion health management systems (HMS). Information and capabilities required to utilize the S4 approach in support of design phase development of robust health diagnostics are outlined. A merit metric that quantifies diagnostic performance and overall risk reduction potential of individual sensor suites is introduced. The conceptual foundation for this merit metric is presented and the algorithmic organization of the S4 optimization process is described. Representative results from S4 analyses of a boost stage rocket engine previously under development as part of NASA's Next Generation Launch Technology (NGLT) program are presented.

The impact of a national strategy to increase physical activity among older adults on national organizations.

PubMed

Park, Chae-Hee; Chodzko-Zajko, Wojtek; Ory, Marcia G; Gleason-Senior, Jane; Bazzarre, Terry L; Mockenhaupt, Robin

2010-10-01

This study was designed to evaluate the impact of the National Blueprint (NB) on the policies, programs, and organizational culture of selected national organizations. The theoretical model selected to assess the impact of the NB on organizational behavior was Burke's system theory of organizational change. Three organizations, AARP, the American College of Sports Medicine (ACSM), and the Administration on Aging (AoA), were selected for the study. Two individuals in each of these organizations were selected for interview. Semistructured interviews and document reviews were used in the data-collection process. Findings showed that the publication and establishment of the NB resulted in changes in the operating procedures of AARP, ACSM, and AoA. The results were broadly consistent with Burke's system theory of organizational change. The publication of the NB was shown to affect the behavior of organizational leaders, organizational culture, policies, programs, and individual and organizational performance. The new information generated has increased our understanding of the impact of health campaigns on organizational behavior.

Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed anti-diabetic target in mice selected for leanness

PubMed Central

Morton, Nicholas M.; Beltram, Jasmina; Carter, Roderick N.; Michailidou, Zoi; Gorjanc, Gregor; Fadden, Clare Mc; Barrios-Llerena, Martin E.; Rodriguez-Cuenca, Sergio; Gibbins, Matthew T. G.; Aird, Rhona E.; Moreno-Navarrete, José Maria; Munger, Steven C.; Svenson, Karen L.; Gastaldello, Annalisa; Ramage, Lynne; Naredo, Gregorio; Zeyda, Maximilian; Wang, Zhao V.; Howie, Alexander F.; Saari, Aila; Sipilä, Petra; Stulnig, Thomas M.; Gudnason, Vilmundur; Kenyon, Christopher J.; Seckl, Jonathan R.; Walker, Brian R.; Webster, Scott P.; Dunbar, Donald R.; Churchill, Gary A.; Vidal-Puig, Antonio; Fernandez-Real, José Manuel; Emilsson, Valur; Horvat, Simon

2017-01-01

Discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic Lean mouse model, selected for low adiposity over 60 generations, to identify thiosulfate sulfurtransferase (Tst, Rhodanese) as a candidate obesity-resistance gene with selectively increased adipocyte expression. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Tst gene deficiency markedly exacerbated diabetes whereas pharmacological TST activation ameliorated diabetes in mice in vivo. Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, adipose TST mRNA correlated positively with adipose insulin sensitivity and negatively with fat mass. Genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for type 2 diabetes. PMID:27270587

The Effects of Relationship Type, Partner Intent, and Gender on the Selection of Relationship Maintenance Strategies.

ERIC Educational Resources Information Center

Shea, B. Christine; Pearson, Judy C.

1986-01-01

Indicates that relationship type did not affect the maintenance strategies that partners chose; however, the partners' relationship intent and the sex-composition of the dyad had a significant impact on the selection of directness strategies. Suggests that individuals are not necessarily more likely to select directness strategies than balance or…

The Effect of Vocabulary Self-Selection Strategy and Input Enhancement Strategy on the Vocabulary Knowledge of Iranian EFL Learners

ERIC Educational Resources Information Center

Masoudi, Golfam

2017-01-01

The present study was designed to investigate empirically the effect of Vocabulary Self-Selection strategy and Input Enhancement strategy on the vocabulary knowledge of Iranian EFL Learners. After taking a diagnostic pretest, both experimental groups enrolled in two classes. Learners who practiced Vocabulary Self-Selection were allowed to…

Thermal Texture Selection and Correction for Building Facade Inspection Based on Thermal Radiant Characteristics

NASA Astrophysics Data System (ADS)

Lin, D.; Jarzabek-Rychard, M.; Schneider, D.; Maas, H.-G.

2018-05-01

An automatic building façade thermal texture mapping approach, using uncooled thermal camera data, is proposed in this paper. First, a shutter-less radiometric thermal camera calibration method is implemented to remove the large offset deviations caused by changing ambient environment. Then, a 3D façade model is generated from a RGB image sequence using structure-from-motion (SfM) techniques. Subsequently, for each triangle in the 3D model, the optimal texture is selected by taking into consideration local image scale, object incident angle, image viewing angle as well as occlusions. Afterwards, the selected textures can be further corrected using thermal radiant characteristics. Finally, the Gauss filter outperforms the voted texture strategy at the seams smoothing and thus for instance helping to reduce the false alarm rate in façade thermal leakages detection. Our approach is evaluated on a building row façade located at Dresden, Germany.

Precise small molecule recognition of a toxic CUG RNA repeat expansion

PubMed Central

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-01-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

PubMed

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-02-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

User-identified electronic cigarette behavioral strategies and device characteristics for cigarette smoking reduction.

PubMed

Soule, Eric K; Maloney, Sarah F; Guy, Mignonne C; Eissenberg, Thomas; Fagan, Pebbles

2018-04-01

There is limited evidence on how cigarette smokers use electronic cigarettes (ECIGs) for smoking cessation and reduction. This study used concept mapping, a participatory mixed-methods research approach, to identify ECIG use behaviors and device characteristics perceived to be associated with cigarette smoking cessation or reduction. Current ECIG users aged 18-64 were recruited from seven cities selected randomly from U.S. census tract regions. Participants were invited to complete concept mapping tasks: brainstorming, sorting and rating (n=72). During brainstorming, participants generated statements in response to a focus prompt ("A SPECIFIC WAY I HAVE USED electronic cigarettes to reduce my cigarette smoking or a SPECIFIC WAY electronic cigarettes help me reduce my cigarette smoking is…") and then sorted and rated the statements. Multidimensional scaling and hierarchical cluster analyses were used to generate a cluster map that was interpreted by the research team. Eight thematic clusters were identified: Convenience, Perceived Health Effects, Ease of Use, Versatility and Variety, Advantages of ECIGs over Cigarettes, Cigarette Substitutability, Reducing Harms to Self and Others, and Social Benefits. Participants generated several statements that related to specific behavioral strategies used when using ECIGs for smoking reduction/complete switching behaviors such as making rapid transitions from smoking to ECIG use or using certain ECIG liquids or devices. Former smokers rated the Perceived Health Effects cluster and several behavioral strategy statements higher than current smokers. These results help to identify ECIG use behaviors and characteristics perceived by ECIG users to aid in cigarette smoking cessation or reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiatlas whole heart segmentation of CT data using conditional entropy for atlas ranking and selection.

PubMed

Zhuang, Xiahai; Bai, Wenjia; Song, Jingjing; Zhan, Songhua; Qian, Xiaohua; Shi, Wenzhe; Lian, Yanyun; Rueckert, Daniel

2015-07-01

Cardiac computed tomography (CT) is widely used in clinical diagnosis of cardiovascular diseases. Whole heart segmentation (WHS) plays a vital role in developing new clinical applications of cardiac CT. However, the shape and appearance of the heart can vary greatly across different scans, making the automatic segmentation particularly challenging. The objective of this work is to develop and evaluate a multiatlas segmentation (MAS) scheme using a new atlas ranking and selection algorithm for automatic WHS of CT data. Research on different MAS strategies and their influence on WHS performance are limited. This work provides a detailed comparison study evaluating the impacts of label fusion, atlas ranking, and sizes of the atlas database on the segmentation performance. Atlases in a database were registered to the target image using a hierarchical registration scheme specifically designed for cardiac images. A subset of the atlases were selected for label fusion, according to the authors' proposed atlas ranking criterion which evaluated the performance of each atlas by computing the conditional entropy of the target image given the propagated atlas labeling. Joint label fusion was used to combine multiple label estimates to obtain the final segmentation. The authors used 30 clinical cardiac CT angiography (CTA) images to evaluate the proposed MAS scheme and to investigate different segmentation strategies. The mean WHS Dice score of the proposed MAS method was 0.918 ± 0.021, and the mean runtime for one case was 13.2 min on a workstation. This MAS scheme using joint label fusion generated significantly better Dice scores than the other label fusion strategies, including majority voting (0.901 ± 0.276, p < 0.01), locally weighted voting (0.905 ± 0.0247, p < 0.01), and probabilistic patch-based fusion (0.909 ± 0.0249, p < 0.01). In the atlas ranking study, the proposed criterion based on conditional entropy yielded a performance curve with higher WHS Dice scores compared to the conventional schemes (p < 0.03). In the atlas database study, the authors showed that the MAS using larger atlas databases generated better performance curves than the MAS using smaller ones, indicating larger atlas databases could produce more accurate segmentation. The authors have developed a new MAS framework for automatic WHS of CTA and investigated alternative implementations of MAS. With the proposed atlas ranking algorithm and joint label fusion, the MAS scheme is able to generate accurate segmentation within practically acceptable computation time. This method can be useful for the development of new clinical applications of cardiac CT.

Impact of Conflict Management Strategies on the Generation Mechanism of Miners' Unsafe Behavior Tendency

ERIC Educational Resources Information Center

Li, Ji-Zu; Zhang, Ya-Ping; Liu, Xiao-Guang; Liu, Yao-Long; Wang, Tian-Ri

2017-01-01

In this paper, we examine the relationship between the generation mechanism of miners' unsafe behavior tendency and conflict management strategies, including cooperative conflict management strategy, competitive conflict management strategy and avoidant conflict management strategy. Miners from 3 collieries in Shanxi province completed a…

A real-time expert system for self-repairing flight control

NASA Technical Reports Server (NTRS)

Gaither, S. A.; Agarwal, A. K.; Shah, S. C.; Duke, E. L.

1989-01-01

An integrated environment for specifying, prototyping, and implementing a self-repairing flight-control (SRFC) strategy is described. At an interactive workstation, the user can select paradigms such as rule-based expert systems, state-transition diagrams, and signal-flow graphs and hierarchically nest them, assign timing and priority attributes, establish blackboard-type communication, and specify concurrent execution on single or multiple processors. High-fidelity nonlinear simulations of aircraft and SRFC systems can be performed off-line, with the possibility of changing SRFC rules, inference strategies, and other heuristics to correct for control deficiencies. Finally, the off-line-generated SRFC can be transformed into highly optimized application-specific real-time C-language code. An application of this environment to the design of aircraft fault detection, isolation, and accommodation algorithms is presented in detail.

A novel artificial fish swarm algorithm for solving large-scale reliability-redundancy application problem.

PubMed

He, Qiang; Hu, Xiangtao; Ren, Hong; Zhang, Hongqi

2015-11-01

A novel artificial fish swarm algorithm (NAFSA) is proposed for solving large-scale reliability-redundancy allocation problem (RAP). In NAFSA, the social behaviors of fish swarm are classified in three ways: foraging behavior, reproductive behavior, and random behavior. The foraging behavior designs two position-updating strategies. And, the selection and crossover operators are applied to define the reproductive ability of an artificial fish. For the random behavior, which is essentially a mutation strategy, the basic cloud generator is used as the mutation operator. Finally, numerical results of four benchmark problems and a large-scale RAP are reported and compared. NAFSA shows good performance in terms of computational accuracy and computational efficiency for large scale RAP. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

NUclear EVacuation Analysis Code (NUEVAC) : a tool for evaluation of sheltering and evacuation responses following urban nuclear detonations.

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

Yoshimura, Ann S.; Brandt, Larry D.

2009-11-01

The NUclear EVacuation Analysis Code (NUEVAC) has been developed by Sandia National Laboratories to support the analysis of shelter-evacuate (S-E) strategies following an urban nuclear detonation. This tool can model a range of behaviors, including complex evacuation timing and path selection, as well as various sheltering or mixed evacuation and sheltering strategies. The calculations are based on externally generated, high resolution fallout deposition and plume data. Scenario setup and calculation outputs make extensive use of graphics and interactive features. This software is designed primarily to produce quantitative evaluations of nuclear detonation response options. However, the outputs have also proven usefulmore » in the communication of technical insights concerning shelter-evacuate tradeoffs to urban planning or response personnel.« less

New leads for selective GSK-3 inhibition: pharmacophore mapping and virtual screening studies.

PubMed

Patel, Dhilon S; Bharatam, Prasad V

2006-01-01

Glycogen Synthase Kinase-3 is a regulatory serine/threonine kinase, which is being targeted for the treatment of a number of human diseases including type-2 diabetes mellitus, neurodegenerative diseases, cancer and chronic inflammation. Selective GSK-3 inhibition is an important requirement owing to the possibility of side effects arising from other kinases. A pharmacophore mapping strategy is employed in this work to identify new leads for selective GSK-3 inhibition. Ligands known to show selective GSK-3 inhibition were employed in generating a pharmacophore map using distance comparison method (DISCO). The derived pharmacophore map was validated using (i) important interactions involved in selective GSK-3 inhibitions, and (ii) an in-house database containing different classes of GSK-3 selective, non-selective and inactive molecules. New Lead identification was carried out by performing virtual screening using validated pharmacophoric query and three chemical databases namely NCI, Maybridge and Leadquest. Further data reduction was carried out by employing virtual filters based on (i) Lipinski's rule of 5 (ii) van der Waals bumps and (iii) restricting the number of rotatable bonds to seven. Final screening was carried out using FlexX based molecular docking study.

New leads for selective GSK-3 inhibition: pharmacophore mapping and virtual screening studies

NASA Astrophysics Data System (ADS)

Patel, Dhilon S.; Bharatam, Prasad V.

2006-01-01

Glycogen Synthase Kinase-3 is a regulatory serine/threonine kinase, which is being targeted for the treatment of a number of human diseases including type-2 diabetes mellitus, neurodegenerative diseases, cancer and chronic inflammation. Selective GSK-3 inhibition is an important requirement owing to the possibility of side effects arising from other kinases. A pharmacophore mapping strategy is employed in this work to identify new leads for selective GSK-3 inhibition. Ligands known to show selective GSK-3 inhibition were employed in generating a pharmacophore map using distance comparison method (DISCO). The derived pharmacophore map was validated using (i) important interactions involved in selective GSK-3 inhibitions, and (ii) an in-house database containing different classes of GSK-3 selective, non-selective and inactive molecules. New Lead identification was carried out by performing virtual screening using validated pharmacophoric query and three chemical databases namely NCI, Maybridge and Leadquest. Further data reduction was carried out by employing virtual filters based on (i) Lipinski's rule of 5 (ii) van der Waals bumps and (iii) restricting the number of rotatable bonds to seven. Final screening was carried out using FlexX based molecular docking study.

A Comprehensive Strategy to Construct In-house Database for Accurate and Batch Identification of Small Molecular Metabolites.

PubMed

Zhao, Xinjie; Zeng, Zhongda; Chen, Aiming; Lu, Xin; Zhao, Chunxia; Hu, Chunxiu; Zhou, Lina; Liu, Xinyu; Wang, Xiaolin; Hou, Xiaoli; Ye, Yaorui; Xu, Guowang

2018-05-29

Identification of the metabolites is an essential step in metabolomics study to interpret regulatory mechanism of pathological and physiological processes. However, it is still a big headache in LC-MSn-based studies because of the complexity of mass spectrometry, chemical diversity of metabolites, and deficiency of standards database. In this work, a comprehensive strategy is developed for accurate and batch metabolite identification in non-targeted metabolomics studies. First, a well defined procedure was applied to generate reliable and standard LC-MS2 data including tR, MS1 and MS2 information at a standard operational procedure (SOP). An in-house database including about 2000 metabolites was constructed and used to identify the metabolites in non-targeted metabolic profiling by retention time calibration using internal standards, precursor ion alignment and ion fusion, auto-MS2 information extraction and selection, and database batch searching and scoring. As an application example, a pooled serum sample was analyzed to deliver the strategy, 202 metabolites were identified in the positive ion mode. It shows our strategy is useful for LC-MSn-based non-targeted metabolomics study.

Directed evolution of the forkhead-associated domain to generate anti-phosphospecific reagents by phage-display

PubMed Central

Pershad, Kritika; Wypisniak, Karolina; Kay, Brian K.

2012-01-01

While affinity reagents are valuable tools for monitoring protein phosphorylation and studying signaling events in cells, generating them through immunization of animals with phosphopeptides is expensive, laborious and time consuming. An attractive alternative is to use protein evolution techniques and isolate new anti-phosphopeptide binding specificities from a library of variants of a phosphopeptide-binding domain. To explore this strategy, we attempted to display on the surface of bacteriophage M13, the N-terminal Forkhead-associated domain (FHA1) of yeast Rad53p, which is a naturally occurring phosphothreonine (pT)-binding domain, and found it to be non-functional due to misfolding in the bacterial periplasm. To overcome this limitation, a library of FHA1 variants was constructed by mutagenic PCR and functional variants were isolated after three rounds of affinity selection with its pT peptide ligand. A hydrophobic residue at position 34 in the β1-strand was discovered to be essential for phage-display of a functional FHA1 domain. Additionally, by heating the phage library to 50°C prior to affinity selection with its cognate pT peptide, we identified a variant (G2) that was ~8°C more thermal stable than the wild-type domain. Using G2 as a scaffold, we constructed phage-displayed libraries of FHA1 variants and affinity selected for variants that bound selectively to five pT peptides. These reagents are renewable and have high protein yields (~20–25 mg/L), when expressed in Escherichia coli. Thus, we have changed the specificity of the FHA1 domain and demonstrated that engineering phosphopeptide-binding domains is an attractive avenue for generating new anti-phosphopeptide binding specificities in vitro by phage-display. PMID:22985966

Directed evolution of the forkhead-associated domain to generate anti-phosphospecific reagents by phage display.

PubMed

Pershad, Kritika; Wypisniak, Karolina; Kay, Brian K

2012-11-23

While affinity reagents are valuable tools for monitoring protein phosphorylation and studying signaling events in cells, generating them through immunization of animals with phosphopeptides is expensive, laborious, and time-consuming. An attractive alternative is to use protein evolution techniques and isolate new anti-phosphopeptide binding specificities from a library of variants of a phosphopeptide-binding domain. To explore this strategy, we attempted to display on the surface of bacteriophage M13 the N-terminal Forkhead-associated (FHA1) domain of yeast Rad53p, which is a naturally occurring phosphothreonine (pT)-binding domain, and found it to be nonfunctional due to misfolding in the bacterial periplasm. To overcome this limitation, we constructed a library of FHA1 variants by mutagenic PCR and isolated functional variants after three rounds of affinity selection with its pT peptide ligand. A hydrophobic residue at position 34 in the β1 strand was discovered to be essential for phage display of a functional FHA1 domain. Additionally, by heating the phage library to 50°C prior to affinity selection with its cognate pT peptide, we identified a variant (G2) that was ~8°C more thermally stable than the wild-type domain. Using G2 as a scaffold, we constructed phage-displayed libraries of FHA1 variants and affinity selected for variants that bound selectively to five pT peptides. These reagents are renewable and have high protein yields (~20-25mg/L), when expressed in Escherichia coli. Thus, we have changed the specificity of the FHA1 domain and demonstrated that engineering phosphopeptide-binding domains is an attractive avenue for generating new anti-phosphopeptide binding specificities in vitro by phage display. Copyright © 2012 Elsevier Ltd. All rights reserved.

The role of selective attention and action selection in the development of multiple action capabilities

NASA Astrophysics Data System (ADS)

Simione, Luca; Nolfi, Stefano

2014-10-01

In this paper we illustrate how the capacity to select the most appropriate actions when handling contexts affording multiple conflicting actions can be solved either through a selective attention strategy (in which the stimuli affording alternative actions are filtered out at the perceptual level through top-down regulation) or at later processing stages through an action selection strategy (through the suppression of the premotor information eliciting alternative actions). By carrying out a series of experiments in which a neuro-robot develops an ability to choose between conflicting actions, we were able to identify the conditions that lead to the development of solutions based on one strategy or another. Overall, the results indicate that the selective attention strategy constitutes the most simple and straightforward mechanism enabling the acquisition of such capacities. Moreover, the characteristics of the adaptive/learning process influence whether the adaptive robot converges towards a selective attention and/or action selection strategy.

Building strategies for tsunami scenarios databases to be used in a tsunami early warning decision support system: an application to western Iberia

NASA Astrophysics Data System (ADS)

Tinti, S.; Armigliato, A.; Pagnoni, G.; Zaniboni, F.

2012-04-01

One of the most challenging goals that the geo-scientific community is facing after the catastrophic tsunami occurred on December 2004 in the Indian Ocean is to develop the so-called "next generation" Tsunami Early Warning Systems (TEWS). Indeed, the meaning of "next generation" does not refer to the aim of a TEWS, which obviously remains to detect whether a tsunami has been generated or not by a given source and, in the first case, to send proper warnings and/or alerts in a suitable time to all the countries and communities that can be affected by the tsunami. Instead, "next generation" identifies with the development of a Decision Support System (DSS) that, in general terms, relies on 1) an integrated set of seismic, geodetic and marine sensors whose objective is to detect and characterise the possible tsunamigenic sources and to monitor instrumentally the time and space evolution of the generated tsunami, 2) databases of pre-computed numerical tsunami scenarios to be suitably combined based on the information coming from the sensor environment and to be used to forecast the degree of exposition of different coastal places both in the near- and in the far-field, 3) a proper overall (software) system architecture. The EU-FP7 TRIDEC Project aims at developing such a DSS and has selected two test areas in the Euro-Mediterranean region, namely the western Iberian margin and the eastern Mediterranean (Turkish coasts). In this study, we discuss the strategies that are being adopted in TRIDEC to build the databases of pre-computed tsunami scenarios and we show some applications to the western Iberian margin. In particular, two different databases are being populated, called "Virtual Scenario Database" (VSDB) and "Matching Scenario Database" (MSDB). The VSDB contains detailed simulations of few selected earthquake-generated tsunamis. The cases provided by the members of the VSDB are computed "real events"; in other words, they represent the unknowns that the TRIDEC platform must be able to recognise and match during the early crisis management phase. The MSDB contains a very large number (order of thousands) of tsunami simulations performed starting from many different simple earthquake sources of different magnitudes and located in the "vicinity" of the virtual scenario earthquake. Examples from both databases will be presented.

Evolution of conditional cooperation under multilevel selection.

PubMed

Zhang, Huanren; Perc, Matjaž

2016-03-11

We study the emergence of conditional cooperation in the presence of both intra-group and inter-group selection. Individuals play public goods games within their groups using conditional strategies, which are represented as piecewise linear response functions. Accordingly, groups engage in conflicts with a certain probability. In contrast to previous studies, we consider continuous contribution levels and a rich set of conditional strategies, allowing for a wide range of possible interactions between strategies. We find that the existence of conditional strategies enables the stabilization of cooperation even under strong intra-group selection. The strategy that eventually dominates in the population has two key properties: (i) It is unexploitable with strong intra-group selection; (ii) It can achieve full contribution to outperform other strategies in the inter-group selection. The success of this strategy is robust to initial conditions as well as changes to important parameters. We also investigate the influence of different factors on cooperation levels, including group conflicts, group size, and migration rate. Their effect on cooperation can be attributed to and explained by their influence on the relative strength of intra-group and inter-group selection.

Rethinking volitional control over task choice in multitask environments: use of a stimulus set selection strategy in voluntary task switching.

PubMed

Arrington, Catherine M; Weaver, Starla M

2015-01-01

Under conditions of volitional control in multitask environments, subjects may engage in a variety of strategies to guide task selection. The current research examines whether subjects may sometimes use a top-down control strategy of selecting a task-irrelevant stimulus dimension, such as location, to guide task selection. We term this approach a stimulus set selection strategy. Using a voluntary task switching procedure, subjects voluntarily switched between categorizing letter and number stimuli that appeared in two, four, or eight possible target locations. Effects of stimulus availability, manipulated by varying the stimulus onset asynchrony between the two target stimuli, and location repetition were analysed to assess the use of a stimulus set selection strategy. Considered across position condition, Experiment 1 showed effects of both stimulus availability and location repetition on task choice suggesting that only in the 2-position condition, where selection based on location always results in a target at the selected location, subjects may have been using a stimulus set selection strategy on some trials. Experiment 2 replicated and extended these findings in a visually more cluttered environment. These results indicate that, contrary to current models of task selection in voluntary task switching, the top-down control of task selection may occur in the absence of the formation of an intention to perform a particular task.

Multisampling suprathreshold perimetry: a comparison with conventional suprathreshold and full-threshold strategies by computer simulation.

PubMed

Artes, Paul H; Henson, David B; Harper, Robert; McLeod, David

2003-06-01

To compare a multisampling suprathreshold strategy with conventional suprathreshold and full-threshold strategies in detecting localized visual field defects and in quantifying the area of loss. Probability theory was applied to examine various suprathreshold pass criteria (i.e., the number of stimuli that have to be seen for a test location to be classified as normal). A suprathreshold strategy that requires three seen or three missed stimuli per test location (multisampling suprathreshold) was selected for further investigation. Simulation was used to determine how the multisampling suprathreshold, conventional suprathreshold, and full-threshold strategies detect localized field loss. To determine the systematic error and variability in estimates of loss area, artificial fields were generated with clustered defects (0-25 field locations with 8- and 16-dB loss) and, for each condition, the number of test locations classified as defective (suprathreshold strategies) and with pattern deviation probability less than 5% (full-threshold strategy), was derived from 1000 simulated test results. The full-threshold and multisampling suprathreshold strategies had similar sensitivity to field loss. Both detected defects earlier than the conventional suprathreshold strategy. The pattern deviation probability analyses of full-threshold results underestimated the area of field loss. The conventional suprathreshold perimetry also underestimated the defect area. With multisampling suprathreshold perimetry, the estimates of defect area were less variable and exhibited lower systematic error. Multisampling suprathreshold paradigms may be a powerful alternative to other strategies of visual field testing. Clinical trials are needed to verify these findings.

Multivariate Bayesian variable selection exploiting dependence structure among outcomes: Application to air pollution effects on DNA methylation.

PubMed

Lee, Kyu Ha; Tadesse, Mahlet G; Baccarelli, Andrea A; Schwartz, Joel; Coull, Brent A

2017-03-01

The analysis of multiple outcomes is becoming increasingly common in modern biomedical studies. It is well-known that joint statistical models for multiple outcomes are more flexible and more powerful than fitting a separate model for each outcome; they yield more powerful tests of exposure or treatment effects by taking into account the dependence among outcomes and pooling evidence across outcomes. It is, however, unlikely that all outcomes are related to the same subset of covariates. Therefore, there is interest in identifying exposures or treatments associated with particular outcomes, which we term outcome-specific variable selection. In this work, we propose a variable selection approach for multivariate normal responses that incorporates not only information on the mean model, but also information on the variance-covariance structure of the outcomes. The approach effectively leverages evidence from all correlated outcomes to estimate the effect of a particular covariate on a given outcome. To implement this strategy, we develop a Bayesian method that builds a multivariate prior for the variable selection indicators based on the variance-covariance of the outcomes. We show via simulation that the proposed variable selection strategy can boost power to detect subtle effects without increasing the probability of false discoveries. We apply the approach to the Normative Aging Study (NAS) epigenetic data and identify a subset of five genes in the asthma pathway for which gene-specific DNA methylations are associated with exposures to either black carbon, a marker of traffic pollution, or sulfate, a marker of particles generated by power plants. © 2016, The International Biometric Society.

Generating carbyne equivalents with photoredox catalysis

NASA Astrophysics Data System (ADS)

Wang, Zhaofeng; Herraiz, Ana G.; Del Hoyo, Ana M.; Suero, Marcos G.

2018-02-01

Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species—carbocations, carbanions, radicals and carbenes—that is fundamental to our understanding of chemical reactivity. In contrast, the carbyne—a monovalent carbon with three non-bonded electrons—is a relatively unexplored reactive intermediate; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an ‘assembly point’ disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon-hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon-hydrogen bonds, while complementing current translational late-stage functionalization processes. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.

Spirotetramat Resistance Selected in the Phenacoccus solenopsis (Homoptera: Pseudococcidae): Cross-Resistance Patterns, Stability, and Fitness Costs Analysis.

PubMed

Ejaz, Masood; Ali Shad, Sarfraz

2017-06-01

The Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae) is a major agricultural and horticultural pest of crops throughout the world. To develop a better resistance management strategy for P. solenopsis, we conducted a study on life history parameters of different populations of this pest, one selected with spirotetramat (Spiro-SEL), an unselected (UNSEL) population, and their reciprocal crosses. We also studied the cross-resistance and the stability of spirotetramat resistance. The Spiro-SEL of P. solenopsis exhibited a 328.69-fold resistance compared to the susceptible population (Lab-PK). The Spiro-SEL population also displayed a moderate level of cross-resistance to profenofos and bifenthrin and a high level of cross-resistance to abamectin. Resistance to spirotetramat in Spiro-SEL was unstable in the absence of selection. The study of life history parameters showed that there was a significant reduction in fitness parameters of Spiro-SEL population with a relative fitness value of 0.14. There was a significant decrease in survival rate, pupal weight, fecundity, egg hatching percentage, male and female generation time, intrinsic rate of population increase of males and females, biotic potential, and mean relative growth rate. It is concluded that selection with spirotetramat had marked effect on resistance development in P. solenopsis and upon removal of selection pressure spirotetramat resistance declined significantly, indicating unstable resistance. Development of resistance led to high fitness costs for the spirotetramat-selected population. Our study may provide the basic information on spirotetramat resistance and its mechanism to help develop the resistance management strategies. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Baby Boomers and Generation X: strategies to bridge the gap.

PubMed

Bertholf, L; Loveless, S

2001-09-01

Health care staffing challenges for the next few years necessitate the need to develop strategies to integrate the Generation Xer into a predominantly Baby Boomer work force. Strategies to assist Baby Boomers and Generation Xers to engage one another in constructive relationships are discussed. Misunderstanding and stereotyping create barriers that focus on differences and perceived limitations rather than identification of common thinking and focusing on strengths of each generation.

Isozygous and selectable marker-free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP.

PubMed

Bi, Yanzhen; Hua, Zaidong; Liu, Ximei; Hua, Wenjun; Ren, Hongyan; Xiao, Hongwei; Zhang, Liping; Li, Li; Wang, Zhirui; Laible, Götz; Wang, Yan; Dong, Faming; Zheng, Xinmin

2016-08-17

Predictable, clean genetic modification (GM) in livestock is important for reliable phenotyping and biosafety. Here we reported the generation of isozygous, functional myostatin (MSTN) knockout cloned pigs free of selectable marker gene (SMG) by CRISPR/Cas9 and Cre/LoxP. CRISPR/Cas9-mediated homologous recombination (HR) was exploited to knock out (KO) one allele of MSTN in pig primary cells. Cre recombinase was then used to excise the SMG with an efficiency of 82.7%. The SMG-free non-EGFP cells were isolated by flow cytometery and immediately used as donor nuclei for nuclear transfer. A total of 685 reconstructed embryos were transferred into three surrogates with one delivering two male live piglets. Molecular testing verified the mono-allelic MSTN KO and SMG deletion in these cloned pigs. Western blots showed approximately 50% decrease in MSTN and concurrent increased expression of myogenic genes in muscle. Histological examination revealed the enhanced myofiber quantity but myofiber size remained unaltered. Ultrasonic detection showed the increased longissimus muscle size and decreased backfat thickness. Precision editing of pig MSTN gene has generated isozygous, SMG-free MSTN KO cloned founders, which guaranteed a reliable route for elite livestock production and a strategy to minimize potential biological risks.

A Real-time Strategy Agent Framework and Strategy Classifier for Computer Generated Forces

DTIC Science & Technology

2012-06-01

via our strategy definition schema, plays the game according to the defined strategy. 4 ) Generate a quality RTS data set. 5) Create an accurate and...General Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.6 Thesis Overview...Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 4 Agent Framework

Polymer ultrapermeability from the inefficient packing of 2D chains

NASA Astrophysics Data System (ADS)

Rose, Ian; Bezzu, C. Grazia; Carta, Mariolino; Comesaña-Gándara, Bibiana; Lasseuguette, Elsa; Ferrari, M. Chiara; Bernardo, Paola; Clarizia, Gabriele; Fuoco, Alessio; Jansen, Johannes C.; Hart, Kyle E.; Liyana-Arachchi, Thilanga P.; Colina, Coray M.; McKeown, Neil B.

2017-09-01

The promise of ultrapermeable polymers, such as poly(trimethylsilylpropyne) (PTMSP), for reducing the size and increasing the efficiency of membranes for gas separations remains unfulfilled due to their poor selectivity. We report an ultrapermeable polymer of intrinsic microporosity (PIM-TMN-Trip) that is substantially more selective than PTMSP. From molecular simulations and experimental measurement we find that the inefficient packing of the two-dimensional (2D) chains of PIM-TMN-Trip generates a high concentration of both small (<0.7 nm) and large (0.7-1.0 nm) micropores, the former enhancing selectivity and the latter permeability. Gas permeability data for PIM-TMN-Trip surpass the 2008 Robeson upper bounds for O2/N2, H2/N2, CO2/N2, H2/CH4 and CO2/CH4, with the potential for biogas purification and carbon capture demonstrated for relevant gas mixtures. Comparisons between PIM-TMN-Trip and structurally similar polymers with three-dimensional (3D) contorted chains confirm that its additional intrinsic microporosity is generated from the awkward packing of its 2D polymer chains in a 3D amorphous solid. This strategy of shape-directed packing of chains of microporous polymers may be applied to other rigid polymers for gas separations.

Navigating a Mobile Robot Across Terrain Using Fuzzy Logic

NASA Technical Reports Server (NTRS)

Seraji, Homayoun; Howard, Ayanna; Bon, Bruce

2003-01-01

A strategy for autonomous navigation of a robotic vehicle across hazardous terrain involves the use of a measure of traversability of terrain within a fuzzy-logic conceptual framework. This navigation strategy requires no a priori information about the environment. Fuzzy logic was selected as a basic element of this strategy because it provides a formal methodology for representing and implementing a human driver s heuristic knowledge and operational experience. Within a fuzzy-logic framework, the attributes of human reasoning and decision- making can be formulated by simple IF (antecedent), THEN (consequent) rules coupled with easily understandable and natural linguistic representations. The linguistic values in the rule antecedents convey the imprecision associated with measurements taken by sensors onboard a mobile robot, while the linguistic values in the rule consequents represent the vagueness inherent in the reasoning processes to generate the control actions. The operational strategies of the human expert driver can be transferred, via fuzzy logic, to a robot-navigation strategy in the form of a set of simple conditional statements composed of linguistic variables. These linguistic variables are defined by fuzzy sets in accordance with user-defined membership functions. The main advantages of a fuzzy navigation strategy lie in the ability to extract heuristic rules from human experience and to obviate the need for an analytical model of the robot navigation process.

Plan selection strategy for rectum cancer patients: An interobserver study to assess clinical feasibility.

PubMed

de Jong, Rianne; Lutkenhaus, Lotte; van Wieringen, Niek; Visser, Jorrit; Wiersma, Jan; Crama, Koen; Geijsen, Debby; Bel, Arjan

2016-08-01

In radiotherapy for rectum cancer, the target volume is highly deformable. An adaptive plan selection strategy can mitigate the effect of these variations. The purpose of this study was to evaluate the feasibility of an adaptive strategy by assessing the interobserver variation in CBCT-based plan selection. Eleven patients with rectum cancer, treated with a non-adaptive strategy, were selected. Five CBCT scans were available per patient. To simulate the plan selection strategy, per patient three PTVs were created by varying the anterior upper mesorectum margin. For each CBCT scan, twenty observers selected the smallest PTV that encompassed the target volume. After this initial baseline measurement, the gold standard was determined during a consensus meeting, followed by a second measurement one month later. Differences between both measurements were assessed using the Wilcoxon signed-rank test. In the baseline measurement, the concordance with the gold standard was 69% (range: 60-82%), which improved to 75% (range: 60-87%) in the second measurement (p=0.01). For the second measurement, 10% of plan selections were smaller than the gold standard. With a plan selection consistency between observers of 75%, a plan selection strategy for rectum cancer patients is feasible. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Functional genomic hypothesis generation and experimentation by a robot scientist.

PubMed

King, Ross D; Whelan, Kenneth E; Jones, Ffion M; Reiser, Philip G K; Bryant, Christopher H; Muggleton, Stephen H; Kell, Douglas B; Oliver, Stephen G

2004-01-15

The question of whether it is possible to automate the scientific process is of both great theoretical interest and increasing practical importance because, in many scientific areas, data are being generated much faster than they can be effectively analysed. We describe a physically implemented robotic system that applies techniques from artificial intelligence to carry out cycles of scientific experimentation. The system automatically originates hypotheses to explain observations, devises experiments to test these hypotheses, physically runs the experiments using a laboratory robot, interprets the results to falsify hypotheses inconsistent with the data, and then repeats the cycle. Here we apply the system to the determination of gene function using deletion mutants of yeast (Saccharomyces cerevisiae) and auxotrophic growth experiments. We built and tested a detailed logical model (involving genes, proteins and metabolites) of the aromatic amino acid synthesis pathway. In biological experiments that automatically reconstruct parts of this model, we show that an intelligent experiment selection strategy is competitive with human performance and significantly outperforms, with a cost decrease of 3-fold and 100-fold (respectively), both cheapest and random-experiment selection.

Learning reliable manipulation strategies without initial physical models

NASA Technical Reports Server (NTRS)

Christiansen, Alan D.; Mason, Matthew T.; Mitchell, Tom M.

1990-01-01

A description is given of a robot, possessing limited sensory and effectory capabilities but no initial model of the effects of its actions on the world, that acquires such a model through exploration, practice, and observation. By acquiring an increasingly correct model of its actions, it generates increasingly successful plans to achieve its goals. In an apparently nondeterministic world, achieving reliability requires the identification of reliable actions and a preference for using such actions. Furthermore, by selecting its training actions carefully, the robot can significantly improve its learning rate.

The Geostationary Operational Satellite R Series SpaceWire Based Data System Architecture

NASA Technical Reports Server (NTRS)

Krimchansky, Alexander; Anderson, William H.; Bearer, Craig

2010-01-01

The GOES-R program selected SpaceWire as the best solution to satisfy the desire for simple and flexible instrument to spacecraft command and telemetry communications. Data generated by GOES-R instruments is critical for meteorological forecasting, public safety, space weather, and other key applications. In addition, GOES-R instrument data is provided to ground stations on a 24/7 basis. GOES-R requires data errors be detected and corrected from origin to final destination. This paper describes GOES-R developed strategy to satisfy this requirement

Microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in Clostridium difficile infection

PubMed Central

Marchesi, J.R.; Thursz, M.R.; Williams, H.R.T.

2015-01-01

Faecal microbiome transplantation (FMT) has generated huge recent interest as it presents a potential solution to a significant clinical problem—the increasing incidence of Clostridium difficile infection (CDI). In the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. In the longer term, enhanced understanding of the mechanisms of action of FMT may potentiate novel therapies, such as targeted manipulation of the microbiome in CDI and beyond. PMID:25193538

Piloting the membranolytic activities of peptides with a self-organizing map.

PubMed

Lin, Yen-Chu; Hiss, Jan A; Schneider, Petra; Thelesklaf, Peter; Lim, Yi Fan; Pillong, Max; Koehler, Fabian M; Dittrich, Petra S; Halin, Cornelia; Wessler, Silja; Schneider, Gisbert

2014-10-13

Antimicrobial peptides (AMPs) show remarkable selectivity toward lipid membranes and possess promising antibiotic potential. Their modes of action are diverse and not fully understood, and innovative peptide design strategies are needed to generate AMPs with improved properties. We present a de novo peptide design approach that resulted in new AMPs possessing low-nanomolar membranolytic activities. Thermal analysis revealed an entropy-driven mechanism of action. The study demonstrates sustained potential of advanced computational methods for designing peptides with the desired activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Streamlined method for parallel identification of single domain antibodies to membrane receptors on whole cells

PubMed Central

Rossotti, Martín; Tabares, Sofía; Alfaya, Lucía; Leizagoyen, Carmen; Moron, Gabriel; González-Sapienza, Gualberto

2015-01-01

BACKGROUND Owing to their minimal size, high production yield, versatility and robustness, the recombinant variable domain (nanobody) of camelid single chain antibodies are valued affinity reagents for research, diagnostic, and therapeutic applications. While their preparation against purified antigens is straightforward, the generation of nanobodies to difficult targets such as multi-pass or complex membrane cell receptors remains challenging. Here we devised a platform for high throughput identification of nanobodies to cell receptor based on the use of a biotin handle. METHODS Using a biotin-acceptor peptide tag, the in vivo biotinylation of nanobodies in 96 well culture blocks was optimized allowing their parallel analysis by flow cytometry and ELISA, and their direct used for pull-down/MS target identification. RESULTS The potential of this strategy was demonstrated by the selection and characterization of panels of nanobodies to Mac-1 (CD11b/CD18), MHC II and the mouse Ly-5 leukocyte common antigen (CD45) receptors, from a VHH library obtained from a llama immunized with mouse bone marrow derived dendritic cells. By on and off switching of the addition of biotin, the method also allowed the epitope binning of the selected Nbs directly on cells. CONCLUSIONS This strategy streamline the selection of potent nanobodies to complex antigens, and the selected nanobodies constitute ready-to-use biotinylated reagents. GENERAL SIGNIFICANCE This method will accelerate the discovery of nanobodies to cell membrane receptors which comprise the largest group of drug and analytical targets. PMID:25819371

Warning signals are under positive frequency-dependent selection in nature

PubMed Central

Chouteau, Mathieu; Arias, Mónica; Joron, Mathieu

2016-01-01

Positive frequency-dependent selection (FDS) is a selection regime where the fitness of a phenotype increases with its frequency, and it is thought to underlie important adaptive strategies resting on signaling and communication. However, whether and how positive FDS truly operates in nature remains unknown, which hampers our understanding of signal diversity. Here, we test for positive FDS operating on the warning color patterns of chemically defended butterflies forming multiple coexisting mimicry assemblages in the Amazon. Using malleable prey models placed in localities showing differences in the relative frequencies of warningly colored prey, we demonstrate that the efficiency of a warning signal increases steadily with its local frequency in the natural community, up to a threshold where protection stabilizes. The shape of this relationship is consistent with the direct effect of the local abundance of each warning signal on the corresponding avoidance knowledge of the local predator community. This relationship, which differs from purifying selection acting on each mimetic pattern, indicates that predator knowledge, integrated over the entire community, is saturated only for the most common warning signals. In contrast, among the well-established warning signals present in local prey assemblages, most are incompletely known to local predators and enjoy incomplete protection. This incomplete predator knowledge should generate strong benefits to life history traits that enhance warning efficiency by increasing the effective frequency of prey visible to predators. Strategies such as gregariousness or niche convergence between comimics may therefore readily evolve through their effects on predator knowledge and warning efficiency. PMID:26858416

Development of selectable marker free, insect resistant, transgenic mustard (Brassica juncea) plants using Cre/lox mediated recombination

PubMed Central

2013-01-01

Background Antibiotic/ herbicide resistant marker genes have been proven to be very useful in plant transformation for the initial selection of desired transgenic events. However, presence of these genes in the genetically modified crops may render the crop less acceptable to the consumers. Among several different approaches, the effectiveness of Cre/lox mediated recombination strategy for selectable marker gene (SMG) elimination has previously been demonstrated by different groups in several plants including Brassica. In the present study exploiting Cre/lox mediated recombination strategy, attempt has been made for selectable marker gene elimination from Allium sativum leaf agglutinin (ASAL) expressing Brassica plants with hemipteran insect resistant phenotype. Results Allium sativum leaf agglutinin (ASAL) linked with lox flanked hygromycin resistant (hpt) gene was introduced in mustard. Cre recombinase gene cassette was also integrated in separate event. A Cre/lox mediated recombination using crossing strategy was adopted to remove the hpt gene from the subsequent generation of selected hybrid events. Reciprocal crosses were made between T1ASAL-lox-hpt-lox and cre-bar plants. Marker gene elimination was confirmed in the resulting F1 hybrid progenies by PCR analysis, using hpt, cre and ASAL specific primers followed by Southern hybridization. In marker free plants, expression of ASAL was also confirmed by western blotting and ELISA analysis. Retention of functionality of expressed ASAL was investigated by agglutination assay using rabbit erythrocytes. Expressed ASAL was also found to be thermo-sensitive. In planta insect bioassay on F1 hybrid progenies exhibited detrimental effect on the performance of devastating target pest, Lipaphis erysimi. The F1 hybrid hpt negative, ASAL positive plants were allowed to self- fertilize to obtain F2 progeny plants. In some of these plants cre gene was found to be segregated out of the ASAL gene by genetic segregation yielding completely marker free plants. Conclusions The present study establishes the efficient expression of the newly introduced insect resistant ASAL gene even after Cre/lox mediated recombination resulting in elimination of selectable marker gene. PMID:24144281

Metacognition for strategy selection during arithmetic problem-solving in young and older adults.

PubMed

Geurten, Marie; Lemaire, Patrick

2018-04-19

We examined participants' strategy choices and metacognitive judgments during arithmetic problem-solving. Metacognitive judgments were collected either prospectively or retrospectively. We tested whether metacognitive judgments are related to strategy choices on the current problems and on the immediately following problems, and age-related differences in relations between metacognition and strategy choices. Data showed that both young and older adults were able to make accurate retrospective, but not prospective, judgments. Moreover, the accuracy of retrospective judgments was comparable in young and older adults when participants had to select and execute the better strategy. Metacognitive accuracy was even higher in older adults when participants had to only select the better strategy. Finally, low-confidence judgments on current items were more frequently followed by better strategy selection on immediately succeeding items than high-confidence judgments in both young and older adults. Implications of these findings to further our understanding of age-related differences and similarities in adults' metacognitive monitoring and metacognitive regulation for strategy selection in the context of arithmetic problem solving are discussed.

A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long QT Syndrome

PubMed Central

Limpitikul, Worawan B.; Dick, Ivy E.; Tester, David J.; Boczek, Nicole J.; Limphong, Pattraranee; Yang, Wanjun; Choi, Myoung Hyun; Babich, Jennifer; DiSilvestre, Deborah; Kanter, Ronald J.; Tomaselli, Gordon F.; Ackerman, Michael J.; Yue, David T.

2017-01-01

Rationale Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long QT syndrome (LQTS) with mutations involving either CALM1, CALM2, or CALM3. The underlying basis of this form of LQTS is a disruption of Ca2+/CaM-dependent inactivation (CDI) of L-type Ca2+ channels (LTCCs). Objective To gain insight into the mechanistic underpinnings of calmodulinopathies and devise new therapeutic strategies for the treatment of this form of LQTS. Methods and Results We generated and characterized the functional properties of iPSC-derived cardiomyocytes (iPSC-CMs) from a patient with D130G-CALM2-mediated LQTS, thus creating a platform with which to devise and test novel therapeutic strategies. The patient-derived iPSC-CMs display (1) significantly prolonged action potentials (APs), (2) disrupted Ca2+ cycling properties, and (3) diminished CDI of LTCCs. Next, taking advantage of the fact that calmodulinopathy patients harbor a mutation in only one of six redundant CaM-encoding alleles, we devised a strategy using CRISPR interference (CRISPRi) to selectively suppress the mutant gene while sparing the wild-type counterparts. Indeed, suppression of CALM2 expression produced a functional rescue in iPSC-CMs with D130G-CALM2, as shown by the normalization of AP duration and CDI following treatment. Moreover, CRISPRi can be designed to achieve selective knockdown of any of the three CALM genes, making it a generalizable therapeutic strategy for any calmodulinopathy. Conclusions Overall, this therapeutic strategy holds great promise for calmodulinopathy patients as it represents a generalizable intervention capable of specifically altering CaM expression and potentially attenuating LQTS-triggered cardiac events, thus initiating a path towards precision medicine. PMID:27765793

Development of variable pathlength UV-vis spectroscopy combined with partial-least-squares regression for wastewater chemical oxygen demand (COD) monitoring.

PubMed

Chen, Baisheng; Wu, Huanan; Li, Sam Fong Yau

2014-03-01

To overcome the challenging task to select an appropriate pathlength for wastewater chemical oxygen demand (COD) monitoring with high accuracy by UV-vis spectroscopy in wastewater treatment process, a variable pathlength approach combined with partial-least squares regression (PLSR) was developed in this study. Two new strategies were proposed to extract relevant information of UV-vis spectral data from variable pathlength measurements. The first strategy was by data fusion with two data fusion levels: low-level data fusion (LLDF) and mid-level data fusion (MLDF). Predictive accuracy was found to improve, indicated by the lower root-mean-square errors of prediction (RMSEP) compared with those obtained for single pathlength measurements. Both fusion levels were found to deliver very robust PLSR models with residual predictive deviations (RPD) greater than 3 (i.e. 3.22 and 3.29, respectively). The second strategy involved calculating the slopes of absorbance against pathlength at each wavelength to generate slope-derived spectra. Without the requirement to select the optimal pathlength, the predictive accuracy (RMSEP) was improved by 20-43% as compared to single pathlength spectroscopy. Comparing to nine-factor models from fusion strategy, the PLSR model from slope-derived spectroscopy was found to be more parsimonious with only five factors and more robust with residual predictive deviation (RPD) of 3.72. It also offered excellent correlation of predicted and measured COD values with R(2) of 0.936. In sum, variable pathlength spectroscopy with the two proposed data analysis strategies proved to be successful in enhancing prediction performance of COD in wastewater and showed high potential to be applied in on-line water quality monitoring. Copyright © 2013 Elsevier B.V. All rights reserved.

Flowering time and seed dormancy control use external coincidence to generate life history strategy

PubMed Central

Springthorpe, Vicki; Penfield, Steven

2015-01-01

Climate change is accelerating plant developmental transitions coordinated with the seasons in temperate environments. To understand the importance of these timing advances for a stable life history strategy, we constructed a full life cycle model of Arabidopsis thaliana. Modelling and field data reveal that a cryptic function of flowering time control is to limit seed set of winter annuals to an ambient temperature window which coincides with a temperature-sensitive switch in seed dormancy state. This coincidence is predicted to be conserved independent of climate at the expense of flowering date, suggesting that temperature control of flowering time has evolved to constrain seed set environment and therefore frequency of dormant and non-dormant seed states. We show that late flowering can disrupt this bet-hedging germination strategy. Our analysis shows that life history modelling can reveal hidden fitness constraints and identify non-obvious selection pressures as emergent features. DOI: http://dx.doi.org/10.7554/eLife.05557.001 PMID:25824056

ECM and ECM-like materials - Biomaterials for applications in regenerative medicine and cancer therapy.

PubMed

Hinderer, Svenja; Layland, Shannon Lee; Schenke-Layland, Katja

2016-02-01

Regenerative strategies such as stem cell-based therapies and tissue engineering applications are being developed with the aim to replace, remodel, regenerate or support damaged tissues and organs. In addition to careful cell type selection, the design of appropriate three-dimensional (3D) scaffolds is essential for the generation of bio-inspired replacement tissues. Such scaffolds are usually made of degradable or non-degradable biomaterials and can serve as cell or drug carriers. The development of more effective and efficient drug carrier systems is also highly relevant for novel cancer treatment strategies. In this review, we provide a summary of current approaches that employ ECM and ECM-like materials, or ECM-synthetic polymer hybrids, as biomaterials in the field of regenerative medicine. We further discuss the utilization of such materials for cell and drug delivery, and highlight strategies for their use as vehicles for cancer therapy. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Selective killing of tumors deficient in methylthioadenosine phosphorylase: a novel strategy.

PubMed

Lubin, Martin; Lubin, Adam

2009-05-29

The gene for methylthioadenosine phosphorylase (MTAP) lies on 9p21, close to the gene CDKN2A that encodes the tumor suppressor proteins p16 and p14ARF. MTAP and CDKN2A are homozygously co-deleted, with a frequency of 35 to 70%, in lung and pancreatic cancer, glioblastoma, osteosarcoma, soft-tissue sarcoma, mesothelioma, and T-cell acute lymphoblastic leukemia. In normal cells, but not in tumor cells lacking MTAP, MTAP cleaves the natural substrate, 5'-deoxy-5'-methylthioadenosine (MTA), to adenine and 5-methylthioribose-1-phosphate (MTR-1-P), which are then converted to adenine nucleotides and methionine. This distinct difference between normal MTAP-positive cells and tumor MTAP-negative cells led to several proposals for therapy. We offer a novel strategy in which both MTA and a toxic adenine analog, such as 2,6-diaminopurine (DAP), 6-methylpurine (MeP), or 2-fluoroadenine (F-Ade), are administered. In MTAP-positive cells, abundant adenine, generated from supplied MTA, competitively blocks the conversion of an analog, by adenine phosphoribosyltransferase (APRT), to its active nucleotide form. In MTAP-negative tumor cells, the supplied MTA cannot generate adenine; hence conversion of the analog is not blocked. We show that this combination treatment--adenine analog plus MTA--kills MTAP-negative A549 lung tumor cells, while MTAP-positive human fibroblasts (HF) are protected. In co-cultures of the breast tumor cell line, MCF-7, and HF cells, MCF-7 is inhibited or killed, while HF cells proliferate robustly. 5-Fluorouracil (5-FU) and 6-thioguanine (6-TG) may also be used with our strategy. Though neither analog is activated by APRT, in MTAP-positive cells, adenine produced from supplied MTA blocks conversion of 5-FU and 6-TG to their toxic nucleotide forms by competing for 5-phosphoribosyl-1-pyrophosphate (PRPP). The combination of MTA with 5-FU or 6-TG, in the treatment of MTAP-negative tumors, may produce a significantly improved therapeutic index. We describe a selective strategy to kill tumor cells lacking MTAP.

The demonstration of a theory-based approach to the design of localized patient safety interventions

PubMed Central

2013-01-01

Background There is evidence of unsafe care in healthcare systems globally. Interventions to implement recommended practice often have modest and variable effects. Ideally, selecting and adapting interventions according to local contexts should enhance effects. However, the means by which this can happen is seldom systematic, based on theory, or made transparent. This work aimed to demonstrate the applicability, feasibility, and acceptability of a theoretical domains framework implementation (TDFI) approach for co-designing patient safety interventions. Methods We worked with three hospitals to support the implementation of evidence-based guidance to reduce the risk of feeding into misplaced nasogastric feeding tubes. Our stepped process, informed by the TDF and key principles from implementation literature, entailed: involving stakeholders; identifying target behaviors; identifying local factors (barriers and levers) affecting behavior change using a TDF-based questionnaire; working with stakeholders to generate specific local strategies to address key barriers; and supporting stakeholders to implement strategies. Exit interviews and audit data collection were undertaken to assess the feasibility and acceptability of this approach. Results Following audit and discussion, implementation teams for each Trust identified the process of checking the positioning of nasogastric tubes prior to feeding as the key behavior to target. Questionnaire results indicated differences in key barriers between organizations. Focus groups generated innovative, generalizable, and adaptable strategies for overcoming barriers, such as awareness events, screensavers, equipment modifications, and interactive learning resources. Exit interviews identified themes relating to the benefits, challenges, and sustainability of this approach. Time trend audit data were collected for 301 patients over an 18-month period for one Trust, suggesting clinically significant improved use of pH and documentation of practice following the intervention. Conclusions The TDF is a feasible and acceptable framework to guide the implementation of patient safety interventions. The stepped TDFI approach engages healthcare professionals and facilitates contextualization in identifying the target behavior, eliciting local barriers, and selecting strategies to address those barriers. This approach may be of use to implementation teams and policy makers, although our promising findings confirm the need for a more rigorous evaluation; a balanced block evaluation is currently underway. PMID:24131864

A strategy for automatically generating programs in the lucid programming language

NASA Technical Reports Server (NTRS)

Johnson, Sally C.

1987-01-01

A strategy for automatically generating and verifying simple computer programs is described. The programs are specified by a precondition and a postcondition in predicate calculus. The programs generated are in the Lucid programming language, a high-level, data-flow language known for its attractive mathematical properties and ease of program verification. The Lucid programming is described, and the automatic program generation strategy is described and applied to several example problems.

An Optimization Model For Strategy Decision Support to Select Kind of CPO’s Ship

NASA Astrophysics Data System (ADS)

Suaibah Nst, Siti; Nababan, Esther; Mawengkang, Herman

2018-01-01

The selection of marine transport for the distribution of crude palm oil (CPO) is one of strategy that can be considered in reducing cost of transport. The cost of CPO’s transport from one area to CPO’s factory located at the port of destination may affect the level of CPO’s prices and the number of demands. In order to maintain the availability of CPO a strategy is required to minimize the cost of transporting. In this study, the strategy used to select kind of charter ships as barge or chemical tanker. This study aims to determine an optimization model for strategy decision support in selecting kind of CPO’s ship by minimizing costs of transport. The select of ship was done randomly, so that two-stage stochastic programming model was used to select the kind of ship. Model can help decision makers to select either barge or chemical tanker to distribute CPO.

Techno-Economic Analysis of Integration of Low-Temperature Geothermal Resources for Coal-Fired Power Plants

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

Bearden, Mark D.; Davidson, Casie L.; Horner, Jacob A.

Presented here are the results of a techno-economic (TEA) study of the potential for coupling low-grade geothermal resources to boost the electrical output from coal-fired power plants. This study includes identification of candidate 500 MW subcritical coal-fired power plants in the continental United States, followed by down-selection and characterization of the North Valmy generating station, a Nevada coal-fired plant. Based on site and plant characteristics, ASPEN Plus models were designed to evaluate options to integrate geothermal resources directly into existing processes at North Valmy. Energy outputs and capital costing are presented for numerous hybrid strategies, including integration with Organic Rankinemore » Cycles (ORCs), which currently represent the primary technology for baseload geothermal power generation.« less

A multiobjective hybrid genetic algorithm for the capacitated multipoint network design problem.

PubMed

Lo, C C; Chang, W H

2000-01-01

The capacitated multipoint network design problem (CMNDP) is NP-complete. In this paper, a hybrid genetic algorithm for CMNDP is proposed. The multiobjective hybrid genetic algorithm (MOHGA) differs from other genetic algorithms (GAs) mainly in its selection procedure. The concept of subpopulation is used in MOHGA. Four subpopulations are generated according to the elitism reservation strategy, the shifting Prufer vector, the stochastic universal sampling, and the complete random method, respectively. Mixing these four subpopulations produces the next generation population. The MOHGA can effectively search the feasible solution space due to population diversity. The MOHGA has been applied to CMNDP. By examining computational and analytical results, we notice that the MOHGA can find most nondominated solutions and is much more effective and efficient than other multiobjective GAs.

Design and screening of M13 phage display cDNA libraries.

PubMed

Georgieva, Yuliya; Konthur, Zoltán

2011-02-17

The last decade has seen a steady increase in screening of cDNA expression product libraries displayed on the surface of filamentous bacteriophage. At the same time, the range of applications extended from the identification of novel allergens over disease markers to protein-protein interaction studies. However, the generation and selection of cDNA phage display libraries is subjected to intrinsic biological limitations due to their complex nature and heterogeneity, as well as technical difficulties regarding protein presentation on the phage surface. Here, we review the latest developments in this field, discuss a number of strategies and improvements anticipated to overcome these challenges making cDNA and open reading frame (ORF) libraries more readily accessible for phage display. Furthermore, future trends combining phage display with next generation sequencing (NGS) will be presented.

Enzyme-Initiated Quinone-Chitosan Conjugation Chemistry: Toward A General in Situ Strategy for High-Throughput Photoelectrochemical Enzymatic Bioanalysis.

PubMed

Wang, Guang-Li; Yuan, Fang; Gu, Tiantian; Dong, Yuming; Wang, Qian; Zhao, Wei-Wei

2018-02-06

Herein we report a general and novel strategy for high-throughput photoelectrochemical (PEC) enzymatic bioanalysis on the basis of enzyme-initiated quinone-chitosan conjugation chemistry (QCCC). Specifically, the strategy was illustrated by using a model quinones-generating oxidase of tyrosinase (Tyr) to catalytically produce 1,2-bezoquinone or its derivative, which can easily and selectively be conjugated onto the surface of the chitosan deposited PbS/NiO/FTO photocathode via the QCCC. Upon illumination, the covalently attached quinones could act as electron acceptors of PbS quantum dots (QDs), improving the photocurrent generation and thus allowing the elegant probing of Tyr activity. Enzyme cascades, such as alkaline phosphatase (ALP)/Tyr and β-galactosidase (Gal)/Tyr, were further introduced into the system for the successful probing of the corresponding targets. This work features not only the first use of QCCC in PEC bioanalysis but also the separation of enzymatic reaction from the photoelectrode as well as the direct signal recording in a split-type protocol, which enables quite convenient and high-throughput detection as compared to previous formats. More importantly, by using numerous other oxidoreductases that involve quinones as reactants/products, this protocol could serve as a common basis for the development of a new class of QCCC-based PEC enzymatic bioanalysis and further extended for general enzyme-labeled PEC bioanalysis of versatile targets.

Design-for-Six-Sigma To Develop a Bioprocess Knowledge Management Framework.

PubMed

Junker, Beth; Maheshwari, Gargi; Ranheim, Todd; Altaras, Nedim; Stankevicz, Michael; Harmon, Lori; Rios, Sandra; D'anjou, Marc

2011-01-01

Owing to the high costs associated with biopharmaceutical development, considerable pressure has developed for the biopharmaceutical industry to increase productivity by becoming more lean and flexible. The ability to reuse knowledge was identified as one key advantage to streamline productivity, efficiently use resources, and ultimately perform better than the competition. A knowledge management (KM) strategy was assembled for bioprocess-related information using the technique of Design-for-Six-Sigma (DFSS). This strategy supported quality-by-design and process validation efforts for pipeline as well as licensed products. The DFSS technique was selected because it was both streamlined and efficient. These characteristics permitted development of a KM strategy with minimized team leader and team member resources. DFSS also placed a high emphasis on the voice of the customer, information considered crucial to the selection of solutions most appropriate for the current knowledge-based challenges of the organization. The KM strategy developed was comprised of nine workstreams, constructed from related solution buckets which in turn were assembled from the individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the KM strategy project charter and design inputs. Gaps and risks were identified and mitigated as necessary to improve the robustness of the proposed strategy. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and divisional/corporate information technology efforts were leveraged to minimize the additional bioprocess resources required for implementation. Finally, leading and lagging indicator metrics were selected to track the success of pilots and eventual implementation. A knowledge management framework was assembled for bioprocess-related information using a streamlined and efficient technique that minimized team leader and member resources. The technique also highly emphasized input from the staff, who generated and used the knowledge, information considered crucial to selection of solutions most appropriate for the current knowledge-based challenges in the organization. The framework developed was comprised of nine workstreams, constructed from related solution buckets which were assembled from individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the project charter and design inputs. Gaps and risks were identified and mitigated to improve robustness of the proposed framework. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required for implementation. Finally, metrics were selected to track the success of pilots and eventual implementation.

A Robust Decision-Making Technique for Water Management under Decadal Scale Climate Variability

NASA Astrophysics Data System (ADS)

Callihan, L.; Zagona, E. A.; Rajagopalan, B.

2013-12-01

Robust decision making, a flexible and dynamic approach to managing water resources in light of deep uncertainties associated with climate variability at inter-annual to decadal time scales, is an analytical framework that detects when a system is in or approaching a vulnerable state. It provides decision makers the opportunity to implement strategies that both address the vulnerabilities and perform well over a wide range of plausible future scenarios. A strategy that performs acceptably over a wide range of possible future states is not likely to be optimal with respect to the actual future state. The degree of success--the ability to avoid vulnerable states and operate efficiently--thus depends on the skill in projecting future states and the ability to select the most efficient strategies to address vulnerabilities. This research develops a robust decision making framework that incorporates new methods of decadal scale projections with selection of efficient strategies. Previous approaches to water resources planning under inter-annual climate variability combining skillful seasonal flow forecasts with climatology for subsequent years are not skillful for medium term (i.e. decadal scale) projections as decision makers are not able to plan adequately to avoid vulnerabilities. We address this need by integrating skillful decadal scale streamflow projections into the robust decision making framework and making the probability distribution of this projection available to the decision making logic. The range of possible future hydrologic scenarios can be defined using a variety of nonparametric methods. Once defined, an ensemble projection of decadal flow scenarios are generated from a wavelet-based spectral K-nearest-neighbor resampling approach using historical and paleo-reconstructed data. This method has been shown to generate skillful medium term projections with a rich variety of natural variability. The current state of the system in combination with the probability distribution of the projected flow ensembles enables the selection of appropriate decision options. This process is repeated for each year of the planning horizon--resulting in system outcomes that can be evaluated on their performance and resiliency. The research utilizes the RiverSMART suite of software modeling and analysis tools developed under the Bureau of Reclamation's WaterSMART initiative and built around the RiverWare modeling environment. A case study is developed for the Gunnison and Upper Colorado River Basins. The ability to mitigate vulnerability using the framework is gauged by system performance indicators that measure the ability of the system to meet various water demands (i.e. agriculture, environmental flows, hydropower etc.). Options and strategies for addressing vulnerabilities include measures such as conservation, reallocation and adjustments to operational policy. In addition to being able to mitigate vulnerabilities, options and strategies are evaluated based on benefits, costs and reliability. Flow ensembles are also simulated to incorporate mean and variance from climate change projections for the planning horizon and the above robust decision-making framework is applied to evaluate its performance under changing climate.

Glucose Injections into the Dorsal Hippocampus or Dorsolateral Striatum of Rats Prior to T-Maze Training: Modulation of Learning Rates and Strategy Selection

ERIC Educational Resources Information Center

Canal, Clinton E.; Stutz, Sonja J.; Gold, Paul E.

2005-01-01

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial…

Combining experimental evolution with next-generation sequencing: a powerful tool to study adaptation from standing genetic variation.

PubMed

Schlötterer, C; Kofler, R; Versace, E; Tobler, R; Franssen, S U

2015-05-01

Evolve and resequence (E&R) is a new approach to investigate the genomic responses to selection during experimental evolution. By using whole genome sequencing of pools of individuals (Pool-Seq), this method can identify selected variants in controlled and replicable experimental settings. Reviewing the current state of the field, we show that E&R can be powerful enough to identify causative genes and possibly even single-nucleotide polymorphisms. We also discuss how the experimental design and the complexity of the trait could result in a large number of false positive candidates. We suggest experimental and analytical strategies to maximize the power of E&R to uncover the genotype-phenotype link and serve as an important research tool for a broad range of evolutionary questions.

Approaches and incentives to implement integrated pest management that addresses regional and environmental issues.

PubMed

Brewer, Michael J; Goodell, Peter B

2012-01-01

Agricultural, environmental, and social and policy interests have influenced integrated pest management (IPM) from its inception. The first 50 years of IPM paid special attention to field-based management and market-driven decision making. Concurrently, IPM strategies became available that were best applied both within and beyond the bounds of individual fields and that also provided environmental benefits. This generated an incentives dilemma for farmers: selecting IPM activities for individual fields on the basis of market-based economics versus selecting IPM activities best applied regionally that have longer-term benefits, including environmental benefits, that accrue to the broader community as well as the farmer. Over the past several decades, public-supported incentives, such as financial incentives available to farmers from conservation programs for farms, have begun to be employed to encourage use of conservation techniques, including strategies with IPM relevance. Combining private investments with public support may effectively address the incentives dilemma when advanced IPM strategies are used regionally and provide public goods such as those benefiting resource conservation. This review focuses on adaptation of IPM to these broader issues, on transitions of IPM from primarily individual field-based decision making to coordinated community decision making, and on the form of partnerships needed to gain long-lasting regional and environmental benefits. Copyright © 2012 by Annual Reviews. All rights reserved.

Influence of scan strategy and molten pool configuration on microstructures and tensile properties of selective laser melting additive manufactured aluminum based parts

NASA Astrophysics Data System (ADS)

Dai, Donghua; Gu, Dongdong; Zhang, Han; Xiong, Jiapeng; Ma, Chenglong; Hong, Chen; Poprawe, Reinhart

2018-02-01

Selective laser melting additive manufacturing of the AlSi12 material parts through the re-melting of the previously solidified layer using the continuous two layers 90° rotate scan strategy was conducted. The influence of the re-melting behavior and scan strategy on the formation of the ;track-track; and ;layer-layer; molten pool boundaries (MPBs), dimensional accuracy, microstructure feature, tensile properties, microscopic sliding behavior and the fracture mechanism as loaded a tensile force has been studied. It showed that the defects, such as the part distortion, delamination and cracks, were significantly eliminated with the deformation rate less than 1%. The microstructure of a homogeneous distribution of the Si phase, no apparent grain orientation on both sides of the MPBs, was produced in the as-fabricated part, promoting the efficient transition of the load stress. Cracks preferentially initiate at the ;track-track; MPBs when the tensile stress increases to a certain value, resulting in the formation of the cleavage steps along the tensile loading direction. The cracks propagate along the ;layer-layer; MPBs, generating the fine dimples. The mechanical behavior of the SLM-processed AlSi12 parts can be significantly enhanced with the ultimate tensile strength, yield strength and elongation of 476.3 MPa, 315.5 MPa and 6.7%, respectively.

TARGETED CAPTURE IN EVOLUTIONARY AND ECOLOGICAL GENOMICS

PubMed Central

Jones, Matthew R.; Good, Jeffrey M.

2016-01-01

The rapid expansion of next-generation sequencing has yielded a powerful array of tools to address fundamental biological questions at a scale that was inconceivable just a few years ago. Various genome partitioning strategies to sequence select subsets of the genome have emerged as powerful alternatives to whole genome sequencing in ecological and evolutionary genomic studies. High throughput targeted capture is one such strategy that involves the parallel enrichment of pre-selected genomic regions of interest. The growing use of targeted capture demonstrates its potential power to address a range of research questions, yet these approaches have yet to expand broadly across labs focused on evolutionary and ecological genomics. In part, the use of targeted capture has been hindered by the logistics of capture design and implementation in species without established reference genomes. Here we aim to 1) increase the accessibility of targeted capture to researchers working in non-model taxa by discussing capture methods that circumvent the need of a reference genome, 2) highlight the evolutionary and ecological applications where this approach is emerging as a powerful sequencing strategy, and 3) discuss the future of targeted capture and other genome partitioning approaches in light of the increasing accessibility of whole genome sequencing. Given the practical advantages and increasing feasibility of high-throughput targeted capture, we anticipate an ongoing expansion of capture-based approaches in evolutionary and ecological research, synergistic with an expansion of whole genome sequencing. PMID:26137993

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

Hraber, Peter; Korber, Bette; Wagh, Kshitij

Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

Integrated feature extraction and selection for neuroimage classification

NASA Astrophysics Data System (ADS)

Fan, Yong; Shen, Dinggang

2009-02-01

Feature extraction and selection are of great importance in neuroimage classification for identifying informative features and reducing feature dimensionality, which are generally implemented as two separate steps. This paper presents an integrated feature extraction and selection algorithm with two iterative steps: constrained subspace learning based feature extraction and support vector machine (SVM) based feature selection. The subspace learning based feature extraction focuses on the brain regions with higher possibility of being affected by the disease under study, while the possibility of brain regions being affected by disease is estimated by the SVM based feature selection, in conjunction with SVM classification. This algorithm can not only take into account the inter-correlation among different brain regions, but also overcome the limitation of traditional subspace learning based feature extraction methods. To achieve robust performance and optimal selection of parameters involved in feature extraction, selection, and classification, a bootstrapping strategy is used to generate multiple versions of training and testing sets for parameter optimization, according to the classification performance measured by the area under the ROC (receiver operating characteristic) curve. The integrated feature extraction and selection method is applied to a structural MR image based Alzheimer's disease (AD) study with 98 non-demented and 100 demented subjects. Cross-validation results indicate that the proposed algorithm can improve performance of the traditional subspace learning based classification.

Comprehensive clone screening and evaluation of fed-batch strategies in a microbioreactor and lab scale stirred tank bioreactor system: application on Pichia pastoris producing Rhizopus oryzae lipase

PubMed Central

2014-01-01

Background In Pichia pastoris bioprocess engineering, classic approaches for clone selection and bioprocess optimization at small/micro scale using the promoter of the alcohol oxidase 1 gene (PAOX1), induced by methanol, present low reproducibility leading to high time and resource consumption. Results An automated microfermentation platform (RoboLector) was successfully tested to overcome the chronic problems of clone selection and optimization of fed-batch strategies. Different clones from Mut+P. pastoris phenotype strains expressing heterologous Rhizopus oryzae lipase (ROL), including a subset also overexpressing the transcription factor HAC1, were tested to select the most promising clones. The RoboLector showed high performance for the selection and optimization of cultivation media with minimal cost and time. Syn6 medium was better than conventional YNB medium in terms of production of heterologous protein. The RoboLector microbioreactor was also tested for different fed-batch strategies with three clones producing different lipase levels. Two mixed substrates fed-batch strategies were evaluated. The first strategy was the enzymatic release of glucose from a soluble glucose polymer by a glucosidase, and methanol addition every 24 hours. The second strategy used glycerol as co-substrate jointly with methanol at two different feeding rates. The implementation of these simple fed-batch strategies increased the levels of lipolytic activity 80-fold compared to classical batch strategies used in clone selection. Thus, these strategies minimize the risk of errors in the clone selection and increase the detection level of the desired product. Finally, the performance of two fed-batch strategies was compared for lipase production between the RoboLector microbioreactor and 5 liter stirred tank bioreactor for three selected clones. In both scales, the same clone ranking was achieved. Conclusion The RoboLector showed excellent performance in clone selection of P. pastoris Mut+ phenotype. The use of fed-batch strategies using mixed substrate feeds resulted in increased biomass and lipolytic activity. The automated processing of fed-batch strategies by the RoboLector considerably facilitates the operation of fermentation processes, while reducing error-prone clone selection by increasing product titers. The scale-up from microbioreactor to lab scale stirred tank bioreactor showed an excellent correlation, validating the use of microbioreactor as a powerful tool for evaluating fed-batch operational strategies. PMID:24606982

Lack of strategy holding: a new pattern of learning deficit in cortical dementias.

PubMed

Benedet, María J; Lauro-Grotto, Rosapia; Giotti, Chiara

2009-09-01

The aim of this study was to demonstrate, by means of systematic research and qualitative data analysis, the presence, among a group of patients with fronto-temporal lobar degeneration of a subgroup that, at variance with the standard pattern, is able to devise and implement learning strategies, but appear impaired at carrying them on from a trial to the next. In order to provide evidence of the existence of a group of patients showing this type of learning disability, that we refer to as lack of strategy holding, we performed a stepwise hierarchical cluster analysis of a set of variables whose scores were selected from the subject's performance at the Test de Aprendizaje Verbal España-Complutense. Results substantiate the segregation of three groups of subjects characterized by the following patterns of performance: normal elderly individuals, who show a quite preserved ability to discover a semantic strategy along the learning trials and to carry it from a trial to the next, patients presenting with a deficit in implementing semantic learning strategies and possibly use of serial and/or phonological strategies to perform the task, and to patients who, although able to generate and implement appropriate learning strategies, appear unable to carry them over the learning trials. The presence of this new pattern raises a few questions that seem worth trying to address.

The impact of selection on population genetic structure in the clam Meretrix petechialis revealed by microsatellite markers.

PubMed

Lu, Xia; Wang, Hongxia; Li, Yan; Liu, Baozhong

2016-02-01

The aim of our work is to evaluate the impact of mass selection on genetic structure in artificially closed populations of the clam Meretrix petechialis. In the present study, we performed mass selection over four generations (from 2004 to 2010) on two clam populations [shell features of purple lines (SP) and black dots (SB)] and analyzed their temporal genetic variation and structure using microsatellite makers. The two closed populations originated from the natural Shandong population (SD); thus, a natural SD population (10SD) was used to detect the current genetic structure after 6 years of natural selection. The results showed that the genetic diversity of the four generations of SB and SP was gradually reduced but remained at relatively high levels (SB, A = 18.9.4-16.8, Ho = 0.7389-0.6971, and He = 0.8897-0.8591; SP, A = 20.0-17.8, Ho = 0.7512-0.7043, and He = 0.8938-0.8625), which has not been reduced compared with that of the 10SD population (A = 17.8, Ho = 0.6803, and He = 0.8302). The Ne estimates for the two populations were almost at the same levels as the actual numbers of parental individuals. In addition, a low inbreeding coefficient was detected in the two populations (SB, 0.00201-0.00639; SP, 0.00176-0.00541). Based on the results, the present mass selection has not made a large impact on the population genetic structure of the closed populations. The present investigation provides important information for the development of management strategies for genetic breeding of the clam.

Genetic gain and economic values of selection strategies including semen traits in three- and four-way crossbreeding systems for swine production.

PubMed

González-Peña, D; Knox, R V; MacNeil, M D; Rodriguez-Zas, S L

2015-03-01

Four semen traits: volume (VOL), concentration (CON), progressive motility of spermatozoa (MOT), and abnormal spermatozoa (ABN) provide complementary information on boar fertility. Assessment of the impact of selection for semen traits is hindered by limited information on economic parameters. Objectives of this study were to estimate economic values for semen traits and to evaluate the genetic gain when these traits are incorporated into traditional selection strategies in a 3-tier system of swine production. Three-way (maternal nucleus lines A and B and paternal nucleus line C) and 4-way (additional paternal nucleus line D) crossbreeding schemes were compared. A novel population structure that accommodated selection for semen traits was developed. Three selection strategies were simulated. Selection Strategy I (baseline) encompassed selection for maternal traits: number of pigs born alive (NBA), litter birth weight (LBW), adjusted 21-d litter weight (A21), and number of pigs at 21 d (N21); and paternal traits: number of days to 113.5 kg (D113), backfat (BF), ADG, feed efficiency (FE), and carcass lean % (LEAN). Selection Strategy II included Strategy I and the number of usable semen doses per collection (DOSES), a function of the 4 semen traits. Selection Strategy III included Strategy I and the 4 semen traits individually. The estimated economic values of VOL, CON, MOT, ABN, and DOSES for 7 to 1 collections/wk ranged from $0.21 to $1.44/mL, $0.12 to $0.83/10 spermatozoa/mm, $0.61 to $12.66/%, -$0.53 to -$10.88/%, and $2.01 to $41.43/%, respectively. The decrease in the relative economic values of semen traits and DOSES with higher number of collections per wk was sharper between 1 and 2.33 collections/wk than between 2.33 and 7 collections/wk. The higher economic value of MOT and ABN relative to VOL and CON could be linked to the genetic variances and covariances of these traits. Average genetic gains for the maternal traits were comparable across strategies. Genetic gains for paternal traits, excluding semen traits, were greater in selection Strategy I than Strategies III and II. Genetic gains for paternal and maternal traits were greater in the 4- and 3-way schemes, respectively. The selection strategy including the 4 semen traits is recommended because this approach enables genetic gains for these traits without compromising the genetic gains for maternal traits and with minimal losses in genetic gains for paternal traits.

Label-free fluorescence strategy for sensitive microRNA detection based on isothermal exponential amplification and graphene oxide.

PubMed

Li, Wei; Hou, Ting; Wu, Min; Li, Feng

2016-01-01

MicroRNAs (miRNAs) play an important role in many biological processes, and have been regarded as potential targets and biomarkers in cancer diagnosis and therapy. Also, to meet the big challenge imposed by the characteristics of miRNAs, such as small size and vulnerability to enzymatic digestion, it is of great importance to develop accurate, sensitive and simple miRNA assays. Herein, we developed a label-free fluorescence strategy for sensitive miRNA detection by combining isothermal exponential amplification and the unique features of SYBR Green I (SG) and graphene oxide (GO), in which SG gives significantly enhanced fluorescence upon intercalation into double-stranded DNAs (dsDNAs), and GO selectively adsorbs miRNA, single-stranded DNA and SG, to protect miRNA from enzymatic digestion, and to quench the fluorescence of the adsorbed SG. In the presence of the target miRNA, the ingeniously designed hairpin probe (HP) is unfolded and the subsequent polymerization and strand displacement reaction takes place to initiate the target recycling process. The newly formed dsDNAs are then recognized and cleaved by the nicking enzyme, generating new DNA triggers with the same sequence as the target miRNA, which hybridize with intact HPs to initiate new extension reactions. As a result, the circular exponential amplification for target miRNA is achieved and large amount of dsDNAs are formed to generate significantly enhanced fluorescence upon the intercalation of SG. Thus sensitive and selective fluorescence miRNA detection is realized, and the detection limit of 3 fM is obtained. Besides, this method exhibits additional advantages of simplicity and low cost, since expensive and tedious labeling process is avoided. Therefore, the as-proposed label-free fluorescence strategy has great potential in the applications in miRNA-related clinical practices and biochemical researches. Copyright © 2015 Elsevier B.V. All rights reserved.

Fungal-to-bacterial dominance of soil detrital food-webs: Consequences for biogeochemistry

NASA Astrophysics Data System (ADS)

Rousk, Johannes; Frey, Serita

2015-04-01

Resolving fungal and bacterial groups within the microbial decomposer community is thought to capture disparate microbial life strategies, associating bacteria with an r-selected strategy for carbon (C) and nutrient use, and fungi with a K-selected strategy. Additionally, food-web models have established a widely held belief that the bacterial decomposer pathway in soil supports high turnover rates of easily available substrates, while the slower fungal pathway supports the decomposition of more complex organic material, thus characterising the biogeochemistry of the ecosystem. Three field-experiments to generate gradients of SOC-quality were assessed. (1) the Detritus Input, Removal, and Trenching - DIRT - experiment in a temperate forest in mixed hardwood stands at Harvard Forest LTER, US. There, experimentally adjusted litter input and root input had affected the SOC quality during 23 years. (2) field-application of 14-C labelled glucose to grassland soils, sampled over the course of 13 months to generate an age-gradient of SOM (1 day - 13 months). (3) The Park Grass Experiment at Rothamsted, UK, where 150-years continuous N-fertilisation (0, 50, 100, 150 kg N ha-1 y-1) has affected the quality of SOM in grassland soils. A combination of carbon stable and radio isotope studies, fungal and bacterial growth and biomass measurements, and C and N mineralisation (15N pool dilution) assays were used to investigate how SOC-quality influenced fungal and bacterial food-web pathways and the implications this had for C and nutrient turnover. There was no support that decomposer food-webs dominated by bacteria support high turnover rates of easily available substrates, while slower fungal-dominated decomposition pathways support the decomposition of more complex organic material. Rather, an association between high quality SOC and fungi emerges from the results. This suggests that we need to revise our basic understanding for soil microbial communities and the processes they regulate in soil.

Strategies for Selecting Routes through Real-World Environments: Relative Topography, Initial Route Straightness, and Cardinal Direction

PubMed Central

Brunyé, Tad T.; Collier, Zachary A.; Cantelon, Julie; Holmes, Amanda; Wood, Matthew D.; Linkov, Igor; Taylor, Holly A.

2015-01-01

Previous research has demonstrated that route planners use several reliable strategies for selecting between alternate routes. Strategies include selecting straight rather than winding routes leaving an origin, selecting generally south- rather than north-going routes, and selecting routes that avoid traversal of complex topography. The contribution of this paper is characterizing the relative influence and potential interactions of these strategies. We also examine whether individual differences would predict any strategy reliance. Results showed evidence for independent and additive influences of all three strategies, with a strong influence of topography and initial segment straightness, and relatively weak influence of cardinal direction. Additively, routes were also disproportionately selected when they traversed relatively flat regions, had relatively straight initial segments, and went generally south rather than north. Two individual differences, extraversion and sense of direction, predicted the extent of some effects. Under real-world conditions navigators indeed consider a route’s initial straightness, cardinal direction, and topography, but these cues differ in relative influence and vary in their application across individuals. PMID:25992685

REGULATORY STRATEGIES TO MINIMIZE GENERATION OF REGULATED WASTES FROM CLEANUP, CONTINUED USE OR DECOMMISSIONING OF NUCLEAR FACILITIES CONTAMINATED WITH POLYCHLORINATED BIPHENYLS (PCBS) - 11198

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

Lowry, N.

Disposal costs for liquid PCB radioactive waste are among the highest of any category of regulated waste. The high cost is driven by the fact that disposal options are extremely limited. Toxic Substances Control Act (TSCA) regulations require most liquids with PCBs at concentration of {ge} 50 parts-per-million to be disposed by incineration or equivalent destructive treatment. Disposal fees can be as high as $200 per gallon. This figure does not include packaging and the cost to transport the waste to the disposal facility, or the waste generator's labor costs for managing the waste prior to shipment. Minimizing the generationmore » of liquid radioactive PCB waste is therefore a significant waste management challenge. PCB spill cleanups often generate large volumes of waste. That is because the removal of PCBs typically requires the liberal use of industrial solvents followed by a thorough rinsing process. In a nuclear facility, the cleanup process may be complicated by the presence of radiation and other occupational hazards. Building design and construction features, e.g., the presence of open grating or trenches, may also complicate cleanup. In addition to the technical challenges associated with spill cleanup, selection of the appropriate regulatory requirements and approach may be challenging. The TSCA regulations include three different sections relating to the cleanup of PCB contamination or spills. EPA has also promulgated a separate guidance policy for fresh PCB spills that is published as Subpart G of 40 CFR 761 although it is not an actual regulation. Applicability is based on the circumstances of each contamination event or situation. Other laws or regulations may also apply. Identification of the allowable regulatory options is important. Effective communication with stakeholders, particularly regulators, is just as important. Depending on the regulatory path that is taken, cleanup may necessitate the generation of large quantities of regulated waste. Allowable options must be evaluated carefully in order to reduce compliance risks, protect personnel, limit potential negative impacts on facility operations, and minimize the generation of wastes subject to TSCA. This paper will identify critical factors in selecting the appropriate TSCA regulatory path in order to minimize the generation of radioactive PCB waste and reduce negative impacts to facilities. The importance of communicating pertinent technical issues with facility staff, regulatory personnel, and subsequently, the public, will be discussed. Key points will be illustrated by examples from five former production reactors at the DOE Savannah River Site. In these reactors a polyurethane sealant was used to seal piping penetrations in the biological shield walls. During the intense neutron bombardment that occurred during reactor operation, the sealant broke down into a thick, viscous material that seeped out of the piping penetrations over adjacent equipment and walls. Some of the walls were painted with a PCB product. PCBs from the paint migrated into the degraded sealant, creating PCB 'spill areas' in some of these facilities. The regulatory cleanup approach selected for each facility was based on its operational status, e.g., active, inactive or undergoing decommissioning. The selected strategies served to greatly minimize the generation of radioactive liquid PCB waste. It is expected that this information would be useful to other DOE sites, DOD facilities, and commercial nuclear facilities constructed prior to the 1979 TSCA ban on most manufacturing and uses of PCBs.« less

Infection before pregnancy affects immunity and response to social challenge in the next generation.

PubMed

Curno, Olivia; Reader, Tom; McElligott, Alan G; Behnke, Jerzy M; Barnard, Chris J

2011-12-12

Natural selection should favour parents that are able to adjust their offspring's life-history strategy and resource allocation in response to changing environmental and social conditions. Pathogens impose particularly strong and variable selective pressure on host life histories, and parental genes will benefit if offspring are appropriately primed to meet the immunological challenges ahead. Here, we investigated transgenerational immune priming by examining reproductive resource allocation by female mice in response to direct infection with Babesia microti prior to pregnancy. Female mice previously infected with B. microti gained more weight over pregnancy, and spent more time nursing their offspring. These offspring generated an accelerated response to B. microti as adults, clearing the infection sooner and losing less weight as a result of infection. They also showed an altered hormonal response to novel social environments, decreasing instead of increasing testosterone production upon social housing. These results suggest that a dominance-resistance trade-off can be mediated by cues from the previous generation. We suggest that strategic maternal investment in response to an infection leads to increased disease resistance in the following generation. Offspring from previously infected mothers downregulate investment in acquisition of social dominance, which in natural systems would reduce access to mating opportunities. In doing so, however, they avoid the reduced disease resistance associated with increased testosterone and dominance. The benefits of accelerated clearance of infection and reduced weight loss during infection may outweigh costs associated with reduced social dominance in an environment where the risk of disease is high.

β-Globin-Expressing Definitive Erythroid Progenitor Cells Generated from Embryonic and Induced Pluripotent Stem Cell-Derived Sacs.

PubMed

Fujita, Atsushi; Uchida, Naoya; Haro-Mora, Juan J; Winkler, Thomas; Tisdale, John

2016-06-01

Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a potential alternative source for red blood cell transfusion. However, when using traditional methods with embryoid bodies, ES cell-derived erythroid cells predominantly express embryonic type ɛ-globin, with lesser fetal type γ-globin and very little adult type β-globin. Furthermore, no β-globin expression is detected in iPS cell-derived erythroid cells. ES cell-derived sacs (ES sacs) have been recently used to generate functional platelets. Due to its unique structure, we hypothesized that ES sacs serve as hemangioblast-like progenitors capable to generate definitive erythroid cells that express β-globin. With our ES sac-derived erythroid differentiation protocol, we obtained ∼120 erythroid cells per single ES cell. Both primitive (ɛ-globin expressing) and definitive (γ- and β-globin expressing) erythroid cells were generated from not only ES cells but also iPS cells. Primitive erythropoiesis is gradually switched to definitive erythropoiesis during prolonged ES sac maturation, concurrent with the emergence of hematopoietic progenitor cells. Primitive and definitive erythroid progenitor cells were selected on the basis of glycophorin A or CD34 expression from cells within the ES sacs before erythroid differentiation. This selection and differentiation strategy represents an important step toward the development of in vitro erythroid cell production systems from pluripotent stem cells. Further optimization to improve expansion should be required for clinical application. Stem Cells 2016;34:1541-1552. © 2016 AlphaMed Press.

Qualitative analysis of governance trends after health system reforms in Latin America: lessons from Mexico.

PubMed

Arredondo, A; Orozco, E; Recaman, A L

2018-03-01

Health policies in Latin America are centered on the democratization of health. Since 2003, during the last generation of reforms, health systems in this region have promoted governance strategies for better agreements between governments, institutions, and civil society. In this context, we develop an evaluative research to identify trends and evidence of governance after health care reforms in six regions of Mexico. Evaluative research was developed with a retrospective design based on qualitative analysis. Primary data were obtained from 189 semi-structured interviews with purposively selected health care professionals and key informants. Secondary data were extracted from a selection of 95 official documents on results of the reform project at the national level, national health policies, and lines of action for good governance. Data processing and analysis were performed using ATLAS.ti and PolicyMaker. A list of main strengths and weaknesses is presented as evidence of health system governance. Accountability at the federal level remains prescriptive; in the regions, a system of accountability and transparency in the allocation of resources and in terms of health democratization strategies is still absent. Social protection and decentralization schemes are strategies that have allowed for improvements with a proactive role of users and civil society. Regarding challenges, there are still low levels of governance and difficulties in the effective conduct of programs and reform strategies together with a lack of precision in the rules and roles of the different actors of the health system. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The evolution of different maternal investment strategies in two closely related desert vertebrates

USGS Publications Warehouse

Ennen, Joshua R.; Lovich, Jeffrey E.; Averill-Murray, Roy C.; Yackulic, Charles B.; Agha, Mickey; Loughran, Caleb; Tennant, Laura A.; Sinervo, Barry

2017-01-01

We compared egg size phenotypes and tested several predictions from the optimal egg size (OES) and bet-hedging theories in two North American desert-dwelling sister tortoise taxa, Gopherus agassizii and G. morafkai, that inhabit different climate spaces: relatively unpredictable and more predictable climate spaces, respectively. Observed patterns in both species differed from the predictions of OES in several ways. Mean egg size increased with maternal body size in both species. Mean egg size was inversely related to clutch order in G. agassizii, a strategy more consistent with the within-generation hypothesis arising out of bet-hedging theory or a constraint in egg investment due to resource availability, and contrary to theories of density dependence, which posit that increasing hatchling competition from later season clutches should drive selection for larger eggs. We provide empirical evidence that one species, G. agassizii, employs a bet-hedging strategy that is a combination of two different bet-hedging hypotheses. Additionally, we found some evidence for G. morafkai employing a conservative bet-hedging strategy. (e.g., lack of intra- and interclutch variation in egg size relative to body size). Our novel adaptive hypothesis suggests the possibility that natural selection favors smaller offspring in late-season clutches because they experience a more benign environment or less energetically challenging environmental conditions (i.e., winter) than early clutch progeny, that emerge under harsher and more energetically challenging environmental conditions (i.e., summer). We also discuss alternative hypotheses of sexually antagonistic selection, which arise from the trade-offs of son versus daughter production that might have different optima depending on clutch order and variation in temperature-dependent sex determination (TSD) among clutches. Resolution of these hypotheses will require long-term data on fitness of sons versus daughters as a function of incubation environment, data as yet unavailable for any species with TSD.

The evolution of different maternal investment strategies in two closely related desert vertebrates.

PubMed

Ennen, Joshua R; Lovich, Jeffrey E; Averill-Murray, Roy C; Yackulic, Charles B; Agha, Mickey; Loughran, Caleb; Tennant, Laura; Sinervo, Barry

2017-05-01

We compared egg size phenotypes and tested several predictions from the optimal egg size (OES) and bet-hedging theories in two North American desert-dwelling sister tortoise taxa, Gopherus agassizii and G. morafkai , that inhabit different climate spaces: relatively unpredictable and more predictable climate spaces, respectively. Observed patterns in both species differed from the predictions of OES in several ways. Mean egg size increased with maternal body size in both species. Mean egg size was inversely related to clutch order in G. agassizii , a strategy more consistent with the within-generation hypothesis arising out of bet-hedging theory or a constraint in egg investment due to resource availability, and contrary to theories of density dependence, which posit that increasing hatchling competition from later season clutches should drive selection for larger eggs. We provide empirical evidence that one species, G. agassizii , employs a bet-hedging strategy that is a combination of two different bet-hedging hypotheses. Additionally, we found some evidence for G. morafkai employing a conservative bet-hedging strategy. (e.g., lack of intra- and interclutch variation in egg size relative to body size). Our novel adaptive hypothesis suggests the possibility that natural selection favors smaller offspring in late-season clutches because they experience a more benign environment or less energetically challenging environmental conditions (i.e., winter) than early clutch progeny, that emerge under harsher and more energetically challenging environmental conditions (i.e., summer). We also discuss alternative hypotheses of sexually antagonistic selection, which arise from the trade-offs of son versus daughter production that might have different optima depending on clutch order and variation in temperature-dependent sex determination (TSD) among clutches. Resolution of these hypotheses will require long-term data on fitness of sons versus daughters as a function of incubation environment, data as yet unavailable for any species with TSD.

Dispersal Timing: Emigration of Insects Living in Patchy Environments.

PubMed

Lakovic, Milica; Poethke, Hans-Joachim; Hovestadt, Thomas

2015-01-01

Dispersal is a life-history trait affecting dynamics and persistence of populations; it evolves under various known selective pressures. Theoretical studies on dispersal typically assume 'natal dispersal', where individuals emigrate right after birth. But emigration may also occur during a later moment within a reproductive season ('breeding dispersal'). For example, some female butterflies first deposit eggs in their natal patch before migrating to other site(s) to continue egg-laying there. How breeding compared to natal dispersal influences the evolution of dispersal has not been explored. To close this gap we used an individual-based simulation approach to analyze (i) the evolution of timing of breeding dispersal in annual organisms, (ii) its influence on dispersal (compared to natal dispersal). Furthermore, we tested (iii) its performance in direct evolutionary contest with individuals following a natal dispersal strategy. Our results show that evolution should typically result in lower dispersal under breeding dispersal, especially when costs of dispersal are low and population size is small. By distributing offspring evenly across two patches, breeding dispersal allows reducing direct sibling competition in the next generation whereas natal dispersal can only reduce trans-generational kin competition by producing highly dispersive offspring in each generation. The added benefit of breeding dispersal is most prominent in patches with small population sizes. Finally, the evolutionary contests show that a breeding dispersal strategy would universally out-compete natal dispersal.

The Motor and the Brake of the Trailing Leg in Human Walking: Leg Force Control Through Ankle Modulation and Knee Covariance

PubMed Central

Toney, Megan E.; Chang, Young-Hui

2016-01-01

Human walking is a complex task, and we lack a complete understanding of how the neuromuscular system organizes its numerous muscles and joints to achieve consistent and efficient walking mechanics. Focused control of select influential task-level variables may simplify the higher-level control of steady state walking and reduce demand on the neuromuscular system. As trailing leg power generation and force application can affect the mechanical efficiency of step-to-step transitions, we investigated how joint torques are organized to control leg force and leg power during human walking. We tested whether timing of trailing leg force control corresponded with timing of peak leg power generation. We also applied a modified uncontrolled manifold analysis to test whether individual or coordinated joint torque strategies most contributed to leg force control. We found that leg force magnitude was adjusted from step-to-step to maintain consistent leg power generation. Leg force modulation was primarily determined by adjustments in the timing of peak ankle plantar-flexion torque, while knee torque was simultaneously covaried to dampen the effect of ankle torque on leg force. We propose a coordinated joint torque control strategy in which the trailing leg ankle acts as a motor to drive leg power production while trailing leg knee torque acts as a brake to refine leg power production. PMID:27334888

Access to Vocational Education. A Planning System for Local Secondary and Post-Secondary Program and Facility Accessibility. Step 3: Generating Strategies.

ERIC Educational Resources Information Center

Rice, Eric; And Others

This guidebook focuses on the third of five steps included in a planning system for improving local secondary and postsecondary program and facilities accessibility: generating strategies. The guidebook is comprised of four sections, each describing a specific technique for generating strategies. Techniques presented are (1) nominal group…

Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications.

PubMed

Camorani, Simona; Crescenzi, Elvira; Fedele, Monica; Cerchia, Laura

2018-04-01

Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies. In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

Small Molecule Modulators of Pre-mRNA Splicing in Cancer Therapy.

PubMed

Salton, Maayan; Misteli, Tom

2016-01-01

Pre-mRNA splicing is a fundamental process in mammalian gene expression and alternative RNA splicing plays a considerable role in generating protein diversity. RNA splicing events are also key to the pathology of numerous diseases, particularly cancers. Some tumors are molecularly addicted to specific RNA splicing isoforms making interference with pre-mRNA processing a viable therapeutic strategy. Several RNA splicing modulators have recently been characterized, some showing promise in preclinical studies. While the targets of most splicing modulators are constitutive RNA processing components, possibly leading to undesirable side effects, selectivity for individual splicing events has been observed. Given the high prevalence of splicing defects in cancer, small molecule modulators of RNA processing represent a potentially promising novel therapeutic strategy in cancer treatment. Here, we review their reported effects, mechanisms, and limitations. Published by Elsevier Ltd.

 De novo isolation of antibodies with pH-dependent binding properties.

PubMed

Bonvin, Pauline; Venet, Sophie; Fontaine, Gaëlle; Ravn, Ulla; Gueneau, Franck; Kosco-Vilbois, Marie; Proudfoot, Amanda Ei; Fischer, Nicolas

2015-01-01

pH-dependent antibodies are engineered to release their target at a slightly acidic pH, a property making them suitable for clinical as well as biotechnological applications. Such antibodies were previously obtained by histidine scanning of pre-existing antibodies, a labor-intensive strategy resulting in antibodies that displayed residual binding to their target at pH 6.0. We report here the de novo isolation of pH-dependent antibodies selected by phage display from libraries enriched in histidines. Strongly pH-dependent clones with various affinity profiles against CXCL10 were isolated by this method. Our best candidate has nanomolar affinity for CXCL10 at pH 7.2, but no residual binding was detected at pH 6.0. We therefore propose that this new process is an efficient strategy to generate pH-dependent antibodies.

The evolutionary basis of human social learning

PubMed Central

Morgan, T. J. H.; Rendell, L. E.; Ehn, M.; Hoppitt, W.; Laland, K. N.

2012-01-01

Humans are characterized by an extreme dependence on culturally transmitted information. Such dependence requires the complex integration of social and asocial information to generate effective learning and decision making. Recent formal theory predicts that natural selection should favour adaptive learning strategies, but relevant empirical work is scarce and rarely examines multiple strategies or tasks. We tested nine hypotheses derived from theoretical models, running a series of experiments investigating factors affecting when and how humans use social information, and whether such behaviour is adaptive, across several computer-based tasks. The number of demonstrators, consensus among demonstrators, confidence of subjects, task difficulty, number of sessions, cost of asocial learning, subject performance and demonstrator performance all influenced subjects' use of social information, and did so adaptively. Our analysis provides strong support for the hypothesis that human social learning is regulated by adaptive learning rules. PMID:21795267

The evolutionary basis of human social learning.

PubMed

Morgan, T J H; Rendell, L E; Ehn, M; Hoppitt, W; Laland, K N

2012-02-22

Humans are characterized by an extreme dependence on culturally transmitted information. Such dependence requires the complex integration of social and asocial information to generate effective learning and decision making. Recent formal theory predicts that natural selection should favour adaptive learning strategies, but relevant empirical work is scarce and rarely examines multiple strategies or tasks. We tested nine hypotheses derived from theoretical models, running a series of experiments investigating factors affecting when and how humans use social information, and whether such behaviour is adaptive, across several computer-based tasks. The number of demonstrators, consensus among demonstrators, confidence of subjects, task difficulty, number of sessions, cost of asocial learning, subject performance and demonstrator performance all influenced subjects' use of social information, and did so adaptively. Our analysis provides strong support for the hypothesis that human social learning is regulated by adaptive learning rules.

Label fusion based brain MR image segmentation via a latent selective model

NASA Astrophysics Data System (ADS)

Liu, Gang; Guo, Xiantang; Zhu, Kai; Liao, Hengxu

2018-04-01

Multi-atlas segmentation is an effective approach and increasingly popular for automatically labeling objects of interest in medical images. Recently, segmentation methods based on generative models and patch-based techniques have become the two principal branches of label fusion. However, these generative models and patch-based techniques are only loosely related, and the requirement for higher accuracy, faster segmentation, and robustness is always a great challenge. In this paper, we propose novel algorithm that combines the two branches using global weighted fusion strategy based on a patch latent selective model to perform segmentation of specific anatomical structures for human brain magnetic resonance (MR) images. In establishing this probabilistic model of label fusion between the target patch and patch dictionary, we explored the Kronecker delta function in the label prior, which is more suitable than other models, and designed a latent selective model as a membership prior to determine from which training patch the intensity and label of the target patch are generated at each spatial location. Because the image background is an equally important factor for segmentation, it is analyzed in label fusion procedure and we regard it as an isolated label to keep the same privilege between the background and the regions of interest. During label fusion with the global weighted fusion scheme, we use Bayesian inference and expectation maximization algorithm to estimate the labels of the target scan to produce the segmentation map. Experimental results indicate that the proposed algorithm is more accurate and robust than the other segmentation methods.

Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database.

PubMed

Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie; Allen, David; Api, Anne Marie; Ashikaga, Takao; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Goebel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Lalko, Jon F; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Parakhia, Rahul; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

2018-05-01

Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSens TM , h-CLAT (human cell line activation test), U-SENS TM , SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.

Transfer of sclerotinia resistance from wild relative of Brassica oleracea into Brassica napus using a hexaploidy step.

PubMed

Mei, Jiaqin; Liu, Yao; Wei, Dayong; Wittkop, Benjamin; Ding, Yijuan; Li, Qinfei; Li, Jiana; Wan, Huafang; Li, Zaiyun; Ge, Xianhong; Frauen, Martin; Snowdon, Rod J; Qian, Wei; Friedt, Wolfgang

2015-04-01

Sclerotinia resistance was transferred into rapeseed from a wild relative of Brassica oleracea (B. incana) using hexaploids derived from crosses between B. incana and rapeseed as a bridge. A high level of resistance against Sclerotinia sclerotiorum has been documented in wild Brassica oleracea, but not in cultivated rapeseed (Brassica napus). To transfer sclerotinia resistance from a wild relative into rapeseed, a strategy was proposed using hexaploids (AACCCC) derived from crosses between the wild B. oleracea-related B. incana genotype 'C01' and the Chinese rapeseed variety 'Zhongshuang 9' as a bridge. Progenies (BC1F1) generated by backcrossing the hexaploid to 'Zhongshuang 9' could be generated with a high crossability (average 18.3 seeds per pod). Seventy-three individuals in BC1F1 were firstly screened for resistance with five molecular markers linked to the major resistance QTL on chromosome C09 in 'C01', and 11 individuals harboring resistance loci were selected to develop vegetative clones. Of these, five exhibited significantly higher resistance than 'Zhongshuang 9' and the most resistant individual was chosen to develop the BC1F2 progeny. Finally, five individual genotypes with nearly twofold higher resistance than 'Zhongshuang 9' were found among 100 BC1F2 individuals by using marker-assisted selection and resistance evaluation. Hereof, one rapeseed-type individual with 38 chromosomes and good self-fertility (15.0 ± 3.56 seeds/pod) was identified. Our results indicate that the proposed strategy is effective for transferring sclerotinia resistance from a wild relative of B. oleracea into rapeseed.

Brain and Creativity

NASA Astrophysics Data System (ADS)

Oliverio, A.

Creativity can be considered from different points of view. Afirst possibility is to trace its natural history in mammals, mostly in non human primates. A second one is to consider mental processes, such as analogies, that may result in creative associations as evident in many fields, from arts to sciences. These two approaches lead to a better understanding of cognitive systems at the roots of creative behaviour. A third strategy relies on an analysis of primary and secondary states of mind characterizing flow and creativity. Flow, the mental state of operation in which a person is fully immersed in what he or she is doing, typical of intense problem solving activities, has been explained in terms of reduced prefrontal activity. While it is not difficult to carry out tests of problem solving activity, creativity is much more elusive and it is not easy to measure it. Thus, flow has often been simplistically assimilated to creativity and it has been assumed that also creati ve performance depends on low prefrontal activity. It is instead proposed that creativity involves two consecutive steps: 1. Generation of novelty, mostly in the ventral striatum. 2. Analysis of novelty by the prefrontal cortex that transforms it into creative behaviour. The emergence of creativity has been explained through a Darwinian process based upon the classic variation-selection procedure. Thus, basal ganglia, with their implicit strategies and memories, may be regarded as a mechanism that continuously generates novelty (variation) while the prefrontal cortex, possibly its dorsolateral areas, may be considered as the computational mechanism that transforms novelty (selection) into explicit creative behaviours.

Controlling the Growth of Future LEO Debris Populations with Active Debris Removal

NASA Technical Reports Server (NTRS)

Liou, J.-C.; Johnson, N. L.; Hill, N. M.

2008-01-01

Active debris removal (ADR) was suggested as a potential means to remediate the low Earth orbit (LEO) debris environment as early as the 1980s. The reasons ADR has not become practical are due to its technical difficulties and the high cost associated with the approach. However, as the LEO debris populations continue to increase, ADR may be the only option to preserve the near-Earth environment for future generations. An initial study was completed in 2007 to demonstrate that a simple ADR target selection criterion could be developed to reduce the future debris population growth. The present paper summarizes a comprehensive study based on more realistic simulation scenarios, including fragments generated from the 2007 Fengyun-1C event, mitigation measures, and other target selection options. The simulations were based on the NASA long-term orbital debris projection model, LEGEND. A scenario, where at the end of mission lifetimes, spacecraft and upper stages were moved to 25-year decay orbits, was adopted as the baseline environment for comparison. Different annual removal rates and different ADR target selection criteria were tested, and the resulting 200-year future environment projections were compared with the baseline scenario. Results of this parametric study indicate that (1) an effective removal strategy can be developed based on the mass and collision probability of each object as the selection criterion, and (2) the LEO environment can be stabilized in the next 200 years with an ADR removal rate of five objects per year.

Musical Sound Quality in Cochlear Implant Users: A Comparison in Bass Frequency Perception Between Fine Structure Processing and High-Definition Continuous Interleaved Sampling Strategies.

PubMed

Roy, Alexis T; Carver, Courtney; Jiradejvong, Patpong; Limb, Charles J

2015-01-01

Med-El cochlear implant (CI) patients are typically programmed with either the fine structure processing (FSP) or high-definition continuous interleaved sampling (HDCIS) strategy. FSP is the newer-generation strategy and aims to provide more direct encoding of fine structure information compared with HDCIS. Since fine structure information is extremely important in music listening, FSP may offer improvements in musical sound quality for CI users. Despite widespread clinical use of both strategies, few studies have assessed the possible benefits in music perception for the FSP strategy. The objective of this study is to measure the differences in musical sound quality discrimination between the FSP and HDCIS strategies. Musical sound quality discrimination was measured using a previously designed evaluation, called Cochlear Implant-MUltiple Stimulus with Hidden Reference and Anchor (CI-MUSHRA). In this evaluation, participants were required to detect sound quality differences between an unaltered real-world musical stimulus and versions of the stimulus in which various amount of bass (low) frequency information was removed via a high-pass filer. Eight CI users, currently using the FSP strategy, were enrolled in this study. In the first session, participants completed the CI-MUSHRA evaluation with their FSP strategy. Patients were then programmed with the clinical-default HDCIS strategy, which they used for 2 months to allow for acclimatization. After acclimatization, each participant returned for the second session, during which they were retested with HDCIS, and then switched back to their original FSP strategy and tested acutely. Sixteen normal-hearing (NH) controls completed a CI-MUSHRA evaluation for comparison, in which NH controls listened to music samples under normal acoustic conditions, without CI stimulation. Sensitivity to high-pass filtering more closely resembled that of NH controls when CI users were programmed with the clinical-default FSP strategy compared with performance when programmed with HDCIS (mixed-design analysis of variance, p < 0.05). The clinical-default FSP strategy offers improvements in musical sound quality discrimination for CI users with respect to bass frequency perception. This improved bass frequency discrimination may in turn support enhanced musical sound quality. This is the first study that has demonstrated objective improvements in musical sound quality discrimination with the newer-generation FSP strategy. These positive results may help guide the selection of processing strategies for Med-El CI patients. In addition, CI-MUSHRA may also provide a novel method for assessing the benefits of newer processing strategies in the future.

Sequence Ready Characterization of the Pericentromeric Region of 19p12

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

Evan E. Eichler

2006-08-31

Current mapping and sequencing strategies have been inadequate within the proximal portion of 19p12 due, in part, to the presence of a recently expanded ZNF (zinc-finger) gene family and the presence of large (25-50 kb) inverted beta-satellite repeat structures which bracket this tandemly duplicated gene family. The virtual of absence of classically defined “unique” sequence within the region has hampered efforts to identify and characterize a suitable minimal tiling path of clones which can be used as templates required for finished sequencing of the region. The goal of this proposal is to develop and implement a novel sequence-anchor strategy tomore » generate a contiguous BAC map of the most proximal portion of chromosome 19p12 for the purpose of complete sequence characterization. The target region will be an estimated 4.5 Mb of DNA extending from STS marker D19S450 (the beginning of the ZNF gene cluster) to the centromeric (alpha-satellite) junction of 19p11. The approach will entail 1) pre-selection of 19p12 BAC and cosmid clones (NIH approved library) utilizing both 19p12 -unique and 19p12-SPECIFIC repeat probes (Eichler et al., 1998); 2) the generation of a BAC/cosmid end-sequence map across the region with a density of one marker every 8kb; 3) the development of a second-generation of STS (sequence tagged sites) which will be used to identify and verify clonal overlap at the level of the sequence; 4) incorporation of these sequence-anchored overlapping clones into existing cosmid/BAC restriction maps developed at Livermore National Laboratory; and 5) validation of the organization of this region utilizing high-resolution FISH techniques (extended chromatin analysis) on monochromosomal 19 somatic cell hybrids and parental cell lines of source material. The data generated will be used in the selection of the most parsimonious tiling path of BAC clones to be sequenced as part of the JGI effort on chromosome 19 and should serve as a model for the sequence characterization of other difficult regions of the human genome« less

Experimental evolution of insect immune memory versus pathogen resistance.

PubMed

Khan, Imroze; Prakash, Arun; Agashe, Deepa

2017-12-20

Under strong pathogen pressure, insects often evolve resistance to infection. Many insects are also protected via immune memory (immune priming), whereby sublethal exposure to a pathogen enhances survival after secondary infection. Theory predicts that immune memory should evolve when the pathogen is highly virulent, or when pathogen exposure is relatively rare. However, there are no empirical tests of these hypotheses, and the adaptive benefits of immune memory relative to direct resistance against a pathogen are poorly understood. To determine the selective pressures and ecological conditions that shape immune evolution, we imposed strong pathogen selection on flour beetle ( Tribolium castaneum ) populations, infecting them with Bacillus thuringiensis (Bt) for 11 generations. Populations injected first with heat-killed and then live Bt evolved high basal resistance against multiple Bt strains. By contrast, populations injected only with a high dose of live Bt evolved a less effective but strain-specific priming response. Control populations injected with heat-killed Bt did not evolve priming; and in the ancestor, priming was effective only against a low Bt dose. Intriguingly, one replicate population first evolved priming and subsequently evolved basal resistance, suggesting the potential for dynamic evolution of different immune strategies. Our work is the first report showing that pathogens can select for rapid modulation of insect priming ability, allowing hosts to evolve divergent immune strategies (generalized resistance versus specific immune memory) with potentially distinct mechanisms. © 2017 The Author(s).

Enzyme-modified carbon-fiber microelectrode for the quantification of dynamic fluctuations of nonelectroactive analytes using fast-scan cyclic voltammetry.

PubMed

Lugo-Morales, Leyda Z; Loziuk, Philip L; Corder, Amanda K; Toups, J Vincent; Roberts, James G; McCaffrey, Katherine A; Sombers, Leslie A

2013-09-17

Neurotransmission occurs on a millisecond time scale, but conventional methods for monitoring nonelectroactive neurochemicals are limited by slow sampling rates. Despite a significant global market, a sensor capable of measuring the dynamics of rapidly fluctuating, nonelectroactive molecules at a single recording site with high sensitivity, electrochemical selectivity, and a subsecond response time is still lacking. To address this need, we have enabled the real-time detection of dynamic glucose fluctuations in live brain tissue using background-subtracted, fast-scan cyclic voltammetry. The novel microbiosensor consists of a simple carbon fiber surface modified with an electrodeposited chitosan hydrogel encapsulating glucose oxidase. The selectivity afforded by voltammetry enables quantitative and qualitative measurements of enzymatically generated H2O2 without the need for additional strategies to eliminate interfering agents. The microbiosensors possess a sensitivity and limit of detection for glucose of 19.4 ± 0.2 nA mM(-1) and 13.1 ± 0.7 μM, respectively. They are stable, even under deviations from physiological normoxic conditions, and show minimal interference from endogenous electroactive substances. Using this approach, we have quantitatively and selectively monitored pharmacologically evoked glucose fluctuations with unprecedented chemical and spatial resolution. Furthermore, this novel biosensing strategy is widely applicable to the immobilization of any H2O2 producing enzyme, enabling rapid monitoring of many nonelectroactive enzyme substrates.

Inference from habitat-selection analysis depends on foraging strategies.

PubMed

Bastille-Rousseau, Guillaume; Fortin, Daniel; Dussault, Christian

2010-11-01

1. Several methods have been developed to assess habitat selection, most of which are based on a comparison between habitat attributes in used vs. unused or random locations, such as the popular resource selection functions (RSFs). Spatial evaluation of residency time has been recently proposed as a promising avenue for studying habitat selection. Residency-time analyses assume a positive relationship between residency time within habitat patches and selection. We demonstrate that RSF and residency-time analyses provide different information about the process of habitat selection. Further, we show how the consideration of switching rate between habitat patches (interpatch movements) together with residency-time analysis can reveal habitat-selection strategies. 2. Spatially explicit, individual-based modelling was used to simulate foragers displaying one of six foraging strategies in a heterogeneous environment. The strategies combined one of three patch-departure rules (fixed-quitting-harvest-rate, fixed-time and fixed-amount strategy), together with one of two interpatch-movement rules (random or biased). Habitat selection of simulated foragers was then assessed using RSF, residency-time and interpatch-movement analyses. 3. Our simulations showed that RSFs and residency times are not always equivalent. When foragers move in a non-random manner and do not increase residency time in richer patches, residency-time analysis can provide misleading assessments of habitat selection. This is because the overall time spent in the various patch types not only depends on residency times, but also on interpatch-movement decisions. 4. We suggest that RSFs provide the outcome of the entire selection process, whereas residency-time and interpatch-movement analyses can be used in combination to reveal the mechanisms behind the selection process. 5. We showed that there is a risk in using residency-time analysis alone to infer habitat selection. Residency-time analyses, however, may enlighten the mechanisms of habitat selection by revealing central components of resource-use strategies. Given that management decisions are often based on resource-selection analyses, the evaluation of resource-use strategies can be key information for the development of efficient habitat-management strategies. Combining RSF, residency-time and interpatch-movement analyses is a simple and efficient way to gain a more comprehensive understanding of habitat selection. © 2010 The Authors. Journal compilation © 2010 British Ecological Society.

Teaching adolescents with learning disabilities to generate and use task-specific strategies.

PubMed

Ellis, E S; Deshler, D D; Schumaker, J B

1989-02-01

The effects of an intervention designed to enhance students' roles as control agents for strategic functioning were investigated. The goal was to increase the ability of students labeled learning disabled to generate new strategies or adapt existing task-specific strategies for meeting varying demands of the regular classroom. Measures were taken in three areas: (a) metacognitive knowledge related to generating or adapting strategies, (b) ability to generate problem-solving strategies for novel problems, and (c) the effects of the intervention on students' regular classroom grades and teachers' perceptions of the students' self-reliance and work quality. A multiple baseline across subjects design was used. The intervention resulted in dramatic increases in the subjects' verbal expression of metacognitive knowledge and ability to generate task-specific strategies. Students' regular class grades increased; for those students who did not spontaneously generalize use of the strategy to problems encountered in these classes, providing instruction to target specific classes resulted in improved grades. Teacher perceptions of students' self-reliance and work quality did not change, probably because baseline measures were already high in both areas. Implications for instruction and future research are discussed.

Optimum allocation of test resources and comparison of breeding strategies for hybrid wheat.

PubMed

Longin, C Friedrich H; Mi, Xuefei; Melchinger, Albrecht E; Reif, Jochen C; Würschum, Tobias

2014-10-01

The use of a breeding strategy combining the evaluation of line per se with testcross performance maximizes annual selection gain for hybrid wheat breeding. Recent experimental studies confirmed a high commercial potential for hybrid wheat requiring the design of optimum breeding strategies. Our objectives were to (1) determine the optimum allocation of the type and number of testers, the number of test locations and the number of doubled haploid lines for different breeding strategies, (2) identify the best breeding strategy and (3) elaborate key parameters for an efficient hybrid wheat breeding program. We performed model calculations using the selection gain for grain yield as target variable to optimize the number of lines, testers and test locations in four different breeding strategies. A breeding strategy (BS2) combining the evaluation of line per se performance and general combining ability (GCA) had a far larger annual selection gain across all considered scenarios than a breeding strategy (BS1) focusing only on GCA. In the combined strategy, the production of testcross seed conducted in parallel with the first yield trial for line per se performance (BS2rapid) resulted in a further increase of the annual selection gain. For the current situation in hybrid wheat, this relative superiority of the strategy BS2rapid amounted to 67 % in annual selection gain compared to BS1. Varying a large number of parameters, we identified the high costs for hybrid seed production and the low variance of GCA in hybrid wheat breeding as key parameters limiting selection gain in BS2rapid.

Bioenergetics in human evolution and disease: implications for the origins of biological complexity and the missing genetic variation of common diseases.

PubMed

Wallace, Douglas C

2013-07-19

Two major inconsistencies exist in the current neo-Darwinian evolutionary theory that random chromosomal mutations acted on by natural selection generate new species. First, natural selection does not require the evolution of ever increasing complexity, yet this is the hallmark of biology. Second, human chromosomal DNA sequence variation is predominantly either neutral or deleterious and is insufficient to provide the variation required for speciation or for predilection to common diseases. Complexity is explained by the continuous flow of energy through the biosphere that drives the accumulation of nucleic acids and information. Information then encodes complex forms. In animals, energy flow is primarily mediated by mitochondria whose maternally inherited mitochondrial DNA (mtDNA) codes for key genes for energy metabolism. In mammals, the mtDNA has a very high mutation rate, but the deleterious mutations are removed by an ovarian selection system. Hence, new mutations that subtly alter energy metabolism are continuously introduced into the species, permitting adaptation to regional differences in energy environments. Therefore, the most phenotypically significant gene variants arise in the mtDNA, are regional, and permit animals to occupy peripheral energy environments where rarer nuclear DNA (nDNA) variants can accumulate, leading to speciation. The neutralist-selectionist debate is then a consequence of mammals having two different evolutionary strategies: a fast mtDNA strategy for intra-specific radiation and a slow nDNA strategy for speciation. Furthermore, the missing genetic variation for common human diseases is primarily mtDNA variation plus regional nDNA variants, both of which have been missed by large, inter-population association studies.

Genotype-by-environment interactions leads to variable selection on life-history strategy in Common Evening Primrose (Oenothera biennis).

PubMed

Johnson, M T J

2007-01-01

Monocarpic plant species, where reproduction is fatal, frequently exhibit variation in the length of their prereproductive period prior to flowering. If this life-history variation in flowering strategy has a genetic basis, genotype-by-environment interactions (G x E) may maintain phenotypic diversity in flowering strategy. The native monocarpic plant Common Evening Primrose (Oenothera biennis L., Onagraceae) exhibits phenotypic variation for annual vs. biennial flowering strategies. I tested whether there was a genetic basis to variation in flowering strategy in O. biennis, and whether environmental variation causes G x E that imposes variable selection on flowering strategy. In a field experiment, I randomized more than 900 plants from 14 clonal families (genotypes) into five distinct habitats that represented a natural productivity gradient. G x E strongly affected the lifetime fruit production of O. biennis, with the rank-order in relative fitness of genotypes changing substantially between habitats. I detected genetic variation in annual vs. biennial strategies in most habitats, as well as a G x E effect on flowering strategy. This variation in flowering strategy was correlated with genetic variation in relative fitness, and phenotypic and genotypic selection analyses revealed that environmental variation resulted in variable directional selection on annual vs. biennial strategies. Specifically, a biennial strategy was favoured in moderately productive environments, whereas an annual strategy was favoured in low-productivity environments. These results highlight the importance of variable selection for the maintenance of genetic variation in the life-history strategy of a monocarpic plant.

Age-Related Changes in Children's Executive Functions and Strategy Selection: A Study in Computational Estimation

ERIC Educational Resources Information Center

Lemaire, Patrick; Lecacheur, Mireille

2011-01-01

Third, fifth, and seventh graders selected the best strategy (rounding up or rounding down) for estimating answers to two-digit addition problems. Executive function measures were collected for each individual. Data showed that (a) children's skill at both strategy selection and execution improved with age and (b) increased efficiency in executive…

A Stitch in Time: Strategic Self-Control in High School and College Students.

PubMed

Duckworth, Angela L; White, Rachel E; Matteucci, Alyssa J; Shearer, Annie; Gross, James J

2016-04-01

A growing body of research indicates that self-control is critical to academic success. Surprisingly little is known, however, about the diverse strategies students use to implement self-control or how well these strategies work. To address these issues, we conducted a naturalistic investigation of self-control strategies (Study 1) and two field experiments (Studies 2 and 3). In Study 1, high school students described the strategies they use to manage interpersonal conflicts, get academic work done, eat healthfully, and manage other everyday self-control challenges. The majority of strategies in these self-nominated incidents as well as in three hypothetical academic scenarios (e.g., studying instead of texting friends) were reliably classified using the process model of self-control. As predicted by the process model, students rated strategies deployed early in the impulse-generation process (situation selection, situation modification) as being dramatically more effective than strategies deployed later (attentional deployment, cognitive change, response modulation). In Study 2, high school students randomly assigned to implement situation modification were more likely to meet their academic goals during the following week than students assigned either to implement response modulation or no strategy at all. In Study 3, college students randomly assigned to implement situation modification were also more successful in meeting their academic goals, and this effect was partially mediated by decreased feelings of temptation throughout the week. Collectively, these findings suggest that students might benefit from learning to initiate self-control when their impulses are still nascent.

A Stitch in Time: Strategic Self-Control in High School and College Students

PubMed Central

Duckworth, Angela L.; White, Rachel E.; Matteucci, Alyssa J.; Shearer, Annie; Gross, James J.

2015-01-01

A growing body of research indicates that self-control is critical to academic success. Surprisingly little is known, however, about the diverse strategies students use to implement self-control or how well these strategies work. To address these issues, we conducted a naturalistic investigation of self-control strategies (Study 1) and two field experiments (Studies 2 and 3). In Study 1, high school students described the strategies they use to manage interpersonal conflicts, get academic work done, eat healthfully, and manage other everyday self-control challenges. The majority of strategies in these self-nominated incidents as well as in three hypothetical academic scenarios (e.g., studying instead of texting friends) were reliably classified using the process model of self-control. As predicted by the process model, students rated strategies deployed early in the impulse-generation process (situation selection, situation modification) as being dramatically more effective than strategies deployed later (attentional deployment, cognitive change, response modulation). In Study 2, high school students randomly assigned to implement situation modification were more likely to meet their academic goals during the following week than students assigned either to implement response modulation or no strategy at all. In Study 3, college students randomly assigned to implement situation modification were also more successful in meeting their academic goals, and this effect was partially mediated by decreased feelings of temptation throughout the week. Collectively, these findings suggest that students might benefit from learning to initiate self-control when their impulses are still nascent. PMID:27158155

Mechanism, stability and fitness cost of resistance to pyriproxyfen in the house fly, Musca domestica L. (Diptera: Muscidae).

PubMed

Shah, Rizwan Mustafa; Shad, Sarfraz Ali; Abbas, Naeem

2015-03-01

Pyriproxyfen, a bio-rational insecticide, used worldwide for the management of many insect pests including the house fly, Musca domestica. To devise a retrospective resistance management strategy, biological parameters of pyriproxyfen resistant (Pyri-SEL), unselected (UNSEL), Cross1 and Cross2M. domestica strains were studied in the laboratory. Additionally, the stability and mechanism of resistance was also investigated. After 30 generations of pyriproxyfen selection, a field-collected strain developed 206-fold resistance compared with susceptible strain. Synergists such as piperonyl butoxide and S,S,S-tributylphosphorotrithioate did not alter the LC50 values, suggesting another cause of target site resistance to pyriproxyfen in the Pyri-SEL strain. The resistance to all tested insecticides was unstable in Pyri-SEL strain. The relative fitness of 0.51 with lower fecundity, hatchability, lower number of next generation larvae, reduced mean population growth rate and net reproductive rate were observed in the Pyri-SEL strain compared with the UNSEL strain. The cost of fitness associated with pyriproxyfen resistance was evident in Pyri-SEL strain. The present study provides useful information for making pro-active resistance management strategies to delay resistance development. Copyright © 2015 Elsevier Inc. All rights reserved.

Development strategies for the satellite flight software on-board Meteosat Third Generation

NASA Astrophysics Data System (ADS)

Tipaldi, Massimo; Legendre, Cedric; Koopmann, Olliver; Ferraguto, Massimo; Wenker, Ralf; D'Angelo, Gianni

2018-04-01

Nowadays, satellites are becoming increasingly software dependent. Satellite Flight Software (FSW), that is to say, the application software running on the satellite main On-Board Computer (OBC), plays a relevant role in implementing complex space mission requirements. In this paper, we examine relevant technical approaches and programmatic strategies adopted for the development of the Meteosat Third Generation Satellite (MTG) FSW. To begin with, we present its layered model-based architecture, and the means for ensuring a robust and reliable interaction among the FSW components. Then, we focus on the selection of an effective software development life cycle model. In particular, by combining plan-driven and agile approaches, we can fulfill the need of having preliminary SW versions. They can be used for the elicitation of complex system-level requirements as well as for the initial satellite integration and testing activities. Another important aspect can be identified in the testing activities. Indeed, very demanding quality requirements have to be fulfilled in satellite SW applications. This manuscript proposes a test automation framework, which uses an XML-based test procedure language independent of the underlying test environment. Finally, a short overview of the MTG FSW sizing and timing budgets concludes the paper.

The Atmospheric Monitoring Strategy for the Cherenkov Telescope Array

NASA Astrophysics Data System (ADS)

Daniel, M. K.; CTA Consortium

2015-04-01

The Imaging Atmospheric Cherenkov Technique (IACT) is unusual in astronomy as the atmosphere actually forms an intrinsic part of the detector system, with telescopes indirectly detecting very high energy particles by the generation and transport of Cherenkov photons deep within the atmosphere. This means that accurate measurement, characterisation and monitoring of the atmosphere is at the very heart of successfully operating an IACT system. The Cherenkov Telescope Array (CTA) will be the next generation IACT observatory with an ambitious aim to improve the sensitivity of an order of magnitude over current facilities, along with corresponding improvements in angular and energy resolution and extended energy coverage, through an array of Large (23 m), Medium (12 m) and Small (4 m) sized telescopes spread over an area of order ~km2. Whole sky coverage will be achieved by operating at two sites: one in the northern hemisphere and one in the southern hemisphere. This proceedings will cover the characterisation of the candidate sites and the atmospheric calibration strategy. CTA will utilise a suite of instrumentation and analysis techniques for atmospheric modelling and monitoring regarding pointing forecasts, intelligent pointing selection for the observatory operations and for offline data correction.

The development of strategy use in elementary school children: working memory and individual differences.

PubMed

Imbo, Ineke; Vandierendonck, André

2007-04-01

The current study tested the development of working memory involvement in children's arithmetic strategy selection and strategy efficiency. To this end, an experiment in which the dual-task method and the choice/no-choice method were combined was administered to 10- to 12-year-olds. Working memory was needed in retrieval, transformation, and counting strategies, but the ratio between available working memory resources and arithmetic task demands changed across development. More frequent retrieval use, more efficient memory retrieval, and more efficient counting processes reduced the working memory requirements. Strategy efficiency and strategy selection were also modified by individual differences such as processing speed, arithmetic skill, gender, and math anxiety. Short-term memory capacity, in contrast, was not related to children's strategy selection or strategy efficiency.

Design, analysis, operation, and advanced control of hybrid renewable energy systems

NASA Astrophysics Data System (ADS)

Whiteman, Zachary S.

Because using non-renewable energy systems (e.g., coal-powered co-generation power plants) to generate electricity is an unsustainable, environmentally hazardous practice, it is important to develop cost-effective and reliable renewable energy systems, such as photovoltaics (PVs), wind turbines (WTs), and fuel cells (FCs). Non-renewable energy systems, however, are currently less expensive than individual renewable energy systems (IRESs). Furthermore, IRESs based on intermittent natural resources (e.g., solar irradiance and wind) are incapable of meeting continuous energy demands. Such shortcomings can be mitigated by judiciously combining two or more complementary IRESs to form a hybrid renewable energy system (HRES). Although previous research efforts focused on the design, operation, and control of HRESs has proven useful, no prior HRES research endeavor has taken a systematic and comprehensive approach towards establishing guidelines by which HRESs should be designed, operated, and controlled. The overall goal of this dissertation, therefore, is to establish the principles governing the design, operation, and control of HRESs resulting in cost-effective and reliable energy solutions for stationary and mobile applications. To achieve this goal, we developed and demonstrated four separate HRES principles. Rational selection of HRES type: HRES components and their sizes should be rationally selected using knowledge of component costs, availability of renewable energy resources, and expected power demands of the application. HRES design: by default, the components of a HRES should be arranged in parallel for increased efficiency and reliability. However, a series HRES design may be preferred depending on the operational considerations of the HRES components. HRES control strategy selection: the choice of HRES control strategy depends on the dynamics of HRES components, their operational considerations, and the practical limitations of the HRES end-use. HRES data-driven control: information-rich data should be used to assist in the intelligent coordination of HRES components in meeting its operating objectives when additional computation can be afforded and significant benefits can be realized.

The effect of morphometric atlas selection on multi-atlas-based automatic brachial plexus segmentation.

PubMed

Van de Velde, Joris; Wouters, Johan; Vercauteren, Tom; De Gersem, Werner; Achten, Eric; De Neve, Wilfried; Van Hoof, Tom

2015-12-23

The present study aimed to measure the effect of a morphometric atlas selection strategy on the accuracy of multi-atlas-based BP autosegmentation using the commercially available software package ADMIRE® and to determine the optimal number of selected atlases to use. Autosegmentation accuracy was measured by comparing all generated automatic BP segmentations with anatomically validated gold standard segmentations that were developed using cadavers. Twelve cadaver computed tomography (CT) atlases were included in the study. One atlas was selected as a patient in ADMIRE®, and multi-atlas-based BP autosegmentation was first performed with a group of morphometrically preselected atlases. In this group, the atlases were selected on the basis of similarity in the shoulder protraction position with the patient. The number of selected atlases used started at two and increased up to eight. Subsequently, a group of randomly chosen, non-selected atlases were taken. In this second group, every possible combination of 2 to 8 random atlases was used for multi-atlas-based BP autosegmentation. For both groups, the average Dice similarity coefficient (DSC), Jaccard index (JI) and Inclusion index (INI) were calculated, measuring the similarity of the generated automatic BP segmentations and the gold standard segmentation. Similarity indices of both groups were compared using an independent sample t-test, and the optimal number of selected atlases was investigated using an equivalence trial. For each number of atlases, average similarity indices of the morphometrically selected atlas group were significantly higher than the random group (p < 0,05). In this study, the highest similarity indices were achieved using multi-atlas autosegmentation with 6 selected atlases (average DSC = 0,598; average JI = 0,434; average INI = 0,733). Morphometric atlas selection on the basis of the protraction position of the patient significantly improves multi-atlas-based BP autosegmentation accuracy. In this study, the optimal number of selected atlases used was six, but for definitive conclusions about the optimal number of atlases and to improve the autosegmentation accuracy for clinical use, more atlases need to be included.

Minimal Pharmacophoric Elements and Fragment Hopping, an Approach Directed at Molecular Diversity and Isozyme Selectivity. Design of Selective Neuronal Nitric Oxide Synthase Inhibitors

PubMed Central

Ji, Haitao; Stanton, Benjamin Z.; Igarashi, Jotaro; Li, Huiying; Martásek, Pavel; Roman, Linda J.; Poulos, Thomas L.; Silverman, Richard B.

2010-01-01

Fragment hopping, a new fragment-based approach for de novo inhibitor design focusing on ligand diversity and isozyme selectivity, is described. The core of this approach is the derivation of the minimal pharmacophoric element for each pharmacophore. Sites for both ligand binding and isozyme selectivity are considered in deriving the minimal pharmacophoric elements. Five general-purpose libraries are established: the basic fragment library, the bioisostere library, the rules for metabolic stability, the toxicophore library, and the side chain library. These libraries are employed to generate focused fragment libraries to match the minimal pharmacophoric elements for each pharmacophore and then to link the fragment to the desired molecule. This method was successfully applied to neuronal nitric oxide synthase (nNOS), which is implicated in stroke and neurodegenerative diseases. Starting with the nitroarginine-containing dipeptide inhibitors we developed previously, a small organic molecule with a totally different chemical structure was designed, which showed nanomolar nNOS inhibitory potency and more than 1000-fold nNOS selectivity. The crystallographic analysis confirms that the small organic molecule with a constrained conformation can exactly mimic the mode of action of the dipeptide nNOS inhibitors. Therefore, a new peptidomimetic strategy, referred to as fragment hopping, which creates small organic molecules that mimic the biological function of peptides by a pharmacophore-driven strategy for fragment-based de novo design, has been established as a new type of fragment-based inhibitor design. As an open system, the newly established approach efficiently incorporates the concept of early “ADME/Tox” considerations and provides a basic platform for medicinal chemistry-driven efforts. PMID:18321097

Geometric Morphometrics of Nine Field Isolates of Aedes aegypti with Different Resistance Levels to Lambda-Cyhalothrin and Relative Fitness of One Artificially Selected for Resistance

PubMed Central

Jaramillo-O., Nicolás; Fonseca-González, Idalyd; Chaverra-Rodríguez, Duverney

2014-01-01

Aedes aegypti, a mosquito closely associated with humans, is the principal vector of dengue virus which currently infects about 400 million people worldwide. Because there is no way to prevent infection, public health policies focus on vector control; but insecticide-resistance threatens them. However, most insecticide-resistant mosquito populations exhibit fitness costs in absence of insecticides, although these costs vary. Research on components of fitness that vary with insecticide-resistance can help to develop policies for effective integrated management and control. We investigated the relationships in wing size, wing shape, and natural resistance levels to lambda-cyhalothrin of nine field isolates. Also we chose one of these isolates to select in lab for resistance to the insecticide. The main life-traits parameters were assessed to investigate the possible fitness cost and its association with wing size and shape. We found that wing shape, more than wing size, was strongly correlated with resistance levels to lambda-cyhalothrin in field isolates, but founder effects of culture in the laboratory seem to change wing shape (and also wing size) more easily than artificial selection for resistance to that insecticide. Moreover, significant fitness costs were observed in response to insecticide-resistance as proved by the diminished fecundity and survival of females in the selected line and the reversion to susceptibility in 20 generations of the non-selected line. As a practical consequence, we think, mosquito control programs could benefit from this knowledge in implementing efficient strategies to prevent the evolution of resistance. In particular, the knowledge of reversion to susceptibility is important because it can help in planning better strategies of insecticide use to keep useful the few insecticide-molecules currently available. PMID:24801598

Survival ability of Mexican fruit fly males from different strains in presence of the predatory orb-weaving spider Argiope argentata (Araneae: Araneidae).

PubMed

Dor, A; Liedo, P

2018-04-18

The sterile insect technique (SIT) is a key element for the integrated management of pest populations of the Mexican fruit fly, Anastrepha ludens, in Mexico. Its success depends on the survival of mass-reared sterile males and their ability to mate with wild females. However, colonization and mass-rearing conditions can adversely affect their ability to avoid predators. To test if colony management strategies could contribute to improve field survival abilities of mass-reared flies, we compared the survival of males exposed to the orb-weaver spider Argiope argentata. Males compared originated from three strains with different colonization strategies: (a) a colony started from field-collected wild flies (replacement), (b) a colony started by hybridizing wild males with mass-reared adapted females (hybrid) and (c) a colony started with mass-reared males selected on the basis of their survival ability and mating competitiveness in field cages (selected). Mass-reared males and wild males were used as controls. Males were exposed to spiders under laboratory cage conditions. Overall, wild males showed better survival ability than mass-reared males. Regarding the colonization approach, wild males survived better than a hybrid, replaced and selected males. We conclude that mass-rearing conditions have a strong negative effect on the ability of males to escape spiders. The colonization systems evaluated did not counter this effect. The lower survival of males from the selected colony suggests that the selection over one generation did not contribute to improve males' predator avoidance and escape abilities and probably needs to be modified. Possible explanations for this and implications on colonization and colony management for SIT purpose are discussed.

Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment.

PubMed

Rosswog, Carolina; Schmidt, Rene; Oberthuer, André; Juraeva, Dilafruz; Brors, Benedikt; Engesser, Anne; Kahlert, Yvonne; Volland, Ruth; Bartenhagen, Christoph; Simon, Thorsten; Berthold, Frank; Hero, Barbara; Faldum, Andreas; Fischer, Matthias

2017-12-01

Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209). Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO) Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9±3.4 vs 63.6±14.5 vs 31.0±5.4; P<.001), and its prognostic value was validated by multivariable analysis. We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of parallel reduction strategies for fusion of sensory information from a robot team

NASA Astrophysics Data System (ADS)

Lyons, Damian M.; Leroy, Joseph

2015-05-01

The advantage of using a team of robots to search or to map an area is that by navigating the robots to different parts of the area, searching or mapping can be completed more quickly. A crucial aspect of the problem is the combination, or fusion, of data from team members to generate an integrated model of the search/mapping area. In prior work we looked at the issue of removing mutual robots views from an integrated point cloud model built from laser and stereo sensors, leading to a cleaner and more accurate model. This paper addresses a further challenge: Even with mutual views removed, the stereo data from a team of robots can quickly swamp a WiFi connection. This paper proposes and evaluates a communication and fusion approach based on the parallel reduction operation, where data is combined in a series of steps of increasing subsets of the team. Eight different strategies for selecting the subsets are evaluated for bandwidth requirements using three robot missions, each carried out with teams of four Pioneer 3-AT robots. Our results indicate that selecting groups to combine based on similar pose but distant location yields the best results.

How to evade a coevolving brood parasite: egg discrimination versus egg variability as host defences.

PubMed

Spottiswoode, Claire N; Stevens, Martin

2011-12-07

Arms races between avian brood parasites and their hosts often result in parasitic mimicry of host eggs, to evade rejection. Once egg mimicry has evolved, host defences could escalate in two ways: (i) hosts could improve their level of egg discrimination; and (ii) negative frequency-dependent selection could generate increased variation in egg appearance (polymorphism) among individuals. Proficiency in one defence might reduce selection on the other, while a combination of the two should enable successful rejection of parasitic eggs. We compared three highly variable host species of the Afrotropical cuckoo finch Anomalospiza imberbis, using egg rejection experiments and modelling of avian colour and pattern vision. We show that each differed in their level of polymorphism, in the visual cues they used to reject foreign eggs, and in their degree of discrimination. The most polymorphic host had the crudest discrimination, whereas the least polymorphic was most discriminating. The third species, not currently parasitized, was intermediate for both defences. A model simulating parasitic laying and host rejection behaviour based on the field experiments showed that the two host strategies result in approximately the same fitness advantage to hosts. Thus, neither strategy is superior, but rather they reflect alternative potential evolutionary trajectories.

Fluorescence linked enzyme chemoproteomic strategy for discovery of a potent and selective DAPK1 and ZIPK inhibitor.

PubMed

Carlson, David A; Franke, Aaron S; Weitzel, Douglas H; Speer, Brittany L; Hughes, Philip F; Hagerty, Laura; Fortner, Christopher N; Veal, James M; Barta, Thomas E; Zieba, Bartosz J; Somlyo, Avril V; Sutherland, Cindy; Deng, Jing Ti; Walsh, Michael P; MacDonald, Justin A; Haystead, Timothy A J

2013-12-20

DAPK1 and ZIPK (also called DAPK3) are closely related serine/threonine protein kinases that regulate programmed cell death and phosphorylation of non-muscle and smooth muscle myosin. We have developed a fluorescence linked enzyme chemoproteomic strategy (FLECS) for the rapid identification of inhibitors for any element of the purinome and identified a selective pyrazolo[3,4-d]pyrimidinone (HS38) that inhibits DAPK1 and ZIPK in an ATP-competitive manner at nanomolar concentrations. In cellular studies, HS38 decreased RLC20 phosphorylation. In ex vivo studies, HS38 decreased contractile force generated in mouse aorta, rabbit ileum, and calyculin A stimulated arterial muscle by decreasing RLC20 and MYPT1 phosphorylation. The inhibitor also promoted relaxation in Ca(2+)-sensitized vessels. A close structural analogue (HS43) with 5-fold lower affinity for ZIPK produced no effect on cells or tissues. These findings are consistent with a mechanism of action wherein HS38 specifically targets ZIPK in smooth muscle. The discovery of HS38 provides a lead scaffold for the development of therapeutic agents for smooth muscle related disorders and a chemical means to probe the function of DAPK1 and ZIPK across species.

Drug target identification in protozoan parasites.

PubMed

Müller, Joachim; Hemphill, Andrew

2016-08-01

Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

Tone signal generator for producing multioperator tone signals using an operator circuit including a waveform generator, a selector and an enveloper

DOEpatents

Dong, Qiujie; Jenkins, Michael V.; Bernadas, Salvador R.

1997-01-01

A frequency modulation (FM) tone signal generator for generating a FM tone signal is disclosed. The tone signal generator includes a waveform generator having a plurality of wave tables, a selector and an enveloper. The waveform generator furnishes a waveform signal in response to a phase angle address signal. Each wave table stores a different waveform. The selector selects one of the wave tables in response to a plurality of selection signals such that the selected wave table largely provides the waveform signal upon being addressed largely by the phase angle address signal. Selection of the selected wave table varies with each selection signal. The enveloper impresses an envelope signal on the waveform signal. The envelope signal is used as a carrier or modulator for generating the FM tone signal.

Prediction of Cacao (Theobroma cacao) Resistance to Moniliophthora spp. Diseases via Genome-Wide Association Analysis and Genomic Selection.

PubMed

McElroy, Michel S; Navarro, Alberto J R; Mustiga, Guiliana; Stack, Conrad; Gezan, Salvador; Peña, Geover; Sarabia, Widem; Saquicela, Diego; Sotomayor, Ignacio; Douglas, Gavin M; Migicovsky, Zoë; Amores, Freddy; Tarqui, Omar; Myles, Sean; Motamayor, Juan C

2018-01-01

Cacao ( Theobroma cacao ) is a globally important crop, and its yield is severely restricted by disease. Two of the most damaging diseases, witches' broom disease (WBD) and frosty pod rot disease (FPRD), are caused by a pair of related fungi: Moniliophthora perniciosa and Moniliophthora roreri , respectively. Resistant cultivars are the most effective long-term strategy to address Moniliophthora diseases, but efficiently generating resistant and productive new cultivars will require robust methods for screening germplasm before field testing. Marker-assisted selection (MAS) and genomic selection (GS) provide two potential avenues for predicting the performance of new genotypes, potentially increasing the selection gain per unit time. To test the effectiveness of these two approaches, we performed a genome-wide association study (GWAS) and GS on three related populations of cacao in Ecuador genotyped with a 15K single nucleotide polymorphism (SNP) microarray for three measures of WBD infection (vegetative broom, cushion broom, and chirimoya pod), one of FPRD (monilia pod) and two productivity traits (total fresh weight of pods and % healthy pods produced). GWAS yielded several SNPs associated with disease resistance in each population, but none were significantly correlated with the same trait in other populations. Genomic selection, using one population as a training set to estimate the phenotypes of the remaining two (composed of different families), varied among traits, from a mean prediction accuracy of 0.46 (vegetative broom) to 0.15 (monilia pod), and varied between training populations. Simulations demonstrated that selecting seedlings using GWAS markers alone generates no improvement over selecting at random, but that GS improves the selection process significantly. Our results suggest that the GWAS markers discovered here are not sufficiently predictive across diverse germplasm to be useful for MAS, but that using all markers in a GS framework holds substantial promise in accelerating disease-resistance in cacao.

Solid Oxide Fuel Cell Hybrid System for Distributed Power Generation

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

David Deangelis; Rich Depuy; Debashis Dey

2004-09-30

This report summarizes the work performed by Hybrid Power Generation Systems, LLC (HPGS) during the April to October 2004 reporting period in Task 2.3 (SOFC Scaleup for Hybrid and Fuel Cell Systems) under Cooperative Agreement DE-FC26-01NT40779 for the U. S. Department of Energy, National Energy Technology Laboratory (DOE/NETL), entitled ''Solid Oxide Fuel Cell Hybrid System for Distributed Power Generation''. This study analyzes the performance and economics of power generation systems for central power generation application based on Solid Oxide Fuel Cell (SOFC) technology and fueled by natural gas. The main objective of this task is to develop credible scale upmore » strategies for large solid oxide fuel cell-gas turbine systems. System concepts that integrate a SOFC with a gas turbine were developed and analyzed for plant sizes in excess of 20 MW. A 25 MW plant configuration was selected with projected system efficiency of over 65% and a factory cost of under $400/kW. The plant design is modular and can be scaled to both higher and lower plant power ratings. Technology gaps and required engineering development efforts were identified and evaluated.« less

Forward propulsion asymmetry is indicative of changes in plantarflexor coordination during walking in individuals with post-stroke hemiparesis

PubMed Central

Allen, Jessica L.; Kautz, Steven A.; Neptune, Richard R.

2014-01-01

Background A common measure of rehabilitation effectiveness post-stroke is self-selected walking speed, yet individuals may achieve the same speed using different coordination strategies. Asymmetry in the propulsion generated by each leg can provide insight into paretic leg coordination due to its relatively strong correlation with hemiparetic severity. Subjects walking at the same speed can exhibit different propulsion asymmetry, with some subjects relying more on the paretic leg and others on the nonparetic leg. The goal of this study was to assess whether analyzing propulsion asymmetry can help distinguish between improved paretic leg coordination versus nonparetic leg compensation. Methods Three-dimensional forward dynamics simulations were developed for two post-stroke hemiparetic subjects walking at identical speeds before/after rehabilitation with opposite changes in propulsion asymmetry. Changes in the individual muscle contributions to forward propulsion were examined. Findings The major source of increased forward propulsion in both subjects was from the ankle plantarflexors. How they were utilized differed and appears related to changes in propulsion asymmetry. Subject A increased propulsion generated from the paretic plantarflexors, while Subject B increased propulsion generated from the nonparetic plantarflexors. Each subject’s strategy to increase speed also included differences in other muscle groups (e.g. hamstrings) that did not appear related to propulsion asymmetry. Interpretation The results of this study highlight how speed cannot be used to elucidate underlying muscle coordination changes following rehabilitation. In contrast, propulsion asymmetry appears to provide insight into changes in plantarflexor output affecting propulsion generation and may be useful in monitoring rehabilitation outcomes. PMID:24973825

Forward propulsion asymmetry is indicative of changes in plantarflexor coordination during walking in individuals with post-stroke hemiparesis.

PubMed

Allen, Jessica L; Kautz, Steven A; Neptune, Richard R

2014-08-01

A common measure of rehabilitation effectiveness post-stroke is self-selected walking speed, yet individuals may achieve the same speed using different coordination strategies. Asymmetry in the propulsion generated by each leg can provide insight into paretic leg coordination due to its relatively strong correlation with hemiparetic severity. Subjects walking at the same speed can exhibit different propulsion asymmetries, with some subjects relying more on the paretic leg and others on the nonparetic leg. The goal of this study was to assess whether analyzing propulsion asymmetry can help distinguish between improved paretic leg coordination versus nonparetic leg compensation. Three-dimensional forward dynamics simulations were developed for two post-stroke hemiparetic subjects walking at identical speeds before/after rehabilitation with opposite changes in propulsion asymmetry. Changes in the individual muscle contributions to forward propulsion were examined. The major source of increased forward propulsion in both subjects was from the ankle plantarflexors. How they were utilized differed and appears related to changes in propulsion asymmetry. Subject A increased propulsion generated from the paretic plantarflexors, while Subject B increased propulsion generated from the nonparetic plantarflexors. Each subject's strategy to increase speed also included differences in other muscle groups (e.g., hamstrings) that did not appear to be related to propulsion asymmetry. The results of this study highlight how speed cannot be used to elucidate underlying muscle coordination changes following rehabilitation. In contrast, propulsion asymmetry appears to provide insight into changes in plantarflexor output affecting propulsion generation and may be useful in monitoring rehabilitation outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Construction of a high-density genetic map for grape using next generation restriction-site associated DNA sequencing

PubMed Central

2012-01-01

Background Genetic mapping and QTL detection are powerful methodologies in plant improvement and breeding. Construction of a high-density and high-quality genetic map would be of great benefit in the production of superior grapes to meet human demand. High throughput and low cost of the recently developed next generation sequencing (NGS) technology have resulted in its wide application in genome research. Sequencing restriction-site associated DNA (RAD) might be an efficient strategy to simplify genotyping. Combining NGS with RAD has proven to be powerful for single nucleotide polymorphism (SNP) marker development. Results An F1 population of 100 individual plants was developed. In-silico digestion-site prediction was used to select an appropriate restriction enzyme for construction of a RAD sequencing library. Next generation RAD sequencing was applied to genotype the F1 population and its parents. Applying a cluster strategy for SNP modulation, a total of 1,814 high-quality SNP markers were developed: 1,121 of these were mapped to the female genetic map, 759 to the male map, and 1,646 to the integrated map. A comparison of the genetic maps to the published Vitis vinifera genome revealed both conservation and variations. Conclusions The applicability of next generation RAD sequencing for genotyping a grape F1 population was demonstrated, leading to the successful development of a genetic map with high density and quality using our designed SNP markers. Detailed analysis revealed that this newly developed genetic map can be used for a variety of genome investigations, such as QTL detection, sequence assembly and genome comparison. PMID:22908993

Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype-phenotype relationships and its relevance to crop improvement.

PubMed

Cobb, Joshua N; Declerck, Genevieve; Greenberg, Anthony; Clark, Randy; McCouch, Susan

2013-04-01

More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties.

Selecting the Best: Evolutionary Engineering of Chemical Production in Microbes.

PubMed

Shepelin, Denis; Hansen, Anne Sofie Lærke; Lennen, Rebecca; Luo, Hao; Herrgård, Markus J

2018-05-11

Microbial cell factories have proven to be an economical means of production for many bulk, specialty, and fine chemical products. However, we still lack both a holistic understanding of organism physiology and the ability to predictively tune enzyme activities in vivo, thus slowing down rational engineering of industrially relevant strains. An alternative concept to rational engineering is to use evolution as the driving force to select for desired changes, an approach often described as evolutionary engineering. In evolutionary engineering, in vivo selections for a desired phenotype are combined with either generation of spontaneous mutations or some form of targeted or random mutagenesis. Evolutionary engineering has been used to successfully engineer easily selectable phenotypes, such as utilization of a suboptimal nutrient source or tolerance to inhibitory substrates or products. In this review, we focus primarily on a more challenging problem-the use of evolutionary engineering for improving the production of chemicals in microbes directly. We describe recent developments in evolutionary engineering strategies, in general, and discuss, in detail, case studies where production of a chemical has been successfully achieved through evolutionary engineering by coupling production to cellular growth.

Generation of subnanometric platinum with high stability during transformation of a 2D zeolite into 3D.

PubMed

Liu, Lichen; Díaz, Urbano; Arenal, Raul; Agostini, Giovanni; Concepción, Patricia; Corma, Avelino

2017-01-01

Single metal atoms and metal clusters have attracted much attention thanks to their advantageous capabilities as heterogeneous catalysts. However, the generation of stable single atoms and clusters on a solid support is still challenging. Herein, we report a new strategy for the generation of single Pt atoms and Pt clusters with exceptionally high thermal stability, formed within purely siliceous MCM-22 during the growth of a two-dimensional zeolite into three dimensions. These subnanometric Pt species are stabilized by MCM-22, even after treatment in air up to 540 °C. Furthermore, these stable Pt species confined within internal framework cavities show size-selective catalysis for the hydrogenation of alkenes. High-temperature oxidation-reduction treatments result in the growth of encapsulated Pt species to small nanoparticles in the approximate size range of 1 to 2 nm. The stability and catalytic activity of encapsulated Pt species is also reflected in the dehydrogenation of propane to propylene.

Great hammerhead sharks swim on their side to reduce transport costs

PubMed Central

Payne, Nicholas L.; Iosilevskii, Gil; Barnett, Adam; Fischer, Chris; Graham, Rachel T.; Gleiss, Adrian C.; Watanabe, Yuuki Y.

2016-01-01

Animals exhibit various physiological and behavioural strategies for minimizing travel costs. Fins of aquatic animals play key roles in efficient travel and, for sharks, the functions of dorsal and pectoral fins are considered well divided: the former assists propulsion and generates lateral hydrodynamic forces during turns and the latter generates vertical forces that offset sharks' negative buoyancy. Here we show that great hammerhead sharks drastically reconfigure the function of these structures, using an exaggerated dorsal fin to generate lift by swimming rolled on their side. Tagged wild sharks spend up to 90% of time swimming at roll angles between 50° and 75°, and hydrodynamic modelling shows that doing so reduces drag—and in turn, the cost of transport—by around 10% compared with traditional upright swimming. Employment of such a strongly selected feature for such a unique purpose raises interesting questions about evolutionary pathways to hydrodynamic adaptations, and our perception of form and function. PMID:27457414

Comparative safety assessment of plant-derived foods.

PubMed

Kok, E J; Keijer, J; Kleter, G A; Kuiper, H A

2008-02-01

The second generation of genetically modified (GM) plants that are moving towards the market are characterized by modifications that may be more complex and traits that more often are to the benefit of the consumer. These developments will have implications for the safety assessment of the resulting plant products. In part of the cases the same crop plant can, however, also be obtained by 'conventional' breeding strategies. The breeder will decide on a case-by-case basis what will be the best strategy to reach the set target and whether genetic modification will form part of this strategy. This article discusses important aspects of the safety assessment of complex products derived from newly bred plant varieties obtained by different breeding strategies. On the basis of this overview, we conclude that the current process of the safety evaluation of GM versus conventionally bred plants is not well balanced. GM varieties are elaborately assessed, yet at the same time other crop plants resulting from conventional breeding strategies may warrant further food safety assessment for the benefit of the consumer. We propose to develop a general screening frame for all newly developed plant varieties to select varieties that cannot, on the basis of scientific criteria, be considered as safe as plant varieties that are already on the market.

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

DOE PAGES

Hraber, Peter; Korber, Bette; Wagh, Kshitij; ...

2015-10-21

Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

Towards evenly distributed grazing patterns: including social context in sheep management strategies.

PubMed

di Virgilio, Agustina; Morales, Juan Manuel

2016-01-01

Background. A large proportion of natural grasslands around the world is exposed to overgrazing resulting in land degradation and biodiversity loss. Although there is an increasing effort in the promotion of sustainable livestock management, rangeland degradation still occurs because animals' foraging behaviour is highly selective at different spatial scales. The assessment of the ecological mechanisms modulating the spatial distribution of grazing and how to control it has critical implications for long term conservation of resources and the sustainability of livestock production. Considering the relevance of social interactions on animals' space use patterns, our aim was to explore the potential effects of including animals' social context into management strategies using domestic sheep grazing in rangelands as case study. Methods. We used GPS data from 19 Merino sheep (approximately 10% of the flock) grazing on three different paddocks (with sizes from 80 to 1000 Ha) during a year, to estimate resource selection functions of sheep grazing in flocks of different levels of heterogeneity. We assessed the effects of sheep class (i.e., ewes, wethers, and hoggets), age, body condition and time since release on habitat selection patterns. Results. We found that social rank was reflected on sheep habitat use, where dominant individuals (i.e., reproductive females) used more intensively the most preferred areas and low-ranked (i.e., yearlings) used less preferred areas. Our results showed that when sheep grazed on more heterogeneous flocks, grazing patterns were more evenly distributed at all the paddocks considered in this study. On the other hand, when high-ranked individuals were removed from the flock, low-ranked sheep shifted their selection patterns by increasing the use of the most preferred areas and strongly avoided to use less preferred sites (i.e., a highly selective grazing behaviour). Discussion. Although homogenization and segregation of flocks by classes are common practices to increase flock productivity, we are proposing an alternative that employs behavioural interactions in heterogeneous flocks to generate more evenly distributed grazing patterns. This practice can be combined with other practices such as rotational grazing and guardian dogs (to decrease mortality levels that may be generated by sheep grazing on more risky habitats). This does not imply any modifications of livestock stocking rates and densities or any additional investments for labour and materials. Considering livestock behaviour is critical for the design of sustainable management practices that balance landscape conservation and livestock productivity.

Computer image generation: Reconfigurability as a strategy in high fidelity space applications

NASA Technical Reports Server (NTRS)

Bartholomew, Michael J.

1989-01-01

The demand for realistic, high fidelity, computer image generation systems to support space simulation is well established. However, as the number and diversity of space applications increase, the complexity and cost of computer image generation systems also increase. One strategy used to harmonize cost with varied requirements is establishment of a reconfigurable image generation system that can be adapted rapidly and easily to meet new and changing requirements. The reconfigurability strategy through the life cycle of system conception, specification, design, implementation, operation, and support for high fidelity computer image generation systems are discussed. The discussion is limited to those issues directly associated with reconfigurability and adaptability of a specialized scene generation system in a multi-faceted space applications environment. Examples and insights gained through the recent development and installation of the Improved Multi-function Scene Generation System at Johnson Space Center, Systems Engineering Simulator are reviewed and compared with current simulator industry practices. The results are clear; the strategy of reconfigurability applied to space simulation requirements provides a viable path to supporting diverse applications with an adaptable computer image generation system.

Machine-learned and codified synthesis parameters of oxide materials

NASA Astrophysics Data System (ADS)

Kim, Edward; Huang, Kevin; Tomala, Alex; Matthews, Sara; Strubell, Emma; Saunders, Adam; McCallum, Andrew; Olivetti, Elsa

2017-09-01

Predictive materials design has rapidly accelerated in recent years with the advent of large-scale resources, such as materials structure and property databases generated by ab initio computations. In the absence of analogous ab initio frameworks for materials synthesis, high-throughput and machine learning techniques have recently been harnessed to generate synthesis strategies for select materials of interest. Still, a community-accessible, autonomously-compiled synthesis planning resource which spans across materials systems has not yet been developed. In this work, we present a collection of aggregated synthesis parameters computed using the text contained within over 640,000 journal articles using state-of-the-art natural language processing and machine learning techniques. We provide a dataset of synthesis parameters, compiled autonomously across 30 different oxide systems, in a format optimized for planning novel syntheses of materials.

Using Evolutionary Theory to Guide Mental Health Research.

PubMed

Durisko, Zachary; Mulsant, Benoit H; McKenzie, Kwame; Andrews, Paul W

2016-03-01

Evolutionary approaches to medicine can shed light on the origins and etiology of disease. Such an approach may be especially useful in psychiatry, which frequently addresses conditions with heterogeneous presentation and unknown causes. We review several previous applications of evolutionary theory that highlight the ways in which psychiatric conditions may persist despite and because of natural selection. One lesson from the evolutionary approach is that some conditions currently classified as disorders (because they cause distress and impairment) may actually be caused by functioning adaptations operating "normally" (as designed by natural selection). Such conditions suggest an alternative illness model that may generate alternative intervention strategies. Thus, the evolutionary approach suggests that psychiatry should sometimes think differently about distress and impairment. The complexity of the human brain, including normal functioning and potential for dysfunctions, has developed over evolutionary time and has been shaped by natural selection. Understanding the evolutionary origins of psychiatric conditions is therefore a crucial component to a complete understanding of etiology. © The Author(s) 2016.

Using Evolutionary Theory to Guide Mental Health Research

PubMed Central

Mulsant, Benoit H.; McKenzie, Kwame; Andrews, Paul W.

2016-01-01

Evolutionary approaches to medicine can shed light on the origins and etiology of disease. Such an approach may be especially useful in psychiatry, which frequently addresses conditions with heterogeneous presentation and unknown causes. We review several previous applications of evolutionary theory that highlight the ways in which psychiatric conditions may persist despite and because of natural selection. One lesson from the evolutionary approach is that some conditions currently classified as disorders (because they cause distress and impairment) may actually be caused by functioning adaptations operating “normally” (as designed by natural selection). Such conditions suggest an alternative illness model that may generate alternative intervention strategies. Thus, the evolutionary approach suggests that psychiatry should sometimes think differently about distress and impairment. The complexity of the human brain, including normal functioning and potential for dysfunctions, has developed over evolutionary time and has been shaped by natural selection. Understanding the evolutionary origins of psychiatric conditions is therefore a crucial component to a complete understanding of etiology. PMID:27254091

Dehydroxymethylepoxyquinomicin selectively ablates T-CAEBV cells.

PubMed

Zhang, Hui; Yang, Wen-Tao; Wang, Zhao; Yao, Chun-Mei; Wang, Xiao-Fang; Tian, Zhi-Qing; Jin, Ying-Ying; Wang, Lin-Lin; Chen, Tong-Xin

2015-01-01

Chronic active Epstein-Barr virus infection (CAEBV) represents a new subtype of lymphoproliferative disorders characterized by high morbidity and mortality rates and often leads to malignant transformation of infected cells. Efficient therapeutic strategies are presently unavailable; therefore, the development of therapies to prevent CAEBV-mediated transformation and disease progression is crucial. Here, we used microarray analysis and luciferase reporter assays to reveal the potential role of activated nuclear factor kappa B (NF-kB) in T cell type of-CAEBV infection. Using a series of cellular and molecular experiments, we demonstrated that dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kB inhibitor, can selectively induce apoptosis in SNT-16 cells infected with CAEBV. Mechanistic studies suggested that DHMEQ induces SNT-16 cell apoptosis through NF-kB inhibition coupled with oxidative stress generation. Thus, activated NF-kB could be a new target for CAEBV therapeutics. Owing to its selective targeting ability, DHMEQ may be a candidate for a novel therapeutic regimen to control the progression of CAEBV infections.

A ligand-directed divergent catalytic approach to establish structural and functional scaffold diversity

NASA Astrophysics Data System (ADS)

Lee, Yen-Chun; Patil, Sumersing; Golz, Christopher; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert

2017-02-01

The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands. Herein we present a ligand-directed synthesis approach for the gold(I)-catalysed cycloisomerization of oxindole-derived 1,6-enynes that affords distinct molecular scaffolds following different catalytic reaction pathways. Varying electronic properties and the steric demand of the gold(I) ligands steers the fate of a common intermediary gold carbene to selectively form spirooxindoles, quinolones or df-oxindoles. Investigation of a synthesized compound collection in cell-based assays delivers structurally novel, selective modulators of the Hedgehog and Wnt signalling pathways, autophagy and of cellular proliferation.

Detection of genomic loci associated with environmental variables using generalized linear mixed models.

PubMed

Lobréaux, Stéphane; Melodelima, Christelle

2015-02-01

We tested the use of Generalized Linear Mixed Models to detect associations between genetic loci and environmental variables, taking into account the population structure of sampled individuals. We used a simulation approach to generate datasets under demographically and selectively explicit models. These datasets were used to analyze and optimize GLMM capacity to detect the association between markers and selective coefficients as environmental data in terms of false and true positive rates. Different sampling strategies were tested, maximizing the number of populations sampled, sites sampled per population, or individuals sampled per site, and the effect of different selective intensities on the efficiency of the method was determined. Finally, we apply these models to an Arabidopsis thaliana SNP dataset from different accessions, looking for loci associated with spring minimal temperature. We identified 25 regions that exhibit unusual correlations with the climatic variable and contain genes with functions related to temperature stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Evolution of proliferation and the angiogenic switch in tumors with high clonal diversity.

PubMed

Bickel, Scott T; Juliano, Joseph D; Nagy, John D

2014-01-01

Natural selection among tumor cell clones is thought to produce hallmark properties of malignancy. Efforts to understand evolution of one such hallmark--the angiogenic switch--has suggested that selection for angiogenesis can "run away" and generate a hypertumor, a form of evolutionary suicide by extreme vascular hypo- or hyperplasia. This phenomenon is predicted by models of tumor angiogenesis studied with the techniques of adaptive dynamics. These techniques also predict that selection drives tumor proliferative potential towards an evolutionarily stable strategy (ESS) that is also convergence-stable. However, adaptive dynamics are predicated on two key assumptions: (i) no more than two distinct clones or evolutionary strategies can exist in the tumor at any given time; and (ii) mutations cause small phenotypic changes. Here we show, using a stochastic simulation, that relaxation of these assumptions has no effect on the predictions of adaptive dynamics in this case. In particular, selection drives proliferative potential towards, and angiogenic potential away from, their respective ESSs. However, these simulations also show that tumor behavior is highly contingent on mutational history, particularly for angiogenesis. Individual tumors frequently grow to lethal size before the evolutionary endpoint is approached. In fact, most tumor dynamics are predicted to be in the evolutionarily transient regime throughout their natural history, so that clinically, the ESS is often largely irrelevant. In addition, we show that clonal diversity as measured by the Shannon Information Index correlates with the speed of approach to the evolutionary endpoint. This observation dovetails with results showing that clonal diversity in Barrett's esophagus predicts progression to malignancy.

Phage display and kinetic selection of antibodies that specifically inhibit amyloid self-replication.

PubMed

Munke, Anna; Persson, Jonas; Weiffert, Tanja; De Genst, Erwin; Meisl, Georg; Arosio, Paolo; Carnerup, Anna; Dobson, Christopher M; Vendruscolo, Michele; Knowles, Tuomas P J; Linse, Sara

2017-06-20

The aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is a defining characteristic of Alzheimer's disease. Because of the complexity of this aggregation process, effective therapeutic inhibitors will need to target the specific microscopic steps that lead to the production of neurotoxic species. We introduce a strategy for generating fibril-specific antibodies that selectively suppress fibril-dependent secondary nucleation of the 42-residue form of Aβ (Aβ42). We target this step because it has been shown to produce the majority of neurotoxic species during aggregation of Aβ42. Starting from large phage display libraries of single-chain antibody fragments (scFvs), the three-stage approach that we describe includes ( i ) selection of scFvs with high affinity for Aβ42 fibrils after removal of scFvs that bind Aβ42 in its monomeric form; ( ii ) ranking, by surface plasmon resonance affinity measurements, of the resulting candidate scFvs that bind to the Aβ42 fibrils; and ( iii ) kinetic screening and analysis to find the scFvs that inhibit selectively the fibril-catalyzed secondary nucleation process in Aβ42 aggregation. By applying this approach, we have identified four scFvs that inhibit specifically the fibril-dependent secondary nucleation process. Our method also makes it possible to discard antibodies that inhibit elongation, an important factor because the suppression of elongation does not target directly the production of toxic oligomers and may even lead to its increase. On the basis of our results, we suggest that the method described here could form the basis for rationally designed immunotherapy strategies to combat Alzheimer's and related neurodegenerative diseases.

Improving virtual screening predictive accuracy of Human kallikrein 5 inhibitors using machine learning models.

PubMed

Fang, Xingang; Bagui, Sikha; Bagui, Subhash

2017-08-01

The readily available high throughput screening (HTS) data from the PubChem database provides an opportunity for mining of small molecules in a variety of biological systems using machine learning techniques. From the thousands of available molecular descriptors developed to encode useful chemical information representing the characteristics of molecules, descriptor selection is an essential step in building an optimal quantitative structural-activity relationship (QSAR) model. For the development of a systematic descriptor selection strategy, we need the understanding of the relationship between: (i) the descriptor selection; (ii) the choice of the machine learning model; and (iii) the characteristics of the target bio-molecule. In this work, we employed the Signature descriptor to generate a dataset on the Human kallikrein 5 (hK 5) inhibition confirmatory assay data and compared multiple classification models including logistic regression, support vector machine, random forest and k-nearest neighbor. Under optimal conditions, the logistic regression model provided extremely high overall accuracy (98%) and precision (90%), with good sensitivity (65%) in the cross validation test. In testing the primary HTS screening data with more than 200K molecular structures, the logistic regression model exhibited the capability of eliminating more than 99.9% of the inactive structures. As part of our exploration of the descriptor-model-target relationship, the excellent predictive performance of the combination of the Signature descriptor and the logistic regression model on the assay data of the Human kallikrein 5 (hK 5) target suggested a feasible descriptor/model selection strategy on similar targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tone signal generator for producing multioperator tone signals using an operator circuit including a waveform generator, a selector and an enveloper

DOEpatents

Dong, Q.; Jenkins, M.V.; Bernadas, S.R.

1997-09-09

A frequency modulation (FM) tone signal generator for generating a FM tone signal is disclosed. The tone signal generator includes a waveform generator having a plurality of wave tables, a selector and an enveloper. The waveform generator furnishes a waveform signal in response to a phase angle address signal. Each wave table stores a different waveform. The selector selects one of the wave tables in response to a plurality of selection signals such that the selected wave table largely provides the waveform signal upon being addressed largely by the phase angle address signal. Selection of the selected wave table varies with each selection signal. The enveloper impresses an envelope signal on the waveform signal. The envelope signal is used as a carrier or modulator for generating the FM tone signal. 17 figs.

Perceptual support promotes strategy generation: Evidence from equation solving.

PubMed

Alibali, Martha W; Crooks, Noelle M; McNeil, Nicole M

2017-08-30

Over time, children shift from using less optimal strategies for solving mathematics problems to using better ones. But why do children generate new strategies? We argue that they do so when they begin to encode problems more accurately; therefore, we hypothesized that perceptual support for correct encoding would foster strategy generation. Fourth-grade students solved mathematical equivalence problems (e.g., 3 + 4 + 5 = 3 + __) in a pre-test. They were then randomly assigned to one of three perceptual support conditions or to a Control condition. Participants in all conditions completed three mathematical equivalence problems with feedback about correctness. Participants in the experimental conditions received perceptual support (i.e., highlighting in red ink) for accurately encoding the equal sign, the right side of the equation, or the numbers that could be added to obtain the correct solution. Following this intervention, participants completed a problem-solving post-test. Among participants who solved the problems incorrectly at pre-test, those who received perceptual support for correctly encoding the equal sign were more likely to generate new, correct strategies for solving the problems than were those who received feedback only. Thus, perceptual support for accurate encoding of a key problem feature promoted generation of new, correct strategies. Statement of Contribution What is already known on this subject? With age and experience, children shift to using more effective strategies for solving math problems. Problem encoding also improves with age and experience. What the present study adds? Support for encoding the equal sign led children to generate correct strategies for solving equations. Improvements in problem encoding are one source of new strategies. © 2017 The British Psychological Society.

Multiatlas whole heart segmentation of CT data using conditional entropy for atlas ranking and selection

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

Zhuang, Xiahai, E-mail: zhuangxiahai@sjtu.edu.cn; Qian, Xiaohua; Bai, Wenjia

Purpose: Cardiac computed tomography (CT) is widely used in clinical diagnosis of cardiovascular diseases. Whole heart segmentation (WHS) plays a vital role in developing new clinical applications of cardiac CT. However, the shape and appearance of the heart can vary greatly across different scans, making the automatic segmentation particularly challenging. The objective of this work is to develop and evaluate a multiatlas segmentation (MAS) scheme using a new atlas ranking and selection algorithm for automatic WHS of CT data. Research on different MAS strategies and their influence on WHS performance are limited. This work provides a detailed comparison study evaluatingmore » the impacts of label fusion, atlas ranking, and sizes of the atlas database on the segmentation performance. Methods: Atlases in a database were registered to the target image using a hierarchical registration scheme specifically designed for cardiac images. A subset of the atlases were selected for label fusion, according to the authors’ proposed atlas ranking criterion which evaluated the performance of each atlas by computing the conditional entropy of the target image given the propagated atlas labeling. Joint label fusion was used to combine multiple label estimates to obtain the final segmentation. The authors used 30 clinical cardiac CT angiography (CTA) images to evaluate the proposed MAS scheme and to investigate different segmentation strategies. Results: The mean WHS Dice score of the proposed MAS method was 0.918 ± 0.021, and the mean runtime for one case was 13.2 min on a workstation. This MAS scheme using joint label fusion generated significantly better Dice scores than the other label fusion strategies, including majority voting (0.901 ± 0.276, p < 0.01), locally weighted voting (0.905 ± 0.0247, p < 0.01), and probabilistic patch-based fusion (0.909 ± 0.0249, p < 0.01). In the atlas ranking study, the proposed criterion based on conditional entropy yielded a performance curve with higher WHS Dice scores compared to the conventional schemes (p < 0.03). In the atlas database study, the authors showed that the MAS using larger atlas databases generated better performance curves than the MAS using smaller ones, indicating larger atlas databases could produce more accurate segmentation. Conclusions: The authors have developed a new MAS framework for automatic WHS of CTA and investigated alternative implementations of MAS. With the proposed atlas ranking algorithm and joint label fusion, the MAS scheme is able to generate accurate segmentation within practically acceptable computation time. This method can be useful for the development of new clinical applications of cardiac CT.« less

The Development of Children's Strategies for Selective Attention: Evidence for a Transitional Period.

ERIC Educational Resources Information Center

DeMarie-Dreblow, Darlene; Miller, Patricia H.

1988-01-01

This study of 114 children between seven and nine years used a procedure for directly observing child-produced and experimenter-produced strategies to examine the transitional period of strategy development. Findings revealed gradual changes in children's ability to produce, and to benefit from, a strategy of selective attention. (RH)

Variable Selection in the Presence of Missing Data: Imputation-based Methods.

PubMed

Zhao, Yize; Long, Qi

2017-01-01

Variable selection plays an essential role in regression analysis as it identifies important variables that associated with outcomes and is known to improve predictive accuracy of resulting models. Variable selection methods have been widely investigated for fully observed data. However, in the presence of missing data, methods for variable selection need to be carefully designed to account for missing data mechanisms and statistical techniques used for handling missing data. Since imputation is arguably the most popular method for handling missing data due to its ease of use, statistical methods for variable selection that are combined with imputation are of particular interest. These methods, valid used under the assumptions of missing at random (MAR) and missing completely at random (MCAR), largely fall into three general strategies. The first strategy applies existing variable selection methods to each imputed dataset and then combine variable selection results across all imputed datasets. The second strategy applies existing variable selection methods to stacked imputed datasets. The third variable selection strategy combines resampling techniques such as bootstrap with imputation. Despite recent advances, this area remains under-developed and offers fertile ground for further research.

Rescue of Targeted Regions of Mammalian Chromosomes by in Vivo Recombination in Yeast

PubMed Central

Kouprina, Natalya; Kawamoto, Kensaku; Barrett, J. Carl; Larionov, Vladimir; Koi, Minoru

1998-01-01

In contrast to other animal cell lines, the chicken pre-B cell lymphoma line, DT40, exhibits a high level of homologous recombination, which can be exploited to generate site-specific alterations in defined target genes or regions. In addition, the ability to generate human/chicken monochromosomal hybrids in the DT40 cell line opens a way for specific targeting of human genes. Here we describe a new strategy for direct isolation of a human chromosomal region that is based on targeting of the chromosome with a vector containing a yeast selectable marker, centromere, and an ARS element. This procedure allows rescue of the targeted region by transfection of total genomic DNA into yeast spheroplasts. Selection for the yeast marker results in isolation of chromosome sequences in the form of large circular yeast artificial chromosomes (YACs) up to 170 kb in size containing the targeted region. These YACs are generated by homologous recombination in yeast between common repeated sequences in the targeted chromosomal fragment. Alternatively, the targeted region can be rescued as a linear YACs when a YAC fragmentation vector is included in the yeast transformation mixture. Because the entire isolation procedure of the chromosomal region, once a target insertion is obtained, can be accomplished in ∼1 week, the new method greatly expands the utility of the homologous recombinationproficient DT40 chicken cell system. PMID:9647640

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention.

PubMed

Hayes, Spencer J; Andrew, Matthew; Elliott, Digby; Gowen, Emma; Bennett, Simon J

2016-02-01

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only neurotypical adults imitated atypical biological kinematics. Adults with autism did, however, become significantly more accurate at imitating movement time. This confirmed they engaged in the task, and that sensorimotor adaptation was self-regulated. The attentional bias to movement time suggests the attenuation in imitating kinematics might be a compensatory strategy due to deficits in lower-level visuomotor processes associated with self-other mapping, or selective attention modulated the processes that represent biological kinematics.

Experimental and Computational Exploration of para-Selective Silylation with a Hydrogen-Bonded Template.

PubMed

Maji, Arun; Guin, Srimanta; Feng, Sheng; Dahiya, Amit; Singh, Vikas Kumar; Liu, Peng; Maiti, Debabrata

2017-11-20

The regioselective conversion of C-H bonds into C-Si bonds is extremely important owing to the natural abundance and non-toxicity of silicon. Classical silylation reactions often suffer from poor functional group compatibility, low atom economy, and insufficient regioselectivity. Herein, we disclose a template-assisted method for the regioselective para silylation of toluene derivatives. A new template was designed, and the origin of selectivity was analyzed experimentally and computationally. An interesting substrate-solvent hydrogen-bonding interaction was observed. Kinetic, spectroscopic, and computational studies shed light on the reaction mechanism. The synthetic significance of this strategy was highlighted by the generation of a precursor of a potential lipophilic bioisostere of γ-aminobutyric acid (GABA), various late-stage diversifications, and by mimicking enzymatic transformations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rationally designed mineralization for selective recovery of the rare earth elements

NASA Astrophysics Data System (ADS)

Hatanaka, Takaaki; Matsugami, Akimasa; Nonaka, Takamasa; Takagi, Hideki; Hayashi, Fumiaki; Tani, Takao; Ishida, Nobuhiro

2017-05-01

The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ~6.0). This concept for stabilization of an insoluble lanthanide hydroxide complex with an artificial peptide also works in combination with stable scaffolds like synthetic macromolecules and proteins. Our strategy opens the possibility for selective separation of target metal elements from seawater and industrial wastewater under mild conditions without additional energy input.

Rationally designed mineralization for selective recovery of the rare earth elements

PubMed Central

Hatanaka, Takaaki; Matsugami, Akimasa; Nonaka, Takamasa; Takagi, Hideki; Hayashi, Fumiaki; Tani, Takao; Ishida, Nobuhiro

2017-01-01

The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ∼6.0). This concept for stabilization of an insoluble lanthanide hydroxide complex with an artificial peptide also works in combination with stable scaffolds like synthetic macromolecules and proteins. Our strategy opens the possibility for selective separation of target metal elements from seawater and industrial wastewater under mild conditions without additional energy input. PMID:28548098

Rationally designed mineralization for selective recovery of the rare earth elements.

PubMed

Hatanaka, Takaaki; Matsugami, Akimasa; Nonaka, Takamasa; Takagi, Hideki; Hayashi, Fumiaki; Tani, Takao; Ishida, Nobuhiro

2017-05-26

The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ∼6.0). This concept for stabilization of an insoluble lanthanide hydroxide complex with an artificial peptide also works in combination with stable scaffolds like synthetic macromolecules and proteins. Our strategy opens the possibility for selective separation of target metal elements from seawater and industrial wastewater under mild conditions without additional energy input.