Phenotypic selection in natural populations: what limits directional selection?
Kingsolver, Joel G; Diamond, Sarah E
2011-03-01
Studies of phenotypic selection document directional selection in many natural populations. What factors reduce total directional selection and the cumulative evolutionary responses to selection? We combine two data sets for phenotypic selection, representing more than 4,600 distinct estimates of selection from 143 studies, to evaluate the potential roles of fitness trade-offs, indirect (correlated) selection, temporally varying selection, and stabilizing selection for reducing net directional selection and cumulative responses to selection. We detected little evidence that trade-offs among different fitness components reduced total directional selection in most study systems. Comparisons of selection gradients and selection differentials suggest that correlated selection frequently reduced total selection on size but not on other types of traits. The direction of selection on a trait often changes over time in many temporally replicated studies, but these fluctuations have limited impact in reducing cumulative directional selection in most study systems. Analyses of quadratic selection gradients indicated stabilizing selection on body size in at least some studies but provided little evidence that stabilizing selection is more common than disruptive selection for most traits or study systems. Our analyses provide little evidence that fitness trade-offs, correlated selection, or stabilizing selection strongly constrains the directional selection reported for most quantitative traits.
Dynes, Joseph L; Xu, Shuping; Bothner, Sarah; Lahti, Jill M; Hori, Roderick T
2004-03-01
The protein complex Selectivity Factor 1, composed of TBP, TAF(I)48, TAF(I)63 and TAF(I)110, is required for rRNA transcription by RNA polymerase I in the nucleolus. The steps involved in targeting Selectivity Factor 1 will be dependent on the transport pathways that are used and the localization signals that direct this trafficking. In order to investigate these issues, we characterized human TAF(I)48, a subunit of Selectivity Factor 1. By domain analysis of TAF(I)48, the carboxyl-terminal 51 residues were found to be required for the localization of TAF(I)48, as well as sufficient to direct Green Fluorescent Protein to the nucleus and nucleolus. The carboxyl-terminus of TAF(I)48 also has the ability to associate with multiple members of the beta-karyopherin family of nuclear import receptors, including importin beta (karyopherin beta1), transportin (karyopherin beta2) and RanBP5 (karyopherin beta3), in a Ran-dependent manner. This property of interacting with multiple beta-karyopherins has been previously reported for the nuclear localization signals of some ribosomal proteins that are likewise directed to the nucleolus. This study identifies the first nuclear import sequence identified within the TBP-Associated Factor subunits of Selectivity Factor 1.
Apparent directional selection by biased pleiotropic mutation.
Tanaka, Yoshinari
2010-07-01
Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.
Charge Transfer Directed Radical Substitution Enables para-Selective C–H Functionalization
Boursalian, Gregory B.; Ham, Won Seok; Mazzotti, Anthony R.; Ritter, Tobias
2016-01-01
Efficient C–H functionalization requires selectivity for specific C–H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho- and meta- selectivity, but a general strategy for para-selective C–H functionalization has remained elusive. Herein, we introduce a previously unappreciated concept which enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit areneto-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate that the selectivity is predictable by a simple theoretical tool and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of charge transfer directed radical substitution could serve as the basis for the development of new, highly selective C–H functionalization reactions. PMID:27442288
Charge-transfer-directed radical substitution enables para-selective C-H functionalization
NASA Astrophysics Data System (ADS)
Boursalian, Gregory B.; Ham, Won Seok; Mazzotti, Anthony R.; Ritter, Tobias
2016-08-01
Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.
Skinner, Michael K
2015-04-26
Environment has a critical role in the natural selection process for Darwinian evolution. The primary molecular component currently considered for neo-Darwinian evolution involves genetic alterations and random mutations that generate the phenotypic variation required for natural selection to act. The vast majority of environmental factors cannot directly alter DNA sequence. Epigenetic mechanisms directly regulate genetic processes and can be dramatically altered by environmental factors. Therefore, environmental epigenetics provides a molecular mechanism to directly alter phenotypic variation generationally. Lamarck proposed in 1802 the concept that environment can directly alter phenotype in a heritable manner. Environmental epigenetics and epigenetic transgenerational inheritance provide molecular mechanisms for this process. Therefore, environment can on a molecular level influence the phenotypic variation directly. The ability of environmental epigenetics to alter phenotypic and genotypic variation directly can significantly impact natural selection. Neo-Lamarckian concept can facilitate neo-Darwinian evolution. A unified theory of evolution is presented to describe the integration of environmental epigenetic and genetic aspects of evolution. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
ERIC Educational Resources Information Center
Poitras, Sarah-Caroline; Guay, Frederic; Ratelle, Catherine F.
2012-01-01
Using Item Response Theory (IRT) and Confirmatory Factor Analysis (CFA), the goal of this study was to select a reduced pool of items from the French Canadian version of the Self-Directed Search--Activities Section (Holland, Fritzsche, & Powell, 1994). Two studies were conducted. Results of Study 1, involving 727 French Canadian students,…
Spectral and angular-selective thermal emission from gallium-doped zinc oxide thin film structures
NASA Astrophysics Data System (ADS)
Sakr, Enas; Bermel, Peter
2017-02-01
Simultaneously controlling both the spectral and angular emission of thermal photons can qualitatively change the nature of thermal radiation, and offers a great potential to improve a broad range of applications, including infrared light sources and thermophotovoltaic (TPV) conversion of waste heat to electricity. For TPV in particular, frequency-selective emission is necessary for spectral matching with a photovoltaic converter, while directional emission is needed to maximize the fraction of emission reaching the receiver at large separation distances. This can allow the photovoltaics to be moved outside vacuum encapsulation. In this work, we demonstrate both directionally and spectrally-selective thermal emission for p-polarization, using a combination of an epsilon-near-zero (ENZ) thin film backed by a metal reflector, a high contrast grating, and an omnidirectional mirror. Gallium-doped zinc oxide is selected as an ENZ material, with cross-over frequency in the near-infrared. The proposed structure relies on coupling guided modes (instead of plasmonic modes) to the ENZ thin film using the high contrast grating. The angular width is thus controlled by the choice of grating period. Other off-directional modes are then filtered out using the omnidirectional mirror, thus enhancing frequency selectivity. Our emitter design maintains both a high view factor and high frequency selectivity, leading to a factor of 8.85 enhancement over a typical blackbody emitter, through a combination of a 22.26% increase in view factor and a 6.88x enhancement in frequency selectivity. This calculation assumes a PV converter five widths away from the same width emitter in 2D at 1573 K.
Directive 2013/39/EU amending and updating the Water Framework Directive (2000/60/EC) and its Daughter Directive (the so-called EQS Directive: 2008/105/EC) sets Environmental Quality Standards for biota (EQSbiota) for a number of bioaccumulative chemicals which can pose a threat ...
Directive 2013/39/EU amending and updating the Water Framework Directive (2000/60/EC) and its Daughter Directive (the so-called EQS Directive: 2008/105/EC) sets Environmental Quality Standards for biota (EQSbiota) for a number of bioaccumulative chemicals which can pose a threat ...
Using a fuzzy DEMATEL method for analyzing the factors influencing subcontractors selection
NASA Astrophysics Data System (ADS)
Kozik, Renata
2016-06-01
Subcontracting is a long-standing practice in the construction industry. This form of project organization, if manage properly, could provide the better quality, reduction in project time and costs. Subcontractors selection is a multi-criterion problem and can be determined by many factors. Identifying the importance of each of them as well as the direction of cause-effect relations between various types of factors can improve the management process. Their values could be evaluated on the basis of the available expert opinions with the application of a fuzzy multi-stage grading scale. In this paper it is recommended to use fuzzy DEMATEL method to analyze the relationship between factors affecting subcontractors selection.
Yersinia pestis targets neutrophils via complement receptor 3
Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.
2015-01-01
Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083
Kittle, Andrew M; Fryxell, John M; Desy, Glenn E; Hamr, Joe
2008-08-01
Resource selection is a fundamental ecological process impacting population dynamics and ecosystem structure. Understanding which factors drive selection is vital for effective species- and landscape-level management. We used resource selection probability functions (RSPFs) to study the influence of two forms of wolf (Canis lupus) predation risk, snow conditions and habitat variables on white-tailed deer (Odocoileus virginianus), elk (Cervus elaphus) and moose (Alces alces) resource selection in central Ontario's mixed forest French River-Burwash ecosystem. Direct predation risk was defined as the frequency of a predator's occurrence across the landscape and indirect predation risk as landscape features associated with a higher risk of predation. Models were developed for two winters, each at two spatial scales, using a combination of GIS-derived and ground-measured data. Ungulate presence was determined from snow track transects in 64 16- and 128 1-km(2) resource units, and direct predation risk from GPS radio collar locations of four adjacent wolf packs. Ungulates did not select resources based on the avoidance of areas of direct predation risk at any scale, and instead exhibited selection patterns that tradeoff predation risk minimization with forage and/or mobility requirements. Elk did not avoid indirect predation risk, while both deer and moose exhibited inconsistent responses to this risk. Direct predation risk was more important to models than indirect predation risk but overall, abiotic topographical factors were most influential. These results indicate that wolf predation risk does not limit ungulate habitat use at the scales investigated and that responses to spatial sources of predation risk are complex, incorporating a variety of anti-predator behaviours. Moose resource selection was influenced less by snow conditions than cover type, particularly selection for dense forest, whereas deer showed the opposite pattern. Temporal and spatial scale influenced resource selection by all ungulate species, underlining the importance of incorporating scale into resource selection studies.
What Factors Predict Student Self-Rated Physical Health?
ERIC Educational Resources Information Center
Vingilis, Evelyn; Wade, Terrance J.; Adlaf, Edward
1998-01-01
Data from a randomly selected sample of 840 Ontario students were used to examine factors that affect self-rated physical health. Analyses focused on demographics, family structure, financial situation, child-parent relationship, school achievement, self-esteem, alcohol, tobacco, and cannabis use as factors which directly and indirectly influence…
Xu, Shuping; Hori, Roderick T
2004-09-01
RNA polymerase I transcription in human cells requires Selectivity Factor 1, a multisubunit complex composed of the TATA-box-binding protein (TBP) and three TBP-associated factors (TAFs) called TAF(I)48, TAF(I)63 and TAF(I)110. Each of the Selectivity Factor 1 subunits binds directly to the other three components, but these interactions have not been characterized. This study is the initial identification and analysis of a TBP-binding domain within a Selectivity Factor 1 TAF. The interaction between human TBP and human TAF(I)48 was initially examined using the yeast two-hybrid assay, and a TBP-binding domain was identified in the carboxyl-terminus of human (h)TAF(I)48. Consistent with this result, the hTAF(I)48 carboxyl-terminus was able to bind directly to TBP in protein-protein interaction assays. When mutations were introduced into the hTAF(I)48 carboxyl-terminus, we identified changes in uncharged and positive residues that affect its interaction with TBP. By examining TBP mutants, residues within and adjacent to helix 2 of TBP, previously demonstrated to interact with subunits of other TBP-containing complexes [Transcription Factor IID (TFIID) and TFIIIB] were also found to diminish its affinity for the carboxyl-terminus of hTAF(I)48. The regions of hTAF(I)48 and TBP that interact are compared to those identified within other complexes containing TBP.
Ternary complex factor SAP-1 is required for Erk-mediated thymocyte positive selection.
Costello, Patrick S; Nicolas, Robert H; Watanabe, Yasuyuki; Rosewell, Ian; Treisman, Richard
2004-03-01
Thymocyte selection and differentiation requires extracellular signal-regulated kinase (Erk) signaling, but transcription factor substrates of Erk in thymocytes are unknown. We have characterized the function of SAP-1 (Elk4), an Erk-regulated transcription factor, in thymocyte development. Early thymocyte development was normal, but single-positive thymocyte and peripheral T cell numbers were reduced, reflecting a T cell-autonomous defect. T cell receptor-induced activation of SAP-1 target genes such as Egr1 was substantially impaired in double-positive thymocytes, although Erk activation was normal. Analysis of T cell receptor transgenes showed that positive selection was reduced by 80-90% in SAP-1-deficient mice; heterozygous mice showed a moderate defect. Negative selection was unimpaired. SAP-1 thus directly links Erk signaling to the transcriptional events required for thymocyte positive selection.
Morphology and Orientation Selection of Non-metallic Inclusions in Electrified Molten Metal
NASA Astrophysics Data System (ADS)
Zhao, Z. C.; Qin, R. S.
2017-10-01
The effect of electric current on morphology and orientation selection of non-metallic inclusions in molten metal has been investigated using theoretical modeling and numerical calculation. Two geometric factors, namely the circularity ( fc ) and alignment ratio ( fe ) were introduced to describe the inclusions shape and configuration. Electric current free energy was calculated and the values were used to determine the thermodynamic preference between different microstructures. Electric current promotes the development of inclusion along the current direction by either expatiating directional growth or enhancing directional agglomeration. Reconfiguration of the inclusions to reduce the system electric resistance drives the phenomena. The morphology and orientation selection follow the routine to reduce electric free energy. The numerical results are in agreement with our experimental observations.
A model of directional selection applied to the evolution of drug resistance in HIV-1.
Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston
2007-04-01
Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.
ERIC Educational Resources Information Center
Darch, Craig; And Others
Several evaluation formats were used to examine the impact that the Direct Instruction Model had on 600 selected students in Williamsburg County, South Carolina, over a 7-year period. The performance of students in the Direct Instruction Model was contrasted with the performance of similar students (on the basis of family income, ethnicity,…
Selection of nursing teaching strategies in mainland China: A questionnaire survey.
Zhou, HouXiu; Liu, MengJie; Zeng, Jing; Zhu, JingCi
2016-04-01
In nursing education, the traditional lecture and direct demonstration teaching method cannot cultivate the various skills that nursing students need. How to choose a more scientific and rational teaching method is a common concern for nursing educators worldwide. To investigate the basis for selecting teaching methods among nursing teachers in mainland China, the factors affecting the selection of different teaching methods, and the application of different teaching methods in theoretical and skill-based nursing courses. Questionnaire survey. Seventy one nursing colleges from 28 provincial-level administrative regions in mainland China. Following the principle of voluntary informed consent, 262 nursing teachers were randomly selected through a nursing education network platform and a conference platform. The questionnaire contents included the basis for and the factors influencing the selection of nursing teaching methods, the participants' common teaching methods, and the teaching experience of the surveyed nursing teachers. The questionnaires were distributed through the network or conference platform, and the data were analyzed by SPSS 17.0 software. The surveyed nursing teachers selected teaching methods mainly based on the characteristics of the teaching content, the characteristics of the students, and their previous teaching experiences. The factors affecting the selection of teaching methods mainly included large class sizes, limited class time, and limited examination formats. The surveyed nursing teachers primarily used lectures to teach theory courses and the direct demonstration method to teach skills courses, and the application frequencies of these two teaching methods were significantly higher than those of other teaching methods (P=0.000). More attention should be paid to the selection of nursing teaching methods. Every teacher should strategically choose teaching methods before each lesson, and nursing education training focused on selecting effective teaching methods should be more extensive. Copyright © 2016. Published by Elsevier Ltd.
Modelling Knowledge Sharing Behaviour Using Self-Efficacy as a Mediator
ERIC Educational Resources Information Center
Brooke, Jenefer; Mohd Rasdi, Roziah; Abu Samah, Bahaman
2017-01-01
Purpose: The purpose of this paper is to examine the direct and indirect relationships between individual-related factors and environmental-related factors with the knowledge sharing behaviour through the mediating role of self-efficacy among successful farmers in selected states in Malaysia. Design/methodology/approach: The research used survey…
Wallqvist, Anders; Memišević, Vesna; Zavaljevski, Nela; Pieper, Rembert; Rajagopala, Seesandra V; Kwon, Keehwan; Yu, Chenggang; Hoover, Timothy A; Reifman, Jaques
2015-12-29
Francisella tularensis is a select bio-threat agent and one of the most virulent intracellular pathogens known, requiring just a few organisms to establish an infection. Although several virulence factors are known, we lack an understanding of virulence factors that act through host-pathogen protein interactions to promote infection. To address these issues in the highly infectious F. tularensis subsp. tularensis Schu S4 strain, we deployed a combined in silico, in vitro, and in vivo analysis to identify virulence factors and their interactions with host proteins to characterize bacterial infection mechanisms. We initially used comparative genomics and literature to identify and select a set of 49 putative and known virulence factors for analysis. Each protein was then subjected to proteome-scale yeast two-hybrid (Y2H) screens with human and murine cDNA libraries to identify potential host-pathogen protein-protein interactions. Based on the bacterial protein interaction profile with both hosts, we selected seven novel putative virulence factors for mutant construction and animal validation experiments. We were able to create five transposon insertion mutants and used them in an intranasal BALB/c mouse challenge model to establish 50 % lethal dose estimates. Three of these, ΔFTT0482c, ΔFTT1538c, and ΔFTT1597, showed attenuation in lethality and can thus be considered novel F. tularensis virulence factors. The analysis of the accompanying Y2H data identified intracellular protein trafficking between the early endosome to the late endosome as an important component in virulence attenuation for these virulence factors. Furthermore, we also used the Y2H data to investigate host protein binding of two known virulence factors, showing that direct protein binding was a component in the modulation of the inflammatory response via activation of mitogen-activated protein kinases and in the oxidative stress response. Direct interactions with specific host proteins and the ability to influence interactions among host proteins are important components for F. tularensis to avoid host-cell defense mechanisms and successfully establish an infection. Although direct host-pathogen protein-protein binding is only one aspect of Francisella virulence, it is a critical component in directly manipulating and interfering with cellular processes in the host cell.
NASA Astrophysics Data System (ADS)
Wu, Xiuling; Wu, Yilin; Dong, Hongjun; Zhao, Juan; Wang, Chen; Zhou, Shi; Lu, Jian; Yan, Yongsheng; Li, He
2018-01-01
A novel system for harvesting molecularly imprinted nanocomposite membranes (MINcMs) with Au-modified polyaniline (Au@polyaniline) nanocomposite structure was developed for selective enrichment and separation of ibuprofen. This unique nanocomposite structure obviously enhanced the adsorption capacity, perm-selectivity performance, and regeneration ability of MINcMs. The as-prepared MINcMs showed outstanding adsorption capacity (22.02 mg g-1) of ibuprofen, which was four times higher than that of non-imprinted nanocomposite membranes (NINcMs). Furthermore, the selectivity factor of MINcMs for ibuprofen reached up to 4.67 and the perm-selectivity factor β was about 8.74, which indicated MINcMs had a good selective separation performance of ibuprofen. We envision that this novel synthesis method will open a new direction to manipulation of molecularly imprinted membrane materials and provide a simple yet convenient way to selective separation of ibuprofen.
Why Sexually Selected Weapons Are Not Ornaments.
McCullough, Erin L; Miller, Christine W; Emlen, Douglas J
2016-10-01
The elaboration and diversification of sexually selected weapons remain poorly understood. We argue that progress in this topic has been hindered by a strong bias in sexual selection research, and a tendency for weapons to be conflated with ornaments used in mate choice. Here, we outline how male-male competition and female choice are distinct mechanisms of sexual selection, and why weapons and ornaments are fundamentally different types of traits. We call for research on the factors contributing to weapon divergence, the potential for male-male competition to drive speciation, and the specific use of weapons in the context of direct fights versus displays. Given that weapons are first and foremost fighting structures, biomechanical approaches are an especially promising direction for understanding weapon design. Copyright © 2016 Elsevier Ltd. All rights reserved.
Jain, Ashish; Rusten, Tor Erik; Katheder, Nadja; Elvenes, Julianne; Bruun, Jack-Ansgar; Sjøttem, Eva; Lamark, Trond; Johansen, Terje
2015-06-12
The selective autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in oxidative stress signaling in two ways in mammals. First, p62 is transcriptionally induced upon oxidative stress by the NF-E2-related factor 2 (NRF2) by direct binding to an antioxidant response element in the p62 promoter. Second, p62 accumulation, occurring when autophagy is impaired, leads to increased p62 binding to the NRF2 inhibitor KEAP1, resulting in reduced proteasomal turnover of NRF2. This gives chronic oxidative stress signaling through a feed forward loop. Here, we show that the Drosophila p62/SQSTM1 orthologue, Ref(2)P, interacts directly with DmAtg8a via an LC3-interacting region motif, supporting a role for Ref(2)P in selective autophagy. The ref(2)P promoter also contains a functional antioxidant response element that is directly bound by the NRF2 orthologue, CncC, which can induce ref(2)P expression along with the oxidative stress-associated gene gstD1. However, distinct from the situation in mammals, Ref(2)P does not interact directly with DmKeap1 via a KEAP1-interacting region motif; nor does ectopically expressed Ref(2)P or autophagy deficiency activate the oxidative stress response. Instead, DmAtg8a interacts directly with DmKeap1, and DmKeap1 is removed upon programmed autophagy in Drosophila gut cells. Strikingly, CncC induced increased Atg8a levels and autophagy independent of TFEB/MitF in fat body and larval gut tissues. Thus, these results extend the intimate relationship between oxidative stress-sensing NRF2/CncC transcription factors and autophagy and suggest that NRF2/CncC may regulate autophagic activity in other organisms too. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
What Makes a Top-Selling Textbook? Comparing Characteristics of AIS Textbooks
ERIC Educational Resources Information Center
Badua, Frank; Sharifi, Mohsen; Mendez Mediavilla, Francis
2014-01-01
The factors involved in the selection of accounting textbooks are under-investigated, and most of the research is survey-based, largely ignoring the information that could be analyzed by direct inspection of textbook content and its impact on textbook selection. In this study the authors fill this lacuna by deploying content analysis of the…
Jiang, Zheng-Yu; Lu, Meng-Chen; You, Qi-Dong
2016-12-22
The transcription factor Nrf2 is the primary regulator of the cellular defense system, and enhancing Nrf2 activity has potential usages in various diseases, especially chronic age-related and inflammatory diseases. Recently, directly targeting Keap1-Nrf2 protein-protein interaction (PPI) has been an emerging strategy to selectively and effectively activate Nrf2. This Perspective summarizes the progress in the discovery and development of Keap1-Nrf2 PPI inhibitors, including the Keap1-Nrf2 regulatory mechanisms, biochemical techniques for inhibitor identification, and approaches for identifying peptide and small-molecule inhibitors, as well as discusses privileged structures and future directions for further development of Keap1-Nrf2 PPI inhibitors.
e-Portfolios Enhancing Students' Self-Directed Learning: A Systematic Review of Influencing Factors
ERIC Educational Resources Information Center
Beckers, Jorrick; Dolmans, Diana; Van Merriënboer, Jeroen
2016-01-01
e-Portfolios have become increasingly popular among educators as learning tools. Some research even shows that e-portfolios can be utilised to facilitate the development of skills for self-directed learning. Such skills include self-assessment of performance, formulation of learning goals, and selection of future tasks. However, it is not yet…
The effect of social alliances on wolf population on their survival under hunting
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cebrat, S.; Kakol, J.
1997-04-01
We have introduced the modified Verhulst factor to simulate the dynamics of wolves` population. The new factor enlarges the capacity of environment for organisms living in organized groups. Under this factor, social behavior allows the population to reach the larger size in the same ecological niche. The other effect of the introduced factor is that additional non-selective killing factors limit the population size not only directly but also by shrinking the effective ecological niche capacity.
The Effect of Social Alliances on Wolf Population on Their Survival Under Hunting
NASA Astrophysics Data System (ADS)
Cebrat, Stanisław; Kakol, Jerzy
We have introduced the modified Verhulst factor to simulate the dynamics of wolves' population. The new factor enlarges the capacity of environment for organisms living in organized groups. Under this factor, social behavior allows the population to reach the larger size in the same ecological niche. The other effect of the introduced factor is that additional non-selective killing factors limit the population size not only directly but also by shrinking the effective ecological niche capacity.
Factors influencing equipment selection in electron beam processing
NASA Astrophysics Data System (ADS)
Barnard, J. W.
2003-08-01
During the eighties and nineties accelerator manufacturers dramatically increased the beam power available for high-energy equipment. This effort was directed primarily at meeting the demands of the sterilization industry. During this era, the perception that bigger (higher power, higher energy) was always better prevailed since the operating and capital costs of accelerators did not increase with power and energy as fast as the throughput. High power was needed to maintain per unit costs low for treatment. This philosophy runs counter to certain present-day realities of the sterilization business as well as conditions influencing accelerator selection in other electron beam applications. Recent experience in machine selection is described and factors affecting choice are presented.
Estimating causal contrasts involving intermediate variables in the presence of selection bias.
Valeri, Linda; Coull, Brent A
2016-11-20
An important goal across the biomedical and social sciences is the quantification of the role of intermediate factors in explaining how an exposure exerts an effect on an outcome. Selection bias has the potential to severely undermine the validity of inferences on direct and indirect causal effects in observational as well as in randomized studies. The phenomenon of selection may arise through several mechanisms, and we here focus on instances of missing data. We study the sign and magnitude of selection bias in the estimates of direct and indirect effects when data on any of the factors involved in the analysis is either missing at random or not missing at random. Under some simplifying assumptions, the bias formulae can lead to nonparametric sensitivity analyses. These sensitivity analyses can be applied to causal effects on the risk difference and risk-ratio scales irrespectively of the estimation approach employed. To incorporate parametric assumptions, we also develop a sensitivity analysis for selection bias in mediation analysis in the spirit of the expectation-maximization algorithm. The approaches are applied to data from a health disparities study investigating the role of stage at diagnosis on racial disparities in colorectal cancer survival. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Horizontal directional drilling: a green and sustainable technology for site remediation.
Lubrecht, Michael D
2012-03-06
Sustainability has become an important factor in the selection of remedies to clean up contaminated sites. Horizontal directional drilling (HDD) is a relatively new drilling technology that has been successfully adapted to site remediation. In addition to the benefits that HDD provides for the logistics of site cleanup, it also delivers sustainability advantages, compared to alternative construction methods.
Modular control of endothelial sheet migration
Vitorino, Philip; Meyer, Tobias
2008-01-01
Growth factor-induced migration of endothelial cell monolayers enables embryonic development, wound healing, and angiogenesis. Although collective migration is widespread and therapeutically relevant, the underlying mechanism by which cell monolayers respond to growth factor, sense directional signals, induce motility, and coordinate individual cell movements is only partially understood. Here we used RNAi to identify 100 regulatory proteins that enhance or suppress endothelial sheet migration into cell-free space. We measured multiple live-cell migration parameters for all siRNA perturbations and found that each targeted protein primarily regulates one of four functional outputs: cell motility, directed migration, cell–cell coordination, or cell density. We demonstrate that cell motility regulators drive random, growth factor-independent motility in the presence or absence of open space. In contrast, directed migration regulators selectively transduce growth factor signals to direct cells along the monolayer boundary toward open space. Lastly, we found that regulators of cell–cell coordination are growth factor-independent and reorient randomly migrating cells inside the sheet when boundary cells begin to migrate. Thus, cells transition from random to collective migration through a modular control system, whereby growth factor signals convert boundary cells into pioneers, while cells inside the monolayer reorient and follow pioneers through growth factor-independent migration and cell–cell coordination. PMID:19056882
The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery
Späth, Gerald F.; Rachidi, Najma; Prina, Eric
2017-01-01
The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival. PMID:28594938
The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery.
Lamotte, Suzanne; Späth, Gerald F; Rachidi, Najma; Prina, Eric
2017-06-01
The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites' intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host-parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.
Selective Sorting of Cargo Proteins into Bacterial Membrane Vesicles*
Haurat, M. Florencia; Aduse-Opoku, Joseph; Rangarajan, Minnie; Dorobantu, Loredana; Gray, Murray R.; Curtis, Michael A.; Feldman, Mario F.
2011-01-01
In contrast to the well established multiple cellular roles of membrane vesicles in eukaryotic cell biology, outer membrane vesicles (OMV) produced via blebbing of prokaryotic membranes have frequently been regarded as cell debris or microscopy artifacts. Increasingly, however, bacterial membrane vesicles are thought to play a role in microbial virulence, although it remains to be determined whether OMV result from a directed process or from passive disintegration of the outer membrane. Here we establish that the human oral pathogen Porphyromonas gingivalis has a mechanism to selectively sort proteins into OMV, resulting in the preferential packaging of virulence factors into OMV and the exclusion of abundant outer membrane proteins from the protein cargo. Furthermore, we show a critical role for lipopolysaccharide in directing this sorting mechanism. The existence of a process to package specific virulence factors into OMV may significantly alter our current understanding of host-pathogen interactions. PMID:21056982
Gerstein, Aleeza C; Nielsen, Kirsten
2017-04-01
Cryptococcus is predominantly an AIDS-related pathogen that causes significant morbidity and mortality in immunocompromised patients. Research studies have historically focused on understanding how the organism causes human disease through the use of in vivo and in vitro model systems to identify virulence factors. Cryptococcus is not an obligate pathogen, however, as human-human transmission is either absent or rare. Selection in the environment must thus be invoked to shape the evolution of this taxa, and directly influences genotypic and trait diversity. Importantly, the evolution and maintenance of pathogenicity must also stem directly from environmental selection. To that end, here we examine abiotic and biotic stresses in the environment, and discuss how they could shape the factors that are commonly identified as important virulence traits. We identify a number of important unanswered questions about Cryptococcus diversity and evolution that are critical for understanding this deadly pathogen, and discuss how implementation of modern sampling and genomic tools could be utilized to answer these questions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
2017-06-01
protection factors . The success of this research is a direct result of the immense collaboration across a number of institutions that all shared a...at post detonation neutron transport, an exact solution is not needed. Instead, the RPF research campaign uses a statistical-based method through a... factors of selected light vehicles against residual radiation,” United States Army Ballistic Research Laboratory, Aberdeen Proving Ground, MD, 1988
Chun, B H; Bang, W G; Park, Y K; Woo, S K
2001-11-01
The recombinant a and bsubunits for human coagulation factor XIII were transfected into Chinese hamster ovary (CHO) cells. CHO cells were amplified and selected with methotrexate in adherent cultures containing serum, and CHO 1-62 cells were later selected in protein-free medium. To develop a recombinant factor XIII production process in a suspension culture, we have investigated the growth characteristics of CHO cells and the maintenance of factor XIII expression in the culture medium. Suspension adaptation of CHO cells was performed in protein-free medium, GC-CHO-PI, by two methods, such as serum weaning and direct switching from serum containing media to protein-free media. Although the growth of CHO cells in suspension culture was affected initially by serum depletion, cell specific productivity of factor XIII showed only minor changes by the direct switching to protein-free medium during a suspension culture. As for the long-term stability of factor XIII, CHO 1-62 cells showed a stable expression of factor XIII in protein-free condition for 1000 h. These results indicate that the CHO 1-62cells can be adapted to express recombinant human factor XIII in a stable maimer in suspension culture using a protein-free medium. Our results demonstrate that enhanced cell growth in a continuous manner is achievable for factor XIII production in a protein-free medium when a perfusion bioreactor culture system with a spin filter is employed.
Constrained evolution of the sex comb in Drosophila simulans.
Maraqa, M S; Griffin, R; Sharma, M D; Wilson, A J; Hunt, J; Hosken, D J; House, C M
2017-02-01
Male fitness is dependent on sexual traits that influence mate acquisition (precopulatory sexual selection) and paternity (post-copulatory sexual selection), and although many studies have documented the form of selection in one or the other of these arenas, fewer have done it for both. Nonetheless, it appears that the dominant form of sexual selection is directional, although theoretically, populations should converge on peaks in the fitness surface, where selection is stabilizing. Many factors, however, can prevent populations from reaching adaptive peaks. Genetic constraints can be important if they prevent the development of highest fitness phenotypes, as can the direction of selection if it reverses across episodes of selection. In this study, we examine the evidence that these processes influence the evolution of the multivariate sex comb morphology of male Drosophila simulans. To do this, we conduct a quantitative genetic study together with a multivariate selection analysis to infer how the genetic architecture and selection interact. We find abundant genetic variance and covariance in elements of the sex comb. However, there was little evidence for directional selection in either arena. Significant nonlinear selection was detected prior to copulation when males were mated to nonvirgin females, and post-copulation during sperm offence (again with males mated to nonvirgins). Thus, contrary to our predictions, the evolution of the D. simulans sex comb is limited neither by genetic constraints nor by antagonistic selection between pre- and post-copulatory arenas, but nonlinear selection on the multivariate phenotype may prevent sex combs from evolving to reach some fitness maximizing optima. © 2016 The Authors. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.
Hicks, Brian M; Johnson, Wendy; Durbin, C Emily; Blonigen, Daniel M; Iacono, William G; McGue, Matt
2013-02-01
We used a longitudinal twin design to examine selection effects of personality traits at age 11 on high-risk environmental contexts at age 14 and the extent to which these contexts mediated risk for substance abuse at age 17. Socialization at age 11 (willingness to follow rules and endorse conventional values) predicted exposure to contextual risk at age 14. Contextual risk partially mediated the effect of socialization on substance abuse, though socialization also had a direct effect. In contrast, boldness at age 11 (social engagement and assurance, thrill seeking, and stress resilience) also predicted substance abuse directly but was unrelated to contextual risk. There was substantial overlap in the genetic and shared environmental influences on socialization and contextual risk, and genetic risk in socialization contributed to substance abuse indirectly via increased exposure to contextual risk. This suggests that active gene-environment correlations related to individual differences in socialization contributed to an early, high-risk developmental trajectory for adolescent substance abuse. In contrast, boldness appeared to index an independent and direct genetic risk factor for adolescent substance abuse.
Risk factors for human-directed canine aggression in a referral level clinical population.
Lord, M; Casey, R A; Loftus, B A; Blackwell, E J
2017-07-07
Risk factors for human-directed aggression were investigated using retrospective analysis of data from a referral-level clinical behaviour population in the UK. A sample of 200 cases involving human-directed canine aggression and 200 control cases involving no instance of human-directed aggression were selected at random from a population of 746 cases. The final model suggested that clinical cases with human-directed aggression were significantly younger than those presenting with other undesired behaviours (P=0.008) and that male dogs were 1.4 times more likely to be aggressive towards human beings than female dogs (P=0.019). Dogs were 1.7 times more likely to be aggressive towards people if they had attended more than five puppy classes than if they had never attended puppy class (P=0.015) and that dogs were 2.8 times more likely to be aggressive towards human beings if there was another dog between 0 months and 24 months of age in the home (P=0.004). These factors only account for 7 per cent to 10 per cent of the variance between the human-directed aggression population and the control population, but factors such as attendance at puppy classes and numbers of dogs in the household suggest the need for longitudinal studies to investigate temporal relationships.
Zhang, Guomin; Sandanayake, Malindu; Setunge, Sujeeva; Li, Chunqing; Fang, Jun
2017-02-01
Emissions from equipment usage and transportation at the construction stage are classified as the direct emissions which include both greenhouse gas (GHG) and non-GHG emissions due to partial combustion of fuel. Unavailability of a reliable and complete inventory restricts an accurate emission evaluation on construction work. The study attempts to review emission factor standards readily available worldwide for estimating emissions from construction equipment. Emission factors published by United States Environmental Protection Agency (US EPA), Australian National Greenhouse Accounts (AUS NGA), Intergovernmental Panel on Climate Change (IPCC) and European Environmental Agency (EEA) are critically reviewed to identify their strengths and weaknesses. A selection process based on the availability and applicability is then developed to help identify the most suitable emission factor standards for estimating emissions from construction equipment in the Australian context. A case study indicates that a fuel based emission factor is more suitable for GHG emission estimation and a time based emission factor is more appropriate for estimation of non-GHG emissions. However, the selection of emission factor standards also depends on factors like the place of analysis (country of origin), data availability and the scope of analysis. Therefore, suitable modifications and assumptions should be incorporated in order to represent these factors. Copyright © 2016 Elsevier Ltd. All rights reserved.
Karvonen, Anssi; Kristjánsson, Bjarni K; Skúlason, Skúli; Lanki, Maiju; Rellstab, Christian; Jokela, Jukka
2013-06-01
Parasite communities of fishes are known to respond directly to the abiotic environment of the host, for example, to water quality and water temperature. Biotic factors are also important as they affect the exposure profile through heterogeneities in parasite distribution in the environment. Parasites in a particular environment may pose a strong selection on fish. For example, ecological differences in selection by parasites have been hypothesized to facilitate evolutionary differentiation of freshwater fish morphs specializing on different food types. However, as parasites may also respond directly to abiotic environment the parasite risk does not depend only on biotic features of the host environment. It is possible that different morphs experience specific selection gradients by parasites but it is not clear how consistent the selection is when abiotic factors change. We examined parasite pressure in sympatric morphs of threespine stickleback (Gasterosteus aculeatus) across a temperature gradient in two large Icelandic lakes, Myvatn and Thingvallavatn. Habitat-specific temperature gradients in these lakes are opposite. Myvatn lava rock morph lives in a warm environment, while the mud morph lives in the cold. In Thingvallavatn, the lava rock morph lives in a cold environment and the mud morph in a warm habitat. We found more parasites in fish living in higher temperature in both lakes, independent of the fish morph, and this pattern was similar for the two dominating parasite taxa, trematodes and cestodes. However, at the same time, we also found higher parasite abundance in a third morph living in deep cold-water habitat in Thingvallavatn compared to the cold-water lava morph, indicating strong effect of habitat-specific biotic factors. Our results suggest complex interactions between water temperature and biotic factors in determining the parasite community structure, a pattern that may have implications for differentiation of stickleback morphs.
Chauhan, Rinki; Ravi, Janani; Datta, Pratik; Chen, Tianlong; Schnappinger, Dirk; Bassler, Kevin E.; Balázsi, Gábor; Gennaro, Maria Laura
2016-01-01
Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics. PMID:27029515
Allen, Cerisse E; Beldade, Patrícia; Zwaan, Bas J; Brakefield, Paul M
2008-03-26
There is spectacular morphological diversity in nature but lineages typically display a limited range of phenotypes. Because developmental processes generate the phenotypic variation that fuels natural selection, they are a likely source of evolutionary biases, facilitating some changes and limiting others. Although shifts in developmental regulation are associated with morphological differences between taxa, it is unclear how underlying mechanisms affect the rate and direction of evolutionary change within populations under selection. Here we focus on two ecologically relevant features of butterfly wing color patterns, eyespot size and color composition, which are similarly and strongly correlated across the serially repeated eyespots. Though these two characters show similar patterns of standing variation and covariation within a population, they differ in key features of their underlying development. We targeted pairs of eyespots with artificial selection for coordinated (concerted selection) versus independent (antagonistic selection) change in their color composition and size and compared evolutionary responses of the two color pattern characters. The two characters respond to selection in strikingly different ways despite initially similar patterns of variation in all directions present in the starting population. Size (determined by local properties of a diffusing inductive signal) evolves flexibly in all selected directions. However, color composition (determined by a tissue-level response to the signal concentration gradient) evolves only in the direction of coordinated change. There was no independent evolutionary change in the color composition of two eyespots in response to antagonistic selection. Moreover, these differences in the directions of short-term evolutionary change in eyespot size and color composition within a single species are consistent with the observed wing pattern diversity in the genus. Both characters respond rapidly to selection for coordinated change, but there are striking differences in their response to selection for antagonistic, independent change across eyespots. While many additional factors may contribute to both short- and long-term evolutionary response, we argue that the compartmentalization of developmental processes can influence the diversification of serial repeats such as butterfly eyespots, even under strong selection.
Hirano, Koji; Miura, Masahiro
2018-01-07
A 2-pyridone ring is a frequently occurring subunit in natural products, biologically active compounds, and pharmaceutical targets. Thus, the selective synthesis of substituted 2-pyridone derivatives through decoration and/or formation of pyridone rings has been one of the important longstanding subjects in organic synthetic chemistry. This minireview focuses on recent advances in site-selective C-H functionalization on 2-pyridone. The reported procedures are categorized according to the site selectivity that is achieved, and the substrate scope, limitations, mechanism, and controlling factors are briefly summarized.
2017-01-01
A 2-pyridone ring is a frequently occurring subunit in natural products, biologically active compounds, and pharmaceutical targets. Thus, the selective synthesis of substituted 2-pyridone derivatives through decoration and/or formation of pyridone rings has been one of the important longstanding subjects in organic synthetic chemistry. This minireview focuses on recent advances in site-selective C–H functionalization on 2-pyridone. The reported procedures are categorized according to the site selectivity that is achieved, and the substrate scope, limitations, mechanism, and controlling factors are briefly summarized. PMID:29629070
McDevitt, Roland D; Haviland, Amelia M; Lore, Ryan; Laudenberger, Laura; Eisenberg, Matthew; Sood, Neeraj
2014-04-01
To identify the degree of selection into consumer-directed health plans (CDHPs) versus traditional plans over time, and factors that influence choice and temper risk selection. Sixteen large employers offering both CDHP and traditional plans during the 2004–2007 period, more than 200,000 families. We model CDHP choice with logistic regression; predictors include risk scores, in addition to family, choice setting, and plan characteristics. Additional models stratify by account type or single enrollee versus family. Risk scores, family characteristics, and enrollment decisions are derived from medical claims and enrollment files. Interviews with human resources executives provide additional data. CDHP risk scores were 74 percent of traditional plan scores in the first year, and this difference declined over time. Employer contributions to accounts and employee premium savings fostered CDHP enrollment and reduced risk selection. Having to make an active choice of plan increased CDHP enrollment but also increased risk selection. Risk selection was greater for singles than families and did not differ between HRA and HSA-based CDHPs. Risk selection was not severe and it was well managed. Employers have effective methods to encourage CDHP enrollment and temper selection against traditional plans.
Designing Intervention Studies: Selected Populations, Range Restrictions, and Statistical Power
Miciak, Jeremy; Taylor, W. Pat; Stuebing, Karla K.; Fletcher, Jack M.; Vaughn, Sharon
2016-01-01
An appropriate estimate of statistical power is critical for the design of intervention studies. Although the inclusion of a pretest covariate in the test of the primary outcome can increase statistical power, samples selected on the basis of pretest performance may demonstrate range restriction on the selection measure and other correlated measures. This can result in attenuated pretest-posttest correlations, reducing the variance explained by the pretest covariate. We investigated the implications of two potential range restriction scenarios: direct truncation on a selection measure and indirect range restriction on correlated measures. Empirical and simulated data indicated direct range restriction on the pretest covariate greatly reduced statistical power and necessitated sample size increases of 82%–155% (dependent on selection criteria) to achieve equivalent statistical power to parameters with unrestricted samples. However, measures demonstrating indirect range restriction required much smaller sample size increases (32%–71%) under equivalent scenarios. Additional analyses manipulated the correlations between measures and pretest-posttest correlations to guide planning experiments. Results highlight the need to differentiate between selection measures and potential covariates and to investigate range restriction as a factor impacting statistical power. PMID:28479943
Designing Intervention Studies: Selected Populations, Range Restrictions, and Statistical Power.
Miciak, Jeremy; Taylor, W Pat; Stuebing, Karla K; Fletcher, Jack M; Vaughn, Sharon
2016-01-01
An appropriate estimate of statistical power is critical for the design of intervention studies. Although the inclusion of a pretest covariate in the test of the primary outcome can increase statistical power, samples selected on the basis of pretest performance may demonstrate range restriction on the selection measure and other correlated measures. This can result in attenuated pretest-posttest correlations, reducing the variance explained by the pretest covariate. We investigated the implications of two potential range restriction scenarios: direct truncation on a selection measure and indirect range restriction on correlated measures. Empirical and simulated data indicated direct range restriction on the pretest covariate greatly reduced statistical power and necessitated sample size increases of 82%-155% (dependent on selection criteria) to achieve equivalent statistical power to parameters with unrestricted samples. However, measures demonstrating indirect range restriction required much smaller sample size increases (32%-71%) under equivalent scenarios. Additional analyses manipulated the correlations between measures and pretest-posttest correlations to guide planning experiments. Results highlight the need to differentiate between selection measures and potential covariates and to investigate range restriction as a factor impacting statistical power.
Cyclone tolerance in new world arecaceae: biogeographic variation and abiotic natural selection.
Griffith, M Patrick; Noblick, Larry R; Dowe, John L; Husby, Chad E; Calonje, Michael A
2008-10-01
Consistent abiotic factors can affect directional selection; cyclones are abiotic phenomena with near-discrete geographic limits. The current study investigates selective pressure of cyclones on plants at the species level, testing for possible natural selection. New World Arecaceae (palms) are used as a model system, as plants with monopodial, unbranched arborescent form are most directly affected by the selective pressure of wind load. Living specimens of known provenance grown at a common site were affected by the same cyclone. Data on percentage mortality were compiled and analysed in biogeographic and phylogenetic contexts. Palms of cyclone-prone provenance exhibited a much lower (one order of magnitude) range in cyclone tolerance, and significantly lower (P < 0.001) mean percentage mortality than collections from cyclone-free areas. Palms of cyclone-free provenance had much greater variation in tolerance, and significantly greater mean percentage mortality. A test for serial independence recovered no significant phylogenetic autocorrelation of percentage mortality. Variation in cyclone tolerance in New World Arecaceae correlates with biogeography, and is not confounded with phylogeny. These results suggest natural selection of cyclone tolerance in cyclone-prone areas.
James P. Barnett; James B. Baker
1991-01-01
Southern pines can be regenerated naturally, by clearcutting, seedtree, shelterwood, or selection reproduction culling methods, or artificially, by direct seeding or by planting either container or bareroot seedlings. All regeneration methods have inherent advantages: and disadvantages; thus, land managers must consider many factors before deciding on a specific method...
Estes, Chris; Lee, Christopher
2009-01-01
Objectives. We quantified the economic cost of selected environmental factors among North Carolina children living in substandard housing. Methods. We gathered data on direct medical care costs for specific childhood medical conditions associated with environmental factors commonly found in substandard housing. Medical claims data for 2006 and 2007 were obtained from BlueCross BlueShield of North Carolina and the North Carolina Department of Health and Human Services. Indirect costs were based in part on nonmedical data obtained from several previous studies. Results. Total (direct and indirect) costs for the conditions assessed exceeded $92 million in 2006 and $108 million in 2007. Neurobehavioral conditions contributed to more than 52% of all costs, followed by lead poisoning (20%) and respiratory conditions (12%). Neurobehavioral conditions were the largest contributor to direct medical costs (44%), followed by respiratory conditions (38%) and accidental burns and falls (10%). Conclusions. Direct and indirect costs associated with environmental factors appear to be increasing at about twice the rate of medical inflation. More aggressive policies and funding are needed to reduce the substantial financial impact of childhood illnesses associated with substandard housing in North Carolina. PMID:19890173
Santos, Daniel; Gonzalez-Perez, Francisco; Navarro, Xavier
2016-01-01
Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo. PMID:27867665
Research on the Decision Method of Maintenance Materials Direct Supply
NASA Astrophysics Data System (ADS)
Zhu, Qian; Shi, Xiaopei; Liu, Shenyang; Luo, Guangxu; Zhu, Chen
2018-05-01
With the further development of civil military integration, more and more maintenance materials will be supplied by the factory directly. Aiming at the mode condition of maintenance materials factory direct supply, maintenance materials needs equipment support in the process of facing a number of direct supply manufacturers how to decision problems, using AHP, considering many factors optimization of direct supply manufacturers involved, and gives the weights of the evaluation indexes of the direct supply manufacturers to evaluate optimal. Finally, with 4 straights for the manufacturer as an example, considering the various evaluation indexes to carry out evaluation and drawing the correct evaluation of direct supply manufacturers, the best manufacturers direct supply is selected. An example shows that, AHP can provide scientific and theoretical basis to materials factory direct supply security.
Chen, Chung-De; Huang, Yen-Chieh; Chiang, Hsin-Lin; Hsieh, Yin-Cheng; Guan, Hong-Hsiang; Chuankhayan, Phimonphan; Chen, Chun-Jung
2014-09-01
Optimization of the initial phasing has been a decisive factor in the success of the subsequent electron-density modification, model building and structure determination of biological macromolecules using the single-wavelength anomalous dispersion (SAD) method. Two possible phase solutions (φ1 and φ2) generated from two symmetric phase triangles in the Harker construction for the SAD method cause the well known phase ambiguity. A novel direct phase-selection method utilizing the θ(DS) list as a criterion to select optimized phases φ(am) from φ1 or φ2 of a subset of reflections with a high percentage of correct phases to replace the corresponding initial SAD phases φ(SAD) has been developed. Based on this work, reflections with an angle θ(DS) in the range 35-145° are selected for an optimized improvement, where θ(DS) is the angle between the initial phase φ(SAD) and a preliminary density-modification (DM) phase φ(DM)(NHL). The results show that utilizing the additional direct phase-selection step prior to simple solvent flattening without phase combination using existing DM programs, such as RESOLVE or DM from CCP4, significantly improves the final phases in terms of increased correlation coefficients of electron-density maps and diminished mean phase errors. With the improved phases and density maps from the direct phase-selection method, the completeness of residues of protein molecules built with main chains and side chains is enhanced for efficient structure determination.
Study on Quality Indicator System of Rhythmic Gymnasts in Analytic Hierarchy Process
NASA Astrophysics Data System (ADS)
Luo, Lin
2017-08-01
The rhythmic gymnastics (RG) is a sport item with the direct aim of winning as well as a good ornamental value. The scientific selection by the rhythmic gymnasts is necessary for the success, and also the beginning for the scientific training of the gymnasts in their special training stage. According to RG characteristics and the physical characteristics of the gymnasts, also in combination with the investigations & interviews to the coaches who have years of training experience in RG, the experts & scholars on RG study & teaching in universities, and by referring to relevant documents, this paper established the quality indicator system in analytic hierarchy process (AHP). We summarized and selected several indicators obviously influencing the RG training and divided them into the three types of factors: physical factors, flexibility & strength factors, and speed & dexterity factors, according to which 12 specific indicators, their weights and comprehensive evaluation coefficients. Based on these indicators, we established the quality indicator system of the gymnasts, and developed corresponding software system, providing scientific theoretical basis & practical application basis for the selection & evaluation of the gymnasts.
Hicks, Brian M.; Johnson, Wendy; Durbin, C. Emily; Blonigen, Daniel M.; Iacono, William G.; McGue, Matt
2012-01-01
We used a longitudinal twin design to examine selection effects of personality traits at age 11 on high-risk environmental contexts at age 14, and the extent to which these contexts mediated risk for substance abuse at age 17. Socialization at age 11—willingness to follow rules and endorse conventional values—predicted exposure to contextual risk at age 14. Contextual risk partially mediated the effect of socialization on substance abuse, though socialization also had a direct effect. In contrast, boldness at age 11—social engagement and assurance, thrill-seeking, and stress resilience— also predicted substance abuse directly, but was unrelated to contextual risk. There was substantial overlap in the genetic and shared environmental influences on socialization and contextual risk, and genetic risk in socialization contributed to substance abuse indirectly via increased exposure to contextual risk. This suggests that active gene-environment correlations related to individual differences in socialization contributed to an early, high-risk developmental trajectory for adolescent substance abuse. In contrast, boldness appeared to index an independent and direct genetic risk factor for adolescent substance abuse. PMID:23398757
2001-08-01
Benefit the Direct and Indirect Methods 16 Figure Figure 1: Military Exchanges’ Food Sales for Fiscal Year 1999 6 Abbreviations AAFES Army and Air Force...military installation. As the franchisee , the exchange service builds and operates the restaurants and directly employs and trains the personnel. In...they do not routinely develop a business case analysis, which would include weighing financial benefits with other factors, when determining which
Load emphasizes muscle effort minimization during selection of arm movement direction
2012-01-01
Background Directional preferences during center-out horizontal shoulder-elbow movements were previously established for both the dominant and non-dominant arm with the use of a free-stroke drawing task that required random selection of movement directions. While the preferred directions were mirror-symmetrical in both arms, they were attributed to a tendency specific for the dominant arm to simplify control of interaction torque by actively accelerating one joint and producing largely passive motion at the other joint. No conclusive evidence has been obtained in support of muscle effort minimization as a contributing factor to the directional preferences. Here, we tested whether distal load changes directional preferences, making the influence of muscle effort minimization on the selection of movement direction more apparent. Methods The free-stroke drawing task was performed by the dominant and non-dominant arm with no load and with 0.454 kg load at the wrist. Motion of each arm was limited to rotation of the shoulder and elbow in the horizontal plane. Directional histograms of strokes produced by the fingertip were calculated to assess directional preferences in each arm and load condition. Possible causes for directional preferences were further investigated by studying optimization across directions of a number of cost functions. Results Preferences in both arms to move in the diagonal directions were revealed. The previously suggested tendency to actively accelerate one joint and produce passive motion at the other joint was supported in both arms and load conditions. However, the load increased the tendency to produce strokes in the transverse diagonal directions (perpendicular to the forearm orientation) in both arms. Increases in required muscle effort caused by the load suggested that the higher frequency of movements in the transverse directions represented increased influence of muscle effort minimization on the selection of movement direction. This interpretation was supported by cost function optimization results. Conclusions While without load, the contribution of muscle effort minimization was minor, and therefore, not apparent, the load revealed this contribution by enhancing it. Unlike control of interaction torque, the revealed tendency to minimize muscle effort was independent of arm dominance. PMID:23035925
The Key Factors Analysis of Palisades Temperature in Deep Open-pit Mine
NASA Astrophysics Data System (ADS)
Wang, Yuan; Du, Cuifeng; Jin, Wenbo; Wang, Puyu
2018-01-01
In order to study the key factors of palisades temperature field in a deep open-pit mine in the natural environment, the influence of natural factors on the palisades temperature in a deep open-pit mine were analysed based on the principle of heat transfer. Four typical places with different ways of solar radiation were selected to carry out the field test. The results show that solar radiation, atmospheric temperature, and wind speed are three main factors affecting the temperature of palisades and that the direct sunlight plays a leading role. The time period of the sun shining directly on the shady slope of the palisades is short because of blocking effect, whose temperature changes in a smaller scale. At the same time, the sun slope of the palisades suffers from the solar radiation for a long time, whose temperature changes in a larger scale, and the variation is similar to the air temperature.
Fisher, R P; Topper, J N; Clayton, D A
1987-07-17
Selective transcription of human mitochondrial DNA requires a transcription factor (mtTF) in addition to an essentially nonselective RNA polymerase. Partially purified mtTF is able to sequester promoter-containing DNA in preinitiation complexes in the absence of mitochondrial RNA polymerase, suggesting a DNA-binding mechanism for factor activity. Functional domains, required for positive transcriptional regulation by mtTF, are identified within both major promoters of human mtDNA through transcription of mutant promoter templates in a reconstituted in vitro system. These domains are essentially coextensive with DNA sequences protected from nuclease digestion by mtTF-binding. Comparison of the sequences of the two mtTF-responsive elements reveals significant homology only when one sequence is inverted; the binding sites are in opposite orientations with respect to the predominant direction of transcription. Thus mtTF may function bidirectionally, requiring additional protein-DNA interactions to dictate transcriptional polarity. The mtTF-responsive elements are arrayed as direct repeats, separated by approximately 80 bp within the displacement-loop region of human mitochondrial DNA; this arrangement may reflect duplication of an ancestral bidirectional promoter, giving rise to separate, unidirectional promoters for each strand.
Gravi- and photostimuli in moss protonema growth movements
NASA Astrophysics Data System (ADS)
Demkiv, O. T.; Kordyum, E. L.; Khorkavtsiv, Ya D.; Kardash, O. R.; Chaban, Ch. I.
Moss protonemal growth direction is controlled by at least three factors, photo-, gravi- and autotropism. It is possible to experimentally separate these factors and to control selectively their morphological appearance. In darkness protonema grow negatively gravitropically, and unilateral illumination initiated positive phototropism. Red light suppressed auto- and gravitropism, blue light suppressed only gravitropism. Green light allowed both gravi- and autotropism. The effect of light on gravitropism might involve changes in starch synthesis.
Gravi- and photostimuli in moss protonema growth movements.
Demkiv, O T; Kordyum, E L; Khorkavtsiv YaD; Kardash, O R; Chaban ChI
1998-01-01
Moss protonemal growth direction is controlled by at least three factors, photo-, gravi- and autotropism. It is possible to experimentally separate these factors and to control selectively their morphological appearance. In darkness protonema grow negatively gravitropically, and unilateral illumination initiated positive phototropism. Red light suppressed auto- and gravitropism, blue light suppressed only gravitropism. Green light allowed both gravi- and autotropism. The effect of light on gravitropism might involve changes in starch synthesis.
McDevitt, Roland D; Haviland, Amelia M; Lore, Ryan; Laudenberger, Laura; Eisenberg, Matthew; Sood, Neeraj
2014-01-01
Objective To identify the degree of selection into consumer-directed health plans (CDHPs) versus traditional plans over time, and factors that influence choice and temper risk selection. Data Sources/Study Setting Sixteen large employers offering both CDHP and traditional plans during the 2004–2007 period, more than 200,000 families. Study Design We model CDHP choice with logistic regression; predictors include risk scores, in addition to family, choice setting, and plan characteristics. Additional models stratify by account type or single enrollee versus family. Data Collection/Extraction Methods Risk scores, family characteristics, and enrollment decisions are derived from medical claims and enrollment files. Interviews with human resources executives provide additional data. Principal Findings CDHP risk scores were 74 percent of traditional plan scores in the first year, and this difference declined over time. Employer contributions to accounts and employee premium savings fostered CDHP enrollment and reduced risk selection. Having to make an active choice of plan increased CDHP enrollment but also increased risk selection. Risk selection was greater for singles than families and did not differ between HRA and HSA-based CDHPs. Conclusions Risk selection was not severe and it was well managed. Employers have effective methods to encourage CDHP enrollment and temper selection against traditional plans. PMID:24800305
SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis.
Muhar, Matthias; Ebert, Anja; Neumann, Tobias; Umkehrer, Christian; Jude, Julian; Wieshofer, Corinna; Rescheneder, Philipp; Lipp, Jesse J; Herzog, Veronika A; Reichholf, Brian; Cisneros, David A; Hoffmann, Thomas; Schlapansky, Moritz F; Bhat, Pooja; von Haeseler, Arndt; Köcher, Thomas; Obenauf, Anna C; Popow, Johannes; Ameres, Stefan L; Zuber, Johannes
2018-05-18
Defining direct targets of transcription factors and regulatory pathways is key to understanding their roles in physiology and disease. We combined SLAM-seq [thiol(SH)-linked alkylation for the metabolic sequencing of RNA], a method for direct quantification of newly synthesized messenger RNAs (mRNAs), with pharmacological and chemical-genetic perturbation in order to define regulatory functions of two transcriptional hubs in cancer, BRD4 and MYC, and to interrogate direct responses to BET bromodomain inhibitors (BETis). We found that BRD4 acts as general coactivator of RNA polymerase II-dependent transcription, which is broadly repressed upon high-dose BETi treatment. At doses triggering selective effects in leukemia, BETis deregulate a small set of hypersensitive targets including MYC. In contrast to BRD4, MYC primarily acts as a selective transcriptional activator controlling metabolic processes such as ribosome biogenesis and de novo purine synthesis. Our study establishes a simple and scalable strategy to identify direct transcriptional targets of any gene or pathway. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
A survey of industry practices regarding shielding of substations against direct lightning strokes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mousa, A.M.; Wehling, R.J.
1993-01-01
A survey of industry practices regarding shielding of substations against direct lightning strokes is presented and analyzed. The survey is based on responses from 114 companies including consultants and utilities both from within and from outside North America. The survey identifies the shielding design methods in use, the factors affecting the selection of a shielding method, the shielding design criteria and the governing factors, the performance of the different shielding methods and miscellaneous related aspects. The survey revealed a large number (35) of shielding failure incidents; 34 of which occurred in systems designed using either the fixed shielding angle methodmore » or Wagner's 1942 method.« less
School-Based Clinics That Work.
ERIC Educational Resources Information Center
Public Health Service (DHHS), Rockville, MD.
This paper describes a small set of successful school-based clinics (SBCs) that provide primary health care services for the underserved and identifies factors contributing to their success. Six sites were selected on the basis of three general criteria: (1) direct involvement between the SBC and a federally-funded community health center (CHC);…
Investigation of Intra-Firm Upward Mobility among Selected Skilled Craftsmen.
ERIC Educational Resources Information Center
Barnes, Clarence Harold
The objective was to investigate the factors which influence the upward movement of skilled craftsmen within the firm. Particular attention was directed to the importance of apprenticeship training in causing intrafirm upgrading; that is: were apprentice-trained craftsmen more inclined to be promoted than nonapprentice-trained craftsmen. Observed…
CURRENT PRACTICES OBSERVED IN DESIGN AND DRAFTING OCCUPATIONS.
ERIC Educational Resources Information Center
SQUIRES, CARL E.
DATA WHICH HAD SIGNIFICANCE FOR DESIGN AND DRAFTING CURRICULUMS WERE COLLECTED BY DIRECT OBSERVATION OF 21 DESIGN AND DRAFTING FACTORS WITHIN 16 SELECTED INDUSTRIAL COMPANIES EMPLOYING 869 DESIGNERS AND DRAFTSMEN. OBSERVATIONS COVERED (1) THE NUMBER OF DESIGN AND DRAFTING EMPLOYEES, (2) THE SYSTEM OF DRAFTING ROOM ORGANIZATION, (3) JOB…
Demanet, Jelle; Verbruggen, Frederick; Liefooghe, Baptist; Vandierendonck, André
2010-06-01
The present study investigated the relative contribution of bottom-up and top-down control to task selection in the voluntary task-switching (VTS) procedure. In order to manipulate the efficiency of top-down control, a concurrent working memory load was imposed during VTS. In three experiments, bottom-up factors, such as stimulus repetitions, repetition of irrelevant information, and stimulus-task associations, were introduced in order to investigate their influence on task selection. We observed that the tendency to repeat tasks was stronger under load, suggesting that top-down control counteracts the automatic tendency to repeat tasks. The results also indicated that task selection can be guided by several elements in the environment, but that only the influence of stimulus repetitions depends on the efficiency of top-down control. The theoretical implications of these findings are discussed within the interplay between top-down and bottom-up control that underlies the voluntary selection of tasks.
Health information technology vendor selection strategies and total factor productivity.
Ford, Eric W; Huerta, Timothy R; Menachemi, Nir; Thompson, Mark A; Yu, Feliciano
2013-01-01
The aim of this study was to compare health information technology (HIT) adoption strategies' relative performance on hospital-level productivity measures. The American Hospital Association's Annual Survey and Healthcare Information and Management Systems Society Analytics for fiscal years 2002 through 2007 were used for this study. A two-stage approach is employed. First, a Malmquist model is specified to calculate hospital-level productivity measures. A logistic regression model is then estimated to compare the three HIT adoption strategies' relative performance on the newly constructed productivity measures. The HIT vendor selection strategy impacts the amount of technological change required of an organization but does not appear to have either a positive or adverse impact on technical efficiency or total factor productivity. The higher levels in technological change experienced by hospitals using the best of breed and best of suite HIT vendor selection strategies may have a more direct impact on the organization early on in the process. However, these gains did not appear to translate into either increased technical efficiency or total factor productivity during the period studied. Over a longer period, one HIT vendor selection strategy may yet prove to be more effective at improving efficiency and productivity.
Karvonen, Anssi; Kristjánsson, Bjarni K; Skúlason, Skúli; Lanki, Maiju; Rellstab, Christian; Jokela, Jukka
2013-01-01
Parasite communities of fishes are known to respond directly to the abiotic environment of the host, for example, to water quality and water temperature. Biotic factors are also important as they affect the exposure profile through heterogeneities in parasite distribution in the environment. Parasites in a particular environment may pose a strong selection on fish. For example, ecological differences in selection by parasites have been hypothesized to facilitate evolutionary differentiation of freshwater fish morphs specializing on different food types. However, as parasites may also respond directly to abiotic environment the parasite risk does not depend only on biotic features of the host environment. It is possible that different morphs experience specific selection gradients by parasites but it is not clear how consistent the selection is when abiotic factors change. We examined parasite pressure in sympatric morphs of threespine stickleback (Gasterosteus aculeatus) across a temperature gradient in two large Icelandic lakes, Myvatn and Thingvallavatn. Habitat-specific temperature gradients in these lakes are opposite. Myvatn lava rock morph lives in a warm environment, while the mud morph lives in the cold. In Thingvallavatn, the lava rock morph lives in a cold environment and the mud morph in a warm habitat. We found more parasites in fish living in higher temperature in both lakes, independent of the fish morph, and this pattern was similar for the two dominating parasite taxa, trematodes and cestodes. However, at the same time, we also found higher parasite abundance in a third morph living in deep cold–water habitat in Thingvallavatn compared to the cold-water lava morph, indicating strong effect of habitat-specific biotic factors. Our results suggest complex interactions between water temperature and biotic factors in determining the parasite community structure, a pattern that may have implications for differentiation of stickleback morphs. PMID:23789063
Wang, Haiyong; Yang, Liu; Wu, Kuo; Li, Guanghui
2014-01-16
Transcriptional engineering has presented a strong ability of phenotypic improvement in microorganisms. However, it could not be directly applied to Actinoplanes teichomyceticus L-27 because of the paucity of endogenous transcription factors in the strain. In this study, exogenous transcription factors were rationally selected and transcriptional engineering was carried out to increase the productivity of teicoplanin in L-27. It was illuminated that the σ(HrdB) molecules shared strong similarity of amino acid sequences among some genera of actinomycetes. Combining this advantage with the ability of transcriptional engineering, exogenous sigma factor σ(HrdB) molecules were rationally selected and engineered to improve L-27. hrdB genes from Actinoplanes missouriensis 431, Micromonospora aurantiaca ATCC 27029 and Salinispora arenicola CNS-205 were selected based on molecular evolutionary analysis. Random mutagenesis, DNA shuffling and point mutation were subsequently performed to generate diversified mutants. A recombinant was identified through screening program, yielding 5.3 mg/ml of teicoplanin, over 2-fold compared to that of L-27. More significantly, the engineered strain presented a good performance in 500-l pilot scale fermentation, which meant its valuable potential application in industry. Through rational selection and engineering of exogenous transcriptional factor, we have extended the application of transcriptional engineering. To our knowledge, it is the first time to focus on the related issue. In addition, possessing the advantage of efficient metabolic perturbation in transcription level, this strategy could be useful in analyzing metabolic and physiological mechanisms of strains, especially those with the only information on taxonomy.
Charles Darwin's Origin of Species, directional selection, and the evolutionary sciences today.
Kutschera, Ulrich
2009-11-01
The book On the Origin of Species, published in November 1859, is an "abstract" without references, compiled by Charles Darwin from a much longer manuscript entitled "Natural Selection." Here, I summarize the five theories that can be extracted from Darwin's monograph, explain the true meaning of the phrase "struggle for life" (i.e., competition and cooperation), and outline Darwin's original concept of natural selection in populations of animals and plants. Since neither Darwin nor Alfred R. Wallace distinguished between stabilizing and directional natural selection, the popular argument that "selection only eliminates but is not creative" is still alive today. However, I document that August Weismann (Die Bedeutung der sexuellen Fortpflanzung für die Selektions-Theorie. Gustav Fischer-Verlag, Jena, 1886) and Ivan Schmalhausen (Factors of evolution. The theory of stabilizing selection. The Blackiston Company, Philadelphia, 1949) provided precise definitions for directional (dynamic) selection in nature and illustrate this "Weismann-Schmalhausen principle" with respect to the evolutionary development of novel phenotypes. Then, the modern (synthetic) theory of biological evolution that is based on the work of Theodosius Dobzhansky (Genetics and the origin of species. Columbia University Press, New York, 1937) and others, and the expanded version of this system of theories, are outlined. Finally, I document that symbiogenesis (i.e., primary endosymbiosis, a process that gave rise to the first eukaryotic cells), ongoing directional natural selection, and the dynamic Earth (plate tectonics, i.e., geological events that both created and destroyed terrestrial and aquatic habitats) were the key processes responsible for the documented macroevolutionary patterns in all five kingdoms of life. Since the evolutionary development of the earliest archaic bacteria more than 3,500 mya, the biosphere of our dynamic planet has been dominated by prokaryotic microbes. Eubacteria, Archaea, and Cyanobacteria are, together with eukaryotic microorganisms (marine phytoplankton, etc.), the hidden "winners" in the Darwinian struggle for existence in nature.
Charles Darwin's Origin of Species, directional selection, and the evolutionary sciences today
NASA Astrophysics Data System (ADS)
Kutschera, Ulrich
2009-11-01
The book On the Origin of Species, published in November 1859, is an “abstract” without references, compiled by Charles Darwin from a much longer manuscript entitled “Natural Selection.” Here, I summarize the five theories that can be extracted from Darwin’s monograph, explain the true meaning of the phrase “struggle for life” (i.e., competition and cooperation), and outline Darwin’s original concept of natural selection in populations of animals and plants. Since neither Darwin nor Alfred R. Wallace distinguished between stabilizing and directional natural selection, the popular argument that “selection only eliminates but is not creative” is still alive today. However, I document that August Weismann ( Die Bedeutung der sexuellen Fortpflanzung für die Selektions-Theorie. Gustav Fischer-Verlag, Jena, 1886) and Ivan Schmalhausen ( Factors of evolution. The theory of stabilizing selection. The Blackiston Company, Philadelphia, 1949) provided precise definitions for directional (dynamic) selection in nature and illustrate this “Weismann-Schmalhausen principle” with respect to the evolutionary development of novel phenotypes. Then, the modern (synthetic) theory of biological evolution that is based on the work of Theodosius Dobzhansky ( Genetics and the origin of species. Columbia University Press, New York, 1937) and others, and the expanded version of this system of theories, are outlined. Finally, I document that symbiogenesis (i.e., primary endosymbiosis, a process that gave rise to the first eukaryotic cells), ongoing directional natural selection, and the dynamic Earth (plate tectonics, i.e., geological events that both created and destroyed terrestrial and aquatic habitats) were the key processes responsible for the documented macroevolutionary patterns in all five kingdoms of life. Since the evolutionary development of the earliest archaic bacteria more than 3,500 mya, the biosphere of our dynamic planet has been dominated by prokaryotic microbes. Eubacteria, Archaea, and Cyanobacteria are, together with eukaryotic microorganisms (marine phytoplankton, etc.), the hidden “winners” in the Darwinian struggle for existence in nature.
Selection of Drought Tolerant Maize Hybrids Using Path Coefficient Analysis and Selection Index.
Dao, Abdalla; Sanou, Jacob; V S Traore, Edgar; Gracen, Vernon; Danquah, Eric Y
2017-01-01
In drought-prone environments, direct selection for yield is not adequate because of the variable environment and genotype x environment interaction. Therefore, the use of secondary traits in addition to yield has been suggested. The relative usefulness of secondary traits as indirect selection criteria for maize grain yield is determined by the magnitudes of their genetic variance, heritability and genetic correlation with the grain yield. Forty eight testcross hybrids derived from lines with different genetic background and geographical origins plus 7 checks were evaluated in both well-watered and water-stressed conditions over two years for grain yield and secondary traits to determine the most appropriate secondary traits and select drought tolerant hybrids. Study found that broad-sense heritability of grain yield and Ear Per Plant (EPP) increased under drought stress. Ear aspect (EASP) and ear height (EHT) had larger correlation coefficients and direct effect on grain yield but in opposite direction, negative and positive respectively. Traits like, EPP, Tassel Size (TS) and Plant Recovery (PR) contributed to increase yield via EASP by a large negative indirect effect. Under drought stress, EHT had positive and high direct effect and negative indirect effect via plant height on grain yield indicating that the ratio between ear and plant heights (R-EPH) was associated to grain yield. Path coefficient analysis showed that traits EPP, TS, PR, EASP, R-EPH were important secondary traits in the present experiment. These traits were used in a selection index to classify hybrids according to their performance under drought. The selection procedure included also a Relative Decrease in Yield (RDY) index. Some secondary traits reported as significant selection criteria for selection under drought stress were not finally established in the present study. This is because the relationship between grain and secondary traits can be affected by various factors including germplasm, environment and applied statistical analysis. Therefore, different traits and selection procedure should be applied in the selection process of drought tolerant genotypes for diverse genetic materials and growing conditions.
NASA Astrophysics Data System (ADS)
Zhao, C. S.; Shao, N. F.; Yang, S. T.; Xiang, H.; Lou, H. Z.; Sun, Y.; Yang, Z. Y.; Zhang, Y.; Yu, X. Y.; Zhang, C. B.; Yu, Q.
2018-01-01
The world's aquatic ecosystems yield numerous vital services, which are essential to human existence but have deteriorated seriously in recent years. By studying the mechanisms of interaction between ecosystems and habitat processes, the constraining factors can be identified, and this knowledge can be used to improve the success rate of ecological restoration initiatives. At present, there is insufficient data on the link between hydrological, water quality factors and the changes in the structure of aquatic communities to allow any meaningful study of driving factors of aquatic ecosystems. In this study, the typical monitoring stations were selected by fuzzy clustering analysis based on the spatial and temporal distribution characteristics of water ecology in Jinan City, the first pilot city for the construction of civilized aquatic ecosystems in China. The dominant species identification model was used to identify the dominant species of the aquatic community. The driving effect of hydrological and water quality factors on dominant species was analyzed by Canonical Correspondence Analysis. Then, the principal factors of aquatic ecosystem dependence were selected. The results showed that there were 10 typical monitoring stations out of 59 monitoring sites, which were representative of aquatic ecosystems, 9 dominant fish species, and 20 dominant invertebrate species. The selection of factors for aquatic ecosystem dependence in Jinan were highly influenced by its regional conditions. Chemical environmental parameters influence the temporal and spatial variation of invertebrate much more than that of fish in Jinan City. However, the methodologies coupling typical monitoring stations selection, dominant species determination and driving factors identification were certified to be a cost-effective way, which can provide in-deep theoretical and technical directions for the restoration of aquatic ecosystems elsewhere.
Cost Analysis for Large Civil Transport Rotorcraft
NASA Technical Reports Server (NTRS)
Coy, John J.
2006-01-01
This paper presents cost analysis of purchase price and DOC+I (direct operating cost plus interest) that supports NASA s study of three advanced rotorcraft concepts that could enter commercial transport service within 10 to 15 years. The components of DOC+I are maintenance, flight crew, fuel, depreciation, insurance, and finance. The cost analysis aims at VTOL (vertical takeoff and landing) and CTOL (conventional takeoff and landing) aircraft suitable for regional transport service. The resulting spreadsheet-implemented cost models are semi-empirical and based on Department of Transportation and Army data from actual operations of such aircraft. This paper describes a rationale for selecting cost tech factors without which VTOL is more costly than CTOL by a factor of 10 for maintenance cost and a factor of two for purchase price. The three VTOL designs selected for cost comparisons meet the mission requirement to fly 1,200 nautical miles at 350 knots and 30,000 ft carrying 120 passengers. The lowest cost VTOL design is a large civil tilt rotor (LCTR) aircraft. With cost tech factors applied, the LCTR is reasonably competitive with the Boeing 737-700 when operated in economy regional service following the business model of the selected baseline operation, that of Southwest Airlines.
Goossens, V; Grooten, J; De Vos, K; Fiers, W
1995-01-01
Tumor necrosis factor (TNF) is selectively cytotoxic to some types of tumor cells in vitro and exerts antitumor activity in vivo. Reactive oxygen intermediates (ROIs) have been implicated in the direct cytotoxic activity of TNF. By using confocal microscopy, flow cytometry, and the ROI-specific probe dihydrorhodamine 123, we directly demonstrate that intracellular ROIs are formed after TNF stimulation. These ROIs are observed exclusively under conditions where cells are sensitive to the cytotoxic activity of TNF, suggesting a direct link between both phenomena. ROI scavengers, such as butylated hydroxyanisole, effectively blocked the formation of free radicals and arrested the cytotoxic response, confirming that the observed ROIs are cytocidal. The mitochondrial glutathione system scavenges the major part of the produced ROIs, an activity that could be blocked by diethyl maleate; under these conditions, TNF-induced ROIs detectable by dihydrorhodamine 123 oxidation were 5- to 20-fold higher. Images Fig. 1 Fig. 4 PMID:7667254
Demographic drivers of age-dependent sexual selection.
Martin, A M; Festa-Bianchet, M; Coltman, D W; Pelletier, F
2016-07-01
Sexual selection has a critical role in evolution, and it is fundamental to identify what ecological factors drive its variation. Disentangling the ecological correlates of sexual selection over the long term, however, is challenging and has rarely been done in nature. We sought to assess how demographic changes influenced the intensity, direction and form of sexual selection and whether selective pressures varied with age. We tested whether breeder sex ratio, number of competitors and age structure influenced selection differentials on horn length of wild bighorn rams (Ovis canadensis) of different age classes on Ram Mountain, Alberta. We used 21 years of data including a detailed pedigree, demographic parameters and repeated morphological measurements. Sexual selection on horn length of males of all ages was directional and positive. Selection intensity increased with the number of competitors, reflecting male-male encounter rate during the rut, but was independent of breeder sex ratio or age structure. This result can also be linked to changes in population size because the number of competitors was highly correlated to total number of sheep. This demographic effect likely arises from age-dependent mating tactics. Males aged 2-4 years are weakly competitive and experienced stronger sexual selection as they accounted for a greater proportion of all males. Selection experienced by mature males appeared independent of demography. Our study provides a rare description of the demographic determinants of sexual selection in nature. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.
Drosophila Heartless Acts with Heartbroken/Dof in Muscle Founder Differentiation
Dutta, Devkanya; Shaw, Sanjeev; Maqbool, Tariq; Pandya, Hetal
2005-01-01
The formation of a multi-nucleate myofibre is directed, in Drosophila, by a founder cell. In the embryo, founders are selected by Notch-mediated lateral inhibition, while during adult myogenesis this mechanism of selection does not appear to operate. We show, in the muscles of the adult abdomen, that the Fibroblast growth factor pathway mediates founder cell choice in a novel manner. We suggest that the developmental patterns of Heartbroken/Dof and Sprouty result in defining the domain and timing of activation of the Fibroblast growth factor receptor Heartless in specific myoblasts, thereby converting them into founder cells. Our results point to a way in which muscle differentiation could be initiated and define a critical developmental function for Heartbroken/Dof in myogenesis. PMID:16207075
Tulchinsky, Alexander Y; Johnson, Norman A; Watt, Ward B; Porter, Adam H
2014-11-01
Postzygotic isolation between incipient species results from the accumulation of incompatibilities that arise as a consequence of genetic divergence. When phenotypes are determined by regulatory interactions, hybrid incompatibility can evolve even as a consequence of parallel adaptation in parental populations because interacting genes can produce the same phenotype through incompatible allelic combinations. We explore the evolutionary conditions that promote and constrain hybrid incompatibility in regulatory networks using a bioenergetic model (combining thermodynamics and kinetics) of transcriptional regulation, considering the bioenergetic basis of molecular interactions between transcription factors (TFs) and their binding sites. The bioenergetic parameters consider the free energy of formation of the bond between the TF and its binding site and the availability of TFs in the intracellular environment. Together these determine fractional occupancy of the TF on the promoter site, the degree of subsequent gene expression and in diploids, and the degree of dominance among allelic interactions. This results in a sigmoid genotype-phenotype map and fitness landscape, with the details of the shape determining the degree of bioenergetic evolutionary constraint on hybrid incompatibility. Using individual-based simulations, we subjected two allopatric populations to parallel directional or stabilizing selection. Misregulation of hybrid gene expression occurred under either type of selection, although it evolved faster under directional selection. Under directional selection, the extent of hybrid incompatibility increased with the slope of the genotype-phenotype map near the derived parental expression level. Under stabilizing selection, hybrid incompatibility arose from compensatory mutations and was greater when the bioenergetic properties of the interaction caused the space of nearly neutral genotypes around the stable expression level to be wide. F2's showed higher hybrid incompatibility than F1's to the extent that the bioenergetic properties favored dominant regulatory interactions. The present model is a mechanistically explicit case of the Bateson-Dobzhansky-Muller model, connecting environmental selective pressure to hybrid incompatibility through the molecular mechanism of regulatory divergence. The bioenergetic parameters that determine expression represent measurable properties of transcriptional regulation, providing a predictive framework for empirical studies of how phenotypic evolution results in epistatic incompatibility at the molecular level in hybrids. Copyright © 2014 by the Genetics Society of America.
Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers.
Loft, Anne; Forss, Isabel; Siersbæk, Majken Storm; Schmidt, Søren Fisker; Larsen, Ann-Sofie Bøgh; Madsen, Jesper Grud Skat; Pisani, Didier F; Nielsen, Ronni; Aagaard, Mads Malik; Mathison, Angela; Neville, Matt J; Urrutia, Raul; Karpe, Fredrik; Amri, Ez-Zoubir; Mandrup, Susanne
2015-01-01
Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced browning of human adipocytes activates a comprehensive gene program that leads to increased mitochondrial oxidative capacity. Once induced, this gene program and oxidative capacity are maintained independently of rosiglitazone, suggesting that additional browning factors are activated. Browning triggers reprogramming of PPARγ binding, leading to the formation of PPARγ "superenhancers" that are selective for brown-in-white (brite) adipocytes. These are highly associated with key brite-selective genes. Based on such an association, we identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning, including the increase in mitochondrial oxidative capacity. KLF11 is directly induced by PPARγ and appears to cooperate with PPARγ in a feed-forward manner to activate and maintain the brite-selective gene program. © 2015 Loft et al.; Published by Cold Spring Harbor Laboratory Press.
USDA-ARS?s Scientific Manuscript database
SNP effects estimated in genomic selection programs allow for the prediction of direct genomic values (DGV) both at genome-wide and chromosomal level. As a consequence, genome-wide (G_GW) or chromosomal (G_CHR) correlation matrices between genomic predictions for different traits can be calculated. ...
Women in Management: Leadership Theories, Research Results, and Future Directions.
ERIC Educational Resources Information Center
Putnam, Linda L.
This review of the literature about women in management advocates the pursuit of research on women executives as unique components in the organizational setting, with the warning that careful and unremitting attention be paid to the selection of theoretical perspectives. It examines trait and role theory, and discusses such factors as…
Instructional Computing. An Action Guide for Educators.
ERIC Educational Resources Information Center
Dennis, J. Richard; Kansky, Robert J.
This book is directed to any educator who is interested in the use of the computer to improve classroom instruction. It is a book about the materials, human factors, and decision-making procedures that make up the instructional application of computers. This document's single goal is to promote educators' thoughtful selection and use of both…
Gyurcsányi, R E; Pergel, E; Nagy, R; Kapui, I; Lan, B T; Tóth, K; Bitter, I; Lindner, E
2001-05-01
Scanning electrochemical microscopy (SECM) supplemented with potentiometric measurements was used to follow the time-dependent buildup of a steady-state diffusion layer at the aqueous-phase boundary of lead ion-selective electrodes (ISEs). Differential pulse voltammetry is adapted to SECM for probing the local concentration profiles at the sample side of solvent polymeric membranes. Major factors affecting the membrane transport-related surface concentrations were identified from SECM data and the potentiometric transients obtained under different experimental conditions (inner filling solution composition, membrane thickness, surface pretreatment). The amperometrically determined surface concentrations correlated well with the lower detection limits of the lead ion-selective electrodes.
Endogenous circulating sympatholytic factor in orthostatic intolerance
NASA Technical Reports Server (NTRS)
Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.
2000-01-01
Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.
Wheelwright, Nathaniel T; Keller, Lukas F; Postma, Erik
2014-11-01
The heritability (h(2) ) of fitness traits is often low. Although this has been attributed to directional selection having eroded genetic variation in direct proportion to the strength of selection, heritability does not necessarily reflect a trait's additive genetic variance and evolutionary potential ("evolvability"). Recent studies suggest that the low h(2) of fitness traits in wild populations is caused not by a paucity of additive genetic variance (VA ) but by greater environmental or nonadditive genetic variance (VR ). We examined the relationship between h(2) and variance-standardized selection intensities (i or βσ ), and between evolvability (IA :VA divided by squared phenotypic trait mean) and mean-standardized selection gradients (βμ ). Using 24 years of data from an island population of Savannah sparrows, we show that, across diverse traits, h(2) declines with the strength of selection, whereas IA and IR (VR divided by squared trait mean) are independent of the strength of selection. Within trait types (morphological, reproductive, life-history), h(2) , IA , and IR are all independent of the strength of selection. This indicates that certain traits have low heritability because of increased residual variance due to the age at which they are expressed or the multiple factors influencing their expression, rather than their association with fitness. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.
Simultaneous inhibition assay for human and microbial kinases via MALDI-MS/MS.
Smith, Anne Marie E; Brennan, John D
2014-03-03
Selective inhibition of one kinase over another is a critical issue in drug development. For antimicrobial development, it is particularly important to selectively inhibit bacterial kinases, which can phosphorylate antimicrobial compounds such as aminoglycosides, without affecting human kinases. Previous work from our group showed the development of a MALDI-MS/MS assay for the detection of small molecule modulators of the bacterial aminoglycoside kinase APH3'IIIa. Herein, we demonstrate the development of an enhanced kinase MALDI-MS/MS assay involving simultaneous assaying of two kinase reactions, one for APH3'IIIa, and the other for human protein kinase A (PKA), which leads to an output that provides direct information on selectivity and mechanism of action. Specificity of the respective enzyme substrates were verified, and the assay was validated through generation of Z'-factors of 0.55 for APH3'IIIa with kanamycin and 0.60 for PKA with kemptide. The assay was used to simultaneously screen a kinase-directed library of mixtures of ten compounds each against both enzymes, leading to the identification of selective inhibitors for each enzyme as well as one non-selective inhibitor following mixture deconvolution. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Lee, Yuh-Shiow
2013-01-01
This study examined how encoding and retrieval factors affected directed forgetting costs and benefits in an item-method procedure. Experiment 1 used a typical item-method procedure and revealed a levels-of-processing effect in overall recall. However, the deep encoding condition showed a smaller directed forgetting effect than the shallow encoding conditions. More importantly, "remember" (R) words were selectively rehearsed as indicated by greater recall from the primacy portion of the list and more apt to be recalled before "forget" (F) words. Experiment 2 showed that a deep encoding operation reduced directed forgetting costs and that directed forgetting benefits occurred only when R words were recalled before F words. These findings supported the hypotheses that encoding manipulation affected directed forgetting costs and that directed forgetting benefits were associated with output order bias. Results were discussed in terms of mechanisms that produce item-method directed forgetting.
Treatment of renal cell carcinoma: Current status and future directions.
Barata, Pedro C; Rini, Brian I
2017-11-01
Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents-including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor-have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society. © 2017 American Cancer Society.
Wang, Jianli; Schmitz, Norbert; Smailes, Elizabeth; Sareen, Jitender; Patten, Scott
2010-08-01
To investigate the relationships between workplace psychosocial factors, work/family conflicts, depression, and health-related presenteeism in a sample of employees who were randomly selected from the communities. A cross-sectional study of 4032 employees representative of the working population aged 25 to 64 years in Alberta, Canada. Data about workplace characteristics, depression, and health-related presenteeism were collected through telephone. In the participants, 47.3% and 42.9% reported some degree of impaired job performance in completing work and avoiding distraction, respectively. Major depression is the strongest factor associated with avoiding distraction. Job strain and effort-reward imbalance seemed to affect job performance through severity of depression but not major depression. Negative work environment may directly and indirectly affect job performance. Workplace health promotion activities should target organizational factors such as job strain and effort-reward imbalance and work/family conflicts so as to reduce the risk of depression and the direct and indirect effects of these risk factors and depression on productivity.
Krause, Jason; Frost, Carminita L
2018-04-01
Cancer procoagulant (CP), a direct activator of coagulation factor X, is among one of the tumour cell products or activities which may promote fibrin formation and has been suggested to be selectively associated with the malignant phenotype. At present, the most reliable assay for the quantification of CP activity is the three-stage chromogenic assay which utilises the ability of CP to activate factor X. In this assay, the activation of factor X leads to the formation of activated thrombin from prothrombin and the eventual hydrolyses of a thrombin chromogenic substrate which contains a p-nitroaniline leaving group. The complexity of the three-stage chromogenic assay suggests a need for a direct method of assaying CP activity. This study focuses on the design of a fluorogenic substrate that would enable the direct quantification of CP activity. The results of the study show two promising substrates for the determination of CP activity: Boc-PQVR-AMC and PQVR-AMC. Further analysis showed that Boc-PQVR-AMC could be excluded as a potential substrate for CP since it was also cleaved by collagenase.
2014-01-01
Background Transcriptional engineering has presented a strong ability of phenotypic improvement in microorganisms. However, it could not be directly applied to Actinoplanes teichomyceticus L-27 because of the paucity of endogenous transcription factors in the strain. In this study, exogenous transcription factors were rationally selected and transcriptional engineering was carried out to increase the productivity of teicoplanin in L-27. Results It was illuminated that the σHrdB molecules shared strong similarity of amino acid sequences among some genera of actinomycetes. Combining this advantage with the ability of transcriptional engineering, exogenous sigma factor σHrdB molecules were rationally selected and engineered to improve L-27. hrdB genes from Actinoplanes missouriensis 431, Micromonospora aurantiaca ATCC 27029 and Salinispora arenicola CNS-205 were selected based on molecular evolutionary analysis. Random mutagenesis, DNA shuffling and point mutation were subsequently performed to generate diversified mutants. A recombinant was identified through screening program, yielding 5.3 mg/ml of teicoplanin, over 2-fold compared to that of L-27. More significantly, the engineered strain presented a good performance in 500-l pilot scale fermentation, which meant its valuable potential application in industry. Conclusions Through rational selection and engineering of exogenous transcriptional factor, we have extended the application of transcriptional engineering. To our knowledge, it is the first time to focus on the related issue. In addition, possessing the advantage of efficient metabolic perturbation in transcription level, this strategy could be useful in analyzing metabolic and physiological mechanisms of strains, especially those with the only information on taxonomy. PMID:24428890
A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice
Illendula, Anuradha; Pulikkan, John A.; Zong, Hongliang; Grembecka, Jolanta; Xue, Liting; Sen, Siddhartha; Zhou, Yunpeng; Boulton, Adam; Kuntimaddi, Aravinda; Gao, Yan; Rajewski, Roger A.; Guzman, Monica L.; Castilla, Lucio H.; Bushweller, John H.
2015-01-01
Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFβ-SMMHC (core binding factor β and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFβ for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers. PMID:25678665
Gehring, Marta; Taylor, Rod S; Mellody, Marie; Casteels, Brigitte; Piazzi, Angela; Gensini, Gianfranco; Ambrosio, Giuseppe
2013-11-15
Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe.
Graveland, Haitske; Wagenaar, Jaap A; Heesterbeek, Hans; Mevius, Dik; van Duijkeren, Engeline; Heederik, Dick
2010-06-08
Recently a specific MRSA sequence type, ST398, emerged in food production animals and farmers. Risk factors for carrying MRSA ST398 in both animals and humans have not been fully evaluated. In this cross-sectional study, we investigated factors associated with MRSA colonization in veal calves and humans working and living on these farms. A sample of 102 veal calf farms were randomly selected and visited from March 2007-February 2008. Participating farmers were asked to fill in a questionnaire (n = 390) to identify potential risk factors. A nasal swab was taken from each participant. Furthermore, nasal swabs were taken from calves (n = 2151). Swabs were analysed for MRSA by selective enrichment and suspected colonies were confirmed as MRSA by using slide coagulase test and PCR for presence of the mecA-gene. Spa types were identified and a random selection of each spa type was tested with ST398 specific PCR. The Sequence Type of non ST398 strains was determined. Data were analyzed using logistic regression analysis. Human MRSA carriage was strongly associated with intensity of animal contact and with the number of MRSA positive animals on the farm. Calves were more often carrier when treated with antibiotics, while farm hygiene was associated with a lower prevalence of MRSA. This is the first study showing direct associations between animal and human carriage of ST398. The direct associations between animal and human MRSA carriage and the association between MRSA and antimicrobial use in calves implicate prudent use of antibiotics in farm animals.
Zandberg, Lies; Gort, Gerrit; van Oers, Kees; Hinde, Camilla A
2017-10-01
Under sexual selection, mate preferences can evolve for traits advertising fitness benefits. Observed mating patterns (mate choice) are often assumed to represent preference, even though they result from the interaction between preference, sampling strategy and environmental factors. Correlating fitness with mate choice instead of preference will therefore lead to confounded conclusions about the role of preference in sexual selection. Here we show that direct fitness benefits underlie mate preferences for genetic characteristics in a unique experiment on wild great tits. In repeated mate preference tests, both sexes preferred mates that had similar heterozygosity levels to themselves, and not those with which they would optimise offspring heterozygosity. In a subsequent field experiment where we cross fostered offspring, foster parents with more similar heterozygosity levels had higher reproductive success, despite the absence of assortative mating patterns. These results support the idea that selection for preference persists despite constraints on mate choice. © 2017 The Authors Ecology Letters published by CNRS and John Wiley & Sons Ltd.
Charvet, Christine J.; Finlay, Barbara L.
2012-01-01
Brain size, body size, developmental length, life span, costs of raising offspring, behavioral complexity, and social structures are correlated in mammals due to intrinsic life-history requirements. Dissecting variation and direction of causation in this web of relationships often draw attention away from the factors that correlate with basic life parameters. We consider the “social brain hypothesis,” which postulates that overall brain and the isocortex are selectively enlarged to confer social abilities in primates, as an example of this enterprise and pitfalls. We consider patterns of brain scaling, modularity, flexibility of brain organization, the “leverage,” and direction of selection on proposed dimensions. We conclude that the evidence supporting selective changes in isocortex or brain size for the isolated ability to manage social relationships is poor. Strong covariation in size and developmental duration coupled with flexible brains allow organisms to adapt in variable social and ecological environments across the life span and in evolution. PMID:22230623
Direct access: factors that affect physical therapist practice in the state of Ohio.
McCallum, Christine A; DiAngelis, Tom
2012-05-01
Direct access to physical therapist services is permitted by law in the majority of states and across all practice settings. Ohio enacted such legislation in 2004; however, it was unknown how direct access had affected actual clinical practice. The purpose of this study was to describe physical therapist and physical therapist practice environment factors that affect direct access practice. A 2-phase, mixed-method descriptive study was conducted. In the first phase, focus group interviews with 32 purposively selected physical therapists were completed, which resulted in 8 themes for an electronically distributed questionnaire. In the second phase, survey questionnaires were distributed to physical therapists with an e-mail address on file with the Ohio licensing board. An adjusted return rate of 23% was achieved. Data were analyzed for descriptive statistics. A constant comparative method assessed open-ended questions for common themes and patterns. Thirty-one percent of the respondents reported using direct access in physical therapist practice; however, 80% reported they would practice direct access if provided the opportunity. Physical therapists who practiced direct access were more likely to be in practice 6 years or more and hold advanced degrees beyond the entry level, were American Physical Therapy Association members, and had supportive management and organizational practice policies. The direct access physical therapist practice was generally a locally owned suburban private practice or a school-based clinic that saw approximately 6% to 10% of its patients by direct access. The majority of patients treated were adults with musculoskeletal or neuromuscular impairments. Nonresponse from e-mail may be associated with sample frame bias. Implementation of a direct access physical therapist practice model is evident in Ohio. Factors related to reimbursement and organizational policy appear to impede the process.
Ebrahimpour, Anahita; Vaghari-Tabari, Mostafa; Qujeq, Durdi; Moein, Soheila; Moazezi, Zoleikha
2018-05-05
Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue. Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used. Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients. Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Retinal Origin of Direction Selectivity in the Superior Colliculus
Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron; Koren, David; Jin, Yanjiao; Liu, Xiaorong; Wei, Wei; Cang, Jianhua
2017-01-01
Detecting visual features in the environment such as motion direction is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. Here, we optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly-tuned retinal ganglion cells. The direction selective retinal input is linearly amplified by the intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using 2-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC, and reveal a central visual deficit as a consequence of altered feature selectivity in the retina. PMID:28192394
Risk factors of postthrombotic syndrome before and after deep venous thrombosis treatment.
Strijkers, Rob Hw; de Wolf, Mark Af; Wittens, Cees Ha
2017-07-01
Postthrombotic syndrome is the most common complication after deep venous thrombosis. Postthrombotic syndrome is a debilitating disease and associated with decreased quality of life and high healthcare costs. Postthrombotic syndrome is a chronic disease, and causative treatment options are limited. Prevention of postthrombotic syndrome is therefore very important. Not all patients develop postthrombotic syndrome. Risk factors have been identified to try to predict the risk of developing postthrombotic syndrome. Age, gender, and recurrent deep venous thrombosis are factors that cannot be changed. Deep venous thrombosis location and extent seem to predict severity of postthrombotic syndrome and are potentially suitable as patient selection criteria. Residual thrombosis and reflux are known to increase the incidence of postthrombotic syndrome, but are of limited use. More recently developed treatment options for deep venous thrombosis, such as new oral factor X inhibitors and catheter-directed thrombolysis, are available at the moment. Catheter-directed thrombolysis shows promising results in reducing the incidence of postthrombotic syndrome after deep venous thrombosis. The role of new oral factor X inhibitors in preventing postthrombotic syndrome is still to be determined.
Environmental Adaptation Contributes to Gene Polymorphism across the Arabidopsis thaliana Genome
Lee, Cheng-Ruei
2012-01-01
The level of within-species polymorphism differs greatly among genes in a genome. Many genomic studies have investigated the relationship between gene polymorphism and factors such as recombination rate or expression pattern. However, the polymorphism of a gene is affected not only by its physical properties or functional constraints but also by natural selection on organisms in their environments. Specifically, if functionally divergent alleles enable adaptation to different environments, locus-specific polymorphism may be maintained by spatially heterogeneous natural selection. To test this hypothesis and estimate the extent to which environmental selection shapes the pattern of genome-wide polymorphism, we define the "environmental relevance" of a gene as the proportion of genetic variation explained by environmental factors, after controlling for population structure. We found substantial effects of environmental relevance on patterns of polymorphism among genes. In addition, the correlation between environmental relevance and gene polymorphism is positive, consistent with the expectation that balancing selection among heterogeneous environments maintains genetic variation at ecologically important genes. Comparison of the gene ontology annotations shows that genes with high environmental relevance are enriched in unknown function categories. These results suggest an important role for environmental factors in shaping genome-wide patterns of polymorphism and indicate another direction of genomic study. PMID:22798389
Benabarre, Sergio; Olivera, Javier; Lorente, Teófilo; Rodriguez, Mariano; Barros-Loscertales, Alfonso; Pelegrín, Carmelo; Claver, Paula; Galindo, Izarbe; Labarta, María; Rodriguez, Jara
2014-06-01
Mortality risk factors have attracted great research interest in recent years. Physical illness is strongly associated with mortality risk in elderly people. Furthermore, a relationship between mortality risk and psychiatric disease in the elderly has gained research interest. This is a prospective longitudinal multicenter study. A sample of 324 participants was selected as a representative sample of community members aged 65 years and older and living in Huesca (Spain). The following information was collected: affiliation data, severity of physical illness, psychosocial, and psychiatric factors. Statistical analyses were completed with a multivariate analysis in order to control possible confounding variables related to mortality. Of the initially selected sample, 293 participants were assessed. Sixty-four participants died (21.8%, 95% CI [16.9%, 26.7%]), 5.3% annual rate, and 46.1% showed symptomatology of mental disorders. Older people have eight times greater risk of mortality. The risk increased 53 times in patients affected by several physical illness. No relationship between cognitive dysfunction and depressive symptomatology was observed. In fact, physical condition was associated with depression, and the percentage of participants with depressive symptoms increased according to the severity of physical illness. Severity of physical illness and age are independently and directly associated with mortality in the elderly people. Therefore, severity of physical illness seems to be a crucial factor in the bi-directional association between mortality and depression, acting as a risk factor independently for both. So the relationship between depression and mortality can be affected by the severity of physical illness.
Valenzuela, Carlos Y
2013-01-01
The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift as the most important evolutionary factors. The most conspicuous feature of evolution is the genomic stability during paleontological eras and lack of variation among taxa; 98% or more of nucleotide sites are monomorphic within a species. NTE explains this homology by random fixation of neutral bases and negative selection (purifying selection) that does not contribute either to evolution or polymorphisms. Purifying selection is insufficient to account for this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE) included negative selection with coefficients as low as mutation rate. These NTE and N-NTE propositions are thermodynamically (tendency to random distributions, second law), biotically (recurrent mutation), logically and mathematically (resilient equilibria instead of fixation by drift) untenable. Recurrent forward and backward mutation and random fluctuations of base frequencies alone in a site make life organization and fixations impossible. Drift is not a directional evolutionary factor, but a directional tendency of matter-energy processes (second law) which threatens the biotic organization. Drift cannot drive evolution. In a site, the mutation rates among bases and selection coefficients determine the resilient equilibrium frequency of bases that genetic drift cannot change. The expected neutral random interaction among nucleotides is zero; however, huge interactions and periodicities were found between bases of dinucleotides separated by 1, 2... and more than 1,000 sites. Every base is co-adapted with the whole genome. Neutralists found that neutral evolution is independent of population size (N); thus neutral evolution should be independent of drift, because drift effect is dependent upon N. Also, chromosome size and shape as well as protein size are far from random.
ERIC Educational Resources Information Center
Karrick, Brant
1998-01-01
Studies intonation trends of wind instrumentalists with regard to harmonic intervals, including factors such as tuning system, location, interval type, direction of deviation from equal temperament, and group. Compares the performance of two groups, professionals and advanced students. Reports findings and discusses similarities to and differences…
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-16
... consumption. (See Section for ``all flow meters, weigh III.B.6). scales, pressure gauges and thermometers... apportioning consumption. (See Section III.B.8). factors by using direct measurements using gas flow meters or... consumption. Revising 40 CFR 98.94(c)(2)(i) to allow reporters to select a period of the reporting year and...
Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9.
Huang, Hua; Kapeli, Katannya; Jin, Wenhao; Wong, Yuk Peng; Arumugam, Thiruma Valavan; Koh, Joanne Huifen; Srimasorn, Sumitra; Mallilankaraman, Karthik; Chua, John Jia En; Yeo, Gene W; Soong, Tuck Wah
2018-05-04
Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of voltage-gated calcium channel CaV1.3 are subject to brain-selective A-to-I RNA editing by ADAR2. Here, we show that editing of CaV1.3 mRNA is dependent on a 40 bp RNA duplex formed between exon 41 and an evolutionarily conserved editing site complementary sequence (ECS) located within the preceding intron. Heterologous expression of a mouse minigene that contained the ECS, intermediate intronic sequence and exon 41 with ADAR2 yielded robust editing. Interestingly, editing of CaV1.3 was potently inhibited by serine/arginine-rich splicing factor 9 (SRSF9). Mechanistically, the inhibitory effect of SRSF9 required direct RNA interaction. Selective down-regulation of SRSF9 in neurons provides a basis for the neuron-specific editing of CaV1.3 transcripts.
Dynamic nigrostriatal dopamine biases action selection
Howard, Christopher D.; Li, Hao; Geddes, Claire E.; Jin, Xin
2017-01-01
Summary Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here, we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons, or optogenetic manipulation of dopamine concentration, alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions and have important implications for neurological disorders including Parkinson’s disease and substance dependence. PMID:28285820
Dynamic Nigrostriatal Dopamine Biases Action Selection.
Howard, Christopher D; Li, Hao; Geddes, Claire E; Jin, Xin
2017-03-22
Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn't reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson's disease and substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.
Brödel, Andreas K; Jaramillo, Alfonso; Isalan, Mark
2017-09-01
Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene-or gene circuit function-that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ∼7 weeks.
Novel harmonic regularization approach for variable selection in Cox's proportional hazards model.
Chu, Ge-Jin; Liang, Yong; Wang, Jia-Xuan
2014-01-01
Variable selection is an important issue in regression and a number of variable selection methods have been proposed involving nonconvex penalty functions. In this paper, we investigate a novel harmonic regularization method, which can approximate nonconvex Lq (1/2 < q < 1) regularizations, to select key risk factors in the Cox's proportional hazards model using microarray gene expression data. The harmonic regularization method can be efficiently solved using our proposed direct path seeking approach, which can produce solutions that closely approximate those for the convex loss function and the nonconvex regularization. Simulation results based on the artificial datasets and four real microarray gene expression datasets, such as real diffuse large B-cell lymphoma (DCBCL), the lung cancer, and the AML datasets, show that the harmonic regularization method can be more accurate for variable selection than existing Lasso series methods.
Field tuning the g factor in InAs nanowire double quantum dots.
Schroer, M D; Petersson, K D; Jung, M; Petta, J R
2011-10-21
We study the effects of magnetic and electric fields on the g factors of spins confined in a two-electron InAs nanowire double quantum dot. Spin sensitive measurements are performed by monitoring the leakage current in the Pauli blockade regime. Rotations of single spins are driven using electric-dipole spin resonance. The g factors are extracted from the spin resonance condition as a function of the magnetic field direction, allowing determination of the full g tensor. Electric and magnetic field tuning can be used to maximize the g-factor difference and in some cases altogether quench the electric-dipole spin resonance response, allowing selective single spin control. © 2011 American Physical Society
Patient Selection for Drip and Ship Thrombolysis in Acute Ischemic Stroke
Lyerly, Michael J.; Albright, Karen C.; Boehme, Amelia K.; Shahripour, Reza Bavarsad; Donnelly, John P.; Houston, James T.; Rawal, Pawan V.; Kapoor, Niren; Alvi, Muhammad; Sisson, April; Alexandrov, Anne W.; Alexandrov, Andrei V.
2017-01-01
Objectives The drip and ship model is a method used to deliver thrombolysis to acute stroke patients in facilities lacking onsite neurology coverage. We sought to determine whether our drip and ship population differs from patients treated directly at our stroke center (direct presenters). Methods We retrospectively reviewed consecutive patients who received thrombolysis at an outside facility with subsequent transfer to our center between 2009 and 2011. Patients received thrombolysis after telephone consultation with a stroke specialist. We examined demographics, vascular risk factors, laboratory values, and stroke severity in drip and ship patients compared with direct presenters. Results Ninety-six patients were identified who received thrombolysis by drip and ship compared with 212 direct presenters. The two groups did not differ with respect to sex, ethnicity, vascular risk factors, or admission glucose. The odds ratio (OR) of arriving at our hospital as a drip and ship for someone 80 years or older was 0.31 (95% confidence interval [CI] 0.15–0.61, P < 0.001). Only 21% of drip and ship patients were black versus 38% of direct presenters (OR 0.434, 95% CI 0.25–0.76, P = 0.004). Even after stratifying by age (<80 vs ≥80), a smaller proportion of drip and ship patients were black (OR 0.44, 95% CI 0.24–0.81, P = 0.008). Furthermore, we found that fewer black patients with severe strokes arrived by drip and ship (OR 0.33, 95% CI 0.11–0.98, P = 0.0028). Conclusions Our study showed that a smaller proportion of blacks and older adults arrived at our center by the drip and ship model. This may reflect differences in how patients are selected for thrombolysis and transfer to a higher level of care. PMID:26192934
Patient Selection for Drip and Ship Thrombolysis in Acute Ischemic Stroke.
Lyerly, Michael J; Albright, Karen C; Boehme, Amelia K; Shahripour, Reza Bavarsad; Donnelly, John P; Houston, James T; Rawal, Pawan V; Kapoor, Niren; Alvi, Muhammad; Sisson, April; Alexandrov, Anne W; Alexandrov, Andrei V
2015-07-01
The drip and ship model is a method used to deliver thrombolysis to acute stroke patients in facilities lacking onsite neurology coverage. We sought to determine whether our drip and ship population differs from patients treated directly at our stroke center (direct presenters). We retrospectively reviewed consecutive patients who received thrombolysis at an outside facility with subsequent transfer to our center between 2009 and 2011. Patients received thrombolysis after telephone consultation with a stroke specialist. We examined demographics, vascular risk factors, laboratory values, and stroke severity in drip and ship patients compared with direct presenters. Ninety-six patients were identified who received thrombolysis by drip and ship compared with 212 direct presenters. The two groups did not differ with respect to sex, ethnicity, vascular risk factors, or admission glucose. The odds ratio (OR) of arriving at our hospital as a drip and ship for someone 80 years or older was 0.31 (95% confidence interval [CI] 0.15-0.61, P < 0.001). Only 21% of drip and ship patients were black versus 38% of direct presenters (OR 0.434, 95% CI 0.25-0.76, P = 0.004). Even after stratifying by age (<80 vs ≥80), a smaller proportion of drip and ship patients were black (OR 0.44, 95% CI 0.24-0.81, P = 0.008). Furthermore, we found that fewer black patients with severe strokes arrived by drip and ship (OR 0.33, 95% CI 0.11-0.98, P = 0.0028). Our study showed that a smaller proportion of blacks and older adults arrived at our center by the drip and ship model. This may reflect differences in how patients are selected for thrombolysis and transfer to a higher level of care.
Cryogenic Etching of High Aspect Ratio 400 nm Pitch Silicon Gratings.
Miao, Houxun; Chen, Lei; Mirzaeimoghri, Mona; Kasica, Richard; Wen, Han
2016-10-01
The cryogenic process and Bosch process are two widely used processes for reactive ion etching of high aspect ratio silicon structures. This paper focuses on the cryogenic deep etching of 400 nm pitch silicon gratings with various etching mask materials including polymer, Cr, SiO 2 and Cr-on-polymer. The undercut is found to be the key factor limiting the achievable aspect ratio for the direct hard masks of Cr and SiO 2 , while the etch selectivity responds to the limitation of the polymer mask. The Cr-on-polymer mask provides the same high selectivity as Cr and reduces the excessive undercut introduced by direct hard masks. By optimizing the etching parameters, we etched a 400 nm pitch grating to ≈ 10.6 μ m depth, corresponding to an aspect ratio of ≈ 53.
Bender, Angela D; Filmer, Hannah L; Garner, K G; Naughtin, Claire K; Dux, Paul E
2016-11-01
The abilities to select appropriate responses and suppress unwanted actions are key executive functions that enable flexible and goal-directed behavior. However, to date it has been unclear whether these two cognitive operations tap a common action control resource or reflect two distinct processes. In the present study, we used an individual differences approach to examine the underlying relationships across seven paradigms that varied in their response selection and response inhibition requirements: stop-signal, go-no-go, Stroop, flanker, single-response selection, psychological refractory period, and attentional blink tasks. A confirmatory factor analysis suggested that response inhibition and response selection are separable, with stop-signal and go-no-go task performance being related to response inhibition, and performance in the psychological refractory period, Stroop, single-response selection, and attentional blink tasks being related to response selection. These findings provide evidence in support of the hypothesis that response selection and response inhibition reflect two distinct cognitive operations.
Tsai, Ming-Tien; Tsai, Ling-Long
2005-11-01
Nursing practise plays an important role in transferring nursing knowledge to nursing students. From the related literature review, prior knowledge will affect how learners gain new knowledge. There has been no direct examination of the prior knowledge interaction effect on students' performance and its influence on nursing students when evaluating the knowledge transfer success factors. This study explores (1) the critical success factors in transferring nursing knowledge, (2) the impact of prior knowledge when evaluating the success factors for transferring nursing knowledge. This research utilizes in-depth interviews to probe the initial success factor phase. A total of 422 valid questionnaires were conducted by the authors. The data were analysed by comparing the mean score and t-test between two groups. Seventeen critical success factors were identified by the two groups of students. Twelve items were selected to examine the diversity in the two groups. Students with prior knowledge were more independent than the other group. They also preferred self-directed learning over students without prior knowledge. Students who did not have prior knowledge were eager to take every opportunity to gain experience and more readily adopted new knowledge.
[Concepts in anticoagulant therapy - past, present, and future].
Graf, L
2012-11-01
The understanding of the clotting system emerged in parallel to the development of anticoagulants. In contrast to vitamin K-antagonists and heparins that where discovered by chance, new anticoagulants have been systematically designed to specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and thrombin play a crucial role within the new cell-based model of hemostasis. Thus it is obvious that FXa and thrombin turned out to be ideal targets for anticoagulation. The proof of the concept of selective inhibition of thrombin and FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole group of new oral anticoagulants has been licensed: the direct FXa-inhibitors rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from the so far licensed products mainly in pharmacokinetics are in an advanced phase of development. A further innovative concept of anticoagulation that entered its clinical phase of development is the inhibition of factor VIII. Other new concepts such as inhibition of initiation of coagulation by blocking factor VIIa, inhibition of contact factor XII, or inhibition of factor IX are in an early phase of development.
Evaluating foodservice software: a suggested approach.
Fowler, K D
1986-09-01
In an era of cost containment, the computer has become a viable management tool. Its use in health care has demonstrated accelerated growth in recent years, and a literature review supports an increased trend in this direction. Foodservice, which is a major cost center, is no exception to this predicted trend. Because software has proliferated, foodservice managers and dietitians are experiencing growing concern about how to evaluate the numerous software packages from which to choose. A suggested approach to evaluating software is offered to dietitians and managers alike to lessen the confusion in software selection and to improve the system satisfaction level post-purchase. Steps of the software evaluatory approach include: delineation of goals, assessment of needs, assignment of value weight factors, development of a vendor checklist, survey of vendors by means of the vendor checklist and elimination of inappropriate systems, thorough development of the request for proposal (RFP) for submission to the selected vendors, an analysis of the returned RFPs in terms of system features and cost factors, and selection of the system(s) for implementation.
Factors influencing implementation of a preschool-based physical activity intervention
Lau, Erica Y.; Saunders, Ruth P.; Beets, Michael W.; Cai, Bo; Pate, Russell R.
2017-01-01
Abstract Examining factors that influence implementation of key program components that underlie an intervention’s success provides important information to inform the development of effective dissemination strategies. We examined direct and indirect effects of preschool capacity, quality of prevention support system and teacher characteristics on implementation levels of a component, called Move Outside (i.e., preschool classroom teachers to provide at least 40 min of outdoor recess per day), that was fundamental to the success of a preschool-based physical activity intervention. Level of implementation, defined as the percent of daily goal met for the Move Outside component, was assessed via direct observation. Items assessing preschool capacity, quality of prevention support system and teacher characteristics were selected from surveys and an environmental checklist completed by preschool directors and teachers. Preschool classroom was used as the unit of analysis (Year 1: n = 19; Year 2: n = 17). Results from Bayesian path analyses showed that the three factors were not significantly associated with level of implementation in Year 1, but preschool capacity was directly associated with level of implementation in Year 2 (β= 0.528, 95% CI: 0.134, 0.827). The current findings suggest that factors that influence level of implementation appear to differ as an intervention evolved over time. PMID:28158420
DOE Office of Scientific and Technical Information (OSTI.GOV)
Biswas, Kaushik; Shrestha, Som S.; Bhandari, Mahabir S.
In the United States, commercial buildings accounted for about 19 percent of the total primary energy consumption in 2012. Further, 29 percent of the site energy in commercial buildings was consumed for space heating and cooling. Applying insulation materials to building envelopes is an effective way of reducing energy consumption for heating and cooling, and limiting the negative environmental impacts from the buildings sector. While insulation materials have a net positive impact on the environment due to reduced energy consumption, they also have some negative impacts associated with their 'embodied energy'. The total lifetime environmental impacts of insulation materials aremore » a summation of: (1) direct impacts due to their embodied energy, and (2) indirect or impacts avoided due to the reduced building energy consumption. Here, assessments of the lifetime environmental impacts of selected insulation materials are presented. Direct and indirect environmental impact factors were estimated for the cradle-to-grave insulation life cycle stages. Impact factors were calculated for two categories: primary energy consumption and global warming potential. The direct impact factors were calculated using data from existing literature and a life cycle assessment software. The indirect impact factors were calculated through simulations of a set of standard whole-building models.« less
Biswas, Kaushik; Shrestha, Som S.; Bhandari, Mahabir S.; ...
2015-12-12
In the United States, commercial buildings accounted for about 19 percent of the total primary energy consumption in 2012. Further, 29 percent of the site energy in commercial buildings was consumed for space heating and cooling. Applying insulation materials to building envelopes is an effective way of reducing energy consumption for heating and cooling, and limiting the negative environmental impacts from the buildings sector. While insulation materials have a net positive impact on the environment due to reduced energy consumption, they also have some negative impacts associated with their 'embodied energy'. The total lifetime environmental impacts of insulation materials aremore » a summation of: (1) direct impacts due to their embodied energy, and (2) indirect or impacts avoided due to the reduced building energy consumption. Here, assessments of the lifetime environmental impacts of selected insulation materials are presented. Direct and indirect environmental impact factors were estimated for the cradle-to-grave insulation life cycle stages. Impact factors were calculated for two categories: primary energy consumption and global warming potential. The direct impact factors were calculated using data from existing literature and a life cycle assessment software. The indirect impact factors were calculated through simulations of a set of standard whole-building models.« less
Rabara, Roel C; Tripathi, Prateek; Lin, Jun; Rushton, Paul J
2013-02-15
Drought is one of the important environmental factors affecting crop production worldwide and therefore understanding the molecular response of plant to stress is an important step in crop improvement. WRKY transcription factors are one of the 10 largest transcription factor families across the green lineage. In this study, highly upregulated dehydration-induced WRKY and enzyme-coding genes from tobacco and soybean were selected from microarray data for promoter analyses. Putative stress-related cis-regulatory elements such as TGACG motif, ABRE-like elements; W and G-like sequences were identified by an in silico analyses of promoter region of the selected genes. GFP quantification of transgenic BY-2 cell culture showed these promoters direct higher expression in-response to 100 μM JA treatment compared to 100 μM ABA, 10% PEG and 85 mM NaCl treatments. Thus promoter activity upon JA treatment and enrichment of MeJA-responsive elements in the promoter of the selected genes provides insights for these genes to be jasmonic acid responsive with potential of mediating cross-talk during dehydration responses. Copyright © 2013 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Casagli, N.; Catani, F.; Delmonaco, G.; Ermini, L.; Margottini, C.; Puglisi, C.
The present note presents the results of a research project aimed at developing a ge- omorphology based method for the assessment of landslide susceptibility. The work has been carried out in the Virginio River basin, a tributary of the Arno river with confluence located 20 km downstream from Florence (Italy). Starting from a detailed landslide inventory, essentially carried out by aerial-photograph survey, the first phase of the research was directed to geomorphic field investigations, aimed at determining those hillslope factors influencing landslide triggering. This analysis was carried out for a significant sub-sample of the inventoried landslides, allowing the distinction of the most relevant hillslope factors affecting each type of mass movement. Selected factors are a) the past slope gradient in which landslide originated, b) litology and 3) land use. Once defined as thematic vector data, these factors have been handled by GIS overlay mapping, allowing to single out, for the entire Virginio River basin, homogeneous domains (Unique Condition Units) that contain, for each landslide ty- pology, unique combinations of the selected hillslope factors. Those domains are the basic Terrain Units for the following phase of landslide susceptibility assessment and mapping. The hillslope factors not selected in the first phase, however playing an im- portant role in contributing to the activation of the mass movements, have been taken into account for the definition of a landslide susceptibility function. This function is es- sentially a logic function based on the presence/absence of preparatory factors within the previous selected Unique Condition Terrain Units. The final mapping of the ar- eas characterized by different landslide susceptibility levels was performed by vector and raster based GIS techniques on the basis of the number and rank of predisposing factors. These landslide susceptibility classes, defined by a logic and easily replicable function, can be useful in the decision making procedures connected with territorial planning.
Parobek, Christian M.; Lin, Jessica T.; Saunders, David L.; Barnett, Eric J.; Lon, Chanthap; Lanteri, Charlotte A.; Balasubramanian, Sujata; Brazeau, Nicholas; DeConti, Derrick K.; Garba, Deen L.; Meshnick, Steven R.; Spring, Michele D.; Chuor, Char Meng; Bailey, Jeffrey A.; Juliano, Jonathan J.
2016-01-01
Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P. vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P. vivax and 80 P. falciparum isolates collected between 2009 and 2013. We found that although P. falciparum has undergone population fracturing, the coendemic P. vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P. falciparum, P. vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P. vivax and P. falciparum parasites. Although population substructuring in P. falciparum has resulted in clonal outgrowths of resistant parasites, P. vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P. vivax’s resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P. vivax and achieve malaria elimination. PMID:27911780
Interaction of attention and acoustic factors in dichotic listening for fused words.
McCulloch, Katie; Lachner Bass, Natascha; Dial, Heather; Hiscock, Merrill; Jansen, Ben
2017-07-01
Two dichotic listening experiments examined the degree to which the right-ear advantage (REA) for linguistic stimuli is altered by a "top-down" variable (i.e., directed attention) in conjunction with selected "bottom-up" (acoustic) variables. Halwes fused dichotic words were administered to 99 right-handed adults with instructions to attend to the left or right ear, or to divide attention equally. Stimuli in Experiment 1 were presented without noise or mixed with noise that was high-pass or low-pass filtered, or unfiltered. The stimuli themselves in Experiment 2 were high-pass or low-pass filtered, or unfiltered. The initial consonants of each dichotic pair were categorized according to voice onset time (VOT) and place of articulation (PoA). White noise extinguished both the REA and selective attention, and filtered noise nullified selective attention without extinguishing the REA. Frequency filtering of the words themselves did not alter performance. VOT effects were inconsistent across experiments but PoA analyses indicated that paired velar consonants (/k/ and /g/) yield a left-ear advantage and paradoxical selective-attention results. The findings show that ear asymmetry and the effectiveness of directed attention can be altered by bottom-up variables.
Endocrine Responses to Resistance Exercise,
1987-08-30
resistance training responses of selected hormones related to acute stress and growth promoting actions. Hormonal mechanisms appear to be involved with ...an important determinant of hormonal response. Still. little is known with regard to other single and multiple factor variables (e.g.. rest period...hormone through a direct interaction with a cytoplasmic receptor leading to the typical migration of the hormone-receptor complex to the nucleus
Attributes of School Leaders Towards Achieving Sustainable Leadership: A Factor Analysis
ERIC Educational Resources Information Center
Goolamally, Norlia; Ahmad, Jamil
2014-01-01
A principal plays a very important role in deciding the direction and success of a school. Whether a school is dynamic is dependent upon the skills and abilities of the principal. In order to be excellent, the principal must be in possession of an excellent character. Therefore, the selection and promotion of school principals should be conducted…
The Language of Request: Annual Giftgiving to the University. ASHE 1983 Annual Meeting Paper.
ERIC Educational Resources Information Center
Tobin, Katherine
The organization of culture and the language of gift-giving used by a university development office were studied using an ethnographic approach. Attention was directed to the way that an academic institution selects, designs, and expresses its written and oral fund-raising messages, as well as the variety of factors that precede, structure, and…
Hamilton's rule and the causes of social evolution
Bourke, Andrew F. G.
2014-01-01
Hamilton's rule is a central theorem of inclusive fitness (kin selection) theory and predicts that social behaviour evolves under specific combinations of relatedness, benefit and cost. This review provides evidence for Hamilton's rule by presenting novel syntheses of results from two kinds of study in diverse taxa, including cooperatively breeding birds and mammals and eusocial insects. These are, first, studies that empirically parametrize Hamilton's rule in natural populations and, second, comparative phylogenetic analyses of the genetic, life-history and ecological correlates of sociality. Studies parametrizing Hamilton's rule are not rare and demonstrate quantitatively that (i) altruism (net loss of direct fitness) occurs even when sociality is facultative, (ii) in most cases, altruism is under positive selection via indirect fitness benefits that exceed direct fitness costs and (iii) social behaviour commonly generates indirect benefits by enhancing the productivity or survivorship of kin. Comparative phylogenetic analyses show that cooperative breeding and eusociality are promoted by (i) high relatedness and monogamy and, potentially, by (ii) life-history factors facilitating family structure and high benefits of helping and (iii) ecological factors generating low costs of social behaviour. Overall, the focal studies strongly confirm the predictions of Hamilton's rule regarding conditions for social evolution and their causes. PMID:24686934
Hamilton's rule and the causes of social evolution.
Bourke, Andrew F G
2014-05-19
Hamilton's rule is a central theorem of inclusive fitness (kin selection) theory and predicts that social behaviour evolves under specific combinations of relatedness, benefit and cost. This review provides evidence for Hamilton's rule by presenting novel syntheses of results from two kinds of study in diverse taxa, including cooperatively breeding birds and mammals and eusocial insects. These are, first, studies that empirically parametrize Hamilton's rule in natural populations and, second, comparative phylogenetic analyses of the genetic, life-history and ecological correlates of sociality. Studies parametrizing Hamilton's rule are not rare and demonstrate quantitatively that (i) altruism (net loss of direct fitness) occurs even when sociality is facultative, (ii) in most cases, altruism is under positive selection via indirect fitness benefits that exceed direct fitness costs and (iii) social behaviour commonly generates indirect benefits by enhancing the productivity or survivorship of kin. Comparative phylogenetic analyses show that cooperative breeding and eusociality are promoted by (i) high relatedness and monogamy and, potentially, by (ii) life-history factors facilitating family structure and high benefits of helping and (iii) ecological factors generating low costs of social behaviour. Overall, the focal studies strongly confirm the predictions of Hamilton's rule regarding conditions for social evolution and their causes.
Ecological and personal predictors of science achievement in an urban center
NASA Astrophysics Data System (ADS)
Guidubaldi, John Michael
This study sought to examine selected personal and environmental factors that predict urban students' achievement test scores on the science subject area of the Ohio standardized test. Variables examined were in the general categories of teacher/classroom, student, and parent/home. It assumed that these clusters might add independent variance to a best predictor model, and that discovering relative strength of different predictors might lead to better selection of intervention strategies to improve student performance. This study was conducted in an urban school district and was comprised of teachers and students enrolled in ninth grade science in three of this district's high schools. Consenting teachers (9), students (196), and parents (196) received written surveys with questions designed to examine the predictive power of each variable cluster. Regression analyses were used to determine which factors best correlate with student scores and classroom science grades. Selected factors were then compiled into a best predictive model, predicting success on standardized science tests. Students t tests of gender and racial subgroups confirmed that there were racial differences in OPT scores, and both gender and racial differences in science grades. Additional examinations were therefore conducted for all 12 variables to determine whether gender and race had an impact on the strength of individual variable predictions and on the final best predictor model. Of the 15 original OPT and cluster variable hypotheses, eight showed significant positive relationships that occurred in the expected direction. However, when more broadly based end-of-the-year science class grade was used as a criterion, 13 of the 15 hypotheses showed significant relationships in the expected direction. With both criteria, significant gender and racial differences were observed in the strength of individual predictors and in the composition of best predictor models.
ICU-acquired candidemia within selective digestive decontamination studies: a meta-analysis.
Hurley, James C
2015-11-01
To estimate the direct and indirect (contextual) effects of the factorized constituents of selective digestive decontamination and selective oropharyngeal decontamination (SDD/SOD), being topical antibiotic (TA) and protocolized antifungal prophylaxis (PAFP), on ICU-acquired candidemia. A broad range of ICU candidemia incidence studies were sourced to serve as points of reference. The candidemia incidence was extracted from component (control and intervention) groups decanted from studies of various designs (concurrent or non-concurrent) and whether investigating SDD/SOD versus non-TA methods of ICU infection prevention. The candidemia incidences were summarized in regression models using generalized estimating equation (GEE) methods. Groups derived from observational studies (no prevention method under study) provided an overarching external benchmark candidemia incidence for calibration. Within studies investigating SDD/SOD, the mean (and 95% confidence interval) candidemia incidence among concurrent component groups (40 control; 2.4%; 1.7-3.2% and 43 intervention groups; 2.4%; 1.6-3.1%), but not non-concurrent control groups (11 groups; 1.6%; 0.1-2.7%), is higher than that of the benchmark candidemia incidence derived from 54 observational groups (1.5%; 1.2-1.9%). The TA constituent within SDD/SOD has significant direct and indirect (contextual) effects in GEE models even after adjusting for the publication year and the group-wide presence of either candidemia risk factors or PAFP use. The TA constituent of SDD/SOD is associated with a contextual effect on candidemia incidence which is similar in magnitude to that of the conventional candidemia risk factors and against which PAFP partially attenuates. This increase is inapparent within individual SDD/SOD studies examined in isolation.
Paszkiewicz-Gadek, A; Chlabicz, J; Gałasiński, W
1988-01-01
Five potential oncostatics of plant origin (reserpine, amphotericin B, rutoside, digoxin, dry aloe extract), and cyclic AMP were investigated for their effect on protein synthesis. The solutions of digoxin and dry aloe extract inhibited protein biosynthesis in vitro. The direct inhibiting effect of digoxin on the ribosomes suggests that this drug forms an inactive complex with this organelle. Therefore it can be concluded that ribosome is the target site of digoxin action. Aloin and aloeemodin are responsible for the inhibitory effect of the solution of dry aloe extract. They inhibit markedly [14C]-leucine incorporation into proteins. Aloin and aloeemodin do not influence directly the ribosomes, but they inhibit elongation factors and peptidyltransferase activities in the complete elongation system. Some preliminary experiments have shown that direct interaction between these substances and elongation factor EF-2 should be taken in account. This observation is the subject of further experiments, in which the characteristics of the inhibitory effect of the components isolated from dry aloe extract will be performed.
Modeling HIV-1 Drug Resistance as Episodic Directional Selection
Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L.; Scheffler, Konrad
2012-01-01
The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance. PMID:22589711
Modeling HIV-1 drug resistance as episodic directional selection.
Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad
2012-01-01
The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.
Structure of collagen-glycosaminoglycan matrix and the influence to its integrity and stability.
Bi, Yuying; Patra, Prabir; Faezipour, Miad
2014-01-01
Glycosaminoglycan (GAG) is a chain-like disaccharide that is linked to polypeptide core to connect two collagen fibrils/fibers and provide the intermolecular force in Collagen-GAG matrix (C-G matrix). Thus, the distribution of GAG in C-G matrix contributes to the integrity and mechanical properties of the matrix and related tissue. This paper analyzes the transverse isotropic distribution of GAG in C-G matrix. The angle of GAGs related to collagen fibrils is used as parameters to qualify the GAGs isotropic characteristic in both 3D and 2D rendering. Statistical results included that over one third of GAGs were perpendicular directed to collagen fibril with symmetrical distribution for both 3D matrix and 2D plane cross through collagen fibrils. The three factors tested in this paper: collagen radius, collagen distribution, and GAGs density, were not statistically significant for the strength of Collagen-GAG matrix in 3D rendering. However in 2D rendering, a significant factor found was the radius of collagen in matrix for the GAGs directed to orthogonal plane of Collagen-GAG matrix. Between two cross-section selected from Collagen-GAG matrix model, the plane cross through collagen fibrils was symmetrically distributed but the total percentage of perpendicular directed GAG was deducted by decreasing collagen radius. There were some symmetry features of GAGs angle distribution in selected 2D plane that passed through space between collagen fibrils, but most models showed multiple peaks in GAGs angle distribution. With less GAGs directed to perpendicular of collagen fibril, strength in collagen cross-section weakened. Collagen distribution was also a factor that influences GAGs angle distribution in 2D rendering. True hexagonal collagen packaging is reported in this paper to have less strength at collagen cross-section compared to quasi-hexagonal collagen arrangement. In this work focus is on GAGs matrix within the collagen and its relevance to anisotropy.
Ågren, Jon; Hellström, Frida; Toräng, Per; Ehrlén, Johan
2013-01-01
Spatial variation in the direction of selection drives the evolution of adaptive differentiation. However, few experimental studies have examined the relative importance of different environmental factors for variation in selection and evolutionary trajectories in natural populations. Here, we combine 8 y of observational data and field experiments to assess the relative importance of mutualistic and antagonistic interactions for spatial variation in selection and short-term evolution of a genetically based floral display dimorphism in the short-lived perennial herb Primula farinosa. Natural populations of this species include two floral morphs: long-scaped plants that present their flowers well above the ground and short-scaped plants with flowers positioned close to the ground. The direction and magnitude of selection on scape morph varied among populations, and so did the frequency of the short morph (median 19%, range 0–100%; n = 69 populations). A field experiment replicated at four sites demonstrated that variation in the strength of interactions with grazers and pollinators were responsible for among-population differences in relative fitness of the two morphs. Selection exerted by grazers favored the short-scaped morph, whereas pollinator-mediated selection favored the long-scaped morph. Moreover, variation in selection among natural populations was associated with differences in morph frequency change, and the experimental removal of grazers at nine sites significantly reduced the frequency of the short-scaped morph over 8 y. The results demonstrate that spatial variation in intensity of grazing and pollination produces a selection mosaic, and that changes in biotic interactions can trigger rapid genetic changes in natural plant populations. PMID:24145439
Agren, Jon; Hellström, Frida; Toräng, Per; Ehrlén, Johan
2013-11-05
Spatial variation in the direction of selection drives the evolution of adaptive differentiation. However, few experimental studies have examined the relative importance of different environmental factors for variation in selection and evolutionary trajectories in natural populations. Here, we combine 8 y of observational data and field experiments to assess the relative importance of mutualistic and antagonistic interactions for spatial variation in selection and short-term evolution of a genetically based floral display dimorphism in the short-lived perennial herb Primula farinosa. Natural populations of this species include two floral morphs: long-scaped plants that present their flowers well above the ground and short-scaped plants with flowers positioned close to the ground. The direction and magnitude of selection on scape morph varied among populations, and so did the frequency of the short morph (median 19%, range 0-100%; n = 69 populations). A field experiment replicated at four sites demonstrated that variation in the strength of interactions with grazers and pollinators were responsible for among-population differences in relative fitness of the two morphs. Selection exerted by grazers favored the short-scaped morph, whereas pollinator-mediated selection favored the long-scaped morph. Moreover, variation in selection among natural populations was associated with differences in morph frequency change, and the experimental removal of grazers at nine sites significantly reduced the frequency of the short-scaped morph over 8 y. The results demonstrate that spatial variation in intensity of grazing and pollination produces a selection mosaic, and that changes in biotic interactions can trigger rapid genetic changes in natural plant populations.
Selective autophagy: ubiquitin-mediated recognition and beyond.
Kraft, Claudine; Peter, Matthias; Hofmann, Kay
2010-09-01
Eukaryotic cells use autophagy and the ubiquitin-proteasome system as their major protein degradation pathways. Whereas the ubiquitin-proteasome system is involved in the rapid degradation of proteins, autophagy pathways can selectively remove protein aggregates and damaged or excess organelles. Proteasome-mediated degradation requires previous ubiquitylation of the cargo, which is then recognized by ubiquitin receptors directing it to 26S proteasomes. Although autophagy has long been viewed as a random cytoplasmic degradation system, the involvement of ubiquitin as a specificity factor for selective autophagy is rapidly emerging. Recent evidence also suggests active crosstalk between proteasome-mediated degradation and selective autophagy. Here, we discuss the molecular mechanisms that link autophagy and the proteasome system, as well as the emerging roles of ubiquitin and ubiquitin-binding proteins in selective autophagy. On the basis of the evolutionary history of autophagic ubiquitin receptors, we propose a common origin for metazoan ubiquitin-dependent autophagy and the cytoplasm-to-vacuole targeting pathway of yeast.
Novel Harmonic Regularization Approach for Variable Selection in Cox's Proportional Hazards Model
Chu, Ge-Jin; Liang, Yong; Wang, Jia-Xuan
2014-01-01
Variable selection is an important issue in regression and a number of variable selection methods have been proposed involving nonconvex penalty functions. In this paper, we investigate a novel harmonic regularization method, which can approximate nonconvex Lq (1/2 < q < 1) regularizations, to select key risk factors in the Cox's proportional hazards model using microarray gene expression data. The harmonic regularization method can be efficiently solved using our proposed direct path seeking approach, which can produce solutions that closely approximate those for the convex loss function and the nonconvex regularization. Simulation results based on the artificial datasets and four real microarray gene expression datasets, such as real diffuse large B-cell lymphoma (DCBCL), the lung cancer, and the AML datasets, show that the harmonic regularization method can be more accurate for variable selection than existing Lasso series methods. PMID:25506389
The roles of gender, age and cognitive development in children's pedestrian route selection.
Barton, B K; Ulrich, T; Lyday, B
2012-03-01
Thousands of American children under the age of 10 years are injured annually as pedestrians. Despite the scope of this public health problem, knowledge about behavioural control and developmental factors involved in the aetiology of child pedestrian safety is limited. The present study examined the roles of gender, age and two aspects of cognitive development (visual search and efficiency of processing) in children's safe pedestrian route selection. Measures of cognitive functioning (visual search and efficiency) and selections of risky pedestrian routes were collected from 65 children aged 5-9 years. Boys, younger children and those with less developed cognitive functioning selected riskier pedestrian routes. Cognitive functioning also subsumed age as a predictor of risky route selections. Our findings suggest developmental differences, specifically less developed cognitive functioning, play important roles in children's pedestrian decision making. Directions for future examination are discussed. © 2011 Blackwell Publishing Ltd.
Finding Direction in the Search for Selection.
Thiltgen, Grant; Dos Reis, Mario; Goldstein, Richard A
2017-01-01
Tests for positive selection have mostly been developed to look for diversifying selection where change away from the current amino acid is often favorable. However, in many cases we are interested in directional selection where there is a shift toward specific amino acids, resulting in increased fitness in the species. Recently, a few methods have been developed to detect and characterize directional selection on a molecular level. Using the results of evolutionary simulations as well as HIV drug resistance data as models of directional selection, we compare two such methods with each other, as well as against a standard method for detecting diversifying selection. We find that the method to detect diversifying selection also detects directional selection under certain conditions. One method developed for detecting directional selection is powerful and accurate for a wide range of conditions, while the other can generate an excessive number of false positives.
Shorebird roost-site selection at two temporal scales: Is human disturbance a factor?
Peters, K.A.; Otis, D.L.
2007-01-01
1. Roost-site selection in shorebirds is governed by ambient factors, including environmental conditions and human disturbance. Determination of the extent to which these factors affect roost use and the associated implications for shorebird habitat protection is important for conservation strategies and informed management of human recreational use of these habitats. Shorebird conservation as a whole is a high priority world-wide because a large proportion of shorebird species is in decline. However, little is understood about the consistency of roost use by different species, what conditions affect species-specific roost-site selection, and at what spatial and temporal scales conditions influence selection. 2. We studied high-tide roost-site selection by eight species of non-breeding shorebirds on a critically important stopover and wintering refuge. We calculated spatial and temporal variability in roost use for each species based on counts and consistency of incidence. We then examined roost-site selection in relation to structural, environmental and human disturbance factors, and how this varied across spatial and temporal scales. 3. Most roosts were used less than 50% of the time, although larger roosts were used more consistently. This varied among species, with red knot Calidris canutus tending to concentrate at a few roosts and American oystercatcher Haematopus palliatus, dowitcher Limnodromus griseus and Limnodromus scolopaceus and ruddy turnstone Arenaria interpres more diffusely distributed among roosts. 4. At an annual scale, the principal factors affecting shorebird presence at roosts were roost length (size), local region, substrate and aspect. The extent and direction of these effects varied among species. Among years, red knots avoided roosts that had high average boat activity within 1000 m, but disturbance did not appear to be a factor for other species. 5. Daily roost use was influenced primarily by wind speed and the ability of roosts to provide shelter from the wind. Only dowitchers appeared to track daily disturbance, avoiding prospective roosts when boat activity within 100 m was high. 6. Synthesis and applications. Our findings emphasize the need to consider species-specific differences in temporal- and spatial-scale effects of roost-site selection factors, including human disturbance, when employing conservation measures for shorebirds. We suggest that conservation management should aim to provide a wide range of potential roosts (both natural and artificial) that could be used under different wind conditions and that are within reasonable travelling distance of preferred feeding areas. Roost use is often highly variable, and monitoring efforts must take this into account before making inferences about changes in use or selection of roost sites. ?? 2006 The Authors.
Wong, Cho Lee; Ip, Wan Yim; Choi, Kai Chow; Lam, Lai Wah
2015-05-01
To test a hypothesized model that examines the relationship between selected basic conditioning factors, self-care agency, and self-care behaviors among adolescent girls with dysmenorrhea using Orem's self-care deficit nursing theory as a framework. This was a predictive correlational study conducted with a total of 531 secondary school girls. Self-care agency, self-care behaviors, and 11 variables that have been theoretically or empirically justified in previous studies as relevant to basic conditioning factors were selected and collected by means of structured questionnaires. Path analyses were performed to test the hypothesized linkages among variables. Path analysis revealed that age and received menstrual education had both direct and indirect effects through self-care agency on self-care behaviors. Mother's and father's educational level, pain intensity, and self-medication used when experiencing dysmenorrhea only affected the self-care behaviors directly. This is the first study that provided information about the relationship between basic conditioning factors, self-care agency, and self-care behaviors among adolescent girls with dysmenorrhea. Knowledge of the factors influencing self-care behaviors in these adolescent girls will assist healthcare professionals in developing effective interventions to promote self-care and ameliorate the adverse impact of this condition. Interventional strategies that aim at promoting self-care behaviors among adolescent girls with dysmenorrhea should strengthen girls' self-care agency and should target those with a younger age, higher pain intensity, mother with a higher educational level, father with a lower educational level, and those who do not take self-medication for dysmenorrhea. © 2015 Sigma Theta Tau International.
Measurement of M²-Curve for Asymmetric Beams by Self-Referencing Interferometer Wavefront Sensor.
Du, Yongzhao
2016-11-29
For asymmetric laser beams, the values of beam quality factor M x 2 and M y 2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this non-uniqueness, a new beam quality characterization method named as M²-curve is developed. The M²-curve not only contains the beam quality factor M x 2 and M y 2 in the x -direction and y -direction, respectively; but also introduces a curve of M x α 2 versus rotation angle α of coordinate axis. Moreover, we also present a real-time measurement method to demonstrate beam propagation factor M²-curve with a modified self-referencing Mach-Zehnder interferometer based-wavefront sensor (henceforth SRI-WFS). The feasibility of the proposed method is demonstrated with the theoretical analysis and experiment in multimode beams. The experimental results showed that the proposed measurement method is simple, fast, and a single-shot measurement procedure without movable parts.
Measurement of M2-Curve for Asymmetric Beams by Self-Referencing Interferometer Wavefront Sensor
Du, Yongzhao
2016-01-01
For asymmetric laser beams, the values of beam quality factor Mx2 and My2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this non-uniqueness, a new beam quality characterization method named as M2-curve is developed. The M2-curve not only contains the beam quality factor Mx2 and My2 in the x-direction and y-direction, respectively; but also introduces a curve of Mxα2 versus rotation angle α of coordinate axis. Moreover, we also present a real-time measurement method to demonstrate beam propagation factor M2-curve with a modified self-referencing Mach-Zehnder interferometer based-wavefront sensor (henceforth SRI-WFS). The feasibility of the proposed method is demonstrated with the theoretical analysis and experiment in multimode beams. The experimental results showed that the proposed measurement method is simple, fast, and a single-shot measurement procedure without movable parts. PMID:27916845
The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis.
Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M; Munoz, Manuel J; Botti, Flavia; Kornblihtt, Alberto R; Sette, Claudio
2014-04-01
Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5' splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival.
The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M; Munoz, Manuel J; Botti, Flavia; Kornblihtt, Alberto R; Sette, Claudio
2014-01-01
Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5′ splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival. PMID:24514149
Factors influencing individual variation in perceptual directional microphone benefit.
Keidser, Gitte; Dillon, Harvey; Convery, Elizabeth; Mejia, Jorge
2013-01-01
Large variations in perceptual directional microphone benefit, which far exceed the variation expected from physical performance measures of directional microphones, have been reported in the literature. The cause for the individual variation has not been systematically investigated. To determine the factors that are responsible for the individual variation in reported perceptual directional benefit. A correlational study. Physical performance measures of the directional microphones obtained after they had been fitted to individuals, cognitive abilities of individuals, and measurement errors were related to perceptual directional benefit scores. Fifty-nine hearing-impaired adults with varied degrees of hearing loss participated in the study. All participants were bilaterally fitted with a Motion behind-the-ear device (500 M, 501 SX, or 501 P) from Siemens according to the National Acoustic Laboratories' non-linear prescription, version two (NAL-NL2). Using the Bamford-Kowal-Bench (BKB) sentences, the perceptual directional benefit was obtained as the difference in speech reception threshold measured in babble noise (SRTn) with the devices in directional (fixed hypercardioid) and in omnidirectional mode. The SRTn measurements were repeated three times with each microphone mode. Physical performance measures of the directional microphone included the angle of the microphone ports to loudspeaker axis, the frequency range dominated by amplified sound, the in situ signal-to-noise ratio (SNR), and the in situ three-dimensional, articulation-index weighted directivity index (3D AI-DI). The cognitive tests included auditory selective attention, speed of processing, and working memory. Intraparticipant variation on the repeated SRTn's and the interparticipant variation on the average SRTn were used to determine the effect of measurement error. A multiple regression analysis was used to determine the effect of other factors. Measurement errors explained 52% of the variation in perceptual directional microphone benefit (95% confidence interval [CI]: 34-78%), while another 37% of variation was explained primarily by the physical performance of the directional microphones after they were fitted to individuals. The most contributing factor was the in situ 3D AI-DI measured across the low frequencies. Repeated SRTn measurements are needed to obtain a reliable indication of the perceptual directional benefit in an individual. Further, to obtain optimum benefit from directional microphones, the effectiveness of the microphones should be maximized across the low frequencies. American Academy of Audiology.
A generalization of Hamilton's rule--love others how much?
Alger, Ingela; Weibull, Jörgen W
2012-04-21
According to Hamilton's (1964a, b) rule, a costly action will be undertaken if its fitness cost to the actor falls short of the discounted benefit to the recipient, where the discount factor is Wright's index of relatedness between the two. We propose a generalization of this rule, and show that if evolution operates at the level of behavior rules, rather than directly at the level of actions, evolution will select behavior rules that induce a degree of cooperation that may differ from that predicted by Hamilton's rule as applied to actions. In social dilemmas there will be less (more) cooperation than under Hamilton's rule if the actions are strategic substitutes (complements). Our approach is based on natural selection, defined in terms of personal (direct) fitness, and applies to a wide range of pairwise interactions. Copyright © 2011 Elsevier Ltd. All rights reserved.
A Mutation in the Bacillus subtilis rsbU Gene That Limits RNA Synthesis during Sporulation.
Rothstein, David M; Lazinski, David; Osburne, Marcia S; Sonenshein, Abraham L
2017-07-15
Mutants of Bacillis subtilis that are temperature sensitive for RNA synthesis during sporulation were isolated after selection with a 32 P suicide agent. Whole-genome sequencing revealed that two of the mutants carried an identical lesion in the rsbU gene, which encodes a phosphatase that indirectly activates SigB, the stress-responsive RNA polymerase sigma factor. The mutation appeared to cause RsbU to be hyperactive, because the mutants were more resistant than the parent strain to ethanol stress. In support of this hypothesis, pseudorevertants that regained wild-type levels of sporulation at high temperature had secondary mutations that prevented expression of the mutant rsbU gene. The properties of these RsbU mutants support the idea that activation of SigB diminishes the bacterium's ability to sporulate. IMPORTANCE Most bacterial species encode multiple RNA polymerase promoter recognition subunits (sigma factors). Each sigma factor directs RNA polymerase to different sets of genes; each gene set typically encodes proteins important for responses to specific environmental conditions, such as changes in temperature, salt concentration, and nutrient availability. A selection for mutants of Bacillus subtilis that are temperature sensitive for RNA synthesis during sporulation unexpectedly yielded strains with a point mutation in rsbU , a gene that encodes a protein that normally activates sigma factor B (SigB) under conditions of salt stress. The mutation appears to cause RsbU, and therefore SigB, to be active inappropriately, thereby inhibiting, directly or indirectly, the ability of the cells to transcribe sporulation genes. Copyright © 2017 American Society for Microbiology.
Development of the reasons for living inventory for young adults.
Gutierrez, Peter M; Osman, Augustine; Barrios, Francisco X; Kopper, Beverly A; Baker, Monty T; Haraburda, Cheryl M
2002-04-01
Assessment of the reliability, validity, and predictive power of a new measure, the Reasons for Living Inventory for Young Adults (RFL-YA) is described. A series of three studies was conducted at two Midwestern universities to develop initial items for this new measure, refine item selection, and demonstrate the psychometric properties of the RFL-YA. The theoretical differences between the RFL-YA and the College Student Reasons for Living Inventory (CS-RFL) are discussed. Although the two measures were not directly compared, it appears that the RFL-YA has greater specificity for exploring aspects of the protective construct and may be more parsimonious than the CS-RFL. Principal-axis factor analysis yielded a five-factor solution for the RFL-YA accounting for 61.5% of the variance. This five-factor oblique model was confirmed in the final phase of investigation. Alpha estimates for the five subscales ranged from.89 to.94. Concurrent, convergent-discriminant, and criterion validity also were demonstrated. The importance of assessing protective factors in addition to negative risk factors for suicidality is discussed. Directions for future research with the RFL-YA also are discussed. Copyright 2002 Wiley Periodicals, Inc.
Senseless acts as a binary switch during sensory organ precursor selection
NASA Technical Reports Server (NTRS)
Jafar-Nejad, Hamed; Acar, Melih; Nolo, Riitta; Lacin, Haluk; Pan, Hongling; Parkhurst, Susan M.; Bellen, Hugo J.
2003-01-01
During sensory organ precursor (SOP) specification, a single cell is selected from a proneural cluster of cells. Here, we present evidence that Senseless (Sens), a zinc-finger transcription factor, plays an important role in this process. We show that Sens is directly activated by proneural proteins in the presumptive SOPs and a few cells surrounding the SOP in most tissues. In the cells that express low levels of Sens, it acts in a DNA-binding-dependent manner to repress transcription of proneural genes. In the presumptive SOPs that express high levels of Sens, it acts as a transcriptional activator and synergizes with proneural proteins. We therefore propose that Sens acts as a binary switch that is fundamental to SOP selection.
NASA Astrophysics Data System (ADS)
Minsker, Karl S.; Ivanova, S. R.; Biglova, Raisa Z.
1995-05-01
The Bronsted acids formed as a result of the interaction of aluminium chlorides with Group I and II metal chlorides in the presence of proton-donating compounds are promising polyfunctional catalysts for electrophilic processes (polymerisation, depolymerisation and degradation of macromolecules, alkylation, desulfurisation, and hydrogenation). The factor determing the electrophilic activity and selectivity of the action of the catalysts is their acidity. This makes it possible to predict the direction of the changes in the activity and selectivity of the catalyst in specific chemical processes in conformity with the opposite variation rule: with increase in the acidity of the electrophilic catalyst, their activity increases but the selectivity of their action diminishes. The bibliography includes 72 references.
Linking seasonal home range size with habitat selection and movement in a mountain ungulate.
Viana, Duarte S; Granados, José Enrique; Fandos, Paulino; Pérez, Jesús M; Cano-Manuel, Francisco Javier; Burón, Daniel; Fandos, Guillermo; Aguado, María Ángeles Párraga; Figuerola, Jordi; Soriguer, Ramón C
2018-01-01
Space use by animals is determined by the interplay between movement and the environment, and is thus mediated by habitat selection, biotic interactions and intrinsic factors of moving individuals. These processes ultimately determine home range size, but their relative contributions and dynamic nature remain less explored. We investigated the role of habitat selection, movement unrelated to habitat selection and intrinsic factors related to sex in driving space use and home range size in Iberian ibex, Capra pyrenaica . We used GPS collars to track ibex across the year in two different geographical areas of Sierra Nevada, Spain, and measured habitat variables related to forage and roost availability. By using integrated step selection analysis (iSSA), we show that habitat selection was important to explain space use by ibex. As a consequence, movement was constrained by habitat selection, as observed displacement rate was shorter than expected under null selection. Selection-independent movement, selection strength and resource availability were important drivers of seasonal home range size. Both displacement rate and directional persistence had a positive relationship with home range size while accounting for habitat selection, suggesting that individual characteristics and state may also affect home range size. Ibex living at higher altitudes, where resource availability shows stronger altitudinal gradients across the year, had larger home ranges. Home range size was larger in spring and autumn, when ibex ascend and descend back, and smaller in summer and winter, when resources are more stable. Therefore, home range size decreased with resource availability. Finally, males had larger home ranges than females, which might be explained by differences in body size and reproductive behaviour. Movement, selection strength, resource availability and intrinsic factors related to sex determined home range size of Iberian ibex. Our results highlight the need to integrate and account for process dependencies, here the interdependence of movement and habitat selection, to understand how animals use space. This study contributes to understand how movement links environmental and geographical space use and determines home range behaviour in large herbivores.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Husain, Tausif; Hasan, Iftekhar; Sozer, Yilmaz
This paper presents the design considerations of a double-sided transverse flux machine (TFM) for direct-drive wind turbine applications. The TFM has a modular structure with quasi-U stator cores and ring windings. The rotor is constructed with ferrite magnets in a flux-concentrating arrangement to achieve high air gap flux density. The design considerations for this TFM with respect to initial sizing, pole number selection, key design ratios, and pole shaping are presented in this paper. Pole number selection is critical in the design process of a TFM because it affects both the torque density and power factor under fixed magnetic andmore » changing electrical loading. Several key design ratios are introduced to facilitate the design procedure. The effect of pole shaping on back-emf and inductance is also analyzed. These investigations provide guidance toward the required design of a TFM for direct-drive applications. The analyses are carried out using analytical and three-dimensional finite element analysis. A prototype is under construction for experimental verification.« less
Design Considerations of a Transverse Flux Machine for Direct-Drive Wind Turbine Applications
DOE Office of Scientific and Technical Information (OSTI.GOV)
Husain, Tausif; Hasan, Iftekhar; Sozer, Yilmaz
This paper presents the design considerations of a double-sided transverse flux machine (TFM) for direct-drive wind turbine applications. The TFM has a modular structure with quasi-U stator cores and ring windings. The rotor is constructed with ferrite magnets in a flux-concentrating arrangement to achieve high air gap flux density. The design considerations for this TFM with respect to initial sizing, pole number selection, key design ratios, and pole shaping are presented in this paper. Pole number selection is critical in the design process of a TFM because it affects both the torque density and power factor under fixed magnetic andmore » changing electrical loading. Several key design ratios are introduced to facilitate the design procedure. The effect of pole shaping on back-emf and inductance is also analyzed. These investigations provide guidance toward the required design of a TFM for direct-drive applications. The analyses are carried out using analytical and three-dimensional finite element analysis. A prototype is under construction for experimental verification.« less
Selective memory retrieval can impair and improve retrieval of other memories.
Bäuml, Karl-Heinz T; Samenieh, Anuscheh
2012-03-01
Research from the past decades has shown that retrieval of a specific memory (e.g., retrieving part of a previous vacation) typically attenuates retrieval of other memories (e.g., memories for other details of the event), causing retrieval-induced forgetting. More recently, however, it has been shown that retrieval can both attenuate and aid recall of other memories (K.-H. T. Bäuml & A. Samenieh, 2010). To identify the circumstances under which retrieval aids recall, the authors examined retrieval dynamics in listwise directed forgetting, context-dependent forgetting, proactive interference, and in the absence of any induced memory impairment. They found beneficial effects of selective retrieval in listwise directed forgetting and context-dependent forgetting but detrimental effects in all the other conditions. Because context-dependent forgetting and listwise directed forgetting arguably reflect impaired context access, the results suggest that memory retrieval aids recall of memories that are subject to impaired context access but attenuates recall in the absence of such circumstances. The findings are consistent with a 2-factor account of memory retrieval and suggest the existence of 2 faces of memory retrieval. 2012 APA, all rights reserved
Hakkennes, Sharon; Hill, Keith D; Brock, Kim; Bernhardt, Julie; Churilov, Leonid
2013-01-01
This study aimed to identify factors that assessors considered important in decision-making regarding suitability for inpatient rehabilitation after acute severe stroke. Multi-site prospective observational cohort study. Consecutive acute, severe stroke patients and their assessors for inpatient rehabilitation. Rehabilitation assessors completed a questionnaire, rating the importance (10 point visual analogue scale) and direction (positive, negative or neutral) of 15 patient related and 2 organisational items potentially affecting their decision regarding patients' acceptance to rehabilitation. Of the 75 patients referred to rehabilitation and included in this study 61 (81.3%) were accepted for inpatient rehabilitation. The items considered to be most important in the decision to accept the patient for rehabilitation were pre-morbid cognition, pre-morbid mobility and pre-morbid communication. For those not accepted the most important items were current mobility, social support and current cognition. Factor analysis revealed 3 underlying factors, interpreted as post-stroke status, pre-morbid status, and social attributes, accounting for 61.8% of the total variance. All were independently associated with acceptance for rehabilitation (p < 0.05). This study highlights the importance of pre-morbid function and social factors in addition to post-stroke function in the decision making process for acceptance to rehabilitation following severe stroke. Future models for selection for rehabilitation should consider inclusion of these factors.
Puddu, Paolo Emilio; Piras, Paolo; Menotti, Alessandro
2017-02-01
To study coronary heart disease (CHD) death versus 11 other causes of death using the cumulative incidence function (CIF) and the competing risks procedures to disentangle the differential role of risk factors for different end-points. Standard Cox and Fine-Gray models among 1712 middle-aged men were compared during 50years of follow-up. CHD death was the primary event, while deaths from 11 selected causes, mutually exclusive from the primary end-point, were considered as secondary events. Reverse solutions were also performed. We considered 10 selected risk factors. CHD death risk was the second highest among 12 mostly specific causes of death. Some risk factors were specific: serum cholesterol for CHD death whereas, systolic blood pressure, cigarette smoking and age may have a differential role in other causes of death. Application of the Fine-Gray model based on CIF enabled to dissect, at least in part, the respective role that baseline covariates may have to segregate the probabilities of two types of death in contrast from each other. They also point to the absence of contributing significance for some of the selected risk factors and this calls for a parsimonious approach in predictions. The relative rarity of competing risk challenges when defining the risk factors role at long-term needs now be corrected since we have clearly shown, with Fine-Gray model, at direct or reverse use, that comparing different end-points heavily influences the risk factor predictive capacity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
An Approach to Greater Specificity for Glucocorticoids
Chow, Carson C.; Simons, S. Stoney
2018-01-01
Glucocorticoid steroids are among the most prescribed drugs each year. Nonetheless, the many undesirable side effects, and lack of selectivity, restrict their greater usage. Research to increase glucocorticoid specificity has spanned many years. These efforts have been hampered by the ability of glucocorticoids to both induce and repress gene transcription and also by the lack of success in defining any predictable properties that control glucocorticoid specificity. Correlations of transcriptional specificity have been observed with changes in steroid structure, receptor and chromatin conformation, DNA sequence for receptor binding, and associated cofactors. However, none of these studies have progressed to the point of being able to offer guidance for increased specificity. We summarize here a mathematical theory that allows a novel and quantifiable approach to increase selectivity. The theory applies to all three major actions of glucocorticoid receptors: induction by agonists, induction by antagonists, and repression by agonists. Simple graphical analysis of competition assays involving any two factors (steroid, chemical, peptide, protein, DNA, etc.) yields information (1) about the kinetically described mechanism of action for each factor at that step where the factor acts in the overall reaction sequence and (2) about the relative position of that step where each factor acts. These two pieces of information uniquely provide direction for increasing the specificity of glucocorticoid action. Consideration of all three modes of action indicate that the most promising approach for increased specificity is to vary the concentrations of those cofactors/pharmaceuticals that act closest to the observed end point. The potential for selectivity is even greater when varying cofactors/pharmaceuticals in conjunction with a select class of antagonists. PMID:29593646
Selective Logging, Fire, and Biomass in Amazonia
NASA Technical Reports Server (NTRS)
Houghton, R. A.
1999-01-01
Biomass and rates of disturbance are major factors in determining the net flux of carbon between terrestrial ecosystems and the atmosphere, and neither of them is well known for most of the earth's surface. Satellite data over large areas are beginning to be used systematically to measure rates of two of the most important types of disturbance, deforestation and reforestation, but these are not the only types of disturbance that affect carbon storage. Other examples include selective logging and fire. In northern mid-latitude forests, logging and subsequent regrowth of forests have, in recent decades, contributed more to the net flux of carbon between terrestrial ecosystems and the atmosphere than any other type of land use. In the tropics logging is also becoming increasingly important. According to the FAO/UNEP assessment of tropical forests, about 25% of total area of productive forests have been logged one or more times in the 60-80 years before 1980. The fraction must be considerably greater at present. Thus, deforestation by itself accounts for only a portion of the emissions carbon from land. Furthermore, as rates of deforestation become more accurately measured with satellites, uncertainty in biomass will become the major factor accounting for the remaining uncertainty in estimates of carbon flux. An approach is needed for determining the biomass of terrestrial ecosystems. 3 Selective logging is increasingly important in Amazonia, yet it has not been included in region-wide, satellite-based assessments of land-cover change, in part because it is not as striking as deforestation. Nevertheless, logging affects terrestrial carbon storage both directly and indirectly. Besides the losses of carbon directly associated with selective logging, logging also increases the likelihood of fire.
The evolution of trade-offs under directional and correlational selection.
Roff, Derek A; Fairbairn, Daphne J
2012-08-01
Using quantitative genetic theory, we develop predictions for the evolution of trade-offs in response to directional and correlational selection. We predict that directional selection favoring an increase in one trait in a trade-off will result in change in the intercept but not the slope of the trade-off function, with the mean value of the selected trait increasing and that of the correlated trait decreasing. Natural selection will generally favor an increase in some combination of trait values, which can be represented as directional selection on an index value. Such selection induces both directional and correlational selection on the component traits. Theory predicts that selection on an index value will also change the intercept but not the slope of the trade-off function but because of correlational selection, the direction of change in component traits may be in the same or opposite directions. We test these predictions using artificial selection on the well-established trade-off between fecundity and flight capability in the cricket, Gryllus firmus and compare the empirical results with a priori predictions made using genetic parameters from a separate half-sibling experiment. Our results support the predictions and illustrate the complexity of trade-off evolution when component traits are subject to both directional and correlational selection. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.
[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].
Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng
2012-10-01
The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.
Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Primmer, Craig R
2018-06-01
Understanding the genomic basis of host-parasite adaptation is important for predicting the long-term viability of species and developing successful management practices. However, in wild populations, identifying specific signatures of parasite-driven selection often presents a challenge, as it is difficult to unravel the molecular signatures of selection driven by different, but correlated, environmental factors. Furthermore, separating parasite-mediated selection from similar signatures due to genetic drift and population history can also be difficult. Populations of Atlantic salmon (Salmo salar L.) from northern Europe have pronounced differences in their reactions to the parasitic flatworm Gyrodactylus salaris Malmberg 1957 and are therefore a good model to search for specific genomic regions underlying inter-population differences in pathogen response. We used a dense Atlantic salmon SNP array, along with extensive sampling of 43 salmon populations representing the two G. salaris response extremes (extreme susceptibility vs resistant), to screen the salmon genome for signatures of directional selection while attempting to separate the parasite effect from other factors. After combining the results from two independent genome scan analyses, 57 candidate genes potentially under positive selection were identified, out of which 50 were functionally annotated. This candidate gene set was shown to be functionally enriched for lymph node development, focal adhesion genes and anti-viral response, which suggests that the regulation of both innate and acquired immunity might be an important mechanism for salmon response to G. salaris. Overall, our results offer insights into the apparently complex genetic basis of pathogen susceptibility in salmon and highlight methodological challenges for separating the effects of various environmental factors. Copyright © 2018 Elsevier B.V. All rights reserved.
The spatial patterns of directional phenotypic selection.
Siepielski, Adam M; Gotanda, Kiyoko M; Morrissey, Michael B; Diamond, Sarah E; DiBattista, Joseph D; Carlson, Stephanie M
2013-11-01
Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Friday, G.P.; Cummins, C.L.; Schwartzman, A.L.
Since the early 1950s, the Savannah River Site (SRS) released over 50 radionuclides into the environment while producing nuclear defense materials. These releases directly exposed aquatic and terrestrial biota to ionizing radiation from surface water, soil, and sediment, and also indirectly by the ingestion of items in the food chain. As part of new missions to develop waste management strategies and identify cost-effective environmental restoration options, knowledge concerning the uptake and distribution of these radionuclides is essential. This report compiles and summarizes site-specific bioconcentration factors for selected radionuclides released at SRS.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ngo, Van; Wang, Yibo; Haas, Stephan
Crystal structures of several bacterial Na v channels have been recently published and molecular dynamics simulations of ion permeation through these channels are consistent with many electrophysiological properties of eukaryotic channels. Bacterial Na v channels have been characterized as functionally asymmetric, and the mechanism of this asymmetry has not been clearly understood. To address this question, we combined non-equilibrium simulation data with two-dimensional equilibrium unperturbed landscapes generated by umbrella sampling and Weighted Histogram Analysis Methods for multiple ions traversing the selectivity filter of bacterial Na vAb channel. This approach provided new insight into the mechanism of selective ion permeation inmore » bacterial Nav channels. The non-equilibrium simulations indicate that two or three extracellular K + ions can block the entrance to the selectivity filter of Na vAb in the presence of applied forces in the inward direction, but not in the outward direction. The block state occurs in an unstable local minimum of the equilibrium unperturbed free-energy landscape of two K+ ions that can be ‘locked’ in place bymodest applied forces. In contrast to K +, three Na + ions move favorably through the selectivity filter together as a unit in a loose “knock-on” mechanism of permeation in both inward and outward directions, and there is no similar local minimum in the two-dimensional free-energy landscape of two Na + ions for a block state. The useful work predicted by the non-equilibrium simulations that is required to break the K + block is equivalent to large applied potentials experimentally measured for two bacterial Na v channels to induce inward currents of K + ions. Here, these results illustrate how inclusion of non-equilibrium factors in the simulations can provide detailed information about mechanisms of ion selectivity that is missing from mechanisms derived from either crystal structures or equilibrium unperturbed free-energy landscapes.« less
Wang, Xun; Sun, Beibei; Liu, Boyang; Fu, Yaping; Zheng, Pan
2017-01-01
Experimental design focuses on describing or explaining the multifactorial interactions that are hypothesized to reflect the variation. The design introduces conditions that may directly affect the variation, where particular conditions are purposely selected for observation. Combinatorial design theory deals with the existence, construction and properties of systems of finite sets whose arrangements satisfy generalized concepts of balance and/or symmetry. In this work, borrowing the concept of "balance" in combinatorial design theory, a novel method for multifactorial bio-chemical experiments design is proposed, where balanced templates in combinational design are used to select the conditions for observation. Balanced experimental data that covers all the influencing factors of experiments can be obtianed for further processing, such as training set for machine learning models. Finally, a software based on the proposed method is developed for designing experiments with covering influencing factors a certain number of times.
Contemporary approach to stroke prevention in atrial fibrillation: Risks, benefits, and new options.
Stock, Jonathan; Malm, Brian J
2018-04-04
Atrial fibrillation is a common diagnosis affecting nearly 3 million adults in the United States. Morbidity and mortality in these patients is driven largely by the associated increased risk of thromboembolic complications, especially stroke. Atrial fibrillation is a stronger risk factor than hypertension, coronary disease, or heart failure and is associated with an approximately five-fold increased risk. Mitigating stroke risk can be challenging and requires accurate assessment of stroke risk factors and careful selection of appropriate therapy. Anticoagulation, including the more recently introduced direct oral anticoagulants, is the standard of care for most patients. In addition, emerging non-pharmacologic mechanical interventions are playing an expanding role in reducing stroke risk in select patients. In this review we highlight the current approach to stroke risk stratification in atrial fibrillation and discuss in detail the mechanism, risks, and benefits of current and evolving therapies. Copyright © 2018 Elsevier Inc. All rights reserved.
The Responsiveness of Biological Motion Processing Areas to Selective Attention Towards Goals
Herrington, John; Nymberg, Charlotte; Faja, Susan; Price, Elinora; Schultz, Robert
2012-01-01
A growing literature indicates that visual cortex areas viewed as primarily responsive to exogenous stimuli are susceptible to top-down modulation by selective attention. The present study examines whether brain areas involved in biological motion perception are among these areas – particularly with respect to selective attention towards human movement goals. Fifteen participants completed a point-light biological motion study following a two-by-two factorial design, with one factor representing an exogenous manipulation of human movement goals (goal-directed versus random movement), and the other an endogenous manipulation (a goal identification task versus an ancillary color-change task). Both manipulations yielded increased activation in the human homologue of motion-sensitive area MT+ (hMT+) as well as the extrastriate body area (EBA). The endogenous manipulation was associated with increased right posterior superior temporal sulcus (STS) activation, whereas the exogenous manipulation was associated with increased activation in left posterior STS. Selective attention towards goals activated portion of left hMT+/EBA only during the perception of purposeful movement consistent with emerging theories associating this area with the matching of visual motion input to known goal-directed actions. The overall pattern of results indicates that attention towards the goals of human movement activates biological motion areas. Ultimately, selective attention may explain why some studies examining biological motion show activation in hMT+ and EBA, even when using control stimuli with comparable motion properties. PMID:22796987
NASA Astrophysics Data System (ADS)
Zelenović Vasiljević, Tamara; Srdjević, Zorica; Bajčetić, Ratko; Vojinović Miloradov, Mirjana
2012-02-01
The Serbian National Waste Management Strategy for the Period 2010-2019, harmonized with the European Union Directives, mandates new and very strict requirements for landfill sites. To enable analysis of a number of required qualitative and quantitative factors for landfill site selection, the traditional method of site selection must be replaced with a new approach. The combination of GIS and the Analytic Hierarchy Process (AHP) was selected to solve this complex problem. The Srem region in northern Serbia, being one of the most environmentally sensitive areas, was chosen as a case study. Seventeen factors selected as criteria/sub-criteria were recognized as most important, divided into geo-natural, environmental, social and techno-economic factors, and were evaluated by experts from different fields using an AHP extension in Arc GIS. Weighted spatial layers were combined into a landfill suitability map which was then overlapped with four restriction maps, resulting in a final suitability map. According to the results, 82.65% of the territory of Srem is unsuitable for regional landfill siting. The most suitable areas cover 9.14%, suitable areas 5.24%, while areas with low and very low suitability cover 2.21 and 0.76% of the territory, respectively. Based on these findings, five sites close to two large urban agglomerations were suggested as possible locations for a regional landfill site in Srem. However, the final decision will require further field investigation, a public acceptance survey, and consideration of ownership status and price of the land.
AP1 Keeps Chromatin Poised for Action | Center for Cancer Research
The human genome harbors gene-encoding DNA, the blueprint for building proteins that regulate cellular function. Embedded across the genome, in non-coding regions, are DNA elements to which regulatory factors bind. The interaction of regulatory factors with DNA at these sites modifies gene expression to modulate cell activity. In cells, DNA exists in a complex with proteins called chromatin that compacts the DNA in the nucleus, strongly restricting access to DNA sequences. As a result, regulatory factors only interact with a small subset of their potential binding elements in a given cell to regulate genes. How factors recognize and select sites in chromatin across the genome is not well understood -- but several discoveries in CCR’s Laboratory of Receptor Biology and Gene Expression (LRBGE) have shed light on the mechanisms that direct factors to DNA.
Task frequency influences stimulus-driven effects on task selection during voluntary task switching.
Arrington, Catherine M; Reiman, Kaitlin M
2015-08-01
Task selection during voluntary task switching involves both top-down (goal-directed) and bottom-up (stimulus-driven) mechanisms. The factors that shift the balance between these two mechanisms are not well characterized. In the present research, we studied the role that task frequency plays in determining the extent of stimulus-driven task selection. In two experiments, we used the basic paradigm adapted from Arrington (Memory & Cognition, 38, 991-997, 2008), in which the effect of stimulus availability serves as a marker of stimulus-driven task selection. A number and letter appeared on each trial with varying stimulus onset asynchronies, and participants performed either a consonant/vowel or an even/odd judgment. In Experiment 1, participants were instructed as to the relative frequency with which each task was to be performed (i.e., 50/50, 60/40, or 75/25) and were further instructed to make their transitions between tasks unpredictable. In Experiment 2, participants were given no instructions about how to select tasks, resulting in naturally occurring variation in task frequency. With both instructed (Exp. 1) and naturally occurring (Exp. 2) relative task frequencies, the less frequently performed task showed a greater effect of stimulus availability on task selection, suggestive of a larger influence of stimulus-driven mechanisms during task performance for the less frequent task. When goal-directed mechanisms of task choice are engaged less frequently, the relative influence of the stimulus environment increases.
Tissue engineering: Dentin - pulp complex regeneration approaches (A review).
Hashemi-Beni, Batool; Khoroushi, Maryam; Foroughi, Mohammad Reza; Karbasi, Saeed; Khademi, Abbas Ali
2017-10-01
Dental pulp is a highly specialized tissue that preserves teeth. It is important to maintain the capabilities of dental pulp before a pulpectomy by creating a local restoration of the dentin-pulp complex from residual dental pulp. The articles identified were selected by two reviewers based on entry and exit criteria. All relevant articles indexed in PubMed, Springer, Science Direct, and Scopus with no limitations from 1961 to 2016 were searched. Factors investigated in the selected articles included the following key words: Dentin-Pulp Complex, Regeneration, Tissue Engineering, Scaffold, Stem Cell, and Growth Factors. Of the 233 abstracts retrieved, the papers which were selected had evaluated the clinical aspects of the application of dentin-pulp regeneration. Generally, this study has introduced a new approach to provoke the regeneration of the dentin-pulp complex after a pulpectomy, so that exogenous growth factors and the scaffold are able to induce cells and blood vessels from the residual dental pulp in the tooth root canal. This study further presents a new strategy for local regeneration therapy of the dentin-pulp complex. This review summarizes the current knowledge of the potential beneficial effects derived from the interaction of dental materials with the dentin-pulp complex as well as potential future developments in this exciting field. Copyright © 2017 Elsevier Ltd. All rights reserved.
Direction selectivity of blowfly motion-sensitive neurons is computed in a two-stage process.
Borst, A; Egelhaaf, M
1990-01-01
Direction selectivity of motion-sensitive neurons is generally thought to result from the nonlinear interaction between the signals derived from adjacent image points. Modeling of motion-sensitive networks, however, reveals that such elements may still respond to motion in a rather poor directionally selective way. Direction selectivity can be significantly enhanced if the nonlinear interaction is followed by another processing stage in which the signals of elements with opposite preferred directions are subtracted from each other. Our electrophysiological experiments in the fly visual system suggest that here direction selectivity is acquired in such a two-stage process. Images PMID:2251278
Post-deployment family violence among UK military personnel.
Kwan, Jamie; Jones, Margaret; Somaini, Greta; Hull, Lisa; Wessely, Simon; Fear, Nicola T; MacManus, Deirdre
2017-12-19
Research into violence among military personnel has not differentiated between stranger- and family-directed violence. While military factors (combat exposure and post-deployment mental health problems) are risk factors for general violence, there has been limited research on their impact on violence within the family environment. This study aims to compare the prevalence of family-directed and stranger-directed violence among a deployed sample of UK military personnel and to explore risk factors associated with both family- and stranger-directed violence. This study utilised data from a large cohort study which collected information by questionnaire from a representative sample of randomly selected deployed UK military personnel (n = 6711). The prevalence of family violence immediately following return from deployment was 3.6% and 7.8% for stranger violence. Family violence was significantly associated with having left service, while stranger violence was associated with younger age, male gender, being single, having a history of antisocial behaviour as well as having left service. Deployment in a combat role was significantly associated with both family and stranger violence after adjustment for confounders [adjusted odds ratio (aOR) = 1.92 (1.25-2.94), p = 0.003 and aOR = 1.77 (1.31-2.40), p < 0.001, respectively], as was the presence of symptoms of post-traumatic stress disorder, common mental disorders and aggression. Exposure to combat and post-deployment mental health problems are risk factors for violence both inside and outside the family environment and should be considered in violence reduction programmes for military personnel. Further research using a validated measurement tool for family violence would improve comparability with other research.
Fast Selective Detection of Pyocyanin Using Cyclic Voltammetry
Alatraktchi, Fatima AlZahra’a; Breum Andersen, Sandra; Krogh Johansen, Helle; Molin, Søren; Svendsen, Winnie E.
2016-01-01
Pyocyanin is a virulence factor uniquely produced by the pathogen Pseudomonas aeruginosa. The fast and selective detection of pyocyanin in clinical samples can reveal important information about the presence of this microorganism in patients. Electrochemical sensing of the redox-active pyocyanin is a route to directly quantify pyocyanin in real time and in situ in hospitals and clinics. The selective quantification of pyocyanin is, however, limited by other redox-active compounds existing in human fluids and by other metabolites produced by pathogenic bacteria. Here we present a direct selective method to detect pyocyanin in a complex electroactive environment using commercially available electrodes. It is shown that cyclic voltammetry measurements between −1.0 V to 1.0 V reveal a potential detection window of pyocyanin of 0.58–0.82 V that is unaffected by other redox-active interferents. The linear quantification of pyocyanin has an R2 value of 0.991 across the clinically relevant concentration range of 2–100 µM. The proposed method was tested on human saliva showing a standard deviation of 2.5% ± 1% (n = 5) from the known added pyocyanin concentration to the samples. This inexpensive procedure is suggested for clinical use in monitoring the presence and state of P. aeruginosa infection in patients. PMID:27007376
Fast Selective Detection of Pyocyanin Using Cyclic Voltammetry.
Alatraktchi, Fatima AlZahra'a; Andersen, Sandra Breum; Johansen, Helle Krogh; Molin, Søren; Svendsen, Winnie E
2016-03-19
Pyocyanin is a virulence factor uniquely produced by the pathogen Pseudomonas aeruginosa. The fast and selective detection of pyocyanin in clinical samples can reveal important information about the presence of this microorganism in patients. Electrochemical sensing of the redox-active pyocyanin is a route to directly quantify pyocyanin in real time and in situ in hospitals and clinics. The selective quantification of pyocyanin is, however, limited by other redox-active compounds existing in human fluids and by other metabolites produced by pathogenic bacteria. Here we present a direct selective method to detect pyocyanin in a complex electroactive environment using commercially available electrodes. It is shown that cyclic voltammetry measurements between -1.0 V to 1.0 V reveal a potential detection window of pyocyanin of 0.58-0.82 V that is unaffected by other redox-active interferents. The linear quantification of pyocyanin has an R² value of 0.991 across the clinically relevant concentration range of 2-100 µM. The proposed method was tested on human saliva showing a standard deviation of 2.5% ± 1% (n = 5) from the known added pyocyanin concentration to the samples. This inexpensive procedure is suggested for clinical use in monitoring the presence and state of P. aeruginosa infection in patients.
NASA Technical Reports Server (NTRS)
Usher, D. A.; Needels, M. C.
1986-01-01
Examples of chiral selection in nonenzymatic aminoacylation of internal 2-prime hydroxyl groups of oligo- and polynucleotides are discussed as an evidence for the early evolution of bionucleotides. Some factors that could influence the degree of this chiral selection and its direction are discussed. These include the structure of the aminoacyl component, the structure of the nucleoside component, and the reaction conditions. Investigation of the mechanism of this reaction was aided by the use of 3-prime inosine methyl phosphate (as a simplified model for a dinucleoside monophosphate) and proton NMR spectroscopy of t-butoxycarbonyl-alanyl esters of nucleosides as models for the transition state of the aminoacylation reaction itself.
Applications of nuclear reactor power systems to electric propulsion missions.
NASA Technical Reports Server (NTRS)
Schaupp, R. W.; Sawyer, C. D.
1971-01-01
The performance of nuclear electric propulsion systems (NEP) has been evaluated for a wide variety of missions in an attempt to establish the commonality of NEP system requirements. Emphasis was given to those requirements and system characteristics that serve as guidelines for current technology development programs. Various interactions and tradeoffs between NEP system and mission parameters are described. The results show that the most significant factors in selecting NEP system size are launch mode (direct or spiral escape) and, to a weaker extent, launch vehicle capability. Other factors such as mission, payload, and thrust time constraints, have little influence, thus allowing one NEP system to be used for many missions. The results indicated that a 100 kWe NEP would be suitable for most direct escape missions and a 250 kWe NEP system would be suitable for more demanding missions that use the spiral escape mode.
Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors.
Heller, Elizabeth A; Cates, Hannah M; Peña, Catherine J; Sun, Haosheng; Shao, Ningyi; Feng, Jian; Golden, Sam A; Herman, James P; Walsh, Jessica J; Mazei-Robison, Michelle; Ferguson, Deveroux; Knight, Scott; Gerber, Mark A; Nievera, Christian; Han, Ming-Hu; Russo, Scott J; Tamminga, Carol S; Neve, Rachael L; Shen, Li; Zhang, H Steve; Zhang, Feng; Nestler, Eric J
2014-12-01
Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior.
Hogarth, Lee; Lam-Cassettari, Christa; Pacitti, Helena; Currah, Tara; Mahlberg, Justin; Hartley, Lucie; Moustafa, Ahmed
2018-05-22
Animal studies have demonstrated that chronic exposure to drugs of abuse impairs goal-directed control over action selection indexed by the outcome-devaluation and specific Pavlovian to instrumental transfer procedures, suggesting this impairment might underpin addiction. However, there is currently only weak evidence for impaired goal-directed control in human drug users. Two experiments were undertaken in which treatment-seeking drug users and non-matched normative reference samples (controls) completed outcome-devaluation and specific Pavlovian to instrumental transfer procedures notionally translatable to animal procedures (Experiment 2 used a more challenging biconditional schedule). The two experiments found significant outcome-devaluation and specific Pavlovian to instrumental transfer effects overall and there was no significant difference between groups in the magnitude of these effects. Moreover, Bayes factor supported the null hypothesis for these group comparisons. Although limited by non-matched group comparisons and small sample sizes, the two studies suggest that treatment-seeking drug users have intact goal-directed control over action selection, adding uncertainty to already mixed evidence concerning the role of habit learning in human drug dependence. Neuro-interventions might seek to tackle goal-directed drug-seeking rather than habit formation in drug users. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Schaschl, Helmut; Huber, Susanne; Schaefer, Katrin; Windhager, Sonja; Wallner, Bernard; Fieder, Martin
2015-05-13
The evolutionary highly conserved neurohypophyseal hormones oxytocin and arginine vasopressin play key roles in regulating social cognition and behaviours. The effects of these two peptides are meditated by their specific receptors, which are encoded by the oxytocin receptor (OXTR) and arginine vasopressin receptor 1a genes (AVPR1A), respectively. In several species, polymorphisms in these genes have been linked to various behavioural traits. Little, however, is known about whether positive selection acts on sequence variants in genes influencing variation in human behaviours. We identified, in both neuroreceptor genes, signatures of balancing selection in the cis-regulative acting sequences such as transcription factor binding and enhancer sequences, as well as in a transcriptional repressor sequence motif. Additionally, in the intron 3 of the OXTR gene, the SNP rs59190448 appears to be under positive directional selection. For rs59190448, only one phenotypical association is known so far, but it is in high LD' (>0.8) with loci of known association; i.e., variants associated with key pro-social behaviours and mental disorders in humans. Only for one SNP on the OXTR gene (rs59190448) was a sign of positive directional selection detected with all three methods of selection detection. For rs59190448, however, only one phenotypical association is known, but rs59190448 is in high LD' (>0.8), with variants associated with important pro-social behaviours and mental disorders in humans. We also detected various signatures of balancing selection on both neuroreceptor genes.
Hoskinson, Reed L [Rigby, ID; Svoboda, John M [Idaho Falls, ID; Bauer, William F [Idaho Falls, ID; Elias, Gracy [Idaho Falls, ID
2008-05-06
A method and apparatus is provided for monitoring a flow path having plurality of different solid components flowing therethrough. For example, in the harvesting of a plant material, many factors surrounding the threshing, separating or cleaning of the plant material and may lead to the inadvertent inclusion of the component being selectively harvested with residual plant materials being discharged or otherwise processed. In accordance with the present invention the detection of the selectively harvested component within residual materials may include the monitoring of a flow path of such residual materials by, for example, directing an excitation signal toward of flow path of material and then detecting a signal initiated by the presence of the selectively harvested component responsive to the excitation signal. The detected signal may be used to determine the presence or absence of a selected plant component within the flow path of residual materials.
Cappella, Joseph N.; Kim, Hyun Suk; Albarracín, Dolores
2014-01-01
The emerging media environment introduced fundamental changes in the quality and format of information available to the public, which can now flexibly seek, alter, and disseminate the information they receive. Therefore, the two processes of information selection and information retransmission are crucial for understanding the reach of any information available in the online information environment. From this starting point, we examine the common psychological motives driving information selection and transmission of attitude-relevant information: Defense and accuracy motives adding a focus on interpersonal motives. We also review message factors that can activate psychological motives leading to selection of retransmission of information, such as the desire for novelty and emotional stimulation. We speculate about the directions for the next generation of research necessary to understand exposure as a core outcome in media effects research and theory. PMID:26190944
Basman, Craig; Tariq, Afnan; Parmar, Yuvrajsinh J; Asti, Deepak; Coplan, Neil L; Singh, Varinder P; Reimers, Carl D
2018-06-19
Pharmacotherapy for percutaneous coronary interventions is essential to optimize the balance between thrombosis and bleeding. Currently, choices abound for the selection of antiplatelet and anticoagulation therapies during percutaneous intervention (PCI). This review article discusses the mechanisms, pharmacokinetics/dynamics, and clinical data behind the various pharmacotherapies including; aspirin, thienopyridines, glycoprotein IIb/IIIa inhibitors, vorapaxar, heparin, direct thrombin inhibitors, and factor Xa inhibitors. © 2018, Wiley Periodicals, Inc.
Row, Jeffrey R.; Knick, Steven T.; Oyler-McCance, Sara J.; Lougheed, Stephen C.; Fedy, Bradley C.
2017-01-01
Dispersal can impact population dynamics and geographic variation, and thus, genetic approaches that can establish which landscape factors influence population connectivity have ecological and evolutionary importance. Mixed models that account for the error structure of pairwise datasets are increasingly used to compare models relating genetic differentiation to pairwise measures of landscape resistance. A model selection framework based on information criteria metrics or explained variance may help disentangle the ecological and landscape factors influencing genetic structure, yet there are currently no consensus for the best protocols. Here, we develop landscape-directed simulations and test a series of replicates that emulate independent empirical datasets of two species with different life history characteristics (greater sage-grouse; eastern foxsnake). We determined that in our simulated scenarios, AIC and BIC were the best model selection indices and that marginal R2 values were biased toward more complex models. The model coefficients for landscape variables generally reflected the underlying dispersal model with confidence intervals that did not overlap with zero across the entire model set. When we controlled for geographic distance, variables not in the underlying dispersal models (i.e., nontrue) typically overlapped zero. Our study helps establish methods for using linear mixed models to identify the features underlying patterns of dispersal across a variety of landscapes.
Mendez, Yesenia P; Ralston, Penny A; Wickrama, Kandauda K A S; Bae, Dayoung; Young-Clark, Iris; Ilich, Jasminka Z
2018-06-01
This study examined lower life satisfaction, active coping and cardiovascular disease risk factors (diastolic and systolic blood pressure, body mass index, and circumferences) in older African Americans over the phases of an 18-month church-based intervention, using a quasi-experimental design. Participants (n = 89) were 45 years of age and older from six churches (three treatment, three comparison) in North Florida. Lower life satisfaction had a persistent unfavorable effect on weight variables. Active coping showed a direct beneficial effect on selected weight variables. However, active coping was adversely associated with blood pressure, and did not moderate the association between lower life satisfaction and cardiovascular risk factors. The intervention had a beneficial moderating influence on the association between lower life satisfaction and weight variables and on the association between active coping and these variables. Yet, this pattern did not hold for the association between active coping and blood pressure. The relationship of lower life satisfaction and selected cardiovascular risk factors and the positive effect of active coping were established, but findings regarding blood pressure suggest further study is needed.
Perception of earthquake risk in Taiwan: effects of gender and past earthquake experience.
Kung, Yi-Wen; Chen, Sue-Huei
2012-09-01
This study explored how individuals in Taiwan perceive the risk of earthquake and the relationship of past earthquake experience and gender to risk perception. Participants (n= 1,405), including earthquake survivors and those in the general population without prior direct earthquake exposure, were selected and interviewed through a computer-assisted telephone interviewing procedure using a random sampling and stratification method covering all 24 regions of Taiwan. A factor analysis of the interview data yielded a two-factor structure of risk perception in regard to earthquake. The first factor, "personal impact," encompassed perception of threat and fear related to earthquakes. The second factor, "controllability," encompassed a sense of efficacy of self-protection in regard to earthquakes. The findings indicated prior earthquake survivors and females reported higher scores on the personal impact factor than males and those with no prior direct earthquake experience, although there were no group differences on the controllability factor. The findings support that risk perception has multiple components, and suggest that past experience (survivor status) and gender (female) affect the perception of risk. Exploration of potential contributions of other demographic factors such as age, education, and marital status to personal impact, especially for females and survivors, is discussed. Future research on and intervention program with regard to risk perception are suggested accordingly. © 2012 Society for Risk Analysis.
Zaltsman, Julia B.; Heimel, J. Alexander
2015-01-01
Classic studies of lateral geniculate nucleus (LGN) and visual cortex (V1) in carnivores and primates have found that a majority of neurons in LGN exhibit a center-surround organization, while V1 neurons exhibit strong orientation selectivity and, in many species, direction selectivity. Recent work in the mouse and the monkey has discovered previously unknown classes of orientation- and direction-selective neurons in LGN. Furthermore, some recent studies in the mouse report that many LGN cells exhibit pronounced orientation biases that are of comparable strength to the subthreshold inputs to V1 neurons. These results raise the possibility that, in rodents, orientation biases of individual LGN cells make a substantial contribution to cortical orientation selectivity. Alternatively, the size and contribution of orientation- or direction-selective channels from LGN to V1 may vary across mammals. To address this question, we examined orientation and direction selectivity in LGN and V1 neurons of a highly visual diurnal rodent: the gray squirrel. In the representation of central vision, only a few LGN neurons exhibited strong orientation or direction selectivity. Across the population, LGN neurons showed weak orientation biases and were much less selective for orientation compared with V1 neurons. Although direction selectivity was weak overall, LGN layers 3abc, which contain neurons that express calbindin, exhibited elevated direction selectivity index values compared with LGN layers 1 and 2. These results suggest that, for central visual fields, the contribution of orientation- and direction-selective channels from the LGN to V1 is small in the squirrel. As in other mammals, this small contribution is elevated in the calbindin-positive layers of the LGN PMID:25717157
Comparison of a polymeric pseudostationary phase in EKC with ODS stationary phase in RP-HPLC.
Ni, Xinjiong; Zhang, Min; Xing, Xiaoping; Cao, Yuhua; Cao, Guangqun
2018-01-01
Poly(stearyl methacrylate-co-methacrylic acid) (P(SMA-co-MAA)) was induced as pseudostationary phase (PSP) in electrokinetic chromatography (EKC). The n-octadecyl groups in SMA were the same as that in octadecylsilane (ODS) C18 column. Thus, the present work focused on the comparison of selectivity between polymeric PSP and ODS stationary phase (SP), and the effect of organic modifiers on the selectivity of polymeric PSP and ODS SP. 1-butanol could directly interacted with PSP as a Class I modifier, and improved both of the methylene selectivity and polar group selectivity. When the analysis times were similar, the polymeric PSP exhibited better methylene selectivity and polar group selectivity. Although the hydrophobic groups were similar, the substituted benzenes elution order was different between polymeric PSP and ODS SP. Linear solvation energy relationships (LSER) model analysis found that polymeric PSP and ODS SP exhibited two same key factors in selectivity: hydrophobic interaction and hydrogen bonding acidity. But polymeric PSP exhibited relatively strong n- and π-electrons interaction to the analytes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Morgen, C S; Ängquist, L; Baker, J L; Andersen, A M N; Michaelsen, K F; Sørensen, T I A
2018-04-01
Prenatal risk factors for childhood overweight may operate indirectly through development in body size in early life and/or directly independent hereof. We quantified the effects of maternal and paternal body mass index (BMI), maternal age, socioeconomic position (SEP), parity, gestational weight gain, maternal smoking during pregnancy, caesarean section, birth weight, and BMI at 5 and 12 months on BMI and overweight at 7 and 11 years. Family triads with information on maternal, paternal and child BMI at ages 7 (n=29 374) and 11 years (n=18 044) were selected from the Danish National Birth Cohort. Information originated from maternal interviews and medical health examinations. Path analysis was used to estimate the direct and indirect effects of prenatal risk factors on childhood BMI z-scores (BMIz per unit score of the risk factor). Logistic regression was used to examine associations with overweight. The strongest direct effects on BMIz at age 7 were found for maternal and paternal BMI (0.19 BMIz and 0.14 BMIz per parental BMIz), low SEP (0.08 BMIz), maternal smoking (0.12 BMIz) and higher BMIz at 5 and 12 months (up to 0.19 BMIz per infant BMIz). For BMIz at age 11 with BMIz at age 7 included in the model, similar effects were found, but the direct effects of BMIz at age 5 and 12 months were mediated through BMI at age 7 (0.62 BMIz per BMIz). Same results were found for overweight. The sum of the direct effects can be translated to approximate absolute measures: 2.4 kg at 7 years, 5.7 kg at 11 years, in a child with average height and BMI. Parental BMI, low SEP and smoking during pregnancy have persisting, strong and direct effects on child BMI and overweight independent of birth weight and infancy BMI.
Delayed innocent bystander cell death following hypoxia in Caenorhabditis elegans
Sun, C-L; Kim, E; Crowder, C M
2014-01-01
After hypoxia, cells may die immediately or have a protracted course, living or dying depending on an incompletely understood set of cell autonomous and nonautonomous factors. In stroke, for example, some neurons are thought to die from direct hypoxic injury by cell autonomous primary mechanisms, whereas other so called innocent bystander neurons die from factors released from the primarily injured cells. A major limitation in identifying these factors is the inability of current in vivo models to selectively target a set of cells for hypoxic injury so that the primarily injured cells and the innocent bystanders are clearly delineated. In order to develop such a model, we generated transgenic Caenorhabditis elegans strains where 2–3% of somatic cells were made selectively sensitive to hypoxia. This was accomplished by cell type-specific wild-type rescue in either pharyngeal myocytes or GABAergic neurons of a hypoxia resistance-producing translation factor mutation. Surprisingly, hypoxic targeting of these relatively small subsets of non-essential cells produced widespread innocent bystander cell injury, behavioral dysfunction and eventual organismal death. The hypoxic injury phenotypes of the myocyte or neuron sensitized strains were virtually identical. Using this model, we show that the C. elegans insulin receptor/FOXO transcription factor pathway improves survival when activated only after hypoxic injury and blocks innocent bystander death. PMID:24317200
Delayed innocent bystander cell death following hypoxia in Caenorhabditis elegans.
Sun, C-L; Kim, E; Crowder, C M
2014-04-01
After hypoxia, cells may die immediately or have a protracted course, living or dying depending on an incompletely understood set of cell autonomous and nonautonomous factors. In stroke, for example, some neurons are thought to die from direct hypoxic injury by cell autonomous primary mechanisms, whereas other so called innocent bystander neurons die from factors released from the primarily injured cells. A major limitation in identifying these factors is the inability of current in vivo models to selectively target a set of cells for hypoxic injury so that the primarily injured cells and the innocent bystanders are clearly delineated. In order to develop such a model, we generated transgenic Caenorhabditis elegans strains where 2-3% of somatic cells were made selectively sensitive to hypoxia. This was accomplished by cell type-specific wild-type rescue in either pharyngeal myocytes or GABAergic neurons of a hypoxia resistance-producing translation factor mutation. Surprisingly, hypoxic targeting of these relatively small subsets of non-essential cells produced widespread innocent bystander cell injury, behavioral dysfunction and eventual organismal death. The hypoxic injury phenotypes of the myocyte or neuron sensitized strains were virtually identical. Using this model, we show that the C. elegans insulin receptor/FOXO transcription factor pathway improves survival when activated only after hypoxic injury and blocks innocent bystander death.
Exercise-induced biochemical changes and their potential influence on cancer: a scientific review
Thomas, Robert James; Kenfield, Stacey A; Jimenez, Alfonso
2017-01-01
Aim To review and discuss the available international literature regarding the indirect and direct biochemical mechanisms that occur after exercise, which could positively, or negatively, influence oncogenic pathways. Methods The PubMed, MEDLINE, Embase and Cochrane libraries were searched for papers up to July 2016 addressing biochemical changes after exercise with a particular reference to cancer. The three authors independently assessed their appropriateness for inclusion in this review based on their scientific quality and relevance. Results 168 papers were selected and categorised into indirect and direct biochemical pathways. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin-like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, oxidative stress and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and insulin resistance. Summary Exercise is one of several lifestyle factors known to lower the risk of developing cancer and is associated with lower relapse rates and better survival. This review highlights the numerous biochemical processes, which explain these potential anticancer benefits. PMID:27993842
MicroRNA-integrated and network-embedded gene selection with diffusion distance.
Huang, Di; Zhou, Xiaobo; Lyon, Christopher J; Hsueh, Willa A; Wong, Stephen T C
2010-10-29
Gene network information has been used to improve gene selection in microarray-based studies by selecting marker genes based both on their expression and the coordinate expression of genes within their gene network under a given condition. Here we propose a new network-embedded gene selection model. In this model, we first address the limitations of microarray data. Microarray data, although widely used for gene selection, measures only mRNA abundance, which does not always reflect the ultimate gene phenotype, since it does not account for post-transcriptional effects. To overcome this important (critical in certain cases) but ignored-in-almost-all-existing-studies limitation, we design a new strategy to integrate together microarray data with the information of microRNA, the major post-transcriptional regulatory factor. We also handle the challenges led by gene collaboration mechanism. To incorporate the biological facts that genes without direct interactions may work closely due to signal transduction and that two genes may be functionally connected through multi paths, we adopt the concept of diffusion distance. This concept permits us to simulate biological signal propagation and therefore to estimate the collaboration probability for all gene pairs, directly or indirectly-connected, according to multi paths connecting them. We demonstrate, using type 2 diabetes (DM2) as an example, that the proposed strategies can enhance the identification of functional gene partners, which is the key issue in a network-embedded gene selection model. More importantly, we show that our gene selection model outperforms related ones. Genes selected by our model 1) have improved classification capability; 2) agree with biological evidence of DM2-association; and 3) are involved in many well-known DM2-associated pathways.
In vitro Fab display: a cell-free system for IgG discovery
Stafford, Ryan L.; Matsumoto, Marissa L.; Yin, Gang; Cai, Qi; Fung, Juan Jose; Stephenson, Heather; Gill, Avinash; You, Monica; Lin, Shwu-Hwa; Wang, Willie D.; Masikat, Mary Rose; Li, Xiaofan; Penta, Kalyani; Steiner, Alex R.; Baliga, Ramesh; Murray, Christopher J.; Thanos, Christopher D.; Hallam, Trevor J.; Sato, Aaron K.
2014-01-01
Selection technologies such as ribosome display enable the rapid discovery of novel antibody fragments entirely in vitro. It has been assumed that the open nature of the cell-free reactions used in these technologies limits selections to single-chain protein fragments. We present a simple approach for the selection of multi-chain proteins, such as antibody Fab fragments, using ribosome display. Specifically, we show that a two-chain trastuzumab (Herceptin) Fab domain can be displayed in a format which tethers either the heavy or light chain to the ribosome while retaining functional antigen binding. Then, we constructed synthetic Fab HC and LC libraries and performed test selections against carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The Fab selection output was reformatted into full-length immunoglobulin Gs (IgGs) and directly expressed at high levels in an optimized cell-free system for immediate screening, purification and characterization. Several novel IgGs were identified using this cell-free platform that bind to purified CEA, CEA positive cells and VEGF. PMID:24586053
CHOW, Sze Loon; TING, Anselm Su; SU, Tin Tin
2014-01-01
Abstract This systematic review was conducted to develop a conceptual framework that addresses various factors associated with return to work among cancer survivors. Databases Medline, EMBASE, ProQuest, PubMed and ScienceDirect were systematically searched using medical subject headings [MeSH] for studies published in English from 1990 to 2013. Studies that described adult cancer patients’ self-reported data or patients’ point of view on factors associated with return to work or employment status following cancer diagnosis were included. Articles selection was conducted in three steps: selection based on title and abstract, retrieval of full text and additions of articles from reference lists and recommendations from experts. Disagreement in data extraction was solved by consultation of third reviewer. Out of twenty seven articles, breast cancer was the most studied type of cancer (30%) while colorectal cancer was studied independently in two articles (7.4%). Conceptual framework on return to work identifies factors under environmental, personal, work demand, work ability, health status and financial factors. Extensive search of scientific databases over last 24 years and the development of the conceptual frame-work are the strength of this review. Conceptual framework reveals the various factors including non-medical factors associated with return to work upon cancer diagnosis. It serves as a reminder to the policy makers to focus on modifiable factors as potential areas for intervention to assist cancer survivors return to work, especially those with little financial assistance and health insurance. PMID:28435811
Children's selective trust decisions: rational competence and limiting performance factors.
Hermes, Jonas; Behne, Tanya; Bich, Anna Elisa; Thielert, Christa; Rakoczy, Hannes
2018-03-01
Recent research has amply documented that even preschoolers learn selectively from others, preferring, for example, reliable over unreliable and competent over incompetent models. It remains unclear, however, what the cognitive foundations of such selective learning are, in particular, whether it builds on rational inferences or on less sophisticated processes. The current study, therefore, was designed to test directly the possibility that children are in principle capable of selective learning based on rational inference, yet revert to simpler strategies such as global impression formation under certain circumstances. Preschoolers (N = 75) were shown pairs of models that either differed in their degree of competence within one domain (strong vs. weak or knowledgeable vs. ignorant) or were both highly competent, but in different domains (e.g., strong vs. knowledgeable model). In the test trials, children chose between the models for strength- or knowledge-related tasks. The results suggest that, in fact, children are capable of rational inference-based selective trust: when both models were highly competent, children preferred the model with the competence most predictive and relevant for a given task. However, when choosing between two models that differed in competence on one dimension, children reverted to halo-style wide generalizations and preferred the competent models for both relevant and irrelevant tasks. These findings suggest that the rational strategies for selective learning, that children master in principle, can get masked by various performance factors. © 2017 John Wiley & Sons Ltd.
A Flight Evaluation of the Factors which Influence the Selection of Landing Approach Speeds
NASA Technical Reports Server (NTRS)
Drinkwater, Fred J., III; Cooper, George E.
1958-01-01
The factors which influence the selection of landing approach speeds are discussed from the pilot's point of view. Concepts were developed and data were obtained during a landing approach flight investigation of a large number of jet airplane configurations which included straight-wing, swept-wing, and delta-wing airplanes as well as several applications of boundary-layer control. Since the fundamental limitation to further reductions in approach speed on most configurations appeared to be associated with the reduction in the pilot's ability to control flight path angle and airspeed, this problem forms the basis of the report. A simplified equation is presented showing the basic parameters which govern the flight path angle and airspeed changes, and pilot control techniques are discussed in relation to this equation. Attention is given to several independent aerodynamic characteristics which do not affect the flight path angle or airspeed directly but which determine to a large extent the effort and attention required of the pilot in controlling these factors during the approach. These include stall characteristics, stability about all axes, and changes in trim due to thrust adjustments. The report considers the relationship between piloting technique and all of the factors previously mentioned. A piloting technique which was found to be highly desirable for control of high-performance airplanes is described and the pilot's attitudes toward low-speed flight which bear heavily on the selection of landing approach speeds under operational conditions are discussed.
Law, Andrew J.; Rivlis, Gil
2014-01-01
Pioneering studies demonstrated that novel degrees of freedom could be controlled individually by directly encoding the firing rate of single motor cortex neurons, without regard to each neuron's role in controlling movement of the native limb. In contrast, recent brain-computer interface work has emphasized decoding outputs from large ensembles that include substantially more neurons than the number of degrees of freedom being controlled. To bridge the gap between direct encoding by single neurons and decoding output from large ensembles, we studied monkeys controlling one degree of freedom by comodulating up to four arbitrarily selected motor cortex neurons. Performance typically exceeded random quite early in single sessions and then continued to improve to different degrees in different sessions. We therefore examined factors that might affect performance. Performance improved with larger ensembles. In contrast, other factors that might have reflected preexisting synaptic architecture—such as the similarity of preferred directions—had little if any effect on performance. Patterns of comodulation among ensemble neurons became more consistent across trials as performance improved over single sessions. Compared with the ensemble neurons, other simultaneously recorded neurons showed less modulation. Patterns of voluntarily comodulated firing among small numbers of arbitrarily selected primary motor cortex (M1) neurons thus can be found and improved rapidly, with little constraint based on the normal relationships of the individual neurons to native limb movement. This rapid flexibility in relationships among M1 neurons may in part underlie our ability to learn new movements and improve motor skill. PMID:24920030
Inferring directions of evolution from patterns of variation: The legacy of Sergei Meyen
Sharov, Alexei A.; Igamberdiev, Abir U.
2014-01-01
In the era of the Extended Evolutionary Synthesis, which no longer considers natural selection as the only leading factor of evolution, it is meaningful to revisit the legacy of biologists who discussed the role of alternative factors. Here we analyze the evolutionary views of Sergei Meyen (1935-1987), a paleobotanist who argued that the theory of evolution should incorporate a “nomothetical” approach which infers the laws of morphogenesis (i.e., form generation) from the observed patterns of variation in living organisms and in the fossil records. Meyen developed a theory of “repeated polymorphic sets” (RPSs), which he applied consistently to describe inter-organism variation in populations, intra-organism variation of metameric organs, variation of abnormalities, heterotopy, changes during embryo development, and inter-species variation within evolutionary lineages. The notion of RPS assumes the active nature of organisms that possess hidden morphogenic and behavioural capacities. Meyen's theory is compatible with Darwin's natural selection; however Meyen emphasized the importance of other forms of selection (e.g., selection of developmental trajectories, habitats, and behaviours) in choosing specific elements from the RPS. Finally, Meyen developed a new typological concept of time, where time represents variability (i.e., change) of real objects such as living organisms or geological formations. PMID:25072709
Elbasty, Ahmed; Metcalf, James
2017-12-01
Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration's tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured.
Sadeh, Naomi; Javdani, Shabnam; Finy, M. Sima; Verona, Edelyn
2012-01-01
OBJECTIVE Women and men generally differ in how frequently they engage in other-and self-directed physical violence and may show distinct emotional risk factors for engagement in these high-impact behaviors. To inform this area, we investigated gender differences in the relationship of emotional tendencies (i.e., anger, hostility, and anhedonic depression) that may represent risk for other-directed (i.e., physical fighting, attacking others unprovoked) and self-directed violence (i.e., self-injury, suicide attempts). METHOD The ethnically-diverse sample consisted of 372 adults (252 men and 120 women ages 18–55) with a history of criminal convictions. Facets of emotional risk assessed with the Aggression Questionnaire (Buss & Warren, 2000) and Mood and Anxiety Symptom Questionnaire (Watson et al., 1995) were entered simultaneously as explanatory variables in regression analyses to investigate their unique contributions to other- and self-directed physical violence in men and women. RESULTS Analyses revealed anhedonic depressive tendencies negatively predicted other-directed violence and positively predicted self-directed violence in both men and women, consistent with a model of depression in which aggression is turned inwards (Henriksson et al., 1993). Gender differences, however, emerged for the differential contributions of anger and hostility to other-and self-directed violence. Specifically, trait anger (i.e., difficulty controlling one’s temper) was associated with other-directed violence selectively in men, whereas trait hostility (i.e., suspiciousness and alienation) was associated with self- and other-directed violence among women. CONCLUSIONS The divergent findings for trait anger and hostility underscore the need to examine gender-specific risk factors for physical violence to avoid excluding potentially useful clinical features of these mental health outcomes. PMID:21261437
Donovan, Lisa A; Dudley, Susan A; Rosenthal, David M; Ludwig, Fulco
2007-05-01
Plant water-use efficiency (WUE) is expected to affect plant fitness and thus be under natural selection in arid habitats. Although many natural population studies have assessed plant WUE, only a few related WUE to fitness. The further determination of whether selection on WUE is direct or indirect through functionally related traits has yielded no consistent results. For natural populations of two desert annual sunflowers, Helianthus anomalus and H. deserticola, we used phenotypic selection analysis with vegetative biomass as the proxy for fitness to test (1) whether there was direct and indirect selection on WUE (carbon isotope ratio) and related traits (leaf N, area, succulence) and (2) whether direct selection was consistent with hypothesized drought/dehydration escape and avoidance strategies. There was direct selection for lower WUE in mesic and dry H. anomalus populations, consistent with dehydration escape, even though it is the longer lived of the two species. For mesic H. anomalus, direct selection favored lower WUE and higher N, suggesting that plants may be "wasting water" to increase N delivery via the transpiration stream. For the shorter lived H. deserticola in the direr habitat, there was indirect selection for lower WUE, inconsistent with drought escape. There was also direct selection for higher leaf N, succulence and leaf size. There was no direct selection for higher WUE consistent with dehydration avoidance in either species. Thus, in these natural populations of two desert dune species higher fitness was associated with some combination direct and indirect selection for lower WUE, higher leaf N and larger leaf size. Our understanding of the adaptive value of plant ecophysiological traits will benefit from further consideration of related traits such as leaf nitrogen and more tests in natural populations.
Determining the Effect of Natural Selection on Linked Neutral Divergence across Species
Phung, Tanya N.; Lohmueller, Kirk E.
2016-01-01
A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation. PMID:27508305
Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.
Phung, Tanya N; Huber, Christian D; Lohmueller, Kirk E
2016-08-01
A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation.
Marsden, Clare D; Ortega-Del Vecchyo, Diego; O'Brien, Dennis P; Taylor, Jeremy F; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D; Wayne, Robert K; Lohmueller, Kirk E
2016-01-05
Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.
Marsden, Clare D.; Ortega-Del Vecchyo, Diego; O’Brien, Dennis P.; Taylor, Jeremy F.; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D.; Wayne, Robert K.; Lohmueller, Kirk E.
2016-01-01
Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508
Psychosocial Factors Influencing Smokeless Tobacco Use by Teenage Military Dependents
1994-01-01
age and grade Demographics both show strong bivariate relationships with the outcome MALE-male gender measures, we selected to use only one of these...a positive sign indicating a direct relation- no impact for either gender . Attitude and other tobacco influ- ship and a negative sign an inverse...by both genders . nlficant. However, if the interval includes one but is highly For both genders , the strongest explanatory variable for trial skewed
Improving pedagogic competence using an e-learning approach for pre-service mathematics teachers
NASA Astrophysics Data System (ADS)
Retnowati, E.; Murdiyani, N. M.; Marsigit; Sugiman; Mahmudi, A.
2018-03-01
This article reported a classroom action research that was aimed to improve student’s pedagogic competence during a course namely Methods of Mathematics Instruction. An asynchronous e-learning approach was provided as supplementary material to the main lecture. This e-learning consisted of selected references and educational website addresses and also facilitated online discussions about various methods of mathematics instructions. The subject was twenty-six pre-service teachers in the Department of Mathematics Education, Yogyakarta State University, Indonesia, conducted by the researchers. The research completed three cycles, where each cycle consisted of plan-action-reflection. Through observation, documentation, and interview, it was concluded that asynchronous e-learning might be used to improve pedagogic competence when direct instruction is also applied in the classroom. Direct instruction in this study provided review, explanation, scheme, and examples which could be used by students to select relevant resources in the e-learning portal. Moreover, the pedagogic competence improved after students accomplished assignments to identify aspects of pedagogic instruction either from analyzing videos in e-learning course or simulating in the classroom with direct commentaries. Supporting factors were enthusiasm, discipline, and interactions among students and lecturer that were built throughout the lectures.
Mäkinen, H S; Cano, J M; Merilä, J
2008-08-01
Natural selection is expected to leave an imprint on the neutral polymorphisms at the adjacent genomic regions of a selected gene. While directional selection tends to reduce within-population genetic diversity and increase among-population differentiation, the reverse is expected under balancing selection. To identify targets of natural selection in the three-spined stickleback (Gasterosteus aculeatus) genome, 103 microsatellite and two indel markers including expressed sequence tags (EST) and quantitative trait loci (QTL)-associated loci, were genotyped in four freshwater and three marine populations. The results indicated that a high proportion of loci (14.7%) might be affected by balancing selection and a lower proportion (2.8%) by directional selection. The strongest signatures of directional selection were detected in a microsatellite locus and two indel markers located in the intronic regions of the Eda-gene coding for the number of lateral plates. Yet, other microsatellite loci previously found to be informative in QTL-mapping studies revealed no signatures of selection. Two novel microsatellite loci (Stn12 and Stn90) located in chromosomes I and VIII, respectively, showed signals of directional selection and might be linked to genomic regions containing gene(s) important for adaptive divergence. Although the coverage of the total genomic content was relatively low, the predominance of balancing selection signals is in agreement with the contention that balancing, rather than directional selection is the predominant mode of selection in the wild.
Venetis, Maria K; Chernichky-Karcher, Skye; Gettings, Patricia E
2018-06-01
Within the context of mental illness disclosure between friends, this study tested the disclosure decision-making model (DD-MM; Greene, 2009) to comprehensively investigate factors that predict disclosure enactment strategies. The DD-MM describes how individuals determine whether they will reveal or conceal non-visible health information. Processes of revealing, called disclosures, take various forms including preparation and rehearsal, directness, third-party disclosure, incremental disclosures, entrapment, and indirect mediums (Afifi & Steuber, 2009). We explore the disclosure decision-making process to understand how college students select to disclose their mental illness information with a friend. Participants were 144 students at a Midwestern university who had disclosed their mental illness information to a friend. Structural equation modeling analyses revealed that college students choose strategies based on their evaluation of information assessment and closeness, and that for some strategies, efficacy mediates the relationship between information assessment and strategy. This manuscript discusses implications of findings and suggests direction for future research.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Husain, Tausif; Hasan, Iftekhar; Sozer, Yilmaz
This paper presents the design considerations of a double-sided transverse flux machine (TFM) for direct-drive wind turbine applications. The TFM has a modular structure with quasi-U stator cores and ring windings. The rotor is constructed with ferrite magnets in a flux-concentrating arrangement to achieve high air gap flux density. The design considerations for this TFM with respect to initial sizing, pole number selection, key design ratios, and pole shaping are presented in this paper. Pole number selection is critical in the design process of a TFM because it affects both the torque density and power factor under fixed magnetic andmore » changing electrical loading. Several key design ratios are introduced to facilitate the design procedure. The effect of pole shaping on back-emf and inductance is also analyzed. These investigations provide guidance toward the required design of a TFM for direct-drive applications. The analyses are carried out using analytical and three-dimensional finite element analysis. A prototype is under construction for experimental verification.« less
Ajami, Sima; Rajabzadeh, Ahmad; Ketabi, Saeedeh
2014-01-01
Organizations try to outsource their activities as much as possible in order to prevent the problems and use organizational capabilities in Information Technology (IT) field. The purpose of this paper was first, to express the effective criteria for selecting suppliers of IT services, second, to explain the advantages and disadvantages of outsourcing IT in hospitals. This study was narrative review, which search was conducted with the help of libraries, books, conference proceedings, and databases of Science Direct, PubMed, Proquest, Springer, and SID (Scientific Information Database). In our searches, we employed the following keywords and their combinations: Outsourcing, information technology, hospital, decision making, and criteria. The preliminary search resulted in 120 articles, which were published between 2000 and 2013 during July 2013. After a careful analysis of the content of each paper, a total of 46 papers were selected based on their relevancy. The criteria and sub-criteria influencing outsourcing decisions in Iranian hospitals were identified in six major categories including administrative issues, issues related to the service/product, technology factors, environmental factors, risks, and economic factors associated with 15 sub-criteria containing business integration, dependence on suppliers, human resources, focus on core competencies, facilities and physical capital, innovation, quality, speed of service delivery, flexibility, market capabilities, geographical location, security, management control, cost, and financial capability. Identify the advantages and disadvantages of outsourcing and effective criteria in IT services supplier selection causes the managers be able to take the most appropriate decision to select supplier of IT services. This is a general review on influencing criteria for electing of supplier of information technology services in hospitals. PMID:25540781
Ajami, Sima; Rajabzadeh, Ahmad; Ketabi, Saeedeh
2014-01-01
Organizations try to outsource their activities as much as possible in order to prevent the problems and use organizational capabilities in Information Technology (IT) field. The purpose of this paper was first, to express the effective criteria for selecting suppliers of IT services, second, to explain the advantages and disadvantages of outsourcing IT in hospitals. This study was narrative review, which search was conducted with the help of libraries, books, conference proceedings, and databases of Science Direct, PubMed, Proquest, Springer, and SID (Scientific Information Database). In our searches, we employed the following keywords and their combinations: Outsourcing, information technology, hospital, decision making, and criteria. The preliminary search resulted in 120 articles, which were published between 2000 and 2013 during July 2013. After a careful analysis of the content of each paper, a total of 46 papers were selected based on their relevancy. The criteria and sub-criteria influencing outsourcing decisions in Iranian hospitals were identified in six major categories including administrative issues, issues related to the service/product, technology factors, environmental factors, risks, and economic factors associated with 15 sub-criteria containing business integration, dependence on suppliers, human resources, focus on core competencies, facilities and physical capital, innovation, quality, speed of service delivery, flexibility, market capabilities, geographical location, security, management control, cost, and financial capability. Identify the advantages and disadvantages of outsourcing and effective criteria in IT services supplier selection causes the managers be able to take the most appropriate decision to select supplier of IT services. This is a general review on influencing criteria for electing of supplier of information technology services in hospitals.
Human factors issues for interstellar spacecraft
NASA Technical Reports Server (NTRS)
Cohen, Marc M.; Brody, Adam R.
1991-01-01
Developments in research on space human factors are reviewed in the context of a self-sustaining interstellar spacecraft based on the notion of traveling space settlements. Assumptions about interstellar travel are set forth addressing costs, mission durations, and the need for multigenerational space colonies. The model of human motivation by Maslow (1970) is examined and directly related to the design of space habitat architecture. Human-factors technology issues encompass the human-machine interface, crew selection and training, and the development of spaceship infrastructure during transtellar flight. A scenario for feasible instellar travel is based on a speed of 0.5c, a timeframe of about 100 yr, and an expandable multigenerational crew of about 100 members. Crew training is identified as a critical human-factors issue requiring the development of perceptual and cognitive aids such as expert systems and virtual reality.
Mass extinctions: Persistent problems and new directions
NASA Technical Reports Server (NTRS)
Jablonski, D.
1994-01-01
Few contest that mass extinctions have punctuated the history of life, or that those events were so pervasive environmentally, taxonomically, and geographically that physical forcing factors were probably involved. However, consensus remains elusive on the nature of those factors, and on how a given perturbation - impact, volcanism, sea-level change, or ocean anoxic event - could actually generate the observed intensity and selectivity of biotic losses. At least two basic problems underlie these long-standing disagreements: difficulties in resolving the fine details of taxon ranges and abundances immediately prior to and after an extinction boundary and the scarcity of simple, unitary cause-and-effect relations in complex biological systems.
Lievens, Filip; Sackett, Paul R
2017-01-01
Past reviews and meta-analyses typically conceptualized and examined selection procedures as holistic entities. We draw on the product design literature to propose a modular approach as a complementary perspective to conceptualizing selection procedures. A modular approach means that a product is broken down into its key underlying components. Therefore, we start by presenting a modular framework that identifies the important measurement components of selection procedures. Next, we adopt this modular lens for reviewing the available evidence regarding each of these components in terms of affecting validity, subgroup differences, and applicant perceptions, as well as for identifying new research directions. As a complement to the historical focus on holistic selection procedures, we posit that the theoretical contributions of a modular approach include improved insight into the isolated workings of the different components underlying selection procedures and greater theoretical connectivity among different selection procedures and their literatures. We also outline how organizations can put a modular approach into operation to increase the variety in selection procedures and to enhance the flexibility in designing them. Overall, we believe that a modular perspective on selection procedures will provide the impetus for programmatic and theory-driven research on the different measurement components of selection procedures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Weitz, Jeffrey I; Fredenburgh, James C
2018-02-01
The goal of anticoagulant therapy is to attenuate thrombosis without compromising hemostasis. Although the direct oral anticoagulants are associated with less intracranial hemorrhage than vitamin K antagonists, bleeding remains their major side effect. Factor XI has emerged as a promising target for anticoagulants that may be safer than those currently available. The focus on factor XI stems from epidemiological evidence of its role in thrombosis, the observation of attenuated thrombosis in factor XI-deficient mice, identification of novel activators, and the fact that factor XI deficiency is associated with only a mild bleeding diathesis. Proof-of-concept comes from the demonstration that compared with enoxaparin, factor XI knockdown reduces venous thromboembolism without increasing bleeding after elective knee arthroplasty. This article rationalizes the selection of factor XI as a target for new anticoagulants, reviews the agents under development, and outlines a potential path forward for their development. © 2017 American Heart Association, Inc.
Canine tooth size and fitness in male mandrills (Mandrillus sphinx).
Leigh, Steven R; Setchell, Joanna M; Charpentier, Marie; Knapp, Leslie A; Wickings, E Jean
2008-07-01
Sexual selection theory explains the evolution of exaggerated male morphologies and weaponry, but the fitness consequences of developmental and age-related changes in these features remain poorly understood. This long-term study of mandrill monkeys (Mandrillus sphinx) demonstrates how age-related changes in canine tooth weaponry and adult canine size correlate closely with male lifetime reproductive success. Combining long-term demographic and morphometric data reveals that male fitness covaries simply and directly with canine ontogeny, adult maximum size, and wear. However, fitness is largely independent of other somatometrics. Male mandrills sire offspring almost exclusively when their canines exceed approximately 30 mm, or two-thirds of average adult value (45 mm). Moreover, sires have larger canines than nonsires. The tooth diminishes through wear as animals age, corresponding with, and perhaps influencing, reproductive senescence. These factors combine to constrain male reproductive opportunities to a brief timespan, defined by the period of maximum canine length. Sexually-selected weaponry, especially when it is nonrenewable like the primate canine tooth, is intimately tied to the male life course. Our analyses of this extremely dimorphic species indicate that sexual selection is closely intertwined with growth, development, and aging, pointing to new directions for sexual selection theory. Moreover, the primate canine tooth has potential as a simple mammalian system for testing genetically-based models of aging. Finally, the tooth may record details of life histories in fossil primates, especially when sexual selection has played a role in the evolution of dimorphism.
Attentional selection in visual perception, memory and action: a quest for cross-domain integration
Schneider, Werner X.; Einhäuser, Wolfgang; Horstmann, Gernot
2013-01-01
For decades, the cognitive and neural sciences have benefitted greatly from a separation of mind and brain into distinct functional domains. The tremendous success of this approach notwithstanding, it is self-evident that such a view is incomplete. Goal-directed behaviour of an organism requires the joint functioning of perception, memory and sensorimotor control. A prime candidate for achieving integration across these functional domains are attentional processes. Consequently, this Theme Issue brings together studies of attentional selection from many fields, both experimental and theoretical, that are united in their quest to find overreaching integrative principles of attention between perception, memory and action. In all domains, attention is understood as combination of competition and priority control (‘bias’), with the task as a decisive driving factor to ensure coherent goal-directed behaviour and cognition. Using vision as the predominant model system for attentional selection, many studies of this Theme Issue focus special emphasis on eye movements as a selection process that is both a fundamental action and serves a key function in perception. The Theme Issue spans a wide range of methods, from measuring human behaviour in the real word to recordings of single neurons in the non-human primate brain. We firmly believe that combining such a breadth in approaches is necessary not only for attentional selection, but also to take the next decisive step in all of the cognitive and neural sciences: to understand cognition and behaviour beyond isolated domains. PMID:24018715
The responsiveness of biological motion processing areas to selective attention towards goals.
Herrington, John; Nymberg, Charlotte; Faja, Susan; Price, Elinora; Schultz, Robert
2012-10-15
A growing literature indicates that visual cortex areas viewed as primarily responsive to exogenous stimuli are susceptible to top-down modulation by selective attention. The present study examines whether brain areas involved in biological motion perception are among these areas-particularly with respect to selective attention towards human movement goals. Fifteen participants completed a point-light biological motion study following a two-by-two factorial design, with one factor representing an exogenous manipulation of human movement goals (goal-directed versus random movement), and the other an endogenous manipulation (a goal identification task versus an ancillary color-change task). Both manipulations yielded increased activation in the human homologue of motion-sensitive area MT+ (hMT+) as well as the extrastriate body area (EBA). The endogenous manipulation was associated with increased right posterior superior temporal sulcus (STS) activation, whereas the exogenous manipulation was associated with increased activation in left posterior STS. Selective attention towards goals activated a portion of left hMT+/EBA only during the perception of purposeful movement-consistent with emerging theories associating this area with the matching of visual motion input to known goal-directed actions. The overall pattern of results indicates that attention towards the goals of human movement activates biological motion areas. Ultimately, selective attention may explain why some studies examining biological motion show activation in hMT+ and EBA, even when using control stimuli with comparable motion properties. Copyright © 2012 Elsevier Inc. All rights reserved.
Direct medical cost of overweight and obesity in the United States: a quantitative systematic review
Tsai, Adam Gilden; Williamson, David F.; Glick, Henry A.
2010-01-01
Objectives To estimate per-person and aggregate direct medical costs of overweight and obesity and to examine the effect of study design factors. Methods PubMed (1968–2009), EconLit (1969–2009), and Business Source Premier (1995–2009) were searched for original studies. Results were standardized to compute the incremental cost per overweight person and per obese person, and to compute the national aggregate cost. Results A total of 33 U.S. studies met review criteria. Among the 4 highest quality studies, the 2008 per-person direct medical cost of overweight was $266 and of obesity was $1723. The aggregate national cost of overweight and obesity combined was $113.9 billion. Study design factors that affected cost estimate included: use of national samples versus more selected populations; age groups examined; inclusion of all medical costs versus obesity-related costs only; and BMI cutoffs for defining overweight and obesity. Conclusions Depending on the source of total national health care expenditures used, the direct medical cost of overweight and obesity combined is approximately 5.0% to 10% of U.S. health care spending. Future studies should include nationally representative samples, evaluate adults of all ages, report all medical costs, and use standard BMI cutoffs. PMID:20059703
He, Jing; Guo, Jianglong; Jiang, Bo; Yao, Ruijuan; Wu, Yao
2017-01-01
Abstract While both induction culture media and matrix have been reported to regulate the stem cell fate, little is known about which factor plays a more decisive role in directing the MSC differentiation lineage as well as the underlying mechanisms. To this aim, we seeded MSCs on HA-collagen and HA-synthetic hydrogel matrixes, which had demonstrated highly different potentials toward osteoblastic and chondrocytic differentiation lineages, respectively, and cultured them with osteogenic, chondrogenic and normal culture media, respectively. A systematic comparison has been carried out on the effects of induction media and matrix on MSC adhesion, cytoskeleton organization, proliferation, and in particular differentiation into the osteoblastic and chondrocytic lineages. The results demonstrated that the matrix selection had a much more profound effect on directing the differentiation lineage than the induction media did. The strong modulation effect on the transcription activities might be the critical factor contributing to the above observations in our study, where canonical Wnt-β-Catenin signal pathway was directly involved in the matrix-driven osteoblastic differentiation. Such findings not only provide a critical insight on natural cellular events leading to the osteoblastic and chondrocytic differentiations, but also have important implications in biomaterial design for tissue engineering applications. PMID:29026640
Yu, Ron X.; Liu, Jie; True, Nick; Wang, Wei
2008-01-01
A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets. PMID:18350157
Directional selection effects on patterns of phenotypic (co)variation in wild populations
Patton, J. L.; Hubbe, A.; Marroig, G.
2016-01-01
Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. PMID:27881744
Split marketing as a risk factor for Salmonella enterica infection in swine.
Rostagno, Marcos H; Hurd, H Scott; McKean, James D
2009-09-01
On-farm reduction of Salmonella carriage prevalence in pigs requires the identification of risk factors to direct interventions development. This study was designed to determine if split marketing of finishing pigs constitutes a risk factor for Salmonella infections, by comparing Salmonella prevalence in the first group of pigs selected for harvest ("first pull") versus the prevalence in the last group of pigs selected for harvest ("close out") from multiple commercial finishing lots. Nine paired samplings were conducted consisting in matched groups of pigs from individual barns as the first pull and the close out with a 4-week interval between groups. From each group, fecal and meat samples were collected, on-farm and at harvest, respectively. Fecal samples were selectively enriched, and analyzed for the presence of Salmonella, whereas meat juice samples were analyzed for the presence of antibodies against Salmonella. In 7/9 (77.8%) of the studied barns, an increase in Salmonella prevalence was observed, based on both bacteriologic and serologic analysis. Overall, there was an increase of 9.2% (p < 0.05) in bacteriologic prevalence, and 31.3% (p < 0.05) in serologic prevalence from first pull to close out groups. This study demonstrates that a significant increase in Salmonella prevalence occurs between the first and the last group of pigs harvested from finishing lots, with close out groups of market pigs posing a higher risk for Salmonella contaminations.
Preferred Primary Healthcare Provider Choice Among Insured Persons in Ashanti Region, Ghana
Boachie, Micheal Kofi
2016-01-01
Background: In early 2012, National Health Insurance Scheme (NHIS) members in Ashanti Region were allowed to choose their own primary healthcare providers. This paper investigates the factors that enrolees in the Ashanti Region considered in choosing preferred primary healthcare providers (PPPs) and direction of association of such factors with the choice of PPP. Methods: Using a cross-sectional study design, the study sampled 600 NHIS enrolees in Kumasi Metro area and Kwabre East district. The sampling methods were a combination of simple random and systematic sampling techniques at different stages. Descriptive statistics were used to analyse demographic information and the criteria for selecting PPP. Multinomial logistic regression technique was used to ascertain the direction of association of the factors and the choice of PPP using mission PPPs as the base outcome. Results: Out of the 600 questionnaires administered, 496 were retained for further analysis. The results show that availability of essential drugs (53.63%) and doctors (39.92%), distance or proximity (49.60%), provider reputation (39.52%), waiting time (39.92), additional charges (37.10%), and recommendations (48.79%) were the main criteria adopted by enrolees in selecting PPPs. In the regression, income (-0.0027), availability of doctors (-1.82), additional charges (-2.14) and reputation (-2.09) were statistically significant at 1% in influencing the choice of government PPPs. On the part of private PPPs, availability of drugs (2.59), waiting time (1.45), residence (-2.62), gender (-2.89), and reputation (-2.69) were statistically significant at 1% level. Presence of additional charges (-1.29) was statistically significant at 5% level. Conclusion: Enrolees select their PPPs based on such factors as availability of doctors and essential drugs, reputation, waiting time, income, and their residence. Based on these findings, there is the need for healthcare providers to improve on their quality levels by ensuring constant availability of essential drugs, doctors, and shorter waiting time. However, individual enrolees may value each criterion differently. Thus, not all enrolees may be motivated by same concerns. This requires providers to be circumspect regarding the factors that may attract enrolees. The National Health Insurance Authority (NHIA) should also ensure timely release of funds to help providers procure the necessary medical supplies to ensure quality service PMID:26927586
Preferred Primary Healthcare Provider Choice Among Insured Persons in Ashanti Region, Ghana.
Boachie, Micheal Kofi
2015-10-20
In early 2012, National Health Insurance Scheme (NHIS) members in Ashanti Region were allowed to choose their own primary healthcare providers. This paper investigates the factors that enrolees in the Ashanti Region considered in choosing preferred primary healthcare providers (PPPs) and direction of association of such factors with the choice of PPP. Using a cross-sectional study design, the study sampled 600 NHIS enrolees in Kumasi Metro area and Kwabre East district. The sampling methods were a combination of simple random and systematic sampling techniques at different stages. Descriptive statistics were used to analyse demographic information and the criteria for selecting PPP. Multinomial logistic regression technique was used to ascertain the direction of association of the factors and the choice of PPP using mission PPPs as the base outcome. Out of the 600 questionnaires administered, 496 were retained for further analysis. The results show that availability of essential drugs (53.63%) and doctors (39.92%), distance or proximity (49.60%), provider reputation (39.52%), waiting time (39.92), additional charges (37.10%), and recommendations (48.79%) were the main criteria adopted by enrolees in selecting PPPs. In the regression, income (-0.0027), availability of doctors (-1.82), additional charges (-2.14) and reputation (-2.09) were statistically significant at 1% in influencing the choice of government PPPs. On the part of private PPPs, availability of drugs (2.59), waiting time (1.45), residence (-2.62), gender (-2.89), and reputation (-2.69) were statistically significant at 1% level. Presence of additional charges (-1.29) was statistically significant at 5% level. Enrolees select their PPPs based on such factors as availability of doctors and essential drugs, reputation, waiting time, income, and their residence. Based on these findings, there is the need for healthcare providers to improve on their quality levels by ensuring constant availability of essential drugs, doctors, and shorter waiting time. However, individual enrolees may value each criterion differently. Thus, not all enrolees may be motivated by same concerns. This requires providers to be circumspect regarding the factors that may attract enrolees. The National Health Insurance Authority (NHIA) should also ensure timely release of funds to help providers procure the necessary medical supplies to ensure quality service. © 2016 by Kerman University of Medical Sciences.
Direction selectivity in the larval zebrafish tectum is mediated by asymmetric inhibition.
Grama, Abhinav; Engert, Florian
2012-01-01
The extraction of the direction of motion is an important computation performed by many sensory systems and in particular, the mechanism by which direction-selective retinal ganglion cells (DS-RGCs) in the retina acquire their selective properties, has been studied extensively. However, whether DS-RGCs simply relay this information to downstream areas or whether additional and potentially de novo processing occurs in these recipient structures is a matter of great interest. Neurons in the larval zebrafish tectum, the largest retino-recipent area in this animal, show direction-selective (DS) responses to moving visual stimuli but how these properties are acquired is still unknown. In order to study this, we first used two-photon calcium imaging to classify the population responses of tectal cells to bars moving at different speeds and in different directions. Subsequently, we performed in vivo whole cell electrophysiology on these DS tectal neurons and we found that their inhibitory inputs were strongly biased toward the null direction of motion, whereas the excitatory inputs showed little selectivity. In addition, we found that excitatory currents evoked by a stimulus moving in the preferred direction occurred before the inhibitory currents whereas a stimulus moving in the null direction evoked currents in the reverse temporal order. The membrane potential modulations resulting from these currents were enhanced by the spike generation mechanism to generate amplified direction selectivity in the spike output. Thus, our results implicate a local inhibitory circuit in generating direction selectivity in tectal neurons.
Direction selectivity in the larval zebrafish tectum is mediated by asymmetric inhibition
Grama, Abhinav; Engert, Florian
2012-01-01
The extraction of the direction of motion is an important computation performed by many sensory systems and in particular, the mechanism by which direction-selective retinal ganglion cells (DS-RGCs) in the retina acquire their selective properties, has been studied extensively. However, whether DS-RGCs simply relay this information to downstream areas or whether additional and potentially de novo processing occurs in these recipient structures is a matter of great interest. Neurons in the larval zebrafish tectum, the largest retino-recipent area in this animal, show direction-selective (DS) responses to moving visual stimuli but how these properties are acquired is still unknown. In order to study this, we first used two-photon calcium imaging to classify the population responses of tectal cells to bars moving at different speeds and in different directions. Subsequently, we performed in vivo whole cell electrophysiology on these DS tectal neurons and we found that their inhibitory inputs were strongly biased toward the null direction of motion, whereas the excitatory inputs showed little selectivity. In addition, we found that excitatory currents evoked by a stimulus moving in the preferred direction occurred before the inhibitory currents whereas a stimulus moving in the null direction evoked currents in the reverse temporal order. The membrane potential modulations resulting from these currents were enhanced by the spike generation mechanism to generate amplified direction selectivity in the spike output. Thus, our results implicate a local inhibitory circuit in generating direction selectivity in tectal neurons. PMID:22969706
Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.
Philip, Philip A; Lutz, Manfred P
2015-10-01
Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.
Plant-parasite coevolution: bridging the gap between genetics and ecology.
Brown, James K M; Tellier, Aurélien
2011-01-01
We review current ideas about coevolution of plants and parasites, particularly processes that generate genetic diversity. Frequencies of host resistance and parasite virulence alleles that interact in gene-for-gene (GFG) relationships coevolve in the familiar boom-and-bust cycle, in which resistance is selected when virulence is rare, and virulence is selected when resistance is common. The cycle can result in stable polymorphism when diverse ecological and epidemiological factors cause negative direct frequency-dependent selection (ndFDS) on host resistance, parasite virulence, or both, such that the benefit of a trait to fitness declines as its frequency increases. Polymorphism can also be stabilized by overdominance, when heterozygous hosts have greater resistance than homozygotes to diverse pathogens. Genetic diversity can also persist in the form of statistical polymorphism, sustained by random processes acting on gene frequencies and population size. Stable polymorphism allows alleles to be long-lived and genetic variation to be detectable in natural populations. In agriculture, many of the factors promoting stability in host-parasite interactions have been lost, leading to arms races of host defenses and parasite effectors. Copyright © 2011 by Annual Reviews. All rights reserved.
Effects of rodent species, seed species, and predator cues on seed fate
NASA Astrophysics Data System (ADS)
Sivy, Kelly J.; Ostoja, Steven M.; Schupp, Eugene W.; Durham, Susan
2011-07-01
Seed selection, removal and subsequent management by granivorous animals is thought to be a complex interaction of factors including qualities of the seeds themselves (e.g., seed size, nutritional quality) and features of the local habitat (e.g. perceived predator risk). At the same time, differential seed selection and dispersal is thought to have profound effects on seed fate and potentially vegetation dynamics. In a feeding arena, we tested whether rodent species, seed species, and indirect and direct predation cues influence seed selection and handling behaviors (e.g., scatter hoarding versus larder hoarding) of two heteromyid rodents, Ord's kangaroo rat ( Dipodomys ordii) and the Great Basin pocket mouse ( Perognathus parvus). The indirect cue was shrub cover, a feature of the environment. Direct cues, presented individually, were (1) control, (2) coyote ( Canis latrans) vocalization, (3) coyote scent, (4) red fox ( Vulpes vulpes) scent, or (5) short-eared owl ( Asio flammeus) vocalization. We offered seeds of three sizes: two native grasses, Indian ricegrass ( Achnatherum hymenoides) and bluebunch wheatgrass ( Pseudoroegneria spicata), and the non-native cereal rye ( Secale cereale), each in separate trays. Kangaroo rats preferentially harvested Indian ricegrass while pocket mice predominately harvested Indian ricegrass and cereal rye. Pocket mice were more likely to scatter hoard preferred seeds, whereas kangaroo rats mostly consumed and/or larder hoarded preferred seeds. No predator cue significantly affected seed preferences. However, both species altered seed handling behavior in response to direct predation cues by leaving more seeds available in the seed pool, though they responded to different predator cues. If these results translate to natural dynamics on the landscape, the two rodents are expected to have different impacts on seed survival and plant recruitment via their different seed selection and seed handling behaviors.
Role of Utility and Inference in the Evolution of Functional Information
Sharov, Alexei A.
2009-01-01
Functional information means an encoded network of functions in living organisms from molecular signaling pathways to an organism’s behavior. It is represented by two components: code and an interpretation system, which together form a self-sustaining semantic closure. Semantic closure allows some freedom between components because small variations of the code are still interpretable. The interpretation system consists of inference rules that control the correspondence between the code and the function (phenotype) and determines the shape of the fitness landscape. The utility factor operates at multiple time scales: short-term selection drives evolution towards higher survival and reproduction rate within a given fitness landscape, and long-term selection favors those fitness landscapes that support adaptability and lead to evolutionary expansion of certain lineages. Inference rules make short-term selection possible by shaping the fitness landscape and defining possible directions of evolution, but they are under control of the long-term selection of lineages. Communication normally occurs within a set of agents with compatible interpretation systems, which I call communication system. Functional information cannot be directly transferred between communication systems with incompatible inference rules. Each biological species is a genetic communication system that carries unique functional information together with inference rules that determine evolutionary directions and constraints. This view of the relation between utility and inference can resolve the conflict between realism/positivism and pragmatism. Realism overemphasizes the role of inference in evolution of human knowledge because it assumes that logic is embedded in reality. Pragmatism substitutes usefulness for truth and therefore ignores the advantage of inference. The proposed concept of evolutionary pragmatism rejects the idea that logic is embedded in reality; instead, inference rules are constructed within each communication system to represent reality and they evolve towards higher adaptability on a long time scale. PMID:20160960
Effects of rodent species, seed species, and predator cues on seed fate
Sivy, Kelly J.; Ostoja, Steven M.; Schupp, Eugene W.; Durham, Susan
2011-01-01
Seed selection, removal and subsequent management by granivorous animals is thought to be a complex interaction of factors including qualities of the seeds themselves (e.g., seed size, nutritional quality) and features of the local habitat (e.g. perceived predator risk). At the same time, differential seed selection and dispersal is thought to have profound effects on seed fate and potentially vegetation dynamics. In a feeding arena, we tested whether rodent species, seed species, and indirect and direct predation cues influence seed selection and handling behaviors (e.g., scatter hoarding versus larder hoarding) of two heteromyid rodents, Ord's kangaroo rat (Dipodomys ordii) and the Great Basin pocket mouse (Perognathus parvus). The indirect cue was shrub cover, a feature of the environment. Direct cues, presented individually, were (1) control, (2) coyote (Canis latrans) vocalization, (3) coyote scent, (4) red fox (Vulpes vulpes) scent, or (5) short-eared owl (Asio flammeus) vocalization. We offered seeds of three sizes: two native grasses, Indian ricegrass (Achnatherum hymenoides) and bluebunch wheatgrass (Pseudoroegneria spicata), and the non-native cereal rye (Secale cereale), each in separate trays. Kangaroo rats preferentially harvested Indian ricegrass while pocket mice predominately harvested Indian ricegrass and cereal rye. Pocket mice were more likely to scatter hoard preferred seeds, whereas kangaroo rats mostly consumed and/or larder hoarded preferred seeds. No predator cue significantly affected seed preferences. However, both species altered seed handling behavior in response to direct predation cues by leaving more seeds available in the seed pool, though they responded to different predator cues. If these results translate to natural dynamics on the landscape, the two rodents are expected to have different impacts on seed survival and plant recruitment via their different seed selection and seed handling behaviors.
Progress and issues for high-speed vertical cavity surface emitting lasers
NASA Astrophysics Data System (ADS)
Lear, Kevin L.; Al-Omari, Ahmad N.
2007-02-01
Extrinsic electrical, thermal, and optical issues rather than intrinsic factors currently constrain the maximum bandwidth of directly modulated vertical cavity surface emitting lasers (VCSELs). Intrinsic limits based on resonance frequency, damping, and K-factor analysis are summarized. Previous reports are used to compare parasitic circuit values and electrical 3dB bandwidths and thermal resistances. A correlation between multimode operation and junction heating with bandwidth saturation is presented. The extrinsic factors motivate modified bottom-emitting structures with no electrical pads, small mesas, copper plated heatsinks, and uniform current injection. Selected results on high speed quantum well and quantum dot VCSELs at 850 nm, 980 nm, and 1070 nm are reviewed including small-signal 3dB frequencies up to 21.5 GHz and bit rates up to 30 Gb/s.
2011-01-01
Background Bioinformatics data analysis is often using linear mixture model representing samples as additive mixture of components. Properly constrained blind matrix factorization methods extract those components using mixture samples only. However, automatic selection of extracted components to be retained for classification analysis remains an open issue. Results The method proposed here is applied to well-studied protein and genomic datasets of ovarian, prostate and colon cancers to extract components for disease prediction. It achieves average sensitivities of: 96.2 (sd = 2.7%), 97.6% (sd = 2.8%) and 90.8% (sd = 5.5%) and average specificities of: 93.6% (sd = 4.1%), 99% (sd = 2.2%) and 79.4% (sd = 9.8%) in 100 independent two-fold cross-validations. Conclusions We propose an additive mixture model of a sample for feature extraction using, in principle, sparseness constrained factorization on a sample-by-sample basis. As opposed to that, existing methods factorize complete dataset simultaneously. The sample model is composed of a reference sample representing control and/or case (disease) groups and a test sample. Each sample is decomposed into two or more components that are selected automatically (without using label information) as control specific, case specific and not differentially expressed (neutral). The number of components is determined by cross-validation. Automatic assignment of features (m/z ratios or genes) to particular component is based on thresholds estimated from each sample directly. Due to the locality of decomposition, the strength of the expression of each feature across the samples can vary. Yet, they will still be allocated to the related disease and/or control specific component. Since label information is not used in the selection process, case and control specific components can be used for classification. That is not the case with standard factorization methods. Moreover, the component selected by proposed method as disease specific can be interpreted as a sub-mode and retained for further analysis to identify potential biomarkers. As opposed to standard matrix factorization methods this can be achieved on a sample (experiment)-by-sample basis. Postulating one or more components with indifferent features enables their removal from disease and control specific components on a sample-by-sample basis. This yields selected components with reduced complexity and generally, it increases prediction accuracy. PMID:22208882
Application of Bioassays for the Ecotoxicity Assessment of Contaminated Soils
NASA Astrophysics Data System (ADS)
Fernández, María D.; Babín, Mar; Tarazona, José V.
The use of bioassays for soil characterization is receiving significant attention as a complementary tool to chemical analysis. Bioassays consist of direct toxicity assays of environmental samples that are transferred to the laboratory and analyzed for toxicity against selected organisms. Such soil samples contain the combination of the different pollutants present in situ and enable factors such as the bioavailability of contaminants or the interactions (synergic and antagonic) between them to be simultaneously studied.
Low Shrinkage Cement Concrete Intended for Airfield Pavements
NASA Astrophysics Data System (ADS)
Małgorzata, Linek
2017-10-01
The work concerns the issue of hardened concrete parameters improvement intended for airfield pavements. Factors which have direct or indirect influence on rheological deformation size were of particular interest. The aim of lab testing was to select concrete mixture ratio which would make hardened concrete less susceptible to influence of basic operating factors. Analyses included two research groups. External and internal factors were selected. They influence parameters of hardened cement concrete by increasing rheological deformations. Research referred to innovative cement concrete intended for airfield pavements. Due to construction operation, the research considered the influence of weather conditions and forced thermal loads intensifying concrete stress. Fresh concrete mixture parameters were tested and basic parameters of hardened concrete were defined (density, absorbability, compression strength, tensile strength). Influence of the following factors on rheological deformation value was also analysed. Based on obtained test results, it has been discovered that innovative concrete, made on the basis of modifier, which changes internal structure of concrete composite, has definitely lower values of rheological deformation. Observed changes of microstructure, in connection with reduced deformation values allowed to reach the conclusion regarding advantageous characteristic features of the newly designed cement concrete. Applying such concrete for airfield construction may contribute to extension of its operation without malfunction and the increase of its general service life.
Infants Show Stability of Goal-Directed Imitation
ERIC Educational Resources Information Center
Sakkalou, Elena; Ellis-Davies, Kate; Fowler, Nia C.; Hilbrink, Elma E.; Gattis, Merideth
2013-01-01
Previous studies have reported that infants selectively reproduce observed actions and have argued that this selectivity reflects understanding of intentions and goals, or goal-directed imitation. We reasoned that if selective imitation of goal-directed actions reflects understanding of intentions, infants should demonstrate stability across…
Microanatomy of the intestinal lymphatic system
Miller, Mark J.; Newberry, Rodney D.
2011-01-01
The intestinal lymphatic system is comprised of two non-communicating lymphatic networks; one containing the lacteals draining the villi and the connecting submucosal lymphatic network, and one containing the lymphatics that drain the intestine muscular layer. These systems deliver lymph into a common network of collecting lymphatics originating near the mesenteric border. The intestinal lymphatic system serves vital functions in the regulation of tissue fluid homeostasis, immune surveillance, and the transport of nutrients, and conversely this system is affected by, and directly contributes to, disease processes within the intestine. Recent discoveries of specific lymphatic markers, factors promoting lymphangiogenesis, and factors selectively affecting the development of intestinal lymphatics hold promise for unlocking the role of lymphatics in the pathogenesis of diseases affecting the intestine and for intestinal lymphatic selective therapies. Vital to progress in understanding how the intestinal lymphatic system functions is integrating of recent advances identifying molecular pathways for lymphatic growth and remodeling with advanced imaging modalities to observe lymphatic function and dysfunction in vivo. PMID:20961303
NASA Technical Reports Server (NTRS)
Benzie, M. A.
1998-01-01
The objective of this research project was to examine processing and design parameters in the fabrication of composite components to obtain a better understanding and attempt to minimize springback associated with composite materials. To accomplish this, both processing and design parameters were included in a Taguchi-designed experiment. Composite angled panels were fabricated, by hand layup techniques, and the fabricated panels were inspected for springback effects. This experiment yielded several significant results. The confirmation experiment validated the reproducibility of the factorial effects, error recognized, and experiment as reliable. The material used in the design of tooling needs to be a major consideration when fabricating composite components, as expected. The factors dealing with resin flow, however, raise several potentially serious material and design questions. These questions must be dealt with up front in order to minimize springback: viscosity of the resin, vacuum bagging of the part for cure, and the curing method selected. These factors directly affect design, material selection, and processing methods.
Decision making tools for selecting sustainable wastewater treatment technologies in Thailand
NASA Astrophysics Data System (ADS)
Wongburi, Praewa; Park, Jae K.
2018-05-01
Wastewater consists of valuable resources that could be recovered or reused. Still it is under threat because of ineffective wastewater management and systems. In Thailand, less than 25% of wastewater generated may be treated while then rest is inadequately treated and sent back directly into waterbodies or the environment. Furthermore, the technologies that have been applied may be inefficient and unsustainable. Efficiency, sustainability, and simplicity are important concepts when designing an appropriate wastewater treatment system in developing countries. The objectives of this study were to review and evaluate wastewater treatment technologies and propose a method to improve or select an appropriate technology. An expert system in Excel® program was developed to determine the best solution. Sensitivity analysis was applied to compare and assess uncertainty factors. Due to the different conditions of each area, the key factor of interest was varied. Furthermore, Robust Decision Making tool was applied to determine the best way to improve existing wastewater treatment facility and to choose the most appropriate wastewater treatment technology.
ABO blood grouping: A potential risk factor for early childhood caries - A cross-sectional study.
Govindaraju, Lavanya; Jeevanandan, Ganesh; Subramanian, E M G
2018-01-01
The paradigm of etiology of early childhood caries (ECC) is shifting toward genetics. Of various inherited factors, blood group of an individual is genetically determined. The aim of the study is to determine if blood group of an individual will serve as a potential risk factor in the development of ECC. A cross-sectional study was conducted in Chennai. Blood samples were collected from a total of 500 children <71 months of age for determination of the blood group. Of which 96 children (24 per blood group) were randomly selected and were included in the study. Oral screening of the selected children was done by a pediatric dentist who was blinded to the blood group of the children. Decayed, extracted, and filling index was noted. Details on other associated factors for the development of ECC such as the socioeconomic status, oral hygiene measures, diet, and feeding practices were collected by directly interviewing the parents through a questionnaire. Statistical analysis was done using Chi-square and Kruskal-Wallis test and post hoc Tukey test with significance level set at 0.05. Intergroup analysis of the associated factors showed no significant differences between the children of different blood groups. A statistically significant relation was noted between the blood groups and development of ECC (P = 0.025). Blood group is a potential risk indicator for the development of ECC.
Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I
2015-01-01
Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs.
Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I
2015-01-01
Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs. PMID:26150723
Robles-Rengel, Rocío; Hernández-Prieto, Miguel A.; Muro-Pastor, M. Isabel; Florencio, Francisco J.
2017-01-01
Abstract In cyanobacteria, nitrogen homeostasis is maintained by an intricate regulatory network around transcription factor NtcA. Although mechanisms controlling NtcA activity appear to be well understood, its regulon remains poorly defined. To determine the NtcA regulon during the early stages of nitrogen starvation for the model cyanobacterium Synechocystis sp. PCC 6803, we performed chromatin immunoprecipitation, followed by sequencing (ChIP-seq), in parallel with transcriptome analysis (RNA-seq). Through combining these methods, we determined 51 genes activated and 28 repressed directly by NtcA. In addition to genes associated with nitrogen and carbon metabolism, a considerable number of genes without current functional annotation were among direct targets providing a rich reservoir for further studies. The NtcA regulon also included eight non-coding RNAs, of which Ncr1071, Syr6 and NsiR7 were experimentally validated, and their putative targets were computationally predicted. Surprisingly, we found substantial NtcA binding associated with delayed expression changes indicating that NtcA can reside in a poised state controlled by other factors. Indeed, a role of PipX as modulating factor in nitrogen regulation was confirmed for selected NtcA-targets. We suggest that the indicated poised state of NtcA enables a more differentiated response to nitrogen limitation and can be advantageous in native habitats of Synechocystis. PMID:29036481
Dougherty, Liam R; Shuker, David M
Sexual selection has been shown to be the driving force behind the evolution of the sometimes extreme and elaborate genitalia of many species. Sexual selection may arise before and/or after mating, or vary according to other factors such as the social environment. However, bouts of selection are typically considered in isolation. We measured the strength and pattern of selection acting on the length of the male intromittent organ (or processus) in two closely related species of lygaeid seed bug: Lygaeus equestris and Lygaeus simulans . In both species, we measured both pre- and post-copulatory selection. For L. equestris , we also varied the experimental choice design used in mating trials. We found contrasting pre- and post-copulatory selection on processus length in L. equestris . Furthermore, significant pre-copulatory selection was only seen in mating trials in which two males were present. This selection likely arises indirectly due to selection on a correlated trait, as the processus does not interact with the female prior to copulation. In contrast, we were unable to detect significant pre- or post-copulatory selection on processus length in L. simulans . However, a formal meta-analysis of previous estimates of post-copulatory selection on processus length in L. simulans suggests that there is significant stabilising selection across studies, but the strength of selection varies between experiments. Our results emphasise that the strength and direction of sexual selection on genital traits may be multifaceted and can vary across studies, social contexts and different stages of reproduction. Animal genitalia vary greatly in size and complexity across species, and selection acting on genital size and shape can be complex. In this study, we show that the length of the penis in two species of seed bug is subject to complex patterns of selection, varying depending on the social context and whether selection is measured before or after mating. In one of the species, we show unexpectedly that penis length is correlated with male mating success, despite the fact that the penis does not interact with the female prior to mating. Our results highlight the fact that genitalia may be subject to both direct and indirect selection at different stages of mating and that to fully understand the evolution of such traits we should combine estimates of selection arising from these multiple episodes.
Impact of speciation on the electron charge transfer properties of nanodiamond drug carriers
NASA Astrophysics Data System (ADS)
Sun, Baichuan; Barnard, Amanda S.
2016-07-01
Unpassivated diamond nanoparticles (bucky-diamonds) exhibit a unique surface reconstruction involving graphitization of certain crystal facets, giving rise to hybrid core-shell particles containing both aromatic and aliphatic carbon. Considerable effort is directed toward eliminating the aromatic shell, but persistent graphitization of subsequent subsurface-layers makes perdurable purification a challenge. In this study we use some simple statistical methods, in combination with electronic structure simulations, to predict the impact of different fractions of aromatic and aliphatic carbon on the charge transfer properties of the ensembles of bucky-diamonds. By predicting quality factors for a variety of cases, we find that perfect purification is not necessary to preserve selectivity, and there is a clear motivation for purifying samples to improve the sensitivity of charge transfer reactions. This may prove useful in designing drug delivery systems where the release of (selected) drugs needs to be sensitive to specific conditions at the point of delivery.Unpassivated diamond nanoparticles (bucky-diamonds) exhibit a unique surface reconstruction involving graphitization of certain crystal facets, giving rise to hybrid core-shell particles containing both aromatic and aliphatic carbon. Considerable effort is directed toward eliminating the aromatic shell, but persistent graphitization of subsequent subsurface-layers makes perdurable purification a challenge. In this study we use some simple statistical methods, in combination with electronic structure simulations, to predict the impact of different fractions of aromatic and aliphatic carbon on the charge transfer properties of the ensembles of bucky-diamonds. By predicting quality factors for a variety of cases, we find that perfect purification is not necessary to preserve selectivity, and there is a clear motivation for purifying samples to improve the sensitivity of charge transfer reactions. This may prove useful in designing drug delivery systems where the release of (selected) drugs needs to be sensitive to specific conditions at the point of delivery. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03068h
A multidimensional approach to measuring well-being in students: Application of the PERMA framework
Kern, Margaret L.; Waters, Lea E.; Adler, Alejandro; White, Mathew A.
2015-01-01
Seligman recently introduced the PERMA model with five core elements of psychological well-being: positive emotions, engagement, relationships, meaning, and accomplishment. We empirically tested this multidimensional theory with 516 Australian male students (age 13–18). From an extensive well-being assessment, we selected a subset of items theoretically relevant to PERMA. Factor analyses recovered four of the five PERMA elements, and two ill-being factors (depression and anxiety). We then explored the nomological net surrounding each factor by examining cross-sectional associations with life satisfaction, hope, gratitude, school engagement, growth mindset, spirituality, physical vitality, physical activity, somatic symptoms, and stressful life events. Factors differentially related to these correlates, offering support for the multidimensional approach to measuring well-being. Directly assessing subjective well-being across multiple domains offers the potential for schools to more systematically understand and promote well-being. PMID:25745508
Success Rate of Microimplants in a University Orthodontic Clinic
Sharma, P.; Valiathan, A.; Sivakumar, A.
2011-01-01
Introduction. The purpose of this study was to examine the success rate and find factors affecting the clinical success of microimplants used as orthodontic anchorage. Methods. Seventy-three consecutive patients (25 male, 48 female; mean age, 22.45 years) with a total of 139 screw implants of 2 types were examined. Success rate was determined according to 18 clinical variables. Results. The overall success rate was 87.8%. The clinical variables of microimplant factors (type), patient factors (sex, skeletal and dental relationships, overbite, jaw involved, side involved and site involved), and treatment factors (type of insertion, time of loading, purpose of microimplant insertion, mode of loading, type of anchorage used, direction of forces applied) did not show any statistical difference in success rates. Mandibular angle, vertical position of implant placement, oral hygiene status, and inflammation showed significant difference in success rates. Conclusions. Proper case selection and following the recommended protocol are extremely essential to minimise failures. PMID:22084789
Gyurcsik, Nancy C.
2012-01-01
ABSTRACT Purpose: As the numbers of Canadians aged 65 years and over increases over the next 20 years, the prevalence of chronic conditions, including arthritis, will rise as will the number of falls. Although known fall-risk factors are associated with hip and knee osteoarthritis (OA), minimal research has evaluated fall and fracture risk and/or rates in this population. Thus, the purpose was to summarize research on fall and fracture risk in older adults with hip or knee OA and to develop a conceptual framework of fall-risk screening and assessment. Method: The International Classification of Functioning, Disability and Health, clinical practice guidelines for fall-risk screening, and a selected literature review were used. Results: Gaps exist in our knowledge of fall and fracture risk for this population. Muscle performance, balance, and mobility impairments have been identified, but little is known about whether personal and environmental contextual factors impact fall and fracture risk. Physical activity may help to prevent falls, but non-adherence is a problem. Conclusion: A need exists to assess fall risk in older adults with hip and knee OA. Promoting regular physical activity by focusing on disease- and activity-specific personal contextual factors may help direct treatment planning. PMID:23729967
Melancon, Marites P.; Lu, Wei; Yang, Zhi; Zhang, Rui; Cheng, Zhi; Elliot, Andrew M.; Stafford, Jason; Olson, Tammy; Zhang, Jin Z.; Li, Chun
2009-01-01
Laser-induced phototherapy is a new therapeutic use of electromagnetic radiation for cancer treatment. The use of targeted plasmonic gold nanoparticles can reduce the laser energy necessary for selective tumor cell destruction. However, the ability for targeted delivery of the currently used gold nanoparticles to tumor cells is limited. Here, we describe a new class of molecular specific photothermal coupling agents based on hollow gold nanoshells (HAuNS, average diameter ~30 nm) covalently attached to monoclonal antibody directed at epidermal growth factor receptor (EGFR). The resulting anti-EGFR-HAuNS exhibited excellent colloidal stability and efficient photothermal effect in the near-infrared region. EGFR-mediated, selective uptake of anti-EGFR-HAuNS in EGFR-positive A431 tumor cells but not IgG-HAuNS control was demonstrated in vitro by imaging scattered light from the nanoshells. Irradiation of A431 cells treated with anti-EGFR-HAuNS with near-infrared laser resulted in selective destruction of these cells. In contrast, cells treated with anti-EGFR-HAuNS alone, laser alone, or IgG-HAuNS plus laser did not show observable effect on cell viability. Using 111In-labeled HAuNS, we showed that anti-EGFR-HAuNS could be delivered to EGFR-positive tumors at 6.8% of injected dose per gram of tissue, and the microscopic image of excised tumor with scattering signal from nanoshells confirmed preferential delivery to A431 tumor of anti-EGFR-HAuNS compared with IgG-HAuNS. The absence of silica core, the relatively small particle size and high tumor uptake, and the absence of cytotoxic surfactant required to stabilize other gold nanoparticles suggest that immuno-hollow gold nanoshells have the potential to extend to in vivo molecular therapy. PMID:18566244
Which kind of psychometrics is adequate for patient satisfaction questionnaires?
Konerding, Uwe
2016-01-01
The construction and psychometric analysis of patient satisfaction questionnaires are discussed. The discussion is based upon the classification of multi-item questionnaires into scales or indices. Scales consist of items that describe the effects of the latent psychological variable to be measured, and indices consist of items that describe the causes of this variable. Whether patient satisfaction questionnaires should be constructed and analyzed as scales or as indices depends upon the purpose for which these questionnaires are required. If the final aim is improving care with regard to patients' preferences, then these questionnaires should be constructed and analyzed as indices. This implies two requirements: 1) items for patient satisfaction questionnaires should be selected in such a way that the universe of possible causes of patient satisfaction is covered optimally and 2) Cronbach's alpha, principal component analysis, exploratory factor analysis, confirmatory factor analysis, and analyses with models from item response theory, such as the Rasch Model, should not be applied for psychometric analyses. Instead, multivariate regression analyses with a direct rating of patient satisfaction as the dependent variable and the individual questionnaire items as independent variables should be performed. The coefficients produced by such an analysis can be applied for selecting the best items and for weighting the selected items when a sum score is determined. The lower boundaries of the validity of the unweighted and the weighted sum scores can be estimated by their correlations with the direct satisfaction rating. While the first requirement is fulfilled in the majority of the previous patient satisfaction questionnaires, the second one deviates from previous practice. Hence, if patient satisfaction is actually measured with the final aim of improving care with regard to patients' preferences, then future practice should be changed so that the second requirement is also fulfilled.
Kause, A; Paananen, T; Ritola, O; Koskinen, H
2007-12-01
We assessed whether visceral lipid weight, fillet weight, and percentage fillet from BW, 3 traits laborious to record, could be genetically improved by indirect selection on more easily measured traits in farmed rainbow trout. Visceral lipid is discarded as waste during slaughter, influencing production efficiency and production costs. Fillet weight and fillet percentage directly influence economic returns in trout production. The study comprised 3 steps. First, we assessed the degree to which selection on percentage of visceral weight from BW indirectly changes visceral lipid weight and the size of intestines and internal organs. The phenotypic analysis of weights of viscera, intestines, visceral lipid, liver, and gonads measured from 40 fish revealed that phenotypic selection against visceral weight was most strongly directed to visceral lipid, and to a lesser degree to intestines and gonads. Because genetic relationships among these traits were not established, it is not known whether indirect selection leads to genetic responses. Second, we examined whether direct selection for the fillet traits could be replaced by indirect selection on BW, eviscerated BW, visceral weight, visceral percentage, head volume, and relative head volume (head volume relative to BW). The selection index calculations based on the quantitative genetic parameters obtained from multigenerational pedigree data showed that genetic improvement of fillet percentage through direct selection (selection accuracy, r(TI) = 0.54) was equally efficient compared with indirect selection on visceral percentage ( r(TI) = 0.54). Genetic improvement of fillet weight through direct selection (r(TI) = 0.56) was always more efficient than indirect selection, yet indirect selection for eviscerated BW ( r(TI) = 0.50) was almost as efficient as direct selection. Third, the expected genetic responses to alternative selection indices showed that improved fillet percentage was mainly a result of a moderate decrease in visceral weight rather than of a major increase in absolute fillet weight. Moreover, fillet percentage is challenging to improve, even if it exhibits moderate heritability (h(2) = 0.29). This is because fillet percentage displays low phenotypic variation. In conclusion, fillet weight and fillet percentage can be increased by indirect selection against visceral percentage and for high eviscerated BW.
Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James
2016-03-21
In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells.
Tosic, Milica; Allen, Anita; Willmann, Dominica; Lepper, Christoph; Kim, Johnny; Duteil, Delphine; Schüle, Roland
2018-01-25
Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.
Directional selection effects on patterns of phenotypic (co)variation in wild populations.
Assis, A P A; Patton, J L; Hubbe, A; Marroig, G
2016-11-30
Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. © 2016 The Author(s).
K + block is the mechanism of functional asymmetry in bacterial Na v channels
Ngo, Van; Wang, Yibo; Haas, Stephan; ...
2016-01-04
Crystal structures of several bacterial Na v channels have been recently published and molecular dynamics simulations of ion permeation through these channels are consistent with many electrophysiological properties of eukaryotic channels. Bacterial Na v channels have been characterized as functionally asymmetric, and the mechanism of this asymmetry has not been clearly understood. To address this question, we combined non-equilibrium simulation data with two-dimensional equilibrium unperturbed landscapes generated by umbrella sampling and Weighted Histogram Analysis Methods for multiple ions traversing the selectivity filter of bacterial Na vAb channel. This approach provided new insight into the mechanism of selective ion permeation inmore » bacterial Nav channels. The non-equilibrium simulations indicate that two or three extracellular K + ions can block the entrance to the selectivity filter of Na vAb in the presence of applied forces in the inward direction, but not in the outward direction. The block state occurs in an unstable local minimum of the equilibrium unperturbed free-energy landscape of two K+ ions that can be ‘locked’ in place bymodest applied forces. In contrast to K +, three Na + ions move favorably through the selectivity filter together as a unit in a loose “knock-on” mechanism of permeation in both inward and outward directions, and there is no similar local minimum in the two-dimensional free-energy landscape of two Na + ions for a block state. The useful work predicted by the non-equilibrium simulations that is required to break the K + block is equivalent to large applied potentials experimentally measured for two bacterial Na v channels to induce inward currents of K + ions. Here, these results illustrate how inclusion of non-equilibrium factors in the simulations can provide detailed information about mechanisms of ion selectivity that is missing from mechanisms derived from either crystal structures or equilibrium unperturbed free-energy landscapes.« less
K+ Block Is the Mechanism of Functional Asymmetry in Bacterial Nav Channels
Ngo, Van; Wang, Yibo; Haas, Stephan; Noskov, Sergei Y.; Farley, Robert A.
2016-01-01
Crystal structures of several bacterial Nav channels have been recently published and molecular dynamics simulations of ion permeation through these channels are consistent with many electrophysiological properties of eukaryotic channels. Bacterial Nav channels have been characterized as functionally asymmetric, and the mechanism of this asymmetry has not been clearly understood. To address this question, we combined non-equilibrium simulation data with two-dimensional equilibrium unperturbed landscapes generated by umbrella sampling and Weighted Histogram Analysis Methods for multiple ions traversing the selectivity filter of bacterial NavAb channel. This approach provided new insight into the mechanism of selective ion permeation in bacterial Nav channels. The non-equilibrium simulations indicate that two or three extracellular K+ ions can block the entrance to the selectivity filter of NavAb in the presence of applied forces in the inward direction, but not in the outward direction. The block state occurs in an unstable local minimum of the equilibrium unperturbed free-energy landscape of two K+ ions that can be ‘locked’ in place by modest applied forces. In contrast to K+, three Na+ ions move favorably through the selectivity filter together as a unit in a loose “knock-on” mechanism of permeation in both inward and outward directions, and there is no similar local minimum in the two-dimensional free-energy landscape of two Na+ ions for a block state. The useful work predicted by the non-equilibrium simulations that is required to break the K+ block is equivalent to large applied potentials experimentally measured for two bacterial Nav channels to induce inward currents of K+ ions. These results illustrate how inclusion of non-equilibrium factors in the simulations can provide detailed information about mechanisms of ion selectivity that is missing from mechanisms derived from either crystal structures or equilibrium unperturbed free-energy landscapes. PMID:26727271
Social Factors Influencing Child Health in Ghana.
Quansah, Emmanuel; Ohene, Lilian Akorfa; Norman, Linda; Mireku, Michael Osei; Karikari, Thomas K
2016-01-01
Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals' target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother's health knowledge is emphasised.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-10-24
... DEPARTMENT OF EDUCATION William D. Ford Federal Direct Loan Program Repayment Plan Selection Form; Extension of Public Comment Period; Correction AGENCY: Department of Education. ACTION: Correction notice... entitled, ``William D. Ford Federal Direct Loan Program Repayment Plan Selection Form''. ED is extending...
Rowe, Courtney K; Pierce, Michael W; Tecci, Katherine C; Houck, Constance S; Mandell, James; Retik, Alan B; Nguyen, Hiep T
2012-07-01
Cost in healthcare is an increasing and justifiable concern that impacts decisions about the introduction of new devices such as the da Vinci(®) surgical robot. Because equipment expenses represent only a portion of overall medical costs, we set out to make more specific cost comparisons between open and robot-assisted laparoscopic surgery. We performed a retrospective, observational, matched cohort study of 146 pediatric patients undergoing either open or robot-assisted laparoscopic urologic surgery from October 2004 to September 2009 at a single institution. Patients were matched based on surgery type, age, and fiscal year. Direct internal costs from the institution were used to compare the two surgery types across several procedures. Robot-assisted surgery direct costs were 11.9% (P=0.03) lower than open surgery. This cost difference was primarily because of the difference in hospital length of stay between patients undergoing open vs robot-assisted surgery (3.8 vs 1.6 days, P<0.001). Maintenance fees and equipment expenses were the primary contributors to robotic surgery costs, while open surgery costs were affected most by room and board expenses. When estimates of the indirect costs of robot purchase and maintenance were included, open surgery had a lower total cost. There were no differences in follow-up times or complication rates. Direct costs for robot-assisted surgery were significantly lower than equivalent open surgery. Factors reducing robot-assisted surgery costs included: A consistent and trained robotic surgery team, an extensive history of performing urologic robotic surgery, selection of patients for robotic surgery who otherwise would have had longer hospital stays after open surgery, and selection of procedures without a laparoscopic alternative. The high indirect costs of robot purchase and maintenance remain major factors, but could be overcome by high surgical volume and reduced prices as competitors enter the market.
Šilar, Radoslav; Holátko, Jiří; Rucká, Lenka; Rapoport, Andrey; Dostálová, Hana; Kadeřábková, Pavla; Nešvera, Jan; Pátek, Miroslav
2016-09-01
Promoter activities in Corynebacterium glutamicum strains with deletions of genes encoding sigma factors of RNA polymerase suggested that transcription from some promoters is controlled by two sigma factors. To prove that different sigma factors are involved in the recognition of selected Corynebacterium glutamicum promoters, in vitro transcription system was applied. It was found that a typical housekeeping promoter Pper interacts with the alternative sigma factor σ(B) in addition to the primary sigma factor σ(A). On the other way round, the σ(B)-dependent promoter of the pqo gene that is expressed mainly in the stationary growth phase was active also with σ(A). Some promoters of genes involved in stress responses (P1clgR, P2dnaK, and P2dnaJ2) were found to be recognized by two stress-responding sigma factors, σ(H) and σ(E). In vitro transcription system thus proved to be a useful direct technique for demonstrating the overlap of different sigma factors in recognition of individual promoters in C. glutamicum.
[Study on ecological suitability regionalization of Eucommia ulmoides in Guizhou].
Kang, Chuan-Zhi; Wang, Qing-Qing; Zhou, Tao; Jiang, Wei-Ke; Xiao, Cheng-Hong; Xie, Yu
2014-05-01
To study the ecological suitability regionalization of Eucommia ulmoides, for selecting artificial planting base and high-quality industrial raw material purchase area of the herb in Guizhou. Based on the investigation of 14 Eucommia ulmoides producing areas, pinoresinol diglucoside content and ecological factors were obtained. Using spatial analysis method to carry on ecological suitability regionalization. Meanwhile, combining pinoresinol diglucoside content, the correlation of major active components and environmental factors were analyzed by statistical analysis. The most suitability planting area of Eucommia ulmoides was the northwest of Guizhou. The distribution of Eucommia ulmoides was mainly affected by the type and pH value of soil, and monthly precipitation. The spatial structure of major active components in Eucommia ulmoides were randomly distributed in global space, but had only one aggregation point which had a high positive correlation in local space. The major active components of Eucommia ulmoides had no correlation with altitude, longitude or latitude. Using the spatial analysis method and statistical analysis method, based on environmental factor and pinoresinol diglucoside content, the ecological suitability regionalization of Eucommia ulmoides can provide reference for the selection of suitable planting area, artificial planting base and directing production layout.
Brohm, Thomas; Bottcher, Friedhelm
2000-01-01
A multi-cell storage battery, in particular to a lithium storage battery, which contains a temperature control device and in which groups of one or more individual cells arranged alongside one another are separated from one another by a thermally insulating solid layer whose coefficient of thermal conductivity lies between 0.01 and 0.2 W/(m*K), the thermal resistance of the solid layer being greater by at least a factor .lambda. than the thermal resistance of the individual cell. The individual cell is connected, at least in a region free of insulating material, to a heat exchanger, the thermal resistance of the heat exchanger in the direction toward the neighboring cell being selected to be greater by at least a factor .lambda. than the thermal resistance of the individual cell and, in addition, the thermal resistance of the heat exchanger toward the temperature control medium being selected to be smaller by at least a factor of about 10 than the thermal resistance of the individual cell, and .lambda. being the ratio of the energy content of the individual cell to the amount of energy that is needed to trigger a thermally induced cell failure at a defined upper operating temperature limit.
A matched case-control study of convenience store robbery risk factors.
Hendricks, S A; Landsittel, D P; Amandus, H E; Malcan, J; Bell, J
1999-11-01
Convenience store clerks have been shown to be at high risk for assault and homicide, mostly owing to robbery or robbery attempts. Although the literature consistently indicates that at least some environmental designs are effective deterrents of robbery, the significance of individual interventions and policies has differed across past studies. To address these issues, a matched case-control study of 400 convenience store robberies in three metropolitan areas of Virginia was conducted. Conditional logistic regression was implemented to evaluate the significance of various environmental designs and other factors possibly related to convenience store robbery. Findings indicate that numerous characteristics of the surrounding environment and population were significantly associated with convenience store robbery. Results also showed that, on a univariate level, most crime prevention factors were significantly associated with a lower risk for robbery. Using a forward selection process, a multivariate model, which included cash handling policy, bullet-resistant shielding, and numerous characteristics of the surrounding area and population, was identified. This study addressed numerous limitations of the previous literature by prospectively collecting extensive data on a large sample of diverse convenience stores and directly addressing the current theory on the robbers' selection of a target store through a matched case-control design.
Elbasty, Ahmed; Metcalf, James
2017-01-01
Purpose Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. Materials and Methods MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration’s tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Results Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. Conclusion CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured. PMID:29354622
Moeller, David A; Geber, Monica A
2005-04-01
The repeated evolutionary transition from outcrossing to self-pollination in flowering plants has been suggested to occur because selfing provides reproductive assurance. Reports from biogeographical and ecological surveys indicate that selfing taxa are often associated with stressful and ephemeral environments, situations in which plant abundance is low (e.g., Baker's law) and with novel plant communities, however experimental tests of ecological hypotheses are few. In this study, we examined the ecological context of selection on mating system traits (herkogamy and protandry) in a California annual, Clarkia xantiana, where natural selfing populations differ from outcrossing populations in that they are often of small size or low density and occur mainly outside the range of pollinator-sharing congeners. We constructed artificial populations of plants with broad genetic variation in floral traits and manipulated two ecological factors, plant population size, and the presence versus absence of pollinator-sharing congeners, in the center of the geographic range of outcrossing populations. We found evidence for context-dependent selection on herkogamy and protandry via female fitness in which reduced traits, which promote autonomous selfing, were favored in small populations isolated from congeners whereas selection was comparatively weak in large populations or when congeners were present. In small, isolated populations, the fertility of plants with low herkogamy or protandry was elevated by 66% and 58%, respectively, compared to those with high herkogamy or protandry. The presence of pollinator-sharing congeners augmented bee visitation rates to C. xantiana flowers by 47% for all bees and by 93% for pollen specialists. By facilitating pollinator visitation, congeners mitigated selection on mating system traits in small populations, where outcross mating success is often low (the Allee effect). We also found support for the hypothesis that pollinator availability directly influenced variation in the strength of selection on herkogamy among populations. The striking parallels between our experimental results and patterns of variation in ecological factors across the geographic range of outcrossing and selfing populations suggest that reproductive assurance may play a central role in directing mating system evolution in C. xantiana.
Application of the Systematic Sensor Selection Strategy for Turbofan Engine Diagnostics
NASA Technical Reports Server (NTRS)
Sowers, T. Shane; Kopasakis, George; Simon, Donald L.
2008-01-01
The data acquired from available system sensors forms the foundation upon which any health management system is based, and the available sensor suite directly impacts the overall diagnostic performance that can be achieved. While additional sensors may provide improved fault diagnostic performance, there are other factors that also need to be considered such as instrumentation cost, weight, and reliability. A systematic sensor selection approach is desired to perform sensor selection from a holistic system-level perspective as opposed to performing decisions in an ad hoc or heuristic fashion. The Systematic Sensor Selection Strategy is a methodology that optimally selects a sensor suite from a pool of sensors based on the system fault diagnostic approach, with the ability of taking cost, weight, and reliability into consideration. This procedure was applied to a large commercial turbofan engine simulation. In this initial study, sensor suites tailored for improved diagnostic performance are constructed from a prescribed collection of candidate sensors. The diagnostic performance of the best performing sensor suites in terms of fault detection and identification are demonstrated, with a discussion of the results and implications for future research.
Application of the Systematic Sensor Selection Strategy for Turbofan Engine Diagnostics
NASA Technical Reports Server (NTRS)
Sowers, T. Shane; Kopasakis, George; Simon, Donald L.
2008-01-01
The data acquired from available system sensors forms the foundation upon which any health management system is based, and the available sensor suite directly impacts the overall diagnostic performance that can be achieved. While additional sensors may provide improved fault diagnostic performance there are other factors that also need to be considered such as instrumentation cost, weight, and reliability. A systematic sensor selection approach is desired to perform sensor selection from a holistic system-level perspective as opposed to performing decisions in an ad hoc or heuristic fashion. The Systematic Sensor Selection Strategy is a methodology that optimally selects a sensor suite from a pool of sensors based on the system fault diagnostic approach, with the ability of taking cost, weight and reliability into consideration. This procedure was applied to a large commercial turbofan engine simulation. In this initial study, sensor suites tailored for improved diagnostic performance are constructed from a prescribed collection of candidate sensors. The diagnostic performance of the best performing sensor suites in terms of fault detection and identification are demonstrated, with a discussion of the results and implications for future research.
Selection on skewed characters and the paradox of stasis
Bonamour, Suzanne; Teplitsky, Céline; Charmantier, Anne; Crochet, Pierre-André; Chevin, Luis-Miguel
2018-01-01
Observed phenotypic responses to selection in the wild often differ from predictions based on measurements of selection and genetic variance. An overlooked hypothesis to explain this paradox of stasis is that a skewed phenotypic distribution affects natural selection and evolution. We show through mathematical modelling that, when a trait selected for an optimum phenotype has a skewed distribution, directional selection is detected even at evolutionary equilibrium, where it causes no change in the mean phenotype. When environmental effects are skewed, Lande and Arnold’s (1983) directional gradient is in the direction opposite to the skew. In contrast, skewed breeding values can displace the mean phenotype from the optimum, causing directional selection in the direction of the skew. These effects can be partitioned out using alternative selection estimates based on average derivatives of individual relative fitness, or additive genetic covariances between relative fitness and trait (Robertson-Price identity). We assess the validity of these predictions using simulations of selection estimation under moderate samples size. Ecologically relevant traits may commonly have skewed distributions, as we here exemplify with avian laying date – repeatedly described as more evolutionarily stable than expected –, so this skewness should be accounted for when investigating evolutionary dynamics in the wild. PMID:28921508
Jang, Yikweon; Won, Yong-Jin; Choe, Jae Chun
2009-01-01
Background In ecological character displacement, traits involved in reproductive isolation may not evolve in arbitrary directions when changes in these traits are by-products of adaptation to an ecological niche. In reproductive character displacement, however, selection acts directly on reproductive characters to enhance the degree of reproductive isolation between sympatric populations. Thus, the direction of change in reproductive characters may be arbitrary in relation to changes in other morphological characters. We characterized both tegminal characters and characters indicative of body size in sympatric and allopatric populations of Gryllus fultoni, a species displaying character displacement in its calling song characters in areas of sympatry with G. vernalis populations, to infer the nature and direction of selection acting on reproductive and morphological characters in sympatry. Results Except for mirror area, the number of teeth in a file, and ovipositor length of G. fultoni, all male and female morphological characters in G. fultoni and G. vernalis exhibited a uniform tendency to decrease in size with increasing latitude. There was no significant variation in female morphological characters between sympatric and allopatric G. fultoni populations. However, males of sympatric and allopatric G. fultoni populations significantly differed in head width, hind femur length, and mirror area even after controlling for clinal factors. Head width and hind femur length of G. fultoni were more similar to those of G. vernalis in sympatric populations than in allopatric populations, resulting in morphological convergence of G. fultoni and G. vernalis in sympatry. However, the mirror area of G. fultoni displayed the divergent pattern in relation to the sympatric G. vernalis populations. Conclusion Divergence-enhancing selection may be acting on mirror area as well as calling song characters, whereas local adaptation or clinal effects may explain variation in other morphological characters in sympatric populations of G. fultoni. This study also suggests that structures and behaviors that directly enhance reproductive isolation may evolve together, independently of other morphological traits. PMID:19183503
Jang, Yikweon; Won, Yong-Jin; Choe, Jae Chun
2009-02-01
In ecological character displacement, traits involved in reproductive isolation may not evolve in arbitrary directions when changes in these traits are by-products of adaptation to an ecological niche. In reproductive character displacement, however, selection acts directly on reproductive characters to enhance the degree of reproductive isolation between sympatric populations. Thus, the direction of change in reproductive characters may be arbitrary in relation to changes in other morphological characters. We characterized both tegminal characters and characters indicative of body size in sympatric and allopatric populations of Gryllus fultoni, a species displaying character displacement in its calling song characters in areas of sympatry with G. vernalis populations, to infer the nature and direction of selection acting on reproductive and morphological characters in sympatry. Except for mirror area, the number of teeth in a file, and ovipositor length of G. fultoni, all male and female morphological characters in G. fultoni and G. vernalis exhibited a uniform tendency to decrease in size with increasing latitude. There was no significant variation in female morphological characters between sympatric and allopatric G. fultoni populations. However, males of sympatric and allopatric G. fultoni populations significantly differed in head width, hind femur length, and mirror area even after controlling for clinal factors. Head width and hind femur length of G. fultoni were more similar to those of G. vernalis in sympatric populations than in allopatric populations, resulting in morphological convergence of G. fultoni and G. vernalis in sympatry. However, the mirror area of G. fultoni displayed the divergent pattern in relation to the sympatric G. vernalis populations. Divergence-enhancing selection may be acting on mirror area as well as calling song characters, whereas local adaptation or clinal effects may explain variation in other morphological characters in sympatric populations of G. fultoni. This study also suggests that structures and behaviors that directly enhance reproductive isolation may evolve together, independently of other morphological traits.
Structural equation models to estimate risk of infection and tolerance to bovine mastitis.
Detilleux, Johann; Theron, Léonard; Duprez, Jean-Noël; Reding, Edouard; Humblet, Marie-France; Planchon, Viviane; Delfosse, Camille; Bertozzi, Carlo; Mainil, Jacques; Hanzen, Christian
2013-03-06
One method to improve durably animal welfare is to select, as reproducers, animals with the highest ability to resist or tolerate infection. To do so, it is necessary to distinguish direct and indirect mechanisms of resistance and tolerance because selection on these traits is believed to have different epidemiological and evolutionary consequences. We propose structural equation models with latent variables (1) to quantify the latent risk of infection and to identify, among the many potential mediators of infection, the few ones that influence it significantly and (2) to estimate direct and indirect levels of tolerance of animals infected naturally with pathogens. We applied the method to two surveys of bovine mastitis in the Walloon region of Belgium, in which we recorded herd management practices, mastitis frequency, and results of bacteriological analyses of milk samples. Structural equation models suggested that, among more than 35 surveyed herd characteristics, only nine (age, addition of urea in the rations, treatment of subclinical mastitis, presence of dirty liner, cows with hyperkeratotic teats, machine stripping, pre- and post-milking teat disinfection, and housing of milking cows in cubicles) were directly and significantly related to a latent measure of bovine mastitis, and that treatment of subclinical mastitis was involved in the pathway between post-milking teat disinfection and latent mastitis. These models also allowed the separation of direct and indirect effects of bacterial infection on milk productivity. Results suggested that infected cows were tolerant but not resistant to mastitis pathogens. We revealed the advantages of structural equation models, compared to classical models, for dissecting measurements of resistance and tolerance to infectious diseases, here bovine mastitis. Using our method, we identified nine major risk factors that were directly associated with an increased risk of mastitis and suggested that cows were tolerant but not resistant to mastitis. Selection should aim at improved resistance to infection by mastitis pathogens, although further investigations are needed due to the limitations of the data used in this study.
Highly selective detection of individual nuclear spins with rotary echo on an electron spin probe
Mkhitaryan, V. V.; Jelezko, F.; Dobrovitski, V. V.
2015-01-01
We consider an electronic spin, such as a nitrogen-vacancy center in diamond, weakly coupled to a large number of nuclear spins, and subjected to the Rabi driving with a periodically alternating phase. We show that by switching the driving phase synchronously with the precession of a given nuclear spin, the interaction to this spin is selectively enhanced, while the rest of the bath remains decoupled. The enhancement is of resonant character. The key feature of the suggested scheme is that the width of the resonance is adjustable, and can be greatly decreased by increasing the driving strength. Thus, the resonance can be significantly narrowed, by a factor of 10–100 in comparison with the existing detection methods. Significant improvement in selectivity is explained analytically and confirmed by direct numerical many-spin simulations. The method can be applied to a wide range of solid-state systems. PMID:26497777
NASA Astrophysics Data System (ADS)
Wang, Liwei; Fang, Fei; Liu, Yang; Li, Jing; Huang, Xiaojun
2016-11-01
Low-density lipoprotein (LDL) gains worldwide attention for decades as the key risk factor to atherosclerosis that progressively deteriorating into cardiovascular diseases. Until recent years, LDL-apheresis comes to be extensively used as a direct and efficient LDL removal method, with LDL adsorption materials particularly important. In this paper, a new strategy based on the co-deposition of polydopamine (PDA) with polyethylenimine (PEI) onto polysulfone (PSf) membranes, then subsequent heparinization by amino-carbonyl reactions, to achieve LDL selectivity and simultaneous biocompatibility, is proposed. Surface properties of modified PSf membranes are characterized by ATR-FTIR, XPS, FESEM, Zeta potential and WCA measurements. LDL adsorption ability is investigated by ELISA, while blood biocompatibility is evaluated by platelet adhesion experiments. Results suggest that heparin-modified PSf membranes show high selectivity for LDL removal and fine biocompatibility in contact with plasma, as excellent potential materials for LDL-apheresis.
Nucleocytoplasmic Transport: A Paradigm for Molecular Logistics in Artificial Systems.
Vujica, Suncica; Zelmer, Christina; Panatala, Radhakrishnan; Lim, Roderick Y H
2016-01-01
Artificial organelles, molecular factories and nanoreactors are membrane-bound systems envisaged to exhibit cell-like functionality. These constitute liposomes, polymersomes or hybrid lipo-polymersomes that display different membrane-spanning channels and/or enclose molecular modules. To achieve more complex functionality, an artificial organelle should ideally sustain a continuous influx of essential macromolecular modules (i.e. cargoes) and metabolites against an outflow of reaction products. This would benefit from the incorporation of selective nanopores as well as specific trafficking factors that facilitate cargo selectivity, translocation efficiency, and directionality. Towards this goal, we describe how proteinaceous cargoes are transported between the nucleus and cytoplasm by nuclear pore complexes and the biological trafficking machinery in living cells (i.e. nucleocytoplasmic transport). On this basis, we discuss how biomimetic control may be implemented to selectively import, compartmentalize and accumulate diverse macromolecular modules against concentration gradients in artificial organelles.
Speakman, John R
2007-07-01
The "thrifty gene hypothesis" suggests we evolved genes for efficient food collection and fat deposition to survive periods of famine and that now that food is continuously available, these genes are disadvantageous because they make us obese in preparation for a famine that never comes. However, famines are relatively infrequent modern phenomena that involve insufficient mortality for thrifty genes to propagate. I suggest here that early hominids would have been subjected to stabilizing selection for body fatness, with obesity selected against by the risk of predation. Around two million years ago predation was removed as a significant factor by the development of social behavior, weapons, and fire. The absence of predation led to a change in the population distribution of body fatness due to random mutations and drift. Because this novel hypothesis involves random drift, rather than directed selection, it explains why, even in Western society, most people are not obese.
Hospital closure: a review of current and proposed research.
Hernandez, S R; Kaluzny, A D
1983-01-01
This paper reviews available data describing issues and research findings with implications for hospital closings. Factors contributing to fiscal problems of hospitals (e.g., inadequate reimbursement, inflation, management problems, organizational structure, societal factors) are discussed. Selected studies offering examples of hospital and community characteristics associated with closure are presented. This review suggests that future directions for research should focus not only on hospital cost control but also on insuring equity in the distribution of hospital services. Specifically, research is needed that further describes the hospital closure phenomenon, the effects of closure, and the policy choices that might be pursued to insure equity in the continuation of hospital services to disadvantaged populations. PMID:6360954
Direct conversion from Jerusalem artichoke to hydroxymethylfurfural (HMF) using the Fenton reaction.
Seo, Yeong Hwan; Han, Jong-In
2014-05-15
A simple method for hydroxymethylfurfural (HMF) production from non-crop biomass of the Jerusalem artichoke was developed using the Fenton reaction, in a mixture of 2-butanol and water. Four parameters (temperature, reaction time, Fe(2+) concentration, and H2O2 concentration) were identified as experimental factors, and HMF yield was selected as the response parameter. The experimental factors were optimised by employing Response Surface Methodology (RSM). The maximum HMF yield, of 46%, was obtained with a reaction time of 90 min, Fe(2+) concentration of 1.3 mM, and 0.47 M of H2O2 at 180 °C. Copyright © 2014. Published by Elsevier Ltd.
Hanif, Rumeza; Jabeen, Ishrat; Mansoor, Qaisar; Ismail, Muhammad
2018-01-01
Insulin-like growth factor 1 receptor (IGF-1R) is an important therapeutic target for breast cancer treatment. The alteration in the IGF-1R associated signaling network due to various genetic and environmental factors leads the system towards metastasis. The pharmacophore modeling and logical approaches have been applied to analyze the behaviour of complex regulatory network involved in breast cancer. A total of 23 inhibitors were selected to generate ligand based pharmacophore using the tool, Molecular Operating Environment (MOE). The best model consisted of three pharmacophore features: aromatic hydrophobic (HyD/Aro), hydrophobic (HyD) and hydrogen bond acceptor (HBA). This model was validated against World drug bank (WDB) database screening to identify 189 hits with the required pharmacophore features and was further screened by using Lipinski positive compounds. Finally, the most effective drug, fulvestrant, was selected. Fulvestrant is a selective estrogen receptor down regulator (SERD). This inhibitor was further studied by using both in-silico and in-vitro approaches that showed the targeted effect of fulvestrant in ER+ MCF-7 cells. Results suggested that fulvestrant has selective cytotoxic effect and a dose dependent response on IRS-1, IGF-1R, PDZK1 and ER-α in MCF-7 cells. PDZK1 can be an important inhibitory target using fulvestrant because it directly regulates IGF-1R. PMID:29787591
Khalid, Samra; Hanif, Rumeza; Jabeen, Ishrat; Mansoor, Qaisar; Ismail, Muhammad
2018-01-01
Insulin-like growth factor 1 receptor (IGF-1R) is an important therapeutic target for breast cancer treatment. The alteration in the IGF-1R associated signaling network due to various genetic and environmental factors leads the system towards metastasis. The pharmacophore modeling and logical approaches have been applied to analyze the behaviour of complex regulatory network involved in breast cancer. A total of 23 inhibitors were selected to generate ligand based pharmacophore using the tool, Molecular Operating Environment (MOE). The best model consisted of three pharmacophore features: aromatic hydrophobic (HyD/Aro), hydrophobic (HyD) and hydrogen bond acceptor (HBA). This model was validated against World drug bank (WDB) database screening to identify 189 hits with the required pharmacophore features and was further screened by using Lipinski positive compounds. Finally, the most effective drug, fulvestrant, was selected. Fulvestrant is a selective estrogen receptor down regulator (SERD). This inhibitor was further studied by using both in-silico and in-vitro approaches that showed the targeted effect of fulvestrant in ER+ MCF-7 cells. Results suggested that fulvestrant has selective cytotoxic effect and a dose dependent response on IRS-1, IGF-1R, PDZK1 and ER-α in MCF-7 cells. PDZK1 can be an important inhibitory target using fulvestrant because it directly regulates IGF-1R.
48 CFR 16.104 - Factors in selecting contract types.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Factors in selecting... CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Selecting Contract Types 16.104 Factors in selecting contract types. There are many factors that the contracting officer should consider in selecting and...
48 CFR 16.104 - Factors in selecting contract types.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Factors in selecting... CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Selecting Contract Types 16.104 Factors in selecting contract types. There are many factors that the contracting officer should consider in selecting and...
Population dynamics in the presence of quasispecies effects and changing environments
NASA Astrophysics Data System (ADS)
Forster, Robert Burke
2006-12-01
This thesis explores how natural selection acts on organisms such as viruses that have either highly error-prone reproduction or face variable environmental conditions or both. By modeling population dynamics under these conditions, we gain a better understanding of the selective forces at work, both in our simulations and hopefully also in real organisms. With an understanding of the important factors in natural selection we can forecast not only the immediate fate of an existing population but also in what directions such a population might evolve in the future. We demonstrate that the concept of a quasispecies is relevant to evolution in a neutral fitness landscape. Motivated by RNA viruses such as HIV, we use RNA secondary structure as our model system and find that quasispecies effects arise both rapidly and in realistically small populations. We discover that the evolutionary effects of neutral drift, punctuated equilibrium and the selection for mutational robustness extend to the concept of a quasispecies. In our study of periodic environments, we consider the tradeoffs faced by quasispecies in adapting to environmental change. We develop an analytical model to predict whether evolution favors short-term or long-term adaptation and validate our model through simulation. Our results bear directly on the population dynamics of viruses such as West Nile that alternate between two host species. More generally, we discover that a selective pressure exists under these conditions to fuse or split genes with complementary environmental functions. Lastly, we study the general effects of frequency-dependent selection on two strains competing in a periodic environment. Under very general assumptions, we prove that stable coexistence rather than extinction is the likely outcome. The population dynamics of this system may be as simple as stable equilibrium or as complex as deterministic chaos.
Muir, Graham; Ruiz-Duarte, Paola; Hohmann, Nora; Mable, Barbara K; Novikova, Polina; Schmickl, Roswitha; Guggisberg, Alessia; Koch, Marcus A
2015-04-01
Reciprocal crosses between species often display an asymmetry in the fitness of F1 hybrids. This pattern, referred to as isolation asymmetry or Darwin's corollary to Haldane's rule, is a general feature of reproductive isolation in plants, yet factors determining its magnitude and direction remain unclear. We evaluated reciprocal species crosses between two naturally hybridizing diploid species of Arabidopsis to assess the degree of isolation asymmetry at different postmating life stages. We found that pollen from Arabidopsis arenosa will usually fertilize ovules from Arabidopsis lyrata; the reverse receptivity being less complete. Maternal A. lyrata parents set more F1 hybrid seed, but germinate at lower frequency, reversing the asymmetry. As predicted by theory, A. lyrata (the maternal parent with lower seed viability in crosses) exhibited accelerated chloroplast evolution, indicating that cytonuclear incompatibilities may play a role in reproductive isolation. However, this direction of asymmetrical reproductive isolation is not replicated in natural suture zones, where delayed hybrid breakdown of fertility at later developmental stages, or later-acting selection against A. arenosa maternal hybrids (unrelated to hybrid fertility, e.g., substrate adaptation) may be responsible for an excess of A. lyrata maternal hybrids. Exogenous selection rather than cytonuclear incompatibilities thus shapes the asymmetrical postmating isolation in nature.
NASA Astrophysics Data System (ADS)
Caracciolo, G.; Pozzi, D.; Caminiti, R.; Congiu Castellano, A.
2003-04-01
We investigated, for the first time, by using Energy Dispersive X-ray Diffraction, the structure of a new ternary cationic liposome formulated with dioleoyl trimethylammonium propane (DOTAP), 1,2-dioleoyl-3-phosphatidylethanolamine (DOPE) and cholesterol (Chol) (DDC) which has been recently found to have a selective high gene transfer ability in ovarian cancer cells. Our structural results provide a further experimental support to the widely accepted statement that there is not a simple and direct correlation between structure and transfection efficiency and that the factors controlling cationic lipid/DNA (CL-DNA) complexes-mediated gene transfer depend not only on the formulations of the cationic liposomes and their thermodynamic phase, but also significantly on the cell properties.
Zuo, Jiao; Zhang, Lianju; Song, Xiaoling; Dai, Weimin; Qiang, Sheng
2011-06-01
The compatibility and outcrossing rates between transgenic rice and weedy rice biotypes have been studied in some previous cases. However, few studies have addressed the reasons for these differences. The present study compared the compatibility and outcrossing rates between transgenic rice and selected weedy rice biotypes using manual and natural crossing experiments to elucidate the key innate factors causing the different outcrossing rates. Hybrid seed sets from manual crossing between transgenic rice and weedy rice varied from 31.8 to 82.7%, which correlated directly with genetic compatibility. Moreover, the significant differences in the quantity of germinated donor pollens and pollen tubes entering the weedy rice ovule directly contributed to the different seed sets. The natural outcrossing rates varied from 0 to 6.66‰. The duration of flowering overlap was the key factor influencing natural outcrossing. Plant and panicle height also affected outcrossing success. From this study, it is concluded that the likelihood of gene flow between transgenic rice and weedy rice biotypes is primarily determined by floral synchronisation and secondarily influenced by genetic compatibility and some morphological characteristics. Copyright © 2011 Society of Chemical Industry.
2009-04-01
selected for the prestigious 2008 AACR-Minorities in Cancer Research - Jane Cooke Wright Lectureship Award. 2. Arthur Gutierrez-Hartmann, PI, was...member is encoded by the v-ets oncogene in the E26 retrovirus, which causes hematopoietic malignancies in chickens [1–3]. In humans, ETS factors are also...signaling cascade, with MAPK directly phosphorylating chicken ETS1 [3]. Site-specific mutation of the ETS1 Thr82 MAPK phos- phorylation site to Ala results
New Instrumentation for Phase Partitioning
NASA Technical Reports Server (NTRS)
Harris, J. M.
1985-01-01
Cells and molecules can be purified by partitioning between the two immiscible liquid phases formed by aqueous solutions of poly/ethylene glycol and dextran. Such purification can be more selective, higher yielding, and less destructive to sensitive biological materials than other available techniques. Earth's gravitational field is a hindering factor as it causes sedimentation of particles to be purified and shear-induced particle randomization. The present proposal is directed toward developing new instrumentation for performing phase partitioning both on Earth and in microgravity.
Harano, Tomohiro; Kutsukake, Nobuyuki
2018-06-14
Extremely developed or specialised traits such as the elongated upper canines of extinct sabre-toothed cats are often not analogous to those of any extant species, which limits our understanding of their evolutionary cause. However, an extant species may have undergone directional selection for a similar extreme phenotype. Among living felids, the clouded leopard, Neofelis nebulosa, has exceptionally long upper canines for its body size. We hypothesised that directional selection generated the elongated upper canines of clouded leopards in a manner similar to the process in extinct sabre-toothed cats. To test this, we developed an approach that compared the effect of directional selection among lineages in a phylogeny using a simulation of trait evolution and approximate Bayesian computation. This approach was applied to analyse the evolution of upper canine length in the Felidae phylogeny. Our analyses consistently showed directional selection favouring longer upper canines in the clouded leopard lineage and a lineage leading to the sabre-toothed cat with the longest upper canines, Smilodon. Most of our analyses detected an effect of directional selection for longer upper canines in the lineage leading to another sabre-toothed cat, Homotherium, although this selection may have occurred exclusively in the primitive species. In all the analyses, the clouded leopard and Smilodon lineages showed comparable directional selection. This implies that clouded leopards share a selection advantage with sabre-toothed cats in having elongated upper canines. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Holt, James B.; Zhang, Xingyou; Lu, Hua; Shah, Snehal N.; Dooley, Daniel P.; Matthews, Kevin A.; Croft, Janet B.
2017-01-01
Introduction Local health authorities need small-area estimates for prevalence of chronic diseases and health behaviors for multiple purposes. We generated city-level and census-tract–level prevalence estimates of 27 measures for the 500 largest US cities. Methods To validate the methodology, we constructed multilevel logistic regressions to predict 10 selected health indicators among adults aged 18 years or older by using 2013 Behavioral Risk Factor Surveillance System (BRFSS) data; we applied their predicted probabilities to census population data to generate city-level, neighborhood-level, and zip-code–level estimates for the city of Boston, Massachusetts. Results By comparing the predicted estimates with their corresponding direct estimates from a locally administered survey (Boston BRFSS 2010 and 2013), we found that our model-based estimates for most of the selected health indicators at the city level were close to the direct estimates from the local survey. We also found strong correlation between the model-based estimates and direct survey estimates at neighborhood and zip code levels for most indicators. Conclusion Findings suggest that our model-based estimates are reliable and valid at the city level for certain health outcomes. Local health authorities can use the neighborhood-level estimates if high quality local health survey data are not otherwise available. PMID:29049020
Young, Allison; Petros, Timothy; Karayannis, Theofanis; McKenzie Chang, Melissa; Lavado, Alfonso; Iwano, Tomohiko; Nakajima, Miho; Taniguchi, Hiroki; Huang, Z. Josh; Heintz, Nathaniel; Oliver, Guillermo; Matsuzaki, Fumio; Machold, Robert P.
2015-01-01
Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking. Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons. PMID:26377473
Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?
Ghiglione, Yanina; Hormanstorfer, Macarena; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D.; Pando, María de los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Sued, Omar
2018-01-01
Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied. PMID:29342870
Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?
Turk, Gabriela; Ghiglione, Yanina; Hormanstorfer, Macarena; Laufer, Natalia; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Holgado, María Pía; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D; Pando, María de Los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Pury, Pedro A; Sued, Omar
2018-01-13
Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4⁺ T-cell activation ( p < 0.05). However, none of these cytokines had good predictive values to distinguish "progressors" from "non-progressors". Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.
Zhang, Hang; Xu, Qingyan
2017-10-27
Grain selection is an important process in single crystal turbine blades manufacturing. Selector structure is a control factor of grain selection, as well as directional solidification (DS). In this study, the grain selection and structure design of the spiral selector were investigated through experimentation and simulation. A heat transfer model and a 3D microstructure growth model were established based on the Cellular automaton-Finite difference (CA-FD) method for the grain selector. Consequently, the temperature field, the microstructure and the grain orientation distribution were simulated and further verified. The average error of the temperature result was less than 1.5%. The grain selection mechanisms were further analyzed and validated through simulations. The structural design specifications of the selector were suggested based on the two grain selection effects. The structural parameters of the spiral selector, namely, the spiral tunnel diameter ( d w ), the spiral pitch ( h b ) and the spiral diameter ( h s ), were studied and the design criteria of these parameters were proposed. The experimental and simulation results demonstrated that the improved selector could accurately and efficiently produce a single crystal structure.
Zhang, Hang; Xu, Qingyan
2017-01-01
Grain selection is an important process in single crystal turbine blades manufacturing. Selector structure is a control factor of grain selection, as well as directional solidification (DS). In this study, the grain selection and structure design of the spiral selector were investigated through experimentation and simulation. A heat transfer model and a 3D microstructure growth model were established based on the Cellular automaton-Finite difference (CA-FD) method for the grain selector. Consequently, the temperature field, the microstructure and the grain orientation distribution were simulated and further verified. The average error of the temperature result was less than 1.5%. The grain selection mechanisms were further analyzed and validated through simulations. The structural design specifications of the selector were suggested based on the two grain selection effects. The structural parameters of the spiral selector, namely, the spiral tunnel diameter (dw), the spiral pitch (hb) and the spiral diameter (hs), were studied and the design criteria of these parameters were proposed. The experimental and simulation results demonstrated that the improved selector could accurately and efficiently produce a single crystal structure. PMID:29077067
Moré, Marcela; Amorim, Felipe W.; Benitez-Vieyra, Santiago; Medina, A. Martin; Sazima, Marlies; Cocucci, Andrea A.
2012-01-01
Background Some species of long-spurred orchids achieve pollination by a close association with long-tongued hawkmoths. Among them, several Habenaria species present specialized mechanisms, where pollination success depends on the attachment of pollinaria onto the heads of hawkmoths with very long proboscises. However, in the Neotropical region such moths are less abundant than their shorter-tongued relatives and are also prone to population fluctuations. Both factors may give rise to differences in pollinator-mediated selection on floral traits through time and space. Methodology/Principal Findings We characterized hawkmoth assemblages and estimated phenotypic selection gradients on orchid spur lengths in populations of three South American Habenaria species. We examined the match between hawkmoth proboscis and flower spur lengths to determine whether pollinators may act as selective agents on flower morphology. We found significant directional selection on spur length only in Habenaria gourlieana, where most pollinators had proboscises longer than the mean of orchid spur length. Conclusions/Significance Phenotypic selection is dependent on the mutual match between pollinator and flower morphologies. However, our findings indicate that pollinator-mediated selection may vary through time and space according to local variations in pollinator assemblages. PMID:22848645
Factors that affect the development of nurses' competencies: a systematic review.
Rizany, Ichsan; Hariyati, Rr Tutik Sri; Handayani, Hanny
2018-02-01
To investigate factors affecting the development of nursing competency based on a review of the literature. A systematic review was utilized. The articles were taken from the databases of Pro-Quest, ScienceDirect, SpringerLink, and Scopus. They were retrieved using the following keywords: nursing competence, nurse competencies and clinical competence. Twenty-one papers were selected. Competence development is a continuous process of improving knowledge, attitudes and skills, and is influenced by a myriad of factors. Six factors were identified that affected the development of nursing competence in our systematic review: (1) work experience, (2) type of nursing environment, (3) educational level achieved, (4) adherence to professionalism, (5) critical thinking, and (6) personal factors. Work experience and education were shown to significantly influence the development of competency of nurses. Nurse managers need to support staffing competence through ongoing education, mentoring-preceptorship training, and case-reflection-discussion teaching programs. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.
Evolution in plant populations as a driver of ecological changes in arthropod communities
Johnson, Marc T.J.; Vellend, Mark; Stinchcombe, John R.
2009-01-01
Heritable variation in traits can have wide-ranging impacts on species interactions, but the effects that ongoing evolution has on the temporal ecological dynamics of communities are not well understood. Here, we identify three conditions that, if experimentally satisfied, support the hypothesis that evolution by natural selection can drive ecological changes in communities. These conditions are: (i) a focal population exhibits genetic variation in a trait(s), (ii) there is measurable directional selection on the trait(s), and (iii) the trait(s) under selection affects variation in a community variable(s). When these conditions are met, we expect evolution by natural selection to cause ecological changes in the community. We tested these conditions in a field experiment examining the interactions between a native plant (Oenothera biennis) and its associated arthropod community (more than 90 spp.). Oenothera biennis exhibited genetic variation in several plant traits and there was directional selection on plant biomass, life-history strategy (annual versus biennial reproduction) and herbivore resistance. Genetically based variation in biomass and life-history strategy consistently affected the abundance of common arthropod species, total arthropod abundance and arthropod species richness. Using two modelling approaches, we show that evolution by natural selection in large O. biennis populations is predicted to cause changes in the abundance of individual arthropod species, increases in the total abundance of arthropods and a decline in the number of arthropod species. In small O. biennis populations, genetic drift is predicted to swamp out the effects of selection, making the evolution of plant populations unpredictable. In short, evolution by natural selection can play an important role in affecting the dynamics of communities, but these effects depend on several ecological factors. The framework presented here is general and can be applied to other systems to examine the community-level effects of ongoing evolution. PMID:19414473
The evolution of recombination in a heterogeneous environment.
Lenormand, T; Otto, S P
2000-01-01
Most models describing the evolution of recombination have focused on the case of a single population, implicitly assuming that all individuals are equally likely to mate and that spatial heterogeneity in selection is absent. In these models, the evolution of recombination is driven by linkage disequilibria generated either by epistatic selection or drift. Models based on epistatic selection show that recombination can be favored if epistasis is negative and weak compared to directional selection and if the recombination modifier locus is tightly linked to the selected loci. In this article, we examine the joint effects of spatial heterogeneity in selection and epistasis on the evolution of recombination. In a model with two patches, each subject to different selection regimes, we consider the cases of mutation-selection and migration-selection balance as well as the spread of beneficial alleles. We find that including spatial heterogeneity extends the range of epistasis over which recombination can be favored. Indeed, recombination can be favored without epistasis, with negative and even with positive epistasis depending on environmental circumstances. The selection pressure acting on recombination-modifier loci is often much stronger with spatial heterogeneity, and even loosely linked modifiers and free linkage may evolve. In each case, predicting whether recombination is favored requires knowledge of both the type of environmental heterogeneity and epistasis, as none of these factors alone is sufficient to predict the outcome. PMID:10978305
Directional selection causes decanalization in a group I ribozyme.
Hayden, Eric J; Weikert, Christian; Wagner, Andreas
2012-01-01
A canalized genotype is robust to environmental or genetic perturbations. Canalization is expected to result from stabilizing selection on a well-adapted phenotype. Decanalization, the loss of robustness, might follow periods of directional selection toward a new optimum. The evolutionary forces causing decanalization are still unknown, in part because it is difficult to determine the fitness effects of mutations in populations of organisms with complex genotypes and phenotypes. Here, we report direct experimental measurements of robustness in a system with a simple genotype and phenotype, the catalytic activity of an RNA enzyme. We find that the robustness of a population of RNA enzymes decreases during a period of directional selection in the laboratory. The decrease in robustness is primarily caused by the selective sweep of a genotype that is decanalized relative to the wild-type, both in terms of mutational robustness and environmental robustness (thermodynamic stability). Our results experimentally demonstrate that directional selection can cause decanalization on short time scales, and demonstrate co-evolution of mutational and environmental robustness.
Duan, Ran; Fu, Haoda
2015-08-30
Recurrent event data are an important data type for medical research. In particular, many safety endpoints are recurrent outcomes, such as hypoglycemic events. For such a situation, it is important to identify the factors causing these events and rank these factors by their importance. Traditional model selection methods are not able to provide variable importance in this context. Methods that are able to evaluate the variable importance, such as gradient boosting and random forest algorithms, cannot directly be applied to recurrent events data. In this paper, we propose a two-step method that enables us to evaluate the variable importance for recurrent events data. We evaluated the performance of our proposed method by simulations and applied it to a data set from a diabetes study. Copyright © 2015 John Wiley & Sons, Ltd.
Tang, Wei; Lu, Yi; Tian, Qing-Yun; Zhang, Yan; Guo, Feng-Jin; Liu, Guang-Yi; Syed, Nabeel Muzaffar; Lai, Yongjie; Lin, Edward Alan; Kong, Li; Su, Jeffrey; Yin, Fangfang; Ding, Ai-Hao; Zanin-Zhorov, Alexandra; Dustin, Michael L.; Tao, Jian; Craft, Joseph; Yin, Zhinan; Feng, Jian Q.; Abramson, Steven B.; Yu, Xiu-Ping; Liu, Chuan-ju
2011-01-01
The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFR), and disturbed the TNFα/TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis. PMID:21393509
Mediation of mouse natural cytotoxic activity by tumour necrosis factor
NASA Astrophysics Data System (ADS)
Ortaldo, John R.; Mason, Llewellyn H.; Mathieson, Bonnie J.; Liang, Shu-Mei; Flick, David A.; Herberman, Ronald B.
1986-06-01
Natural cell-mediated cytotoxic activity in the mouse has been associated with two types of effector cells, the natural killer (NK) cell and the natural cytotoxic (NC) cell, which seem to differ with regard to their patterns of target selectivity, cell surface characteristics and susceptibility to regulatory factors1. During studies on the mechanism of action of cytotoxic molecules, it became evident that WEHI-164, the prototype NC target cell, was highly susceptible to direct lysis by both human and mouse recombinant tumour necrosis factor (TNF). Here we show that NC, but not NK activity mediated by normal splenocytes, is abrogated by rabbit antibodies to recombinant and natural TNF, respectively. Thus, the cell-mediated activity defined as NC is due to release of TNF by normal spleen cells and does not represent a unique natural effector mechanism.
Evolution of disease response genes in loblolly pine: insights from candidate genes.
Ersoz, Elhan S; Wright, Mark H; González-Martínez, Santiago C; Langley, Charles H; Neale, David B
2010-12-06
Host-pathogen interactions that may lead to a competitive co-evolution of virulence and resistance mechanisms present an attractive system to study molecular evolution because strong, recent (or even current) selective pressure is expected at many genomic loci. However, it is unclear whether these selective forces would act to preserve existing diversity, promote novel diversity, or reduce linked neutral diversity during rapid fixation of advantageous alleles. In plants, the lack of adaptive immunity places a larger burden on genetic diversity to ensure survival of plant populations. This burden is even greater if the generation time of the plant is much longer than the generation time of the pathogen. Here, we present nucleotide polymorphism and substitution data for 41 candidate genes from the long-lived forest tree loblolly pine, selected primarily for their prospective influences on host-pathogen interactions. This dataset is analyzed together with 15 drought-tolerance and 13 wood-quality genes from previous studies. A wide range of neutrality tests were performed and tested against expectations from realistic demographic models. Collectively, our analyses found that axr (auxin response factor), caf1 (chromatin assembly factor) and gatabp1 (gata binding protein 1) candidate genes carry patterns consistent with directional selection and erd3 (early response to drought 3) displays patterns suggestive of a selective sweep, both of which are consistent with the arm-race model of disease response evolution. Furthermore, we have identified patterns consistent with diversifying selection at erf1-like (ethylene responsive factor 1), ccoaoemt (caffeoyl-CoA-O-methyltransferase), cyp450-like (cytochrome p450-like) and pr4.3 (pathogen response 4.3), expected under the trench-warfare evolution model. Finally, a drought-tolerance candidate related to the plant cell wall, lp5, displayed patterns consistent with balancing selection. In conclusion, both arms-race and trench-warfare models seem compatible with patterns of polymorphism found in different disease-response candidate genes, indicating a mixed strategy of disease tolerance evolution for loblolly pine, a major tree crop in southeastern United States.
Nanoporous membranes with electrochemically switchable, chemically stabilized ionic selectivity
NASA Astrophysics Data System (ADS)
Small, Leo J.; Wheeler, David R.; Spoerke, Erik D.
2015-10-01
Nanopore size, shape, and surface charge all play important roles in regulating ionic transport through nanoporous membranes. The ability to control these parameters in situ provides a means to create ion transport systems tunable in real time. Here, we present a new strategy to address this challenge, utilizing three unique electrochemically switchable chemistries to manipulate the terminal functional group and control the resulting surface charge throughout ensembles of gold plated nanopores in ion-tracked polycarbonate membranes 3 cm2 in area. We demonstrate the diazonium mediated surface functionalization with (1) nitrophenyl chemistry, (2) quinone chemistry, and (3) previously unreported trimethyl lock chemistry. Unlike other works, these chemistries are chemically stabilized, eliminating the need for a continuously applied gate voltage to maintain a given state and retain ionic selectivity. The effect of surface functionalization and nanopore geometry on selective ion transport through these functionalized membranes is characterized in aqueous solutions of sodium chloride at pH = 5.7. The nitrophenyl surface allows for ionic selectivity to be irreversibly switched in situ from cation-selective to anion-selective upon reduction to an aminophenyl surface. The quinone-terminated surface enables reversible changes between no ionic selectivity and a slight cationic selectivity. Alternatively, the trimethyl lock allows ionic selectivity to be reversibly switched by up to a factor of 8, approaching ideal selectivity, as a carboxylic acid group is electrochemically revealed or hidden. By varying the pore shape from cylindrical to conical, it is demonstrated that a controllable directionality can be imparted to the ionic selectivity. Combining control of nanopore geometry with stable, switchable chemistries facilitates superior control of molecular transport across the membrane, enabling tunable ion transport systems.Nanopore size, shape, and surface charge all play important roles in regulating ionic transport through nanoporous membranes. The ability to control these parameters in situ provides a means to create ion transport systems tunable in real time. Here, we present a new strategy to address this challenge, utilizing three unique electrochemically switchable chemistries to manipulate the terminal functional group and control the resulting surface charge throughout ensembles of gold plated nanopores in ion-tracked polycarbonate membranes 3 cm2 in area. We demonstrate the diazonium mediated surface functionalization with (1) nitrophenyl chemistry, (2) quinone chemistry, and (3) previously unreported trimethyl lock chemistry. Unlike other works, these chemistries are chemically stabilized, eliminating the need for a continuously applied gate voltage to maintain a given state and retain ionic selectivity. The effect of surface functionalization and nanopore geometry on selective ion transport through these functionalized membranes is characterized in aqueous solutions of sodium chloride at pH = 5.7. The nitrophenyl surface allows for ionic selectivity to be irreversibly switched in situ from cation-selective to anion-selective upon reduction to an aminophenyl surface. The quinone-terminated surface enables reversible changes between no ionic selectivity and a slight cationic selectivity. Alternatively, the trimethyl lock allows ionic selectivity to be reversibly switched by up to a factor of 8, approaching ideal selectivity, as a carboxylic acid group is electrochemically revealed or hidden. By varying the pore shape from cylindrical to conical, it is demonstrated that a controllable directionality can be imparted to the ionic selectivity. Combining control of nanopore geometry with stable, switchable chemistries facilitates superior control of molecular transport across the membrane, enabling tunable ion transport systems. Electronic supplementary information (ESI) available: Experimental procedures, synthesis, and characterization of molecules 1, 2 and 3. Explanation of the electrochemical method for approximating nanopore diameter. Additional XPS spectra. See DOI: 10.1039/C5NR02939B
Electrically-induced polarization selection rules of a graphene quantum dot
NASA Astrophysics Data System (ADS)
Dong, Qing-Rui; Li, Yan; Jia, Chen; Wang, Fu-Li; Zhang, Ya-Ting; Liu, Chun-Xiang
2018-05-01
We study theoretically the single-electron triangular zigzag graphene quantum dot in uniform in-plane electric fields. The absorption spectra of the dot are calculated by the tight-binding method. The energy spectra and the distribution of wave functions are also presented to analyse the absorption spectra. The orthogonal zero-energy eigenstates are arranged along to the direction of the external field. The remarkable result is that all intraband transitions and some interband transitions are forbidden when the absorbed light is polarized along the direction of the electric field. With x-direction electric field, all intraband absorption is y polarized due to the electric-field-direction-polarization selection rule. Moreover, with y-direction electric field, all absorption is either x or y polarized due to the parity selection rule as well as to the electric-field-direction-polarization selection rule. Our calculation shows that the formation of the absorption spectra is co-decided by the polarization selection rules and the overlap between the eigenstates of the transition.
Genome-wide analysis of codon usage bias in four sequenced cotton species.
Wang, Liyuan; Xing, Huixian; Yuan, Yanchao; Wang, Xianlin; Saeed, Muhammad; Tao, Jincai; Feng, Wei; Zhang, Guihua; Song, Xianliang; Sun, Xuezhen
2018-01-01
Codon usage bias (CUB) is an important evolutionary feature in a genome which provides important information for studying organism evolution, gene function and exogenous gene expression. The CUB and its shaping factors in the nuclear genomes of four sequenced cotton species, G. arboreum (A2), G. raimondii (D5), G. hirsutum (AD1) and G. barbadense (AD2) were analyzed in the present study. The effective number of codons (ENC) analysis showed the CUB was weak in these four species and the four subgenomes of the two tetraploids. Codon composition analysis revealed these four species preferred to use pyrimidine-rich codons more frequently than purine-rich codons. Correlation analysis indicated that the base content at the third position of codons affect the degree of codon preference. PR2-bias plot and ENC-plot analyses revealed that the CUB patterns in these genomes and subgenomes were influenced by combined effects of translational selection, directional mutation and other factors. The translational selection (P2) analysis results, together with the non-significant correlation between GC12 and GC3, further revealed that translational selection played the dominant role over mutation pressure in the codon usage bias. Through relative synonymous codon usage (RSCU) analysis, we detected 25 high frequency codons preferred to end with T or A, and 31 low frequency codons inclined to end with C or G in these four species and four subgenomes. Finally, 19 to 26 optimal codons with 19 common ones were determined for each species and subgenomes, which preferred to end with A or T. We concluded that the codon usage bias was weak and the translation selection was the main shaping factor in nuclear genes of these four cotton genomes and four subgenomes.
Selection on skewed characters and the paradox of stasis.
Bonamour, Suzanne; Teplitsky, Céline; Charmantier, Anne; Crochet, Pierre-André; Chevin, Luis-Miguel
2017-11-01
Observed phenotypic responses to selection in the wild often differ from predictions based on measurements of selection and genetic variance. An overlooked hypothesis to explain this paradox of stasis is that a skewed phenotypic distribution affects natural selection and evolution. We show through mathematical modeling that, when a trait selected for an optimum phenotype has a skewed distribution, directional selection is detected even at evolutionary equilibrium, where it causes no change in the mean phenotype. When environmental effects are skewed, Lande and Arnold's (1983) directional gradient is in the direction opposite to the skew. In contrast, skewed breeding values can displace the mean phenotype from the optimum, causing directional selection in the direction of the skew. These effects can be partitioned out using alternative selection estimates based on average derivatives of individual relative fitness, or additive genetic covariances between relative fitness and trait (Robertson-Price identity). We assess the validity of these predictions using simulations of selection estimation under moderate sample sizes. Ecologically relevant traits may commonly have skewed distributions, as we here exemplify with avian laying date - repeatedly described as more evolutionarily stable than expected - so this skewness should be accounted for when investigating evolutionary dynamics in the wild. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.
Goal-directed, habitual and Pavlovian prosocial behavior
Gęsiarz, Filip; Crockett, Molly J.
2015-01-01
Although prosocial behaviors have been widely studied across disciplines, the mechanisms underlying them are not fully understood. Evidence from psychology, biology and economics suggests that prosocial behaviors can be driven by a variety of seemingly opposing factors: altruism or egoism, intuition or deliberation, inborn instincts or learned dispositions, and utility derived from actions or their outcomes. Here we propose a framework inspired by research on reinforcement learning and decision making that links these processes and explains characteristics of prosocial behaviors in different contexts. More specifically, we suggest that prosocial behaviors inherit features of up to three decision-making systems employed to choose between self- and other- regarding acts: a goal-directed system that selects actions based on their predicted consequences, a habitual system that selects actions based on their reinforcement history, and a Pavlovian system that emits reflexive responses based on evolutionarily prescribed priors. This framework, initially described in the field of cognitive neuroscience and machine learning, provides insight into the potential neural circuits and computations shaping prosocial behaviors. Furthermore, it identifies specific conditions in which each of these three systems should dominate and promote other- or self- regarding behavior. PMID:26074797
NASA Astrophysics Data System (ADS)
Sánchez-Monreal, Juan; García-Salaberri, Pablo A.; Vera, Marcos
2017-09-01
A one-dimensional model is proposed for the anode of a liquid-feed direct ethanol fuel cell. The complex kinetics of the ethanol electro-oxidation reaction is described using a multi-step reaction mechanism that considers free and adsorbed intermediate species on Pt-based binary catalysts. The adsorbed species are modeled using coverage factors to account for the blockage of the active reaction sites on the catalyst surface. The reaction rates are described by Butler-Volmer equations that are coupled to a one-dimensional mass transport model, which incorporates the effect of ethanol and acetaldehyde crossover. The proposed kinetic model circumvents the acetaldehyde bottleneck effect observed in previous studies by incorporating CH3CHOHads among the adsorbed intermediates. A multi-objetive genetic algorithm is used to determine the reaction constants using anode polarization and product selectivity data obtained from the literature. By adjusting the reaction constants using the methodology developed here, different catalyst layers could be modeled and their selectivities could be successfully reproduced.
Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.
Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M; Wong, Margaret; Kiessling, Laura L; Steitz, Thomas A; O'Donoghue, Patrick; Söll, Dieter
2014-11-25
Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate N(ε)-acetyl-Lys (AcK) onto tRNA(Pyl). Here, we examine an N(ε)-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids.
Polyspecific pyrrolysyl-tRNA synthetases from directed evolution
Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M.; Wong, Margaret; Kiessling, Laura L.; Steitz, Thomas A.; O’Donoghue, Patrick; Söll, Dieter
2014-01-01
Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNAPyl have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate Nε-acetyl-Lys (AcK) onto tRNAPyl. Here, we examine an Nε-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids. PMID:25385624
NASA Technical Reports Server (NTRS)
Schmidt, A. F. (Editor)
1972-01-01
Selected information is presented from an assemblage of reports and publications on heat transfer and fluid dynamics with direct applicability to oxygen systems. For each document cited, an abstract has been prepared together with key words and a listing of most important references found in the document. Additionally, an author index, a subject index, and a key word index have been provided to simplify the retrieval of specific information from this work. In each subject area - e.g., boiling heat transfer - the individual citations are listed alphabetically by first author, with review papers dually noted under the appropriate subject category and under review papers. Of the documents reviewed and evaluated for inclusion in this publication, coverage of existing information directly concerned with oxygen was given primary emphasis. However, work not specifically oxygen-designated but considered applicable to oxygen by the reviewer e.g., a two-phase friction factor correlation derived from nitrogen experiments is occasionally given where no actual oxygen data exist, as an aid to the reader. Approximately 130 abstracts are listed.
Factors associated with the nutritional status of children less than 5 years of age
Miglioli, Teresa Cristina; Fonseca, Vania Matos; Gomes, Saint Clair; da Silva, Katia Silveira; de Lira, Pedro Israel Cabral; Batista, Malaquias
2015-01-01
OBJECTIVE To analyze if the nutritional status of children aged less than five years is related to the biological conditions of their mothers, environmental and socioeconomic factors, and access to health services and social programs. METHODS This cross-sectional population-based study analyzed 664 mothers and 790 children using canonical correlation analysis. Dependent variables were characteristics of the children (weight/age, height/age, BMI/age, hemoglobin, and retinol serum levels). Independent variables were those related to the mothers’ nutritional status (BMI, hemoglobin, and retinol serum levels), age, environmental and socioeconomic factors and access to health service and social programs. A < 0.05 significance level was adopted to select the interpreted canonical functions (CF) and ± 0.40 as canonical load value of the analyzed variables. RESULTS Three canonical functions were selected, concentrating 89.9% of the variability of the relationship among the groups. In the first canonical function, weight/age (-0.73) and height/age (-0.99) of the children were directly related to the mother’s height (-0.82), prenatal appointments (-0.43), geographical area of the residence (-0.41), and household income per capita (-0.42). Inverse relationship between the variables related to the children and people/room (0.44) showed that the larger the number of people/room, the poorer their nutritional status. Rural residents were found to have the worse nutritional conditions. In the second canonical function, the BMI of the mother (-0.48) was related to BMI/age and retinol of the children, indicating that as women gained weight so did their children. Underweight women tended to have children with vitamin A deficiency. In the third canonical function, hemoglobin (-0.72) and retinol serum levels (-0.40) of the children were directly related to the mother’s hemoglobin levels (-0.43). CONCLUSIONS Mothers and children were associated concerning anemia, vitamin A deficiency and anthropometric markers. Living in rural areas is a determining factor for the families health status. PMID:26398874
Scholten-Peeters, Gwendolijne G M; Verhagen, Arianne P; Bekkering, Geertruida E; van der Windt, Daniëlle A W M; Barnsley, Les; Oostendorp, Rob A B; Hendriks, Erik J M
2003-07-01
We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e.g. restricted range of motion, high number of complaints), psychosocial (previous psychological problems), neuropsychosocial factors (nervousness), crash related (e.g. accident on highway) and treatment related factors (need to resume physiotherapy) showed limited prognostic value for functional recovery. High initial pain intensity is an important predictor for delayed functional recovery for patients with whiplash injury. Often mentioned factors like age, gender and compensation do not seem to be of prognostic value. Scientific information about prognostic factors can guide physicians or other care providers to direct treatment and to probably prevent chronicity.
Duration on unemployment: geographic mobility and selectivity bias.
Goss, E P; Paul, C; Wilhite, A
1994-01-01
Modeling the factors affecting the duration of unemployment was found to be influenced by the inclusion of migration factors. Traditional models which did not control for migration factors were found to underestimate movers' probability of finding an acceptable job. The empirical test of the theory, based on the analysis of data on US household heads unemployed in 1982 and employed in 1982 and 1983, found that the cumulative probability of reemployment in the traditional model was .422 and in the migration selectivity model was .624 after 30 weeks of searching. In addition, controlling for selectivity eliminated the significance of the relationship between race and job search duration in the model. The relationship between search duration and the county unemployment rate in 1982 became statistically significant, and the relationship between search duration and 1980 population per square mile in the 1982 county of residence became statistically insignificant. The finding that non-Whites have a longer duration of unemployment can better be understood as non-Whites' lower geographic mobility and lack of greater job contacts. The statistical significance of a high unemployment rate in the home labor market reducing the probability of finding employment was more in keeping with expectations. The findings assumed that the duration of employment accurately reflected the length of job search. The sample was redrawn to exclude discouraged workers and the analysis was repeated. The findings were similar to the full sample, with the coefficient for migration variable being negative and statistically significant and the coefficient for alpha remaining positive and statistically significant. Race in the selectivity model remained statistically insignificant. The findings supported the Schwartz model hypothesizing that the expansion of the radius of the search would reduce the duration of unemployment. The exclusion of the migration factor misspecified the equation for unemployment duration. Policy should be directed to the problems of geographic mobility, particularly among non-Whites.
Díaz-Perera, Georgia; Bacallao, Jorge; Alemañy, Eduardo
2013-04-01
A population health profile is a cumulative product of socioenvironmental and political factors that create the contexts in which health problems arise, as well as opportunities and barriers to addressing them. Research on context has focused on demonstrating its effects, direct or indirect, on health indicators, but has made few incursions into assessing its role as a mediator of other factors. While individual risk factors for chronic diseases are well known, the same cannot be said for the complex of contextual factors operating at various levels and over the lifespan. Estimate relative influences by contextual versus individual factors as determinants of diabetes type 2 and heart disease. A cross-sectional study was carried out in populations served by 12 family doctor-and-nurse practices in Havana, in 840 families selected by simple random sampling, 70 per practice. Principal components analysis was used, as well as contextual logistic regression models with a nested model strategy, whose fit was meant to estimate the relative contributions of contextual compared to individual risk factors for diabetes and heart disease. Context was described and analyzed at two levels: that of the family or household and that of the catchment area served by a family doctor-and-nurse practice (geographically defined as a neighborhood). For diabetes, the contextual effect of neighborhood was modified when household effect was removed; that is, the effect of neighborhood was indirect and mediated by household. Individual coefficients were practically invariant; the principal effect of household changed noticeably on removal of individual effects, while age maintained its effect without variation. For heart disease, the effect of neighborhood was slightly modified when household effect was controlled for. Individual coefficients showed little change. There was an important direct effect of household on risk of heart disease. Age and high blood pressure coefficients hardly varied. We confirmed interactions between individual and contextual (neighborhood and household) factors, whose effects on individual health are not entirely mediated by individual factors. Research needs to pay more attention to context beyond its direct effect on individual risk factors.
Persistent directional selection on body size and a resolution to the paradox of stasis.
Rollinson, Njal; Rowe, Locke
2015-09-01
Directional selection on size is common but often fails to result in microevolution in the wild. Similarly, macroevolutionary rates in size are low relative to the observed strength of selection in nature. We show that many estimates of selection on size have been measured on juveniles, not adults. Further, parents influence juvenile size by adjusting investment per offspring. In light of these observations, we help resolve this paradox by suggesting that the observed upward selection on size is balanced by selection against investment per offspring, resulting in little or no net selection gradient on size. We find that trade-offs between fecundity and juvenile size are common, consistent with the notion of selection against investment per offspring. We also find that median directional selection on size is positive for juveniles but no net directional selection exists for adult size. This is expected because parent-offspring conflict exists over size, and juvenile size is more strongly affected by investment per offspring than adult size. These findings provide qualitative support for the hypothesis that upward selection on size is balanced by selection against investment per offspring, where parent-offspring conflict over size is embodied in the opposing signs of the two selection gradients. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.
Jha, Ramesh K; Chakraborti, Subhendu; Kern, Theresa L; Fox, David T; Strauss, Charlie E M
2015-07-01
Structure-based rational mutagenesis for engineering protein functionality has been limited by the scarcity and difficulty of obtaining crystal structures of desired proteins. On the other hand, when high-throughput selection is possible, directed evolution-based approaches for gaining protein functionalities have been random and fortuitous with limited rationalization. We combine comparative modeling of dimer structures, ab initio loop reconstruction, and ligand docking to select positions for mutagenesis to create a library focused on the ligand-contacting residues. The rationally reduced library requirement enabled conservative control of the substitutions by oligonucleotide synthesis and bounding its size within practical transformation efficiencies (∼ 10(7) variants). This rational approach was successfully applied on an inducer-binding domain of an Acinetobacter transcription factor (TF), pobR, which shows high specificity for natural effector molecule, 4-hydroxy benzoate (4HB), but no native response to 3,4-dihydroxy benzoate (34DHB). Selection for mutants with high transcriptional induction by 34DHB was carried out at the single-cell level under flow cytometry (via green fluorescent protein expression under the control of pobR promoter). Critically, this selection protocol allows both selection for induction and rejection of constitutively active mutants. In addition to gain-of-function for 34DHB induction, the selected mutants also showed enhanced sensitivity and response for 4HB (native inducer) while no sensitivity was observed for a non-targeted but chemically similar molecule, 2-hydroxy benzoate (2HB). This is unique application of the Rosetta modeling protocols for library design to engineer a TF. Our approach extends applicability of the Rosetta redesign protocol into regimes without a priori precision structural information. © 2015 Wiley Periodicals, Inc.
Patterns of Positive Selection of the Myogenic Regulatory Factor Gene Family in Vertebrates
Zhao, Xiao; Yu, Qi; Huang, Ling; Liu, Qing-Xin
2014-01-01
The functional divergence of transcriptional factors is critical in the evolution of transcriptional regulation. However, the mechanism of functional divergence among these factors remains unclear. Here, we performed an evolutionary analysis for positive selection in members of the myogenic regulatory factor (MRF) gene family of vertebrates. We selected 153 complete vertebrate MRF nucleotide sequences from our analyses, which revealed substantial evidence of positive selection. Here, we show that sites under positive selection were more frequently detected and identified from the genes encoding the myogenic differentiation factors (MyoG and Myf6) than the genes encoding myogenic determination factors (Myf5 and MyoD). Additionally, the functional divergence within the myogenic determination factors or differentiation factors was also under positive selection pressure. The positive selection sites were more frequently detected from MyoG and MyoD than Myf6 and Myf5, respectively. Amino acid residues under positive selection were identified mainly in their transcription activation domains and on the surface of protein three-dimensional structures. These data suggest that the functional gain and divergence of myogenic regulatory factors were driven by distinct positive selection of their transcription activation domains, whereas the function of the DNA binding domains was conserved in evolution. Our study evaluated the mechanism of functional divergence of the transcriptional regulation factors within a family, whereby the functions of their transcription activation domains diverged under positive selection during evolution. PMID:24651579
Menon, Mitra; Bagley, Justin C; Friedline, Christopher J; Whipple, Amy V; Schoettle, Anna W; Leal-Sàenz, Alejandro; Wehenkel, Christian; Molina-Freaner, Francisco; Flores-Rentería, Lluvia; Gonzalez-Elizondo, M Socorro; Sniezko, Richard A; Cushman, Samuel A; Waring, Kristen M; Eckert, Andrew J
2018-03-01
Interactions between extrinsic factors, such as disruptive selection and intrinsic factors, such as genetic incompatibilities among loci, often contribute to the maintenance of species boundaries. The relative roles of these factors in the establishment of reproductive isolation can be examined using species pairs characterized by gene flow throughout their divergence history. We investigated the process of speciation and the maintenance of species boundaries between Pinus strobiformis and Pinus flexilis. Utilizing ecological niche modelling, demographic modelling and genomic cline analyses, we illustrated a divergence history with continuous gene flow. Our results supported an abundance of advanced generation hybrids and a lack of loci exhibiting steep transition in allele frequency across the hybrid zone. Additionally, we found evidence for climate-associated variation in the hybrid index and niche divergence between parental species and the hybrid zone. These results are consistent with extrinsic factors, such as climate, being an important isolating mechanism. A build-up of intrinsic incompatibilities and of coadapted gene complexes is also apparent, although these appear to be in the earliest stages of development. This supports previous work in coniferous species demonstrating the importance of extrinsic factors in facilitating speciation. Overall, our findings lend support to the hypothesis that varying strength and direction of selection pressures across the long lifespans of conifers, in combination with their other life history traits, delays the evolution of strong intrinsic incompatibilities. © 2018 John Wiley & Sons Ltd.
Constraint, natural selection, and the evolution of human body form
Savell, Kristen R. R.; Auerbach, Benjamin M.; Roseman, Charles C.
2016-01-01
Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics. PMID:27482101
Constraint, natural selection, and the evolution of human body form.
Savell, Kristen R R; Auerbach, Benjamin M; Roseman, Charles C
2016-08-23
Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics.
Liang, Sen; Zhang, Shun-xiang; Ma, Qi-shan; Xiao, He-wei; Lü, Qiu-ying; Xie, Xu; Mei, Shu-jiang; Hu, Dong-sheng; Zhou, Bo-ping; Li, Bing; Chen, Jing-fang; Cui, Fu-qiang; Wang, Fu-zhen; Liang, Xiao-feng
2010-12-01
To investigate the direct, indirect and intangible costs due to hepatitis B-related diseases and to explore main factors associated with the costs in Shenzhen. Cluster sampling for cases collected consecutively during the study period was administrated. Subjects were selected from eligible hepatitis B-related patients. By pre-trained professional investigators, health economics-related information was collected, using a structured questionnaire. Hospitalization expenses were obtained through hospital records after the patients were discharged from hospital. Total economic burden of hepatitis B-related patients would involve direct, indirect and intangible costs. Direct costs were further divided into direct medical costs and direct nonmedical costs. Human Capital Approach was employed to measure the indirect costs both on patients and the caregivers in 1-year time span. Willing to pay method was used to estimate the intangible costs. Multiple linear stepwise regression models were conducted to determine the factors linked to the economic burden. On average, the total annual cost of per patient with hepatitis B-related diseases was 81 590.23 RMB Yuan. Among which, direct, indirect and intangible costs were 30 914.79 Yuan (account for 37.9%), 15 258.01 Yuan (18.7%), 35 417.43 Yuan (43.4%), respectively. The total annual costs per patient for hepatocellular carcinoma, severe hepatitis B, decompensated cirrhosis, compensated cirrhosis, chronic hepatitis B and acute hepatitis B were 194 858.40 Yuan, 144 549.20 Yuan, 120 333.60 Yuan, 79 528.81 Yuan, 66 282.46 Yuan and 39 286.81 Yuan, respectively. The ratio of direct to indirect costs based on the base-case estimation foot add to 2.0:1, increased from hepato-cellular carcinoma (0.7:1) to compensated cirrhosis (3.5:1), followed by acute hepatitis B (3.3:1), severe hepatitis B (2.8:1), decompensate cirrhosis (2.3:1) and chronic hepatitis B (2.2:1). Direct medical costs were more than direct nonmedical. Ratio between the sum total was 16:1. The proportions of total annual cost per patient with hepatitis B-related diseases accounted for annual patient income were 285.3%, and 75.4% for annual household income. Furthermore, proportions of direct costs accounted for annual patient income and annual household income were 108.1% and 28.6%. The total annual indirect cost per person was 8123.38 Yuan for patients of all hepatitis B-related diseases, while 7134.63 Yuan for caregivers. Corresponding work-loss days were 55.74 days for patients and 19.83 days for caregivers. Based on multiple linear stepwise regression analysis, age of patients was a common influencing factor to all kinds of costs. Other factors were as follows: complicated with other diseases, antiviral medication, monthly household income and self-medications. The economic burden of hepatitis B-related diseases was substantial for patients and their families. All costs tended to increase with the severity of disease. The direct costs were larger than the indirect costs. And the direct medical costs were more than the direct ones. Indirect costs based on patients were larger than the ones of caregivers.
Genetic evidence for natural selection in humans in the contemporary United States.
Beauchamp, Jonathan P
2016-07-12
Recent findings from molecular genetics now make it possible to test directly for natural selection by analyzing whether genetic variants associated with various phenotypes have been under selection. I leverage these findings to construct polygenic scores that use individuals' genotypes to predict their body mass index, educational attainment (EA), glucose concentration, height, schizophrenia, total cholesterol, and (in females) age at menarche. I then examine associations between these scores and fitness to test whether natural selection has been occurring. My study sample includes individuals of European ancestry born between 1931 and 1953 who participated in the Health and Retirement Study, a representative study of the US population. My results imply that natural selection has been slowly favoring lower EA in both females and males, and are suggestive that natural selection may have favored a higher age at menarche in females. For EA, my estimates imply a rate of selection of about -1.5 mo of education per generation (which pales in comparison with the increases in EA observed in contemporary times). Although they cannot be projected over more than one generation, my results provide additional evidence that humans are still evolving-albeit slowly, especially compared with the rapid changes that have occurred over the past few generations due to cultural and environmental factors.
Genetic evidence for natural selection in humans in the contemporary United States
Beauchamp, Jonathan P.
2016-01-01
Recent findings from molecular genetics now make it possible to test directly for natural selection by analyzing whether genetic variants associated with various phenotypes have been under selection. I leverage these findings to construct polygenic scores that use individuals’ genotypes to predict their body mass index, educational attainment (EA), glucose concentration, height, schizophrenia, total cholesterol, and (in females) age at menarche. I then examine associations between these scores and fitness to test whether natural selection has been occurring. My study sample includes individuals of European ancestry born between 1931 and 1953 who participated in the Health and Retirement Study, a representative study of the US population. My results imply that natural selection has been slowly favoring lower EA in both females and males, and are suggestive that natural selection may have favored a higher age at menarche in females. For EA, my estimates imply a rate of selection of about −1.5 mo of education per generation (which pales in comparison with the increases in EA observed in contemporary times). Although they cannot be projected over more than one generation, my results provide additional evidence that humans are still evolving—albeit slowly, especially compared with the rapid changes that have occurred over the past few generations due to cultural and environmental factors. PMID:27402742
Dobosz, Cezary; Tyrpień, Krystyna; Pierzchała, Krystyna
2012-01-01
In recent years, the increase in the incidence of multiple sclerosis (MS - Multiple Sclerosis) is observed. and the direct cause of the symptoms of multiple sclerosis is myelin nerves damage. It can be concluded that the environmental factor is at least partly responsible for the occurrence of this disease. For the development of this disease are responsible, in addition to genetic factors, compounds present in many parts of the environment. Many of these compounds may adversely affect the redox equilibrium of the body, exacerbating radicalgenesis and decreasing antioxidant defenses. Multiple sclerosis is usually diagnosed in early adulthood, during most daily activities. Effects of SM on living standards includes not only the medical aspect, but also social, economic and emotional aspect. Polish population is a high risk zone regarding multiple sclerosis. The aim of this study was a preliminary assessment of selected environmental exposure factors in the pathogenesis of multiple sclerosis with regard to exposure to tobacco smoke with the author's survey of patients from the region of Upper Silesia. Most MS patients (32) in the study group (suffering from MS from 2 to 44 years) are inhabitants of agglomeration of over 50 thousand citizens, from the area of Gliwice, Bytom and Zabrze (43.75%). In investigated group 46.88% MS patients from Silesia region were exposed to tobacco smoke, of which 21.88% actively smoke. Patients with MS, in order not to worsen their disease manifestation, should stop smoking and increase, if possible, any physical activities. These data will be incorporated into a wide-ranging research to clarify the role of selected environmental factors in a very complex and still not fully explored the pathogenesis of multiple sclerosis in Upper Silesia.
Fontanillas, Eric; Galzitskaya, Oxana V.; Lecompte, Odile; Lobanov, Mikhail Y.; Tanguy, Arnaud; Mary, Jean; Girguis, Peter R.; Hourdez, Stéphane
2017-01-01
Temperature, perhaps more than any other environmental factor, is likely to influence the evolution of all organisms. It is also a very interesting factor to understand how genomes are shaped by selection over evolutionary timescales, as it potentially affects the whole genome. Among thermophilic prokaryotes, temperature affects both codon usage and protein composition to increase the stability of the transcriptional/translational machinery, and the resulting proteins need to be functional at high temperatures. Among eukaryotes less is known about genome evolution, and the tube-dwelling worms of the family Alvinellidae represent an excellent opportunity to test hypotheses about the emergence of thermophily in ectothermic metazoans. The Alvinellidae are a group of worms that experience varying thermal regimes, presumably having evolved into these niches over evolutionary times. Here we analyzed 423 putative orthologous loci derived from 6 alvinellid species including the thermophilic Alvinella pompejana and Paralvinella sulfincola. This comparative approach allowed us to assess amino acid composition, codon usage, divergence, direction of residue changes and the strength of selection along the alvinellid phylogeny, and to design a new eukaryotic thermophilic criterion based on significant differences in the residue composition of proteins. Contrary to expectations, the alvinellid ancestor of all present-day species seems to have been thermophilic, a trait subsequently maintained by purifying selection in lineages that still inhabit higher temperature environments. In contrast, lineages currently living in colder habitats likely evolved under selective relaxation, with some degree of positive selection for low-temperature adaptation at the protein level. PMID:28082607
Giner-Lamia, Joaquín; Robles-Rengel, Rocío; Hernández-Prieto, Miguel A; Muro-Pastor, M Isabel; Florencio, Francisco J; Futschik, Matthias E
2017-11-16
In cyanobacteria, nitrogen homeostasis is maintained by an intricate regulatory network around transcription factor NtcA. Although mechanisms controlling NtcA activity appear to be well understood, its regulon remains poorly defined. To determine the NtcA regulon during the early stages of nitrogen starvation for the model cyanobacterium Synechocystis sp. PCC 6803, we performed chromatin immunoprecipitation, followed by sequencing (ChIP-seq), in parallel with transcriptome analysis (RNA-seq). Through combining these methods, we determined 51 genes activated and 28 repressed directly by NtcA. In addition to genes associated with nitrogen and carbon metabolism, a considerable number of genes without current functional annotation were among direct targets providing a rich reservoir for further studies. The NtcA regulon also included eight non-coding RNAs, of which Ncr1071, Syr6 and NsiR7 were experimentally validated, and their putative targets were computationally predicted. Surprisingly, we found substantial NtcA binding associated with delayed expression changes indicating that NtcA can reside in a poised state controlled by other factors. Indeed, a role of PipX as modulating factor in nitrogen regulation was confirmed for selected NtcA-targets. We suggest that the indicated poised state of NtcA enables a more differentiated response to nitrogen limitation and can be advantageous in native habitats of Synechocystis. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Imitative and Direct Learning as Interacting Factors in Life History Evolution.
Bullinaria, John A
2017-01-01
The idea that lifetime learning can have a significant effect on life history evolution has recently been explored using a series of artificial life simulations. These involved populations of competing individuals evolving by natural selection to learn to perform well on simplified abstract tasks, with the learning consisting of identifying regularities in their environment. In reality, there is more to learning than that type of direct individual experience, because it often includes a substantial degree of social learning that involves various forms of imitation of what other individuals have learned before them. This article rectifies that omission by incorporating memes and imitative learning into revised versions of the previous approach. To do this reliably requires formulating and testing a general framework for meme-based simulations that will enable more complete investigations of learning as a factor in any life history evolution scenarios. It does that by simulating imitative information transfer in terms of memes being passed between individuals, and developing a process for merging that information with the (possibly inconsistent) information acquired by direct experience, leading to a consistent overall body of learning. The proposed framework is tested on a range of learning variations and a representative set of life history factors to confirm the robustness of the approach. The simulations presented illustrate the types of interactions and tradeoffs that can emerge, and indicate the kinds of species-specific models that could be developed with this approach in the future.
Bilateral Asymmetry in the Human Pelvis.
Kurki, Helen K
2017-04-01
Asymmetry of the human axial skeleton has received much less attention that of the limb skeleton. Pelvic morphology is subject to multiple selective factors, including bipedal locomotion and obstetrics, among others, as well as environmental factors such as biomechanical loading. How these various factors influence or restrict asymmetry of the pelvis is unknown and few studies have investigated levels and patterns of pelvic asymmetry. This study examines percentage directional (%DA) and absolute (%AA) asymmetry in 14 bilaterally paired dimensions of the pelvic canal, non-canal pelvis, and femur in female (n = 111) and male (n = 126) skeletons from nine geographically dispersed skeletal samples. Directional asymmetries were uniformly low for all measures and lacked any consistent patterning across the variables, while %AA was highest in the pelvic canal, particularly the posterior aspects. Few sex differences and no population differences were found for %DA and %AA; however the latter was correlated with coefficients of variation across the 14 variables in both sexes. While sample mean %DA were low, standard deviations of the canal variables were high and the majority of individuals in both sexes displayed %DA values >±0.5, suggesting asymmetry is common, if not directionally consistent. Biomechanical loading of the pelvic girdle may influence asymmetry of both the canal and non-canal aspects of the pelvis; however it is unlikely that these asymmetries negatively affect obstetric function, given the prevalence for %DA found in this study. Anat Rec, 300:653-665, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Kishor, Aparna; Tandukar, Bishal; Ly, Yann V.; Toth, Eric A.; Suarez, Yvelisse; Brewer, Gary
2013-01-01
The AU-rich elements (AREs) encoded within many mRNA 3′ untranslated regions (3′UTRs) are targets for factors that control transcript longevity and translational efficiency. Hsp70, best known as a protein chaperone with well-defined peptide-refolding properties, is known to interact with ARE-like RNA substrates in vitro. Here, we show that cofactor-free preparations of Hsp70 form direct, high-affinity complexes with ARE substrates based on specific recognition of U-rich sequences by both the ATP- and peptide-binding domains. Suppressing Hsp70 in HeLa cells destabilized an ARE reporter mRNA, indicating a novel ARE-directed mRNA-stabilizing role for this protein. Hsp70 also bound and stabilized endogenous ARE-containing mRNAs encoding vascular endothelial growth factor (VEGF) and Cox-2, which involved a mechanism that was unaffected by an inhibitor of its protein chaperone function. Hsp70 recognition and stabilization of VEGF mRNA was mediated by an ARE-like sequence in the proximal 3′UTR. Finally, stabilization of VEGF mRNA coincided with the accumulation of Hsp70 protein in HL60 promyelocytic leukemia cells recovering from acute thermal stress. We propose that the binding and stabilization of selected ARE-containing mRNAs may contribute to the cytoprotective effects of Hsp70 following cellular stress but may also provide a novel mechanism linking constitutively elevated Hsp70 expression to the development of aggressive neoplastic phenotypes. PMID:23109422
Social Factors Influencing Child Health in Ghana
Quansah, Emmanuel; Ohene, Lilian Akorfa; Norman, Linda; Mireku, Michael Osei; Karikari, Thomas K.
2016-01-01
Objectives Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals’ target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. Methods ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. Results Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. Conclusions Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother’s health knowledge is emphasised. PMID:26745277
Zone routing in a torus network
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Dong; Heidelberger, Philip; Kumar, Sameer
A system for routing data in a network comprising a network logic device at a sending node for determining a path between the sending node and a receiving node, wherein the network logic device sets one or more selection bits and one or more hint bits within the data packet, a control register for storing one or more masks, wherein the network logic device uses the one or more selection bits to select a mask from the control register and the network logic device applies the selected mask to the hint bits to restrict routing of the data packet tomore » one or more routing directions for the data packet within the network and selects one of the restricted routing directions from the one or more routing directions and sends the data packet along a link in the selected routing direction toward the receiving node.« less
Yonehara, Keisuke; Fiscella, Michele; Drinnenberg, Antonia; Esposti, Federico; Trenholm, Stuart; Krol, Jacek; Franke, Felix; Scherf, Brigitte Gross; Kusnyerik, Akos; Müller, Jan; Szabo, Arnold; Jüttner, Josephine; Cordoba, Francisco; Reddy, Ashrithpal Police; Németh, János; Nagy, Zoltán Zsolt; Munier, Francis; Hierlemann, Andreas; Roska, Botond
2016-01-01
Summary Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease. Video Abstract PMID:26711119
Wu, Jianqing; Xu, Hao
2017-12-01
Understanding driver behavior is important for traffic safety and operation, especially at intersections where different traffic movements conflict. While most driver-behavior studies are based on simulation, this paper documents the analysis of driver-behavior at signalized intersections with the SHRP 2 Naturalistic Driving Study (NDS) data. This study analyzes the different influencing factors on the operation (speed control) and observation of right-turn drivers. A total of 300 NDS trips at six signalized intersections were used, including the NDS time-series sensor data, the forward videos and driver face videos. Different factors of drivers, vehicles, roads and environments were studied for their influence on driver behavior. An influencing index function was developed and the index was calculated for each influencing factor to quantitatively describe its influencing level. The influencing index was applied to prioritize the factors, which facilitates development and selection of safety countermeasures to improve intersection safety. Drivers' speed control was analyzed under different conditions with consideration of the prioritized influencing factors. Vehicle type, traffic signal status, conflicting traffic, conflicting pedestrian and driver age group were identified as the five major influencing factors on driver observation. This research revealed that drivers have high acceleration and low observation frequency under Right-Turn-On-Red (RTOR), which constituted potential danger for other roadway users, especially for pedestrians. As speed has a direct influence on crash rates and severities, the revealed speed patterns of the different situations also benefit selection of safety countermeasures at signalized intersections. Published by Elsevier Ltd.
Factors Associated with Needlestick Injuries in Health Care Occupations: A Systematic Review.
Motaarefi, Hossein; Mahmoudi, Hosein; Mohammadi, Eesa; Hasanpour-Dehkordi, Ali
2016-08-01
Needlestick and sharps injuries (NSIs), are among the main job-related injuries that health care workers experience. In fact, contraction of hepatitis B or hepatitis C from work-related NSIs is one of the most common occupational hazards among health care workers. The aim of this study was to determine the factors associated with NSIs in health care occupation. In this study, a systematic and purposive review with emphasis on the research question was run to retrieve, evaluate and consolidate the required information. The following four key words were used to search for the relevant articles published from January 1998 to May 2015: NSI health care workers, risk factor and factors associated, in Science direct, EBSCO Host, PubMed, ProQuest, SID and Cochrane Library. Several steps of evaluation were taken to select and analyse the full texts of relevant articles. According to the inclusion criteria, we finally selected 11 articles from the 18642 retrieved articles. The data of the analysed articles indicated that the highest incidence of NSIs was seen in nurses and that the associated factors were age, level of education, number of shifts per month and history of related training. The highest rate of NSIs was related to instrument preparation followed by injection and recapping of used needles. Findings show that health care workers suffer a high rate of needlestick injuries. It was seen that device, location, or action cannot be separately considered as responsible for all types of the NSIs. Rather, each of them has a contribution to the NSIs. Nevertheless, factors with higher frequency should be given a higher priority.
Lapa, Constantin; Schreder, Martin; Schirbel, Andreas; Samnick, Samuel; Kortüm, Klaus Martin; Herrmann, Ken; Kropf, Saskia; Einsele, Herrmann; Buck, Andreas K; Wester, Hans-Jürgen; Knop, Stefan; Lückerath, Katharina
2017-01-01
Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [ 68 Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [ 68 Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [ 18 F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [ 68 Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [ 18 F]FDG was available, [ 68 Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [ 18 F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [ 18 F]FDG-PET positivity correlated with [ 68 Ga]Pentixafor-PET positivity (p=0.018). [ 68 Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.
A purified transcription factor (TIF-IB) binds to essential sequences of the mouse rDNA promoter.
Clos, J; Buttgereit, D; Grummt, I
1986-01-01
A transcription factor that is specific for mouse rDNA has been partially purified from Ehrlich ascites cells. This factor [designated transcription initiation factor (TIF)-IB] is required for accurate in vitro synthesis of mouse rRNA in addition to RNA polymerase I and another regulatory factor, TIF-IA. TIF-IB activity is present in extracts both from growing and nongrowing cells in comparable amounts. Prebinding competition experiments with wild-type and mutant templates suggest that TIF-IB interacts with the core control element of the rDNA promoter, which is located immediately upstream of the initiation site. The specific binding of TIF-IB to the RNA polymerase I promoter is demonstrated by exonuclease III protection experiments. The 3' border of the sequences protected by TIF-IB is shown to be on the coding strand at position -21 and on the noncoding strand at position -7. The results suggest that direct binding of TIF-IB to sequences in the core promoter element is the mechanism by which this factor imparts promoter selectivity to RNA polymerase I. Images PMID:3456157
Wu, Yun; Li, Qing-Jun
2017-10-01
Floral traits have largely been attributed to phenotypic selection in plant-pollinator interactions. However, the strength of this link has rarely been ascertained with real pollinators. We conducted pollinator observations and estimated selection through female fitness on flowering phenology and floral traits between two Primula secundiflora populations. We quantified pollinator-mediated selection by subtracting estimates of selection gradients of plants receiving supplemental hand pollination from those of plants receiving open pollination. There was net directional selection for an earlier flowering start date at populations where the dominant pollinators were syrphid flies, and flowering phenology was also subjected to stabilized quadratic selection. However, a later flowering start date was significantly selected at populations where the dominant pollinators were legitimate (normal pollination through the corolla tube entrance) and illegitimate bumblebees (abnormal pollination through nectar robbing hole which located at the corolla tube), and flowering phenology was subjected to disruptive quadratic selection. Wider corolla tube entrance diameter was selected at both populations. Furthermore, the strength of net directional selection on flowering start date and corolla tube entrance diameter was stronger at the population where the dominant pollinators were syrphid flies. Pollinator-mediated selection explained most of the between-population variations in the net directional selection on flowering phenology and corolla tube entrance diameter. Our results suggested the important influence of pollinator-mediated selection on floral evolution. Variations in pollinator assemblages not only resulted in variation in the direction of selection but also the strength of selection on floral traits.
Psychosomatic factors in pruritus
Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil
2013-01-01
Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). PMID:23245971
NASA Technical Reports Server (NTRS)
Wester, Gene W. (Inventor)
1980-01-01
A unity power factor converter capable of effecting either inversion (dc-to-dc) or rectification (ac-to-dc), and capable of providing bilateral power control from a DC source (or load) through an AC transmission line to a DC load (or source) for power flow in either direction, is comprised of comparators for comparing the AC current i with an AC signal i.sub.ref (or its phase inversion) derived from the AC ports to generate control signals to operate a switch control circuit for high speed switching to shape the AC current waveform to a sine waveform, and synchronize it in phase and frequency with the AC voltage at the AC ports, by selectively switching the connections to a series inductor as required to increase or decrease the current i.
Weights of Evidence Method for Landslide Susceptibility Mapping in Takengon, Central Aceh, Indonesia
NASA Astrophysics Data System (ADS)
Pamela; Sadisun, Imam A.; Arifianti, Yukni
2018-02-01
Takengon is an area prone to earthquake disaster and landslide. On July 2, 2013, Central Aceh earthquake induced large numbers of landslides in Takengon area, which resulted in casualties of 39 people. This location was chosen to assess the landslide susceptibility of Takengon, using a statistical method, referred to as the weight of evidence (WoE). This WoE model was applied to indicate the main factors influencing the landslide susceptible area and to derive landslide susceptibility map of Takengon. The 251 landslides randomly divided into two groups of modeling/training data (70%) and validation/test data sets (30%). Twelve thematic maps of evidence are slope degree, slope aspect, lithology, land cover, elevation, rainfall, lineament, peak ground acceleration, curvature, flow direction, distance to river and roads used as landslide causative factors. According to the AUC, the significant factor controlling the landslide is the slope, the slope aspect, peak ground acceleration, elevation, lithology, flow direction, lineament, and rainfall respectively. Analytical result verified by using test data of landslide shows AUC prediction rate is 0.819 and AUC success rate with all landslide data included is 0.879. This result showed the selective factors and WoE method as good models for assessing landslide susceptibility. The landslide susceptibility map of Takengon shows the probabilities, which represent relative degrees of susceptibility for landslide proneness in Takengon area.
Conceptualizing pathways linking women's empowerment and prematurity in developing countries.
Afulani, Patience A; Altman, Molly; Musana, Joseph; Sudhinaraset, May
2017-11-08
Globally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity. The key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors. There is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies. Women's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed.
An evaluation of the impact of digital imaging on radiographic practice and patient doses
NASA Astrophysics Data System (ADS)
Horrocks, J.; Violaki, K.
2015-09-01
Direct digital imaging technology was implemented in all areas in general and mobile radiology at Barts and the Royal London Hospitals in 2012. Evidence from recent radiation incident investigations indicates optimum exposure factors are not consistently selected, with the greater dynamic range of the digital detectors allowing sub-optimal practice. To investigate further patient dose data were extracted from the Radiology Information System for adult chest X-ray examinations in 2014, covering over 50,000 studies in the Trust. Chest X-ray examinations were selected as they are low dose but frequent examinations. The patient dose data were evaluated taking into account X-ray system type and detector performance measurements, and individual cases studies were used to highlight where practice can be improved.
Criteria for the selection of focusing ultrasonic probes
NASA Technical Reports Server (NTRS)
Schlengermann, U.
1978-01-01
The principles of operation employed in the focusing of a sound field are considered, taking into account the use of solid and liquid coupling media. The focusing limits for a given transducer are investigated. As a diffraction phenomenon, focusing is a function of the system dimensions, the frequency, and the sound velocity. The frequency and the material used for the lenses are in most cases determined in accordance with considerations regarding sound propagation. Changes in the focus are therefore effected mainly by the selection of transducer and lens dimensions. The functions of the focusing factor for a normal immersion probe and a direct contact angle probe are represented in graphs. The deviation of the appropriate parametric values for an ultrasonic probe is illustrated with the aid of examples.
NASA Astrophysics Data System (ADS)
Wang, Lin-Jie; He, Si-Yang; Niu, Dong-Bin; Guo, Jian-Ping; Xu, Yun-Long; Wang, De-Sheng; Cao, Yi; Zhao, Qi; Tan, Cheng; Li, Zhi-Li; Tang, Guo-Hua; Li, Yin-Hui; Bai, Yan-Qiang
2013-11-01
Dynamic variations in early selective attention to the color and direction of moving stimuli were explored during a 30 days period of head-down bed rest. Event-related potentials (ERPs) were recorded at F5, F6, P5, P6 scalp locations in seven male subjects who attended to pairs of bicolored light emitting diodes that flashed sequentially to produce a perception of movement. Subjects were required to attend selectively to a critical feature of the moving target, e.g., color or direction. The tasks included: a no response task, a color selective response task, a moving direction selective response task, and a combined color-direction selective response task. Subjects were asked to perform these four tasks on: the 3rd day before bed rest; the 3rd, 15th and 30th day during the bed rest; and the 5th day after bed rest. Subjects responded quickly to the color than moving direction and combined color-direction response. And they had a longer reaction time during bed rest on the 15th and 30th day during bed rest after a relatively quicker response on the 3rd day. Using brain event-related potentials technique, we found that in the color selective response task, the mean amplitudes of P1 and N1 for target ERPs decreased in the 3rd day during bed rest and 5th day after bed rest in comparison with pre-bed rest, 15th day and 30th day during bed rest. In the combined color-direction selective response task, the P1 latencies for target ERPs on the 3rd and 30th day during bed rest were longer than on the 15th day during bed rest. As 3rd day during bed rest was in the acute adaptation period and 30th day during bed rest was in the relatively adaptation stage of head-down bed rest, the results help to clarify the effects of bed rest on different task loads and patterns of attention. It was suggested that subjects expended more time to give correct decision in the head-down tilt bed rest state. A difficulty in the recruitment of brain resources was found in feature selection task, but no variations were detected in the no response and direction selective response tasks. It is suggested that the negative shift in color selective response task on the 3rd day of bed rest are a result of fluid redistribution. And feature selection was more affected than motion selection in the head down bed rest. The variations in cognitive processing speed observed for the combined color-direction selective response task are suggested to reflect the interaction between top-down mechanisms and hierarchical physiological characteristics during 30 days head-down bed rest.
Weaver, Addie; Greeno, Catherine G; Goughler, Donald H; Yarzebinski, Kathleen; Zimmerman, Tina; Anderson, Carol
2013-07-01
This study examined the effect of using the Toyota Production System (TPS) to change intake procedures on treatment timeliness within a semi-rural community mental health clinic. One hundred randomly selected cases opened the year before the change and 100 randomly selected cases opened the year after the change were reviewed. An analysis of covariance demonstrated that changing intake procedures significantly decreased the number of days consumers waited for appointments (F(1,160) = 4.9; p = .03) from an average of 11 to 8 days. The pattern of difference on treatment timeliness was significantly different between adult and child programs (F(1,160) = 4.2; p = .04), with children waiting an average of 4 days longer than adults for appointments. Findings suggest that small system level changes may elicit important changes and that TPS offers a valuable model to improve processes within community mental health settings. Results also indicate that different factors drive adult and children's treatment timeliness.
In vitro fertilisation treatment and factors affecting success.
Huang, Jack Yu Jen; Rosenwaks, Zev
2012-12-01
The efficacy of assisted reproductive technologies has improved significantly over the past decades. The main indications for in vitro fertilisation include tubal obstruction, severe male-factor infertility, severe endometriosis, ovulatory dysfunction, diminished ovarian reserve, and infertility of unexplained cause. In vitro fertilisation has also become an effective treatment option for couples wishing to undergo pre-implantation genetic diagnosis or screening, and for those wishing to cryopreserve their oocytes or embryos for preservation of fertility. The management of women in late reproductive age poses a major challenge; the optimum in vitro fertilisation treatment for poor responders remains elusive. The success of in vitro fertilisation treatment can be optimised by taking an individualised, patient-centered approach to controlled ovarian hyperstimulation. Key components involve selection of an appropriate controlled ovarian protocol, close-cycle monitoring, adjustment of gonadotropin dosage to avoid hyper-response, and individualised timing of human chorionic gonadotropin injection. Future directions of assisted reproductive technologies include development of non-invasive embryo selection methods, use of transcriptomics, proteomics, metabolomics, and time-lapse imaging technologies. Copyright © 2012 Elsevier Ltd. All rights reserved.
Weaver, A.; Greeno, C.G.; Goughler, D.H.; Yarzebinski, K.; Zimmerman, T.; Anderson, C.
2013-01-01
This study examined the effect of using the Toyota Production System (TPS) to change intake procedures on treatment timeliness within a semi-rural community mental health clinic. One hundred randomly selected cases opened the year before the change and one hundred randomly selected cases opened the year after the change were reviewed. An analysis of covariance (ANCOVA) demonstrated that changing intake procedures significantly decreased the number of days consumers waited for appointments (F(1,160)=4.9; p=.03) from an average of 11 days to 8 days. The pattern of difference on treatment timeliness was significantly different between adult and child programs (F(1,160)=4.2; p=.04), with children waiting an average of 4 days longer than adults for appointments. Findings suggest that small system level changes may elicit important changes and that TPS offers a valuable model to improve processes within community mental health settings. Results also indicate that different factors drive adult and children’s treatment timeliness. PMID:23576137
NASA Astrophysics Data System (ADS)
Syamtinningrum, M. D. P.; Partiwi, S. G.; Dewi, D. S.
2018-04-01
One indicator of a good company is when a safe business environment can be well maintained. In this work environment, the number of industrial accidents is minimum. Industrial accidents are the incidents that occurred in the workplace, especially in industrial area. Industrial accidents are generally caused by two main reasons, unsafe actions & unsafe conditions. Some research indicates that unsafe actions significantly affect the incidence in the workplace. Unsafe action is a failure to follow the proper procedures and requirements, which is led into accidents. From several previous studies it can be concluded that personal factors & OHS management are two most influential factors that affect unsafe actions. However, their relationship in influencing unsafe actions is not fully understood. Based on this reason the authors want to investigate the effect of personal factors and OHS management toward unsafe actions to workers. For this purpose, a company is selected as a case study. In this research, analyses were done by using univariate test, bivariate correlation and linear regression. The results of this study proves that two indicators of personal factors (i.e. knowledge of OHS & OHS training) and OHS management have significant effect on unsafe actions but in negative direction, while two indicators of personal factors (i.e. workload & fatigue) have positive direction of effect on unsafe actions. In addition, this research has developed a mathematical model that can be used to calculate and predict the value of unsafe actions performed by the worker. By using this model, the company will able to take preventive actions toward unsafe actions to reduce workers accidents.
Visual Search for Motion-Form Conjunctions: Selective Attention to Movement Direction.
Von Mühlenen, Adrian; Müller, Hermann J
1999-07-01
In 2 experiments requiring visual search for conjunctions of motion and form, the authors reinvestigated whether motion-based filtering (e.g., P. McLeod, J. Driver, Z. Dienes, & J. Crisp, 1991) is direction selective and whether cuing of the target direction promotes efficient search performance. In both experiments, the authors varied the number of movement directions in the display and the predictability of the target direction. Search was less efficient when items moved in multiple (2, 3, and 4) directions as compared with just 1 direction. Furthermore, precuing of the target direction facilitated the search, even with "wrap-around" displays, relatively more when items moved in multiple directions. The authors proposed 2 principles to explain that pattern of effects: (a) interference on direction computation between items moving in different directions (e.g., N. Qian & R. A. Andersen, 1994) and (b) selective direction tuning of motion detectors involving a receptive-field contraction (cf. J. Moran & R. Desimone, 1985; S. Treue & J. H. R. Maunsell, 1996).
Medrano, Jose V.; Martínez-Arroyo, Ana M.; Míguez, Jose M.; Moreno, Inmaculada; Martínez, Sebastián; Quiñonero, Alicia; Díaz-Gimeno, Patricia; Marqués-Marí, Ana I.; Pellicer, Antonio; Remohí, Jose; Simón, Carlos
2016-01-01
The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells showed a marked switch in their transcriptomic profile and expressed several post-meiotic germ line related markers, showed meiotic progression, evidence of epigenetic reprogramming, and approximately 1% were able to complete meiosis as demonstrated by their haploid status and the expression of several post-meiotic markers. Furthermore, xenotransplantation assays demonstrated that a subset of induced cells properly colonize the spermatogonial niche. Knowledge obtained from this work can be used to create in vitro models to study gamete-related diseases in humans. PMID:27112843
Pulido, José; Vallejo, Fernando; Alonso-López, Ignacio; Regidor, Enrique; Villar, Fernando; de la Fuente, Luis; Domingo-Salvany, Antonia; Barrio, Gregorio
2017-11-01
To assess disparities in directly alcohol-attributable (DAA) mortality by industry/occupation in Spain during 2002-2011 and the contribution of different socio-demographic factors, including socioeconomic position, to explain such disparity. Nationwide cohort study covering 16 million economically active people living in Spain in 2001. Deaths at age 25-64 were analyzed. Subjects were classified by employment status, industry and occupation at baseline. Poisson regression models were built, calculating rate ratios (RRs) compared to all employees or those in the education sector. DAA mortality was much higher in the unemployed than in employees (Crude RR: 2.4; 95% CI: 2.3-2.6) and varied widely across industries/occupations. Crude RRs>3.0 (p<0.05) compared to teachers were found in employees in extractive industries/fishing, agriculture/livestock, construction, catering/accommodation and protective services. Socio-demographic factors, especially age, gender and educational attainment contributed more to explain risk disparities than other factors or potential selection bias. However, after exhaustive sociodemographic adjustment, including education attainment and material wealth, a RR>1.33 (p<0.05) remained in unemployed, catering/accommodation employees and unskilled construction workers. RRs were significantly larger in women than men (p<0.05) among mineworkers/fishworkers/sailors (RR=8.6 vs. 1.2) and drivers (RR=3.7 vs. 1.0). The results could be extrapolated to all alcohol-attributable mortality since disparities for other strongly alcohol-related deaths, although smaller, were in the same direction. Given the wide occupational disparities in alcohol-attributable mortality, implementation of special measures to reduce this mortality in the highest risk groups is fully justified. Future research should better characterize the explanatory factors of disparities and their role in the causal chain. Copyright © 2017. Published by Elsevier B.V.
Gautam, Manu; Chattanahalli Devendrachari, Mruthyunjayachari; Thimmappa, Ravikumar; Raja Kottaichamy, Alagar; Pottachola Shafi, Shahid; Gaikwad, Pramod; Makri Nimbegondi Kotresh, Harish; Ottakam Thotiyl, Musthafa
2017-03-15
Graphene oxide (GO) anisotropically conducts protons with directional dominance of in plane ionic transport (σ IP) over the through plane (σ TP). In a typical H 2 -O 2 fuel cell, since the proton conduction occurs through the plane during its generation at the fuel electrode, it is indeed inevitable to selectively accelerate GO's σ TP for advancement towards a potential fuel cell membrane. We successfully achieved ∼7 times selective amplification of GO's σ TP by tuning the polarity of the dopant molecule in its nanoporous matrix. The coexistence of strongly non-polar and polar domains in the dopant demonstrated a synergistic effect towards σ TP with the former decreasing the number of water molecules coordinated to protons by ∼3 times, diminishing the effects of electroosmotic drag exerted on ionic movements, and the latter selectively accelerating σ TP across the catalytic layers by bridging the individual GO planes via extensive host guest H-bonding interactions. When they are decoupled, the dopant with mainly non-polar or polar features only marginally enhances the σ TP, revealing that polarity factors contribute to fuel cell relevant transport properties of GO membranes only when they coexist. Fuel cell polarization and kinetic analyses revealed that these multitask dopants increased the fuel cell performance metrics of the power and current densities by ∼3 times compared to the pure GO membranes, suggesting that the functional group factors of the dopants are of utmost importance in GO-based proton exchange membrane fuel cells.
Prenatal attitudes and parity predict selection into a U.S. child health program: a short report.
Martin-Anderson, Sarah
2013-10-01
Public policies are a determinant of child health disparities; sound evaluation of these programs is essential for good governance. It is impossible in most countries to randomize assignment into child health programs that directly offer benefits. In the absence of this, researchers face the threat of selection bias-the idea that there are innate, immeasurable differences between those who take-up treatment and those who don't. In the field of Program Evaluation we are most concerned with the differences between the eligible people who take-up a program and the eligible people who choose not to enroll. Using a case study of a large U.S. nutrition program, this report illustrates how the perceived benefits of participation may affect the decision to take-up a program. In turn, this highlights sources of potential selection bias. Using data from a longitudinal study of mothers and infants conducted between May and December of 2005, I show that attitudes and beliefs prenatally toward breastfeeding determine enrollment in a U.S nutrition program that offers free Infant Formula. I also find that the significance of the selection bias differs by parity. Analysis reveals that maternal attitudinal responses are more highly predictive of future behavior, compared to standard demographic variables. In sum, this paper makes a case for rigorously understanding the factors that determine take-up of a program and how those factors can modify the results of a program evaluation. Copyright © 2013 Elsevier Ltd. All rights reserved.
Evaluating intra- and inter-individual variation in the human placental transcriptome.
Hughes, David A; Kircher, Martin; He, Zhisong; Guo, Song; Fairbrother, Genevieve L; Moreno, Carlos S; Khaitovich, Philipp; Stoneking, Mark
2015-03-19
Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. We estimate that on average, 33.2%, 58.9%, and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals, and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they each account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling, and metabolism. Many biological traits demonstrate correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection, directional selection, or diversifying selection. We apportion placental gene expression variation into individual, population, and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.
The evolution of trade-offs: where are we?
Roff, D A; Fairbairn, D J
2007-03-01
Trade-offs are a core component of many evolutionary models, particularly those dealing with the evolution of life histories. In the present paper, we identify four topics of key importance for studies of the evolutionary biology of trade-offs. First, we consider the underlying concept of 'constraint'. We conclude that this term is typically used too vaguely and suggest that 'constraint' in the sense of a bias should be clearly distinguished from 'constraint' in the sense of proscribed combinations of traits or evolutionary trajectories. Secondly, we address the utility of the acquisition-allocation model (the 'Y-model'). We find that, whereas this model and its derivatives have provided new insights, a misunderstanding of the pivotal equation has led to incorrect predictions and faulty tests. Thirdly, we ask how trade-offs are expected to evolve under directional selection. A quantitative genetic model predicts that, under weak or short-term selection, the intercept will change but the slope will remain constant. Two empirical tests support this prediction but these are based on comparisons of geographic populations: more direct tests will come from artificial selection experiments. Finally, we discuss what maintains variation in trade-offs noting that at present little attention has been given to this question. We distinguish between phenotypic and genetic variation and suggest that the latter is most in need of explanation. We suggest that four factors deserving investigation are mutation-selection balance, antagonistic pleiotropy, correlational selection and spatio-temporal variation, but as in the other areas of research on trade-offs, empirical generalizations are impeded by lack of data. Although this lack is discouraging, we suggest that it provides a rich ground for further study and the integration of many disciplines, including the emerging field of genomics.
Feedbacks between community assembly and habitat selection shape variation in local colonization
Kraus, J.M.; Vonesh, J.R.
2010-01-01
1. Non-consumptive effects of predators are increasingly recognized as important drivers of community assembly and structure. Specifically, habitat selection responses to top predators during colonization and oviposition can lead to large differences in aquatic community structure, composition and diversity. 2. These differences among communities due to predators may develop as communities assemble, potentially altering the relative quality of predator vs. predator-free habitats through time. If so, community assembly would be expected to modify the subsequent behavioural responses of colonists to habitats containing top predators. Here, we test this hypothesis by manipulating community assembly and the presence of fish in experimental ponds and measuring their independent and combined effects on patterns of colonization by insects and amphibians. 3. Assembly modified habitat selection of dytscid beetles and hylid frogs by decreasing or even reversing avoidance of pools containing blue-spotted sunfish (Enneacanthus gloriosus). However, not all habitat selection responses to fish depended on assembly history. Hydrophilid beetles and mosquitoes avoided fish while chironomids were attracted to fish pools, regardless of assembly history. 4. Our results show that community assembly causes taxa-dependent feedbacks that can modify avoidance of habitats containing a top predator. Thus, non-consumptive effects of a top predator on community structure change as communities assemble and effects of competitors and other predators combine with the direct effects of top predators to shape colonization. 5. This work reinforces the importance of habitat selection for community assembly in aquatic systems, while illustrating the range of factors that may influence colonization rates and resulting community structure. Directly manipulating communities both during colonization and post-colonization is critical for elucidating how sequential processes interact to shape communities.
Peng, Shaomin; Adelman, Ron A.
2010-01-01
Purpose. Bevacizumab and ranibizumab are currently used to treat age-related macular degeneration by neutralizing vascular endothelial growth factor (VEGF). In this study, the potential side effects on the outer blood–retinal barrier were examined. Methods. Human fetal RPE (hfRPE) cells were used because they are highly differentiated in culture. The claudin composition of RPE tight junctions was determined by RT-PCR, immunoblot analysis, and immunofluorescence. ELISA assays monitored the secretion and trafficking of VEGF and a fluid-phase marker, methylpolyethylene glycol (mPEG). Tight junction functions were assessed by the conductance of K+ and Na+ (derived from the transepithelial electrical resistance, TER) and the flux of NaCl and mPEG. Results. Claudin-3, claudin-10, and claudin-19 were detected in RPE tight junctions. VEGF was secreted in equal amounts across the apical and basolateral membranes, but the apical membrane was more active in endocytosing and degrading VEGF. Exogenous VEGF and mPEG crossed the RPE monolayer by transcytosis, predominantly in the apical-to-basal direction. RPE tight junctions were selective for K+, but did not discriminate between Na+ and Cl−. VEGF, bevacizumab, and ranibizumab had minimal effects on TER, permeation of mPEG, and selectivity for K+, Na+, and Cl−. They had minimal effects on the expression and distribution of the claudins. Conclusions. RPE has mechanisms for maintaining low concentrations of VEGF in the subretinal space that include endocytosis and degradation and fluid-phase transcytosis in the apical-to-basal direction. RPE tight junctions are selective for K+ over Na+ and Cl−. Permeability and selectivity of the junctions are not affected by VEGF, bevacizumab, or ranibizumab. PMID:20042644
Caruso, Christina M; Martin, Ryan A; Sletvold, Nina; Morrissey, Michael B; Wade, Michael J; Augustine, Kate E; Carlson, Stephanie M; MacColl, Andrew D C; Siepielski, Adam M; Kingsolver, Joel G
2017-09-01
Although many selection estimates have been published, the environmental factors that cause selection to vary in space and time have rarely been identified. One way to identify these factors is by experimentally manipulating the environment and measuring selection in each treatment. We compiled and analyzed selection estimates from experimental studies. First, we tested whether the effect of manipulating the environment on selection gradients depends on taxon, trait type, or fitness component. We found that the effect of manipulating the environment was larger when selection was measured on life-history traits or via survival. Second, we tested two predictions about the environmental factors that cause variation in selection. We found support for the prediction that variation in selection is more likely to be caused by environmental factors that have a large effect on mean fitness but not for the prediction that variation is more likely to be caused by biotic factors. Third, we compared selection gradients from experimental and observational studies. We found that selection varied more among treatments in experimental studies than among spatial and temporal replicates in observational studies, suggesting that experimental studies can detect relationships between environmental factors and selection that would not be apparent in observational studies.
Effect of feature-selective attention on neuronal responses in macaque area MT
Chen, X.; Hoffmann, K.-P.; Albright, T. D.
2012-01-01
Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color). PMID:22170961
Effect of feature-selective attention on neuronal responses in macaque area MT.
Chen, X; Hoffmann, K-P; Albright, T D; Thiele, A
2012-03-01
Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).
Park, Briton; Rutter, Matthew T; Fenster, Charles B; Symonds, V Vaughan; Ungerer, Mark C; Townsend, Jeffrey P
2017-08-01
Mutations are crucial to evolution, providing the ultimate source of variation on which natural selection acts. Due to their key role, the distribution of mutational effects on quantitative traits is a key component to any inference regarding historical selection on phenotypic traits. In this paper, we expand on a previously developed test for selection that could be conducted assuming a Gaussian mutation effect distribution by developing approaches to also incorporate any of a family of heavy-tailed Laplace distributions of mutational effects. We apply the test to detect directional natural selection on five traits along the divergence of Columbia and Landsberg lineages of Arabidopsis thaliana , constituting the first test for natural selection in any organism using quantitative trait locus and mutation accumulation data to quantify the intensity of directional selection on a phenotypic trait. We demonstrate that the results of the test for selection can depend on the mutation effect distribution specified. Using the distributions exhibiting the best fit to mutation accumulation data, we infer that natural directional selection caused divergence in the rosette diameter and trichome density traits of the Columbia and Landsberg lineages. Copyright © 2017 by the Genetics Society of America.
Swat, Maciej H; Thomas, Gilberto L; Shirinifard, Abbas; Clendenon, Sherry G; Glazier, James A
2015-01-01
Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.
Electrical Detection of Cancer Biomarker using Aptamers with Nanogap Break-Junctions
Ilyas, Azhar; Asghar, Waseem; Allen, Peter B.; Duhon, Holli; Ellington, Andrew D.; Iqbal, Samir M.
2012-01-01
Epidermal Growth Factor Receptor (EGFR) is a cell surface protein overexpressed in cancerous cells. It is known to be the most common oncongene. EGFR concentration also increases in the serum of cancer patients. The detection of small changes in the concentration of EGFR can be critical for early diagnosis, resulting in better treatment and improved survival rate of cancer patients. This article reports an RNA aptamer based approach to selectively capture EGFR protein and an electrical scheme for its detection. Pairs of gold electrodes with nanometer separation were made through confluence of focused ion beam scratching and electromigration. The aptamer was hybridized to a single stranded DNA molecule, which in turn was immobilized on SiO2 surface between the gold nanoelectrodes. The selectivity of the aptamer was demonstrated by using control chips with mutated non–selective aptamer and with no aptamer. Surface functionalization was characterized by optical detection and two orders of magnitude increase in direct current (DC) was measured when selective capture of EGFR occurred. This represents an electronic biosensor for the detection of proteins of interest for medical applications. PMID:22706642
Swat, Maciej H.; Thomas, Gilberto L.; Shirinifard, Abbas; Clendenon, Sherry G.; Glazier, James A.
2015-01-01
Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors. PMID:26083246
Dissociating the two faces of selective memory retrieval.
Dobler, Ina M; Bäuml, Karl-Heinz T
2012-07-01
Research in the past four decades has repeatedly shown that selective retrieval of some (non-target) memories can impair subsequent retrieval of other (target) information, a finding known as retrieval-induced forgetting. More recently, however, there is evidence that selective retrieval can both impair and enhance recall of related memories (K-H. T. Bäuml & Samenieh, 2010). To identify possible experimental dissociations between the detrimental and the beneficial effects of memory retrieval, we examined retrieval dynamics in listwise directed forgetting, varying the delay between preceding non-target and subsequent target recall. When target recall immediately followed non-target recall, we replicated the prior work and found detrimental effects of memory retrieval on to-be-remembered items but beneficial effects on to-be-forgotten items. In contrast, when a delay was introduced between non-target and target recall, the detrimental effects were present but the beneficial effects were absent. The results demonstrate a first experimental dissociation between the two effects of memory retrieval. They are consistent with a recent two-factor account of the two faces of selective memory retrieval.
Escobar, Gina M.; Maffei, Arianna; Miller, Paul
2014-01-01
The computation of direction selectivity requires that a cell respond to joint spatial and temporal characteristics of the stimulus that cannot be separated into independent components. Direction selectivity in ferret visual cortex is not present at the time of eye opening but instead develops in the days and weeks following eye opening in a process that requires visual experience with moving stimuli. Classic Hebbian or spike timing-dependent modification of excitatory feed-forward synaptic inputs is unable to produce direction-selective cells from unselective or weakly directionally biased initial conditions because inputs eventually grow so strong that they can independently drive cortical neurons, violating the joint spatial-temporal activation requirement. Furthermore, without some form of synaptic competition, cells cannot develop direction selectivity in response to training with bidirectional stimulation, as cells in ferret visual cortex do. We show that imposing a maximum lateral geniculate nucleus (LGN)-to-cortex synaptic weight allows neurons to develop direction-selective responses that maintain the requirement for joint spatial and temporal activation. We demonstrate that a novel form of inhibitory plasticity, postsynaptic activity-dependent long-term potentiation of inhibition (POSD-LTPi), which operates in the developing cortex at the time of eye opening, can provide synaptic competition and enables robust development of direction-selective receptive fields with unidirectional or bidirectional stimulation. We propose a general model of the development of spatiotemporal receptive fields that consists of two phases: an experience-independent establishment of initial biases, followed by an experience-dependent amplification or modification of these biases via correlation-based plasticity of excitatory inputs that compete against gradually increasing feed-forward inhibition. PMID:24598528
Evidence of directional and stabilizing selection in contemporary humans.
Sanjak, Jaleal S; Sidorenko, Julia; Robinson, Matthew R; Thornton, Kevin R; Visscher, Peter M
2018-01-02
Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.
Interactions between Genetic and Ecological Effects on the Evolution of Life Cycles.
Rescan, Marie; Lenormand, Thomas; Roze, Denis
2016-01-01
Sexual reproduction leads to an alternation between haploid and diploid phases, whose relative length varies widely across taxa. Previous genetical models showed that diploid or haploid life cycles may be favored, depending on dominance interactions and on effective recombination rates. By contrast, niche differentiation between haploids and diploids may favor biphasic life cycles, in which development occurs in both phases. In this article, we explore the interplay between genetical and ecological factors, assuming that deleterious mutations affect the competitivity of individuals within their ecological niche and allowing different effects of mutations in haploids and diploids (including antagonistic selection). We show that selection on a modifier gene affecting the relative length of both phases can be decomposed into a direct selection term favoring the phase with the highest mean fitness (due to either ecological differences or differential effects of mutations) and an indirect selection term favoring the phase in which selection is more efficient. When deleterious alleles occur at many loci and in the presence of ecological differentiation between haploids and diploids, evolutionary branching often occurs and leads to the stable coexistence of alleles coding for haploid and diploid cycles, while temporal variations in niche sizes may stabilize biphasic cycles.
Mullon, Charles; Pomiankowski, Andrew; Reuter, Max
2012-12-01
Sexual antagonism (SA) occurs when an allele that is beneficial to one sex, is detrimental to the other. This conflict can result in balancing, directional, or disruptive selection acting on SA alleles. A body of theory predicts the conditions under which sexually antagonistic mutants will invade and be maintained in stable polymorphism under balancing selection. There remains, however, considerable debate over the distribution of SA genetic variation across autosomes and sex chromosomes, with contradictory evidence coming from data and theory. In this article, we investigate how the interplay between selection and genetic drift will affect the genomic distribution of sexually antagonistic alleles. The effective population sizes can differ between the autosomes and the sex chromosomes due to a number of ecological factors and, consequently, the distribution of SA genetic variation in genomes. In general, we predict the interplay of SA selection and genetic drift should lead to the accumulation of SA alleles on the X in male heterogametic (XY) species and, on the autosomes in female heterogametic (ZW) species, especially when sexual competition is strong among males. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.
A Time-Series Water Level Forecasting Model Based on Imputation and Variable Selection Method.
Yang, Jun-He; Cheng, Ching-Hsue; Chan, Chia-Pan
2017-01-01
Reservoirs are important for households and impact the national economy. This paper proposed a time-series forecasting model based on estimating a missing value followed by variable selection to forecast the reservoir's water level. This study collected data from the Taiwan Shimen Reservoir as well as daily atmospheric data from 2008 to 2015. The two datasets are concatenated into an integrated dataset based on ordering of the data as a research dataset. The proposed time-series forecasting model summarily has three foci. First, this study uses five imputation methods to directly delete the missing value. Second, we identified the key variable via factor analysis and then deleted the unimportant variables sequentially via the variable selection method. Finally, the proposed model uses a Random Forest to build the forecasting model of the reservoir's water level. This was done to compare with the listing method under the forecasting error. These experimental results indicate that the Random Forest forecasting model when applied to variable selection with full variables has better forecasting performance than the listing model. In addition, this experiment shows that the proposed variable selection can help determine five forecast methods used here to improve the forecasting capability.
Selection on spur shape in Impatiens capensis.
Young, Helen J
2008-06-01
Rapid speciation within some plant families has been attributed to the evolution of floral spurs and to the effect of spur length on plant reproductive success. The flowers of Impatiens capensis (jewelweed) possess a long, curved spur in which nectar is produced and stored. Spur length and curvature varies among plants within one population. Here I document that spur shape is variable in natural populations, variation within plants is less than variation among plants, and spur shape is correlated with components of female and male reproductive success. The apparent natural selection is weakly directional in 1 of 2 years, with greatest seed production and pollen removal occurring in flowers with the greatest spur curvature. Bee pollinator visit length is longest at flowers with highly curved spurs, and they leave less nectar in these spurs than in flowers with straighter spurs. Spur angle evolution may be limited, at least in part, by opposing selection by nectar-robbers who prefer to visit flowers with greater spur curvature. Other factors that might contribute to the maintenance of spur angle variation are temporal variation in the strength of selection and potential genetic correlations of spur shape with other traits under selection.
Meirelles, S L C; Mokry, F B; Espasandín, A C; Dias, M A D; Baena, M M; de A Regitano, L C
2016-06-10
Correlation between genetic parameters and factors such as backfat thickness (BFT), rib eye area (REA), and body weight (BW) were estimated for Canchim beef cattle raised in natural pastures of Brazil. Data from 1648 animals were analyzed using multi-trait (BFT, REA, and BW) animal models by the Bayesian approach. This model included the effects of contemporary group, age, and individual heterozygosity as covariates. In addition, direct additive genetic and random residual effects were also analyzed. Heritability estimated for BFT (0.16), REA (0.50), and BW (0.44) indicated their potential for genetic improvements and response to selection processes. Furthermore, genetic correlations between BW and the remaining traits were high (P > 0.50), suggesting that selection for BW could improve REA and BFT. On the other hand, genetic correlation between BFT and REA was low (P = 0.39 ± 0.17), and included considerable variations, suggesting that these traits can be jointly included as selection criteria without influencing each other. We found that REA and BFT responded to the selection processes, as measured by ultrasound. Therefore, selection for yearling weight results in changes in REA and BFT.
Specific c-Jun target genes in malignant melanoma.
Schummer, Patrick; Kuphal, Silke; Vardimon, Lily; Bosserhoff, Anja K; Kappelmann, Melanie
2016-05-03
A fundamental event in the development and progression of malignant melanoma is the de-regulation of cancer-relevant transcription factors. We recently showed that c-Jun is a main regulator of melanoma progression and, thus, is the most important member of the AP-1 transcription factor family in this disease. Surprisingly, no cancer-related specific c-Jun target genes in melanoma were described in the literature, so far. Therefore, we focused on pre-existing ChIP-Seq data (Encyclopedia of DNA Elements) of 3 different non-melanoma cell lines to screen direct c-Jun target genes. Here, a specific c-Jun antibody to immunoprecipitate the associated promoter DNA was used. Consequently, we identified 44 direct c-Jun targets and a detailed analysis of 6 selected genes confirmed their deregulation in malignant melanoma. The identified genes were differentially regulated comparing 4 melanoma cell lines and normal human melanocytes and we confirmed their c-Jun dependency. Direct interaction between c-Jun and the promoter/enhancer regions of the identified genes was confirmed by us via ChIP experiments. Interestingly, we revealed that the direct regulation of target gene expression via c-Jun can be independent of the existence of the classical AP-1 (5´-TGA(C/G)TCA-3´) consensus sequence allowing for the subsequent down- or up-regulation of the expression of these cancer-relevant genes. In summary, the results of this study indicate that c-Jun plays a crucial role in the development and progression of malignant melanoma via direct regulation of cancer-relevant target genes and that inhibition of direct c-Jun targets through inhibition of c-Jun is a potential novel therapeutic option for treatment of malignant melanoma.
Cognitive Factors Affecting Freeze-like Behavior in Humans.
Alban, Michael W; Pocknell, Victoria
2017-01-01
Contemporary research on survival-related defensive behaviors has identified physiological markers of freeze/flight/fight. Our research focused on cognitive factors associated with freeze-like behavior in humans. Study 1 tested if an explicit decision to freeze is associated with the psychophysiological state of freezing. Heart rate deceleration occurred when participants chose to freeze. Study 2 varied the efficacy of freezing relative to other defense options and found "freeze" was responsive to variations in the perceived effectiveness of alternative actions. Study 3 tested if individual differences in motivational orientation affect preference for a "freeze" option when the efficacy of options is held constant. A trend in the predicted direction suggested that naturally occurring cognitions led loss-avoiders to select "freeze" more often than reward-seekers. In combination, our attention to the cognitive factors affecting freeze-like behavior in humans represents a preliminary step in addressing an important but neglected research area.
Lunar lander stage requirements based on the Civil Needs Data Base
NASA Technical Reports Server (NTRS)
Mulqueen, John A.
1992-01-01
This paper examines the lunar lander stages that will be necessary for the future exploration and development of the Moon. Lunar lander stage sizing is discussed based on the projected lunar payloads listed in the Civil Needs Data Base. Factors that will influence the lander stage design are identified and discussed. Some of these factors are (1) lunar orbiting and lunar surface lander bases; (2) implications of direct landing trajectories and landing from a parking orbit; (3) implications of landing site and parking orbit; (4) implications of landing site and parking orbit selection; (5) the use of expendable and reusable lander stages; and (6) the descent/ascent trajectories. Data relating the lunar lander stage design requirements to each of the above factors and others are presented in parametric form. These data will provide useful design data that will be applicable to future mission model modifications and design studies.
Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera.
McGrath, John; Eyles, Darryl; Mowry, Bryan; Yolken, Robert; Buka, Stephen
2003-09-01
Evidence from epidemiology suggests that low maternal vitamin D may be a risk factor for schizophrenia. Based on sera taken during the third trimester, we compared the level of 25 hydroxyvitamin D3 in mothers of individuals with schizophrenia or schizoaffective disorders versus mothers of unaffected controls. For each case, we selected two controls matched on race, gender and date of birth of the offspring. There was no significant difference in third trimester maternal vitamin D in the entire sample (cases = 26, controls = 51). Within the subgroup of black individuals (n = 21), there was a trend level difference in the predicted direction. Maternal vitamin D does not operate as a continuous graded risk factor for schizophrenia, however, the results in the black subgroup raise the possibility that below a certain critical threshold, low levels of maternal vitamin D may be associated with an increased risk of schizophrenia.
Young, Martin E.; Bray, Molly S.
2007-01-01
Circadian clocks are intracellular molecular mechanisms designed to allow the cell, organ, and organism to prepare for an anticipated stimulus prior to its onset. In order for circadian clocks to maintain their selective advantage, they must be entrained to the environment. Light, sound, temperature, physical activity (including sleep/wake transitions), and food intake are among the strongest environmental factors influencing mammalian circadian clocks. Normal circadian rhythmicities in these environmental factors have become severely disrupted in our modern day society, concomitant with increased incidence of type 2 diabetes mellitus, obesity, and cardiovascular disease. Here, we review our current knowledge regarding the roles of peripheral circadian clocks, concentrating on those found within tissues directly involved in metabolic homeostasis and cardiovascular function. We propose that both inter- and intra- organ dyssynchronization, through alteration/impairment of peripheral circadian clocks, accelerates the development of cardiovascular disease risk factors associated with cardiometabolic syndrome. PMID:17387040
Narrowband thermal radiation from closed-end microcavities
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kohiyama, Asaka; Shimizu, Makoto; Iguchi, Fumitada
2015-10-07
High spectral selectivity of thermal radiation is important for achieving high-efficiency energy systems. In this study, intense, narrowband, and low directional absorption/radiation were observed in closed-end microcavity which is a conventional open-end microcavity covered by a semi-transparent thin metal film. The quality factor (Q factor) of optical absorption band strongly depended on the film electrical conductivity. Asymmetric and narrow absorption band with a Q factor of 25 at 1.28 μm was obtained for a 6-nm-thick Au film. Numerical simulations suggest that the formation of a fixed-end mode at the cavity aperture contributes to the narrowband optical absorption. The closed-end microcavity filledmore » with SiO{sub 2} exhibits intense and isotropic thermal radiation over a wide solid angle according to numerical simulation. The narrow and asymmetric absorption spectrum was experimentally confirmed in a model of closed-end microcavity.« less
Employment and the associated impact on quality of life in people diagnosed with schizophrenia.
Bouwmans, Clazien; de Sonneville, Caroline; Mulder, Cornelis L; Hakkaart-van Roijen, Leona
2015-01-01
A systematic review was conducted to assess the employment rate of people with schizophrenia. Additionally, information from the selected studies concerning factors associated with employment and health-related quality of life (HRQoL) was examined. Employment rates ranged from 4% to 50.4%. The studies differed considerably in design, patient settings, and methods of recruitment. The most frequently reported factors associated with employment were negative and cognitive symptoms, age of onset, and duration and course of the disease. Individual characteristics associated with unemployment were older age, lower education, and sex (female). Additionally, environmental factors, eg, the availability of welfare benefits and vocational support programs, seemed to play a role. Generally, being employed was positively associated with HRQoL. However, the causal direction of this association remained unclear, as studies on the bidirectional relationship between employment and HRQoL were lacking.
Langan, S M
2009-01-01
Eczema is a major public health problem affecting children worldwide. Few studies have directly assessed triggers for disease flares. This paper presents evidence from a published systematic review and a prospective cohort study looking at flare factors in eczema. This systematic review suggested that foodstuffs in selected groups, dust exposure, unfamiliar pets, seasonal variation, stress, and irritants may be important in eczema flares. We performed a prospective cohort study that focused on environmental factors and identified associations between exposure to nylon clothing, dust, unfamiliar pets, sweating, shampoo, and eczema flares. Results from this study also demonstrated some new key findings. First, the effect of shampoo was found to increase in cold weather, and second, combinations of environmental factors were associated with disease exacerbation, supporting a multiple component disease model. This information is likely to be useful to families and may lead to the ability to reduce disease flares in the future.
Selective and directional actuation of elastomer films using chained magnetic nanoparticles
NASA Astrophysics Data System (ADS)
Mishra, Sumeet R.; Dickey, Michael D.; Velev, Orlin D.; Tracy, Joseph B.
2016-01-01
We report selective and directional actuation of elastomer films utilizing magnetic anisotropy introduced by chains of Fe3O4 magnetic nanoparticles (MNPs). Under uniform magnetic fields or field gradients, dipolar interactions between the MNPs favor magnetization along the chain direction and cause selective lifting. This mechanism is described using a simple model.We report selective and directional actuation of elastomer films utilizing magnetic anisotropy introduced by chains of Fe3O4 magnetic nanoparticles (MNPs). Under uniform magnetic fields or field gradients, dipolar interactions between the MNPs favor magnetization along the chain direction and cause selective lifting. This mechanism is described using a simple model. Electronic supplementary information (ESI) available: Two videos for actuation while rotating the sample, experimental details of nanoparticle synthesis, polymer composite preparation, and alignment and bending studies, details of the theoretical model of actuation, and supplemental figures for understanding the behavior of rotating samples and results from modelling. See DOI: 10.1039/c5nr07410j
Directional selection in temporally replicated studies is remarkably consistent.
Morrissey, Michael B; Hadfield, Jarrod D
2012-02-01
Temporal variation in selection is a fundamental determinant of evolutionary outcomes. A recent paper presented a synthetic analysis of temporal variation in selection in natural populations. The authors concluded that there is substantial variation in the strength and direction of selection over time, but acknowledged that sampling error would result in estimates of selection that were more variable than the true values. We reanalyze their dataset using techniques that account for the necessary effect of sampling error to inflate apparent levels of variation and show that directional selection is remarkably constant over time, both in magnitude and direction. Thus we cannot claim that the available data support the existence of substantial temporal heterogeneity in selection. Nonetheless, we conject that temporal variation in selection could be important, but that there are good reasons why it may not appear in the available data. These new analyses highlight the importance of applying techniques that estimate parameters of the distribution of selection, rather than parameters of the distribution of estimated selection (which will reflect both sampling error and "real" variation in selection); indeed, despite availability of methods for the former, focus on the latter has been common in synthetic reviews of the aspects of selection in nature, and can lead to serious misinterpretations. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.
A genome-wide scan for signatures of directional selection in domesticated pigs.
Moon, Sunjin; Kim, Tae-Hun; Lee, Kyung-Tai; Kwak, Woori; Lee, Taeheon; Lee, Si-Woo; Kim, Myung-Jick; Cho, Kyuho; Kim, Namshin; Chung, Won-Hyong; Sung, Samsun; Park, Taesung; Cho, Seoae; Groenen, Martien Am; Nielsen, Rasmus; Kim, Yuseob; Kim, Heebal
2015-02-25
Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication. Whole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an F ST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness. We show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs.
Directional acceleration vector-driven displacement of fluids (DAVD-DOF)
NASA Technical Reports Server (NTRS)
Clarke, Mark S. F. (Inventor); Feeback, Daniel L. (Inventor)
2004-01-01
Centrifugal analyzer and method for staining biological or non-biological samples in microgravity, wherein the method utilizes an increase in weight of a fluid sample as a function of g-load, to overcome cohesive and frictional forces from preventing its movement in a preselected direction. Apparatus is characterized by plural specimen reservoirs and channels in a slide, each channel being of differing cross-section, wherein respective samples are selectively dispensed, from the reservoirs in response to an imposed g-factor, precedent to sample staining. Within the method, one thus employs microscope slides which define channels, each being of a differing cross-section dimension relative to others. In combination therewith, centrifugal slide mounting apparatus controllably imposes g-vectors of differing magnitudes within a defined structure of the centrifuge such as a chip array.
Nanocapsule-mediated cytosolic siRNA delivery for anti-inflammatory treatment.
Jiang, Ying; Hardie, Joseph; Liu, Yuanchang; Ray, Moumita; Luo, Xiang; Das, Riddha; Landis, Ryan F; Farkas, Michelle E; Rotello, Vincent M
2018-06-05
The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation in vitro and in vivo is reported. These NPSCs deliver siRNA directly to the cytosol of macrophages in vitro with concomitant knockdown of gene expression. In vivo studies showed directed delivery of NPSCs to the spleen, enabling gene silencing of macrophages, with preliminary studies showing 70% gene knockdown at a siRNA dose of 0.28 mg/kg. Significantly, the delivery of siRNA targeting tumor necrosis factor-α efficiently silenced TNF-α expression in LPS-challenged mice, demonstrating efficacy in modulating immune response in an organ-selective manner. This research highlights the potential of the NPSC platform for targeted immunotherapy and further manipulation of the immune system. Copyright © 2018 Elsevier B.V. All rights reserved.
Thermal barrier coatings for aircraft engines: History and directions
NASA Technical Reports Server (NTRS)
Miller, R. A.
1995-01-01
Thin thermal barrier coatings for protecting aircraft turbine section airfoils are examined. The discussion focuses on those advances that led first to their use for component life extension and more recently as an integral part of airfoil design. It is noted that development has been driven by laboratory rig and furnace testing corroborated by engine testing and engine field experience. The technology has also been supported by performance modeling to demonstrate benefits and life modeling for mission analysis. Factors which have led to the selection of the current state-of-the-art plasma sprayed and physical vapor deposited zirconia-yttria/MCrAlY TBC's is emphasized in addition to observations fundamentally related to their behavior. Current directions in research into thermal barrier coatings and recent progress at NASA is also noted.
Shui, Wei; DU, Yong; Chen, Yi Ping; Jian, Xiao Mei; Fan, Bing Xiong
2017-04-18
Anxi County, specializing in tea cultivation, was taken as a case in this research. Pearson correlation analysis, ordinary least squares model (OLS) and geographically weighted regression model (GWR) were used to select four primary influence factors of specialization in tea cultivation (i.e., the average elevation, net income per capita, proportion of agricultural population, and the distance from roads) by analyzing the specialization degree of each town of Anxi County. Meanwhile, the spatial patterns of specialization in tea cultivation of Anxi County were evaluated. The results indicated that specialization in tea cultivation of Anxi County showed an obvious spatial auto-correlation, and a spatial pattern with "low-middle-high" circle structure, which was similar to Von Thünen's circle structure model, appeared from the county town to its surrounding region. Meanwhile, GWR (0.624) had a better fitting degree than OLS (0.595), and GWR could reasonably expound the spatial data. Contrary to the agricultural location theory of Von Thünen's model, which indicated that distance from market was a determination factor, the specialization degree of tea cultivation in Anxi was mainly decided by natural conditions of mountain area, instead of the social factors. Specialization degree of tea cultivation was positively correlated with the average elevation, net income per capita and the proportion of agricultural population, while a negative correlation was found between the distance from roads and specialization degree of tea cultivation. Coefficients of regression between the specialization degree of tea cultivation and two factors (i.e., the average elevation and net income per capita) showed a spatial pattern of higher level in the north direction and lower level in the south direction. On the contrary, the regression coefficients for the proportion of agricultural population increased from south to north of Anxi County. Furthermore, regression coefficient for the distance from roads showed a spatial pattern of higher level in the northeast direction and lower level in the southwest direction of Anxi County.
Critical factors for the success of orthodontic mini-implants: a systematic review.
Chen, Yan; Kyung, Hee Moon; Zhao, Wen Ting; Yu, Won Jae
2009-03-01
This systematic review was undertaken to discuss factors that affect mini-implants as direct and indirect orthodontic anchorage. The data were collected from electronic databases (Medline [Entrez PubMed], Embase, Web of Science, Cochrane Library, and All Evidence Based Medicine Reviews). Randomized clinical trials, prospective and retrospective clinical studies, and clinical trials concerning the properties, affective factors, and requirements of mini-implants were considered. The titles and abstracts that appeared to fulfill the initial selection criteria were collected by consensus, and the original articles were retrieved and evaluated with a methodologic checklist. A hand search of key orthodontic journals was performed to identify recent unindexed literature. The search strategy resulted in 596 articles. By screening titles and abstracts, 126 articles were identified. After the exclusion criteria were applied, 16 articles remained. The analyzed results of the literature were divided into 2 topics: placement-related and loading-related factors. Mini-implants are effective as anchorage, and their success depends on proper initial mechanical stability and loading quality and quantity.
The factors that influence job satisfaction among royal Malaysian customs department employee
NASA Astrophysics Data System (ADS)
Ammar Shafi, Muhammad; Saifullah Rusiman, Mohd; Nor, Maria Elena; Khamis, Azme; Nabilah Syuhada Abdullah, Siti; Syafiq Azmi, Mohd; Sakinah Zainal Abidin, Munirah; Ali, Maselan
2018-04-01
This research aims to spot the factors that influence job satisfaction among Royal Malaysian Customs Department employees. Primary data was used in this research and it was collected from the employees who work in five different departments at Royal Malaysian Customs Department Tower Johor. Those departments were customs department, Internal Taxes, Technical Services, Management and Prevention. The research used stratified random sampling to collect the sample and Structural Equation Modelling (SEM) to measure the relationship between variables using AMOS software. About 127 employees are selected as the respondents from five departments to represent the sample. The result showed that ‘Organizational Commitment’ (p-value = 0.001) has significant and direct effect toward job satisfaction compared to the ‘Stress Condition’ (p-value = 0.819) and ‘Motivation’ factor (p-value = 0.978). It was also concluded that ‘Organizational Commitment’ was the most influential factor toward job satisfaction among Royal Malaysian Customs Department employees at Tower Custom Johor, Johor Bahru.
Poomsrikaew, Ornwanya; Ryan, Catherine J; Zerwic, Julie J
2010-10-01
This study aimed to determine Thais' knowledge of heart attack symptoms and risk factors and whether that knowledge was related to age, gender or education. Via a street-intercept survey method, a convenience sample of people aged ≥ 35 years (n = 192) was recruited. Mean age was 47 ± 9.6 years (range 35-81), and 55.2% were female. Participants identified on average 5.6 of 9 heart attack symptoms (SD 1.8) and 5.3 of 8 heart attack risk factors (SD 2.1). However, 66.7% mistakenly thought the chest discomfort would be severe, sharp and stabbing, and many subjects erroneously selected symptoms that are actually stroke symptoms. There were no gender or educational differences in knowledge of heart attack symptoms and risk factors. Older adults recognized fewer total symptoms than did younger adults. These findings could direct health-care providers to help the Thai population differentiate symptoms of heart attack from stroke. © 2010 Blackwell Publishing Asia Pty Ltd.
Rat Stem-Cell Factor Induces Splenocytes Capable Of Regenerating The Thymus
Migita, Russell T.; Trebasky, Lisa D.; Housman, Jerry M.; Elliott, Gary S.; Hendren, R. Wayne; Deprince, Randolph B.; Greiner, Dale L.
1992-01-01
Cytokine regulation of prethymic T-lymphoid progenitor-cell proliferation and/or differentiation has not been well-defined, although much is known of cytokine regulation of hemopoietic stem- and progenitor-cell development. Here we use a recently identified hemopoietic growth factor, stem-cell factor (SCF) (a form of the c-kit ligand), and a transplant model of thymocyte regeneration to assess the effect of SCF on the in vivo generation of prethymic, thymocyte progenitor-cell activity. We show that recombinant rat SCF (rrSCF164 administered to weanling rats selectively induces an increase in thymocyte progenitor activity in the spleens of treated rats as compared to rats treated with vehicle, polyethylene glycol (PEG)-conjugated rat albumin, or recombinant human granulocyte colony-stimulating factor (rhG-CSF). These data demonstrate that administration of SCF in vivo affects extrathymic-origin thymocyte regenerating cells and may influence, directly or indirectly, early prethymic stages of T-cell lymphopoiesis in addition to its known effect on early stages of myelopoiesis and erythropoiesis. PMID:1285280
Guthold, Regina; Cowan, Melanie; Savin, Stefan; Bhatti, Lubna; Armstrong, Timothy; Bonita, Ruth
2016-01-01
Objectives. We sought to outline the framework and methods used by the World Health Organization (WHO) STEPwise approach to noncommunicable disease (NCD) surveillance (STEPS), describe the development and current status, and discuss strengths, limitations, and future directions of STEPS surveillance. Methods. STEPS is a WHO-developed, standardized but flexible framework for countries to monitor the main NCD risk factors through questionnaire assessment and physical and biochemical measurements. It is coordinated by national authorities of the implementing country. The STEPS surveys are generally household-based and interviewer-administered, with scientifically selected samples of around 5000 participants. Results. To date, 122 countries across all 6 WHO regions have completed data collection for STEPS or STEPS-aligned surveys. Conclusions. STEPS data are being used to inform NCD policies and track risk-factor trends. Future priorities include strengthening these linkages from data to action on NCDs at the country level, and continuing to develop STEPS’ capacities to enable a regular and continuous cycle of risk-factor surveillance worldwide. PMID:26696288
Riley, Leanne; Guthold, Regina; Cowan, Melanie; Savin, Stefan; Bhatti, Lubna; Armstrong, Timothy; Bonita, Ruth
2016-01-01
We sought to outline the framework and methods used by the World Health Organization (WHO) STEPwise approach to noncommunicable disease (NCD) surveillance (STEPS), describe the development and current status, and discuss strengths, limitations, and future directions of STEPS surveillance. STEPS is a WHO-developed, standardized but flexible framework for countries to monitor the main NCD risk factors through questionnaire assessment and physical and biochemical measurements. It is coordinated by national authorities of the implementing country. The STEPS surveys are generally household-based and interviewer-administered, with scientifically selected samples of around 5000 participants. To date, 122 countries across all 6 WHO regions have completed data collection for STEPS or STEPS-aligned surveys. STEPS data are being used to inform NCD policies and track risk-factor trends. Future priorities include strengthening these linkages from data to action on NCDs at the country level, and continuing to develop STEPS' capacities to enable a regular and continuous cycle of risk-factor surveillance worldwide.
NASA Technical Reports Server (NTRS)
Lewis, Michael S.; Mansur, M. Hossein; Chen, Robert T. N.
1987-01-01
A piloted simulation study investigating handling qualities and flight characteristics required for helicopter air to air combat is presented. The Helicopter Air Combat system was used to investigate this role for Army rotorcraft. Experimental variables were the maneuver envelope size (load factor and sideslip), directional axis handling qualities, and pitch and roll control-response type. Over 450 simulated, low altitude, one-on-one engagements were conducted. Results from the experiment indicate that a well damped directional response, low sideforce caused by sideslip, and some effective dihedral are all desirable for weapon system performance, good handling qualities, and low pilot workload. An angular rate command system was favored over the attitude type pitch and roll response for most applications, and an enhanced maneuver envelope size over that of current generation aircraft was found to be advantageous. Pilot technique, background, and experience are additional factors which had a significant effect on performance in the air combat tasks investigated. The implication of these results on design requirements for future helicopters is presented.
Ikaros controls isotype selection during immunoglobulin class switch recombination.
Sellars, MacLean; Reina-San-Martin, Bernardo; Kastner, Philippe; Chan, Susan
2009-05-11
Class switch recombination (CSR) allows the humoral immune response to exploit different effector pathways through specific secondary antibody isotypes. However, the molecular mechanisms and factors that control immunoglobulin (Ig) isotype choice for CSR are unclear. We report that deficiency for the Ikaros transcription factor results in increased and ectopic CSR to IgG(2b) and IgG(2a), and reduced CSR to all other isotypes, regardless of stimulation. Ikaros suppresses active chromatin marks, transcription, and activation-induced cytidine deaminase (AID) accessibility at the gamma2b and gamma2a genes to inhibit class switching to these isotypes. Further, Ikaros directly regulates isotype gene transcription as it directly binds the Igh 3' enhancer and interacts with isotype gene promoters. Finally, Ikaros-mediated repression of gamma2b and gamma2a transcription promotes switching to other isotype genes by allowing them to compete for AID-mediated recombination at the single-cell level. Thus, our results reveal transcriptional competition between constant region genes in individual cells to be a critical and general mechanism for isotype specification during CSR. We show that Ikaros is a master regulator of this competition.
Maher, Geoffrey J.; McGowan, Simon J.; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O. M.
2016-01-01
De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39–90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones. PMID:26858415
Maher, Geoffrey J; McGowan, Simon J; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O M
2016-03-01
De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones.
Assessing different measures of population-level vaccine protection using a case-control study.
Ali, Mohammad; You, Young Ae; Kanungo, Suman; Manna, Byomkesh; Deen, Jacqueline L; Lopez, Anna Lena; Wierzba, Thomas F; Bhattacharya, Sujit K; Sur, Dipika; Clemens, John D
2015-11-27
Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects. 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case-control analyses. The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection. Copyright © 2015. Published by Elsevier Ltd.
Haugan, Gørill
2015-03-01
Spiritual well-being has been found to be a strong individual predictor of overall nursing home satisfaction and a fundamental dimension of global as well as health-related quality-in-life among nursing home patients. Therefore, access to a valid and reliable measure of spiritual well-being among nursing home patients is highly warranted. The aim of this study was to investigate the dimensionality, reliability and construct validity of the Functional Assessment of Chronic Illness Therapy Spiritual Wellbeing scale in a cognitively intact nursing home population. A cross-sectional design was applied, selecting two counties in central Norway from which 20 municipalities representing 44 different nursing homes took part in this study. Long-term care was defined as 24-hour care with duration of 6 months or longer. Participants were 202 cognitively intact long-term nursing home patients fulfilling the inclusion criteria. Approval by all regulatory institutions dealing with research issues in Norway and the Management Unit at the 44 nursing homes was obtained. Explorative and confirmative factor analyses as well as correlation with selected construct were used. Though three items loaded very low (λ = 0.22, 0.26, 0.32) indicating low reliability, the three-factor model for the FACIT-Sp spiritual well-being scale provided an acceptable fit (χ(2) = 101.15 (df = 50), p-value <0.001, RMSEA = 0.075 p = 0.030, NFI = 0.90, GFI = 0.91, AGFI = 0.85) for older nursing home patients, demonstrating acceptable measurement reliability. Construct validity was supported by significant correlations in the hypothesised direction with the selected constructs. The three-factor model is an improvement over the original two-factor construct, based on these nursing home data. The measure yielded significantly factor loadings, good composite reliability and construct validity. © 2014 Nordic College of Caring Science.
Dunning, Jeffery L.; Pant, Santosh; Bass, Aaron; Coburn, Zachary; Prather, Jonathan F.
2014-01-01
In the process of mate selection by female songbirds, male suitors advertise their quality through reproductive displays in which song plays an important role. Females evaluate the quality of each signal and the associated male, and the results of that evaluation guide expression of selective courtship displays. Some studies reveal broad agreement among females in their preferences for specific signal characteristics, indicating that those features are especially salient in female mate choice. Other studies reveal that females differ in their preference for specific characteristics, indicating that in those cases female evaluation of signal quality is influenced by factors other than simply the physical properties of the signal. Thus, both the physical properties of male signals and specific traits of female signal evaluation can impact female mate choice. Here, we characterized the mate preferences of female Bengalese finches. We found that calls and copulation solicitation displays are equally reliable indicators of female preference. In response to songs from an array of males, each female expressed an individual-specific song preference, and those preferences were consistent across tests spanning many months. Across a population of females, songs of some males were more commonly preferred than others, and females preferred female-directed songs more than undirected songs, suggesting that some song features are broadly attractive. Preferences were indistinguishable for females that did or did not have social experience with the singers, indicating that female preference is strongly directed by song features rather than experiences associated with the singer. Analysis of song properties revealed several candidate parameters that may influence female evaluation. In an initial investigation of those parameters, females could be very selective for one song feature yet not selective for another. Therefore, multiple song parameters are evaluated independently. Together these findings reveal the nature of signal evaluation and mate choice in this species. PMID:24558501
Observing relationships in Finnish adoptive families: Oulu Family Rating Scale.
Tienari, Pekka; Wynne, Lyman C; Sorri, Anneli; Lahti, Ilpo; Moring, Juha; Nieminen, Pentti; Joukamaa, Matti; Naarala, Mikko; Seitamaa, Markku; Wahlberg, Karl-Erik; Miettunen, Jouko
2005-01-01
Adoption studies were intended to separate genetic from environmental "causal" factors. In earlier adoption studies, psychiatric diagnostic labels for the adoptive parents were used as a proxy for the multiple dimensions of the family rearing environment. In the Finnish Adoption Study, research design provided the opportunity to study directly the adoptive family rearing environment. For this purpose 33 sub-scales were selected creating what we call Oulu Family Rating Scale (OPAS, Oulun PerheArviointiSkaala). In this paper, the manual for scoring of these sub-scales is presented.
1984-09-01
Harms, Assistant Director for Management Support, and LT% Mike Deems, who was the Contracting Officer’s Representative for the HERO contract. COMMENTS...A1ND gJESTIONS may be directed to US Army Concep*s Aialysis Agency, ATTN: Assistint Director for Management Support, 8120 .uodriont Avenue, Bethesda...APPENDIX A STUDY CONTRIBUTORS 1. STUDY TEAM. Management and Support Directorate. Report Author: Lelma M. Harms Contract COTR: LTC J. M. Deems 2. EXTERNAL
Anticoagulant therapy: basic principles, classic approaches and recent developments.
Sinauridze, Elena I; Panteleev, Mikhail A; Ataullakhanov, Fazoil I
2012-09-01
The standard multipotent anticoagulants (unfractionated and low molecular weight heparins, antagonists of vitamin K) are commonly used for treatment and/or prophylaxis of different thrombotic complications, such as deep vein thrombosis, thrombophilia, pulmonary embolism, myocardial infarction, stroke and so on. Advantages and shortcomings of these anticoagulants are considered. The modern tendencies to use small selective direct inhibitors of thrombin or factor Xa are surveyed. The search of the new targets in the coagulation cascade for development of new promising anticoagulants and improvement in antithrombotic therapy is discussed.
Temporal-spatial variations and driving factors analysis of coastal reclamation in China
NASA Astrophysics Data System (ADS)
Meng, Weiqing; Hu, Beibei; He, Mengxuan; Liu, Baiqiao; Mo, Xunqiang; Li, Hongyuan; Wang, Zhongliang; Zhang, Yu
2017-05-01
Coastal reclamation is the gain of land from the sea or coastal wetlands for agricultural purposes, industrial use or port expansions. Large-scale coastal land reclamation can have adverse effects on the coastal environment, including loss of marine habitats and deterioration of coastal water quality. In recent decades, coastal land reclamation has occurred extensively to meet the increasing needs of rapid economic development and urbanization in China. The overall objective of this study is to understand the coastal reclamation status of China from 1979 to 2014 and analyzed its driving factors for mitigating negative ecological effects. The data of coastal reclamation were done with the ERDAS Imagine V9.2 platform and ArcGIS software based on remote images including Landsat, SPOT, ZY-2 and ZY-3. Potential driving factors for sea reclamation were selected based on statistics bulletins and the knowledge of experts in coastal management. In order to understand the relationships among possible impact factors and coastal reclamation, the Partial Least-Squares Regression models was constructed. The analysis results indicated that the total area of reclamation was 11162.89 km2 based on remote sensing images between 1979 and 2014. Shandong Province is the largest reclamation area, reaching 2736.54 km2, and the reclamation is mainly concentrated in Zhejiang, Jiangsu and Liaoning, where the reclamation areas were all more than 1000 km2. According to the remote sensing images, there are three coastal reclamation hotspot regions including Bohai bay (in which is located Liaoning, Tianjin and Hebei), Jiangsu province coastal area and Hangzhou bay (in Zhejiang province). A large scale land reclamation plan of more than 5880 km2 has been made by local government and 2469 km2 has approved by the State Council. From the analyzed results, there is a significant collinearity between these indicators, and no significant correlation between the area of reclamation and selected indicators. Economic development and employees in marine industries have weak positive correlation and correspondingly, the area of cultivated land (ACL) had a negative correlation. Because of the weak correlation, there is an assumption that economic development, outcome of coastal reclamation and population growth were not only was the direct driving factor, but also the outcome of coastal reclamation and population growth was not the direct driving indicator. Construction land quota and huge economic returns to local government may be the direct driving factors according to our field investigation. To resolve the contradiction between the need for land and coastal wetland conservation, it is recommended that China should establish a special management agency and coordination mechanisms, reconsidered the implementation of the reclamation plans and projects that have been approved, enhance law enforcement and increase penalties and strengthen public participation in reclamation management.
Roberts, Stephen A; Hann, Mark; Brison, Daniel R
2016-02-01
Many studies have identified prognostic factors for IVF treatment outcome; however, little information is available on the mechanism of their action. Embryo-uterus models have the potential to distinguish between factors acting on the embryo directly and those acting through the uterine environment. Here we apply embryo-uterus models to comprehensive UK registry data from two periods, 2000-2005 and 2007-2011, containing 139,444 and 226,542 embryo transfer cycles, respectively. Given this large dataset, the embryo-uterus model is capable of distinguishing between uterine and embryo effects. Maternal age is the predominant predictor of live birth and acts on both the embryo and uterine components, but with larger effects on the embryo. Prolonged embryo culture is associated with greater embryo viability, reflecting the greater degree of selection, but is also associated with greater uterine receptivity. Cryopreserved embryos are less viable and were associated with poorer uterine receptivity. This work suggests that, in addition to the direct effects of in-vitro culture on the embryonic environment during the first few days of the embryo's life, the delay in transfer after extended culture or cryopreservation can lead to an altered uterine environment for the embryo after transfer. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Cai, Yun-Feng; Zhen, Zuo-Jun; Min, Jun; Fang, Tian-Ling; Chu, Zhong-Hua; Chen, Ji-Sheng
2004-11-15
To explore the feasibility of direct separation, selective proliferation and differentiation of the bone marrow-derived liver stem cells (BDLSC) from bone marrow cells with a culture system containing cholestatic serum in vitro. Whole bone marrow cells of rats cultured in routine medium were replaced with conditioning selection media containing 20 mL/L, 50 mL/L, 70 mL/L, and 100 mL/L cholestatic sera, respectively, after they attached to the plates. The optimal concentration of cholestatic serum was determined according to the outcome of the selected cultures. Then the selected BDLSC were induced to proliferate and differentiate with the addition of hepatocyte growth factor (HGF). The morphology and phenotypic markers of BDLSC were characterized using immunohistochemistry, RT-PCR and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay. Bone marrow cells formed fibroblast-like but not hepatocyte-like colonies in the presence of 20 mL/L cholestatic serum. In 70 mL/L cholestatic serum, BDLSC colonies could be selected but could not maintain good growth status. In 100 mL/L cholestatic serum, all of the bone marrow cells were unable to survive. A 50 mL/L cholestatic serum was the optimal concentration for the selection of BDLSC at which BDLSC could survive while the other populations of the bone marrow cells could not. The selected BDLSC proliferated and differentiated after HGF was added. Hepatocyte-like colony-forming units (H-CFU) then were formed. H-CFU expressed markers of embryonic hepatocytes (AFP, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors (HNF-1alpha and HNF-3beta). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. The selected medium containing cholestatic serum can select BDLSC from whole bone marrow cells. It will be a new way to provide a readily available alternate source of cells for clinical hepatocyte therapy.
Angular selective window systems: Assessment of technical potential for energy savings
Fernandes, Luis L.; Lee, Eleanor S.; McNeil, Andrew; ...
2014-10-16
Static angular selective shading systems block direct sunlight and admit daylight within a specific range of incident solar angles. The objective of this study is to quantify their potential to reduce energy use and peak demand in commercial buildings using state-of-the art whole-building computer simulation software that allows accurate modeling of the behavior of optically-complex fenestration systems such as angular selective systems. Three commercial systems were evaluated: a micro-perforated screen, a tubular shading structure, and an expanded metal mesh. This evaluation was performed through computer simulation for multiple climates (Chicago, Illinois and Houston, Texas), window-to-wall ratios (0.15-0.60), building codes (ASHRAEmore » 90.1-2004 and 2010) and lighting control configurations (with and without). The modeling of the optical complexity of the systems took advantage of the development of state-of-the-art versions of the EnergyPlus, Radiance and Window simulation tools. Results show significant reductions in perimeter zone energy use; the best system reached 28% and 47% savings, respectively without and with daylighting controls (ASHRAE 90.1-2004, south facade, Chicago,WWR=0.45). As a result, angular selectivity and thermal conductance of the angle-selective layer, as well as spectral selectivity of low-emissivity coatings, were identified as factors with significant impact on performance.« less
Developing Methods For Linking Surficial Aquifers With Localized Rainfall Data
NASA Astrophysics Data System (ADS)
Lafrenz, W. B.; van Gaalen, J. F.
2008-12-01
Water level hydrographs of the surficial aquifer can be evaluated to identify both the cause and consequence of water supply development. Rainfall, as a source of direct recharge and as a source of delayed or compounded recharge, is often the largest influence on surficial aquifer water level responses. It is clear that proximity of the rain gauge to the observation well is a factor in the degree of correlation, but in central Florida, USA, rainfall patterns change seasonally, with latitude, and with distance from the coast . Thus, for a location in central Florida, correlation of rain events with observed hydrograph responses depends on both distance and direction from an observation well to a rain gauge. In this study, we examine the use of extreme value analysis as a method of selecting the best rainfall data set for describing a given surficial aquifer monitor well. A surficial aquifer monitor well with a substantial suite of data is compared to a series of rainfall data sets from gauges ranging from meters to tens of kilometers in distance from the monitor well. The gauges vary in a wide range of directions from the monitor well in an attempt to identify both a method for rainfall gauge selection to be associated with the monitor well. Each rainfall gauge is described by a correlation coefficient with respect to the surficial aquifer water level data.
Giotto, Nina; Gerard, Jean-François; Ziv, Alon; Bouskila, Amos; Bar-David, Shirli
2015-01-01
The way in which animals move and use the landscape is influenced by the spatial distribution of resources, and is of importance when considering species conservation. We aimed at exploring how landscape-related factors affect a large herbivore's space-use patterns by using a combined approach, integrating movement (displacement and recursions) and habitat selection analyses. We studied the endangered Asiatic wild ass (Equus hemionus) in the Negev Desert, Israel, using GPS monitoring and direct observation. We found that the main landscape-related factors affecting the species' space-use patterns, on a daily and seasonal basis, were vegetation cover, water sources and topography. Two main habitat types were selected: high-elevation sites during the day (specific microclimate: windy on warm summer days) and streambed surroundings during the night (coupled with high vegetation when the animals were active in summer). Distribution of recursion times (duration between visits) revealed a 24-hour periodicity, a pattern that could be widespread among large herbivores. Characterizing frequently revisited sites suggested that recursion movements were mainly driven by a few landscape features (water sources, vegetation patches, high-elevation points), but also by social factors, such as territoriality, which should be further explored. This study provided complementary insights into the space-use patterns of E. hemionus. Understanding of the species' space-use patterns, at both large and fine spatial scale, is required for developing appropriate conservation protocols. Our approach could be further applied for studying the space-use patterns of other species in heterogeneous landscapes.
Giotto, Nina; Gerard, Jean-François; Ziv, Alon; Bouskila, Amos; Bar-David, Shirli
2015-01-01
The way in which animals move and use the landscape is influenced by the spatial distribution of resources, and is of importance when considering species conservation. We aimed at exploring how landscape-related factors affect a large herbivore’s space-use patterns by using a combined approach, integrating movement (displacement and recursions) and habitat selection analyses. We studied the endangered Asiatic wild ass (Equus hemionus) in the Negev Desert, Israel, using GPS monitoring and direct observation. We found that the main landscape-related factors affecting the species’ space-use patterns, on a daily and seasonal basis, were vegetation cover, water sources and topography. Two main habitat types were selected: high-elevation sites during the day (specific microclimate: windy on warm summer days) and streambed surroundings during the night (coupled with high vegetation when the animals were active in summer). Distribution of recursion times (duration between visits) revealed a 24-hour periodicity, a pattern that could be widespread among large herbivores. Characterizing frequently revisited sites suggested that recursion movements were mainly driven by a few landscape features (water sources, vegetation patches, high-elevation points), but also by social factors, such as territoriality, which should be further explored. This study provided complementary insights into the space-use patterns of E. hemionus. Understanding of the species’ space-use patterns, at both large and fine spatial scale, is required for developing appropriate conservation protocols. Our approach could be further applied for studying the space-use patterns of other species in heterogeneous landscapes. PMID:26630393
Roberts, Martin J; Gale, Thomas C E; McGrath, John S; Wilson, Mark R
2016-05-01
The ability to work under pressure is a vital non-technical skill for doctors working in acute medical specialties. Individuals who evaluate potentially stressful situations as challenging rather than threatening may perform better under pressure and be more resilient to stress and burnout. Training programme recruitment processes provide an important opportunity to examine applicants' reactions to acute stress. In the context of multi-station selection centres for recruitment to anaesthesia training programmes, we investigated the factors influencing candidates' pre-station challenge/threat evaluations and the extent to which their evaluations predicted subsequent station performance. Candidates evaluated the perceived stress of upcoming stations using a measure of challenge/threat evaluation-the cognitive appraisal ratio (CAR)-and consented to release their demographic details and station scores. Using regression analyses we determined which candidate and station factors predicted variation in the CAR and whether, after accounting for these factors, the CAR predicted candidate performance in the station. The CAR was affected by the nature of the station and candidate gender, but not age, ethnicity, country of training or clinical experience. Candidates perceived stations involving work related tasks as more threatening. After controlling for candidates' demographic and professional profiles, the CAR significantly predicted station performance: 'challenge' evaluations were associated with better performance, though the effect was weak. Our selection centre model can help recruit prospective anaesthetists who are able to rise to the challenge of performing in stressful situations but results do not support the direct use of challenge/threat data for recruitment decisions.
Golan, Guy; Oksenberg, Adi; Peleg, Zvi
2015-01-01
Wheat is one of the Neolithic founder crops domesticated ~10 500 years ago. Following the domestication episode, its evolution under domestication has resulted in various genetic modifications. Grain weight, embryo weight, and the interaction between those factors were examined among domesticated durum wheat and its direct progenitor, wild emmer wheat. Experimental data show that grain weight has increased over the course of wheat evolution without any parallel change in embryo weight, resulting in a significantly reduced (30%) embryo weight/grain weight ratio in domesticated wheat. The genetic factors associated with these modifications were further investigated using a population of recombinant inbred substitution lines that segregated for chromosome 2A. A cluster of loci affecting grain weight and shape was identified on the long arm of chromosome 2AL. Interestingly, a novel locus controlling embryo weight was mapped on chromosome 2AS, on which the wild emmer allele promotes heavier embryos and greater seedling vigour. To the best of our knowledge, this is the first report of a QTL for embryo weight in wheat. The results suggest a differential selection of grain and embryo weight during the evolution of domesticated wheat. It is argued that conscious selection by early farmers favouring larger grains and smaller embryos appears to have resulted in a significant change in endosperm weight/embryo weight ratio in the domesticated wheat. Exposing the genetic factors associated with endosperm and embryo size improves our understanding of the evolutionary dynamics of wheat under domestication and is likely to be useful for future wheat-breeding efforts. PMID:26019253
Soularue, J-P; Kremer, A
2014-01-01
The timing of bud burst (TBB) in temperate trees is a key adaptive trait, the expression of which is triggered by temperature gradients across the landscape. TBB is strongly correlated with flowering time and is therefore probably mediated by assortative mating. We derived theoretical predictions and realized numerical simulations of evolutionary changes in TBB in response to divergent selection and gene flow in a metapopulation. We showed that the combination of the environmental gradient of TBB and assortative mating creates contrasting genetic clines, depending on the direction of divergent selection. If divergent selection acts in the same direction as the environmental gradient (cogradient settings), genetic clines are established and inflated by assortative mating. Conversely, under divergent selection of the same strength but acting in the opposite direction (countergradient selection), genetic clines are slightly constrained. We explored the consequences of these dynamics for population maladaptation, by monitoring pollen swamping. Depending on the direction of divergent selection with respect to the environmental gradient, pollen filtering owing to assortative mating either facilitates or impedes adaptation in peripheral populations. PMID:24924591
Causes of cine image quality deterioration in cardiac catheterization laboratories.
Levin, D C; Dunham, L R; Stueve, R
1983-10-01
Deterioration of cineangiographic image quality can result from malfunctions or technical errors at a number of points along the cine imaging chain: generator and automatic brightness control, x-ray tube, x-ray beam geometry, image intensifier, optics, cine camera, cine film, film processing, and cine projector. Such malfunctions or errors can result in loss of image contrast, loss of spatial resolution, improper control of film optical density (brightness), or some combination thereof. While the electronic and photographic technology involved is complex, physicians who perform cardiac catheterization should be conversant with the problems and what can be done to solve them. Catheterization laboratory personnel have control over a number of factors that directly affect image quality, including radiation dose rate per cine frame, kilovoltage or pulse width (depending on type of automatic brightness control), cine run time, selection of small or large focal spot, proper object-intensifier distance and beam collimation, aperture of the cine camera lens, selection of cine film, processing temperature, processing immersion time, and selection of developer.
Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria
Adler, Carolyn E; Seidel, Chris W; McKinney, Sean A; Sánchez Alvarado, Alejandro
2014-01-01
Planarian flatworms regenerate every organ after amputation. Adult pluripotent stem cells drive this ability, but how injury activates and directs stem cells into the appropriate lineages is unclear. Here we describe a single-organ regeneration assay in which ejection of the planarian pharynx is selectively induced by brief exposure of animals to sodium azide. To identify genes required for pharynx regeneration, we performed an RNAi screen of 356 genes upregulated after amputation, using successful feeding as a proxy for regeneration. We found that knockdown of 20 genes caused a wide range of regeneration phenotypes and that RNAi of the forkhead transcription factor FoxA, which is expressed in a subpopulation of stem cells, specifically inhibited regrowth of the pharynx. Selective amputation of the pharynx therefore permits the identification of genes required for organ-specific regeneration and suggests an ancient function for FoxA-dependent transcriptional programs in driving regeneration. DOI: http://dx.doi.org/10.7554/eLife.02238.001 PMID:24737865
Highly selective detection of individual nuclear spins with rotary echo on an electron spin probe
Mkhitaryan, V. V.; Jelezko, F.; Dobrovitski, V. V.
2015-10-26
We consider an electronic spin, such as a nitrogen-vacancy center in diamond, weakly coupled to a large number of nuclear spins, and subjected to the Rabi driving with a periodically alternating phase. We show that by switching the driving phase synchronously with the precession of a given nuclear spin, the interaction to this spin is selectively enhanced, while the rest of the bath remains decoupled. The enhancement is of resonant character. The key feature of the suggested scheme is that the width of the resonance is adjustable, and can be greatly decreased by increasing the driving strength. Thus, the resonancemore » can be significantly narrowed, by a factor of 10–100 in comparison with the existing detection methods. Significant improvement in selectivity is explained analytically and confirmed by direct numerical many-spin simulations. As a result, the method can be applied to a wide range of solid-state systems.« less
Introduction to SIMRAND: Simulation of research and development project
NASA Technical Reports Server (NTRS)
Miles, R. F., Jr.
1982-01-01
SIMRAND: SIMulation of Research ANd Development Projects is a methodology developed to aid the engineering and management decision process in the selection of the optimal set of systems or tasks to be funded on a research and development project. A project may have a set of systems or tasks under consideration for which the total cost exceeds the allocated budget. Other factors such as personnel and facilities may also enter as constraints. Thus the project's management must select, from among the complete set of systems or tasks under consideration, a partial set that satisfies all project constraints. The SIMRAND methodology uses analytical techniques and probability theory, decision analysis of management science, and computer simulation, in the selection of this optimal partial set. The SIMRAND methodology is truly a management tool. It initially specifies the information that must be generated by the engineers, thus providing information for the management direction of the engineers, and it ranks the alternatives according to the preferences of the decision makers.
Use of selection indices to model the functional response of predators
Joly, D.O.; Patterson, B.R.
2003-01-01
The functional response of a predator to changing prey density is an important determinant of stability of predatora??prey systems. We show how Manly's selection indices can be used to distinguish between hyperbolic and sigmoidal models of a predator functional response to primary prey density in the presence of alternative prey. Specifically, an inverse relationship between prey density and preference for that prey results in a hyperbolic functional response while a positive relationship can yield either a hyperbolic or sigmoidal functional response, depending on the form and relative magnitudes of the density-dependent preference model, attack rate, and handling time. As an example, we examine wolf (Canis lupus) functional response to moose (Alces alces) density in the presence of caribou (Rangifer tarandus). The use of selection indices to evaluate the form of the functional response has significant advantages over previous attempts to fit Holling's functional response curves to killing-rate data directly, including increased sensitivity, use of relatively easily collected data, and consideration of other explanatory factors (e.g., weather, seasons, productivity).
Fluctuating selection across years and phenotypic variation in food-deceptive orchids.
Scopece, Giovanni; Juillet, Nicolas; Lexer, Christian; Cozzolino, Salvatore
2017-01-01
Nectarless flowers that deceive pollinators offer an opportunity to study asymmetric plant-insect interactions. Orchids are a widely used model for studying these interactions because they encompass several thousand species adopting deceptive pollination systems. High levels of intra-specific phenotypic variation have been reported in deceptive orchids, suggesting a reduced consistency of pollinator-mediated selection on their floral traits. Nevertheless, several studies report on widespread directional selection mediated by pollinators even in these deceptive orchids. In this study we test the hypothesis that the observed selection can fluctuate across years in strength and direction thus likely contributing to the phenotypic variability of this orchid group. We performed a three-year study estimating selection differentials and selection gradients for nine phenotypic traits involved in insect attraction in two Mediterranean orchid species, namely Orchis mascula and O. pauciflora , both relying on a well-described food-deceptive pollination strategy. We found weak directional selection and marginally significant selection gradients in the two investigated species with significant intra-specific differences in selection differentials across years. Our data do not link this variation with a specific environmental cause, but our results suggest that pollinator-mediated selection in food-deceptive orchids can change in strength and in direction over time. In perennial plants, such as orchids, different selection differentials in the same populations in different flowering seasons can contribute to the maintenance of phenotypic variation often reported in deceptive orchids.
Medical student preferences for self-directed study resources in gross anatomy.
Choi-Lundberg, Derek L; Low, Tze Feng; Patman, Phillip; Turner, Paul; Sinha, Sankar N
2016-01-01
Gross anatomy instruction in medical curricula involve a range of resources and activities including dissection, prosected specimens, anatomical models, radiological images, surface anatomy, textbooks, atlases, and computer-assisted learning (CAL). These resources and activities are underpinned by the expectation that students will actively engage in self-directed study (SDS) to enhance their knowledge and understanding of anatomy. To gain insight into preclinical versus clinical medical students' preferences for SDS resources for learning gross anatomy, and whether these vary on demographic characteristics and attitudes toward anatomy, students were surveyed at two Australian medical schools, one undergraduate-entry and the other graduate-entry. Lecture/tutorial/practical notes were ranked first by 33% of 156 respondents (mean rank ± SD, 2.48 ± 1.38), textbooks by 26% (2.62 ± 1.35), atlases 20% (2.80 ± 1.44), videos 10% (4.34 ± 1.68), software 5% (4.78 ± 1.50), and websites 4% (4.24 ± 1.34). Among CAL resources, Wikipedia was ranked highest. The most important factor in selecting CAL resources was cost (ranked first by 46%), followed by self-assessment, ease of use, alignment with curriculum, and excellent graphics (each 6-9%). Compared with preclinical students, clinical students ranked software and Acland's Video Atlas of Human Anatomy higher and felt radiological images were more important in selecting CAL resources. Along with other studies reporting on the quality, features, and impact on learning of CAL resources, the diversity of students' preferences and opinions on usefulness and ease of use reported here can help guide faculty in selecting and recommending a range of CAL and other resources to their students to support their self-directed study. © 2015 American Association of Anatomists.
Spatial attention during saccade decisions.
Jonikaitis, Donatas; Klapetek, Anna; Deubel, Heiner
2017-07-01
Behavioral measures of decision making are usually limited to observations of decision outcomes. In the present study, we made use of the fact that oculomotor and sensory selection are closely linked to track oculomotor decision making before oculomotor responses are made. We asked participants to make a saccadic eye movement to one of two memorized target locations and observed that visual sensitivity increased at both the chosen and the nonchosen saccade target locations, with a clear bias toward the chosen target. The time course of changes in visual sensitivity was related to saccadic latency, with the competition between the chosen and nonchosen targets resolved faster before short-latency saccades. On error trials, we observed an increased competition between the chosen and nonchosen targets. Moreover, oculomotor selection and visual sensitivity were influenced by top-down and bottom-up factors as well as by selection history and predicted the direction of saccades. Our findings demonstrate that saccade decisions have direct visual consequences and show that decision making can be traced in the human oculomotor system well before choices are made. Our results also indicate a strong association between decision making, saccade target selection, and visual sensitivity. NEW & NOTEWORTHY We show that saccadic decisions can be tracked by measuring spatial attention. Spatial attention is allocated in parallel to the two competing saccade targets, and the time course of spatial attention differs for fast-slow and for correct-erroneous decisions. Saccade decisions take the form of a competition between potential saccade goals, which is associated with spatial attention allocation to those locations. Copyright © 2017 the American Physiological Society.
Ramezany, Alireza; Pourkamali, Siavash
2018-04-11
Channel-selective filtering and amplification in ultrahigh frequency (UHF) receiver front-ends are crucial for realization of cognitive radio systems and the future of wireless communication. In the past decade, there have been significant advances in the performance of microscale electromechanical resonant devices. However, such devices have not yet been able to meet the requirements for direct channel selection at RF. They also occupy a relatively large area on the chip making implementation of large arrays to cover several frequency bands challenging. On the other hand, electromechanical piezoresistive resonant devices are active devices that have recently shown the possibility of simultaneous signal amplification and channel-select filtering at lower frequencies. It has been theoretically predicted that if scaled down into the nanoscale, they can operate in the UHF range with a very low power consumption. Here, for the first time nanomechanical piezoresistive amplifiers with active element dimensions as small as 50 nm × 200 nm are demonstrated. With a device area of less than 1.5 μm 2 a piezoresistive amplifier operating at 730 MHz shows effective quality factor ( Q) of 89,000 for a 50Ω load and gains as high as 10 dB and Q of 330,000 for a 250Ω load while consuming 189 μW of power. On the basis of the measurement results, it is shown that for piezoresistor dimensions of 30 nm × 100 nm it is possible to get a similar performance at 2.4 GHz with device footprint of less than 0.2 μm 2 .
Directed forgetting of visual symbols: evidence for nonverbal selective rehearsal.
Hourihan, Kathleen L; Ozubko, Jason D; MacLeod, Colin M
2009-12-01
Is selective rehearsal possible for nonverbal information? Two experiments addressed this question using the item method directed forgetting paradigm, where the advantage of remember items over forget items is ascribed to selective rehearsal favoring the remember items. In both experiments, difficult-to-name abstract symbols were presented for study, followed by a recognition test. Directed forgetting effects were evident for these symbols, regardless of whether they were or were not spontaneously named. Critically, a directed forgetting effect was observed for unnamed symbols even when the symbols were studied under verbal suppression to prevent verbal rehearsal. This pattern indicates that a form of nonverbal rehearsal can be used strategically (i.e., selectively) to enhance memory, even when verbal rehearsal is not possible.
Multiple interactions amongst floral homeotic MADS box proteins.
Davies, B; Egea-Cortines, M; de Andrade Silva, E; Saedler, H; Sommer, H
1996-01-01
Most known floral homeotic genes belong to the MADS box family and their products act in combination to specify floral organ identity by an unknown mechanism. We have used a yeast two-hybrid system to investigate the network of interactions between the Antirrhinum organ identity gene products. Selective heterodimerization is observed between MADS box factors. Exclusive interactions are detected between two factors, DEFICIENS (DEF) and GLOBOSA (GLO), previously known to heterodimerize and control development of petals and stamens. In contrast, a third factor, PLENA (PLE), which is required for reproductive organ development, can interact with the products of MADS box genes expressed at early, intermediate and late stages. We also demonstrate that heterodimerization of DEF and GLO requires the K box, a domain not found in non-plant MADS box factors, indicating that the plant MADS box factors may have different criteria for interaction. The association of PLENA and the temporally intermediate MADS box factors suggests that part of their function in mediating between the meristem and organ identity genes is accomplished through direct interaction. These data reveal an unexpectedly complex network of interactions between the factors controlling flower development and have implications for the determination of organ identity. Images PMID:8861961
Direct selection of Clostridium acetobutylicum fermentation mutants by a proton suicide method
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cueto, P.H.; Mendez, B.S.
Clostridium acetobutylicum ATCC 10132 mutants altered in acetic acid synthesis or in the shift to solventogenesis were directly selected by a proton suicide method after mutagenic treatment, by using bromide and bromate as selective agents. The mutants were characterized according to their solvent and acid production. On the selection plates they differed in colony phenotype from the parent strain.
Pang, Marco Y C; Yang, Jaynie F
2002-07-01
Humans can make smooth, continuous transitions in walking direction from forward to backward. Thus, the processing of sensory input must allow a similar continuum of possibilities. Hip extension and reduced load are two important conditions that control the transition from the stance to swing phase during forward stepping in human infants. The purpose of this study was to determine whether the same factors also regulate the initiation of the swing phase in other directions of stepping. Thirty-seven infants between the ages of 5 and 13 months were studied during supported forward and sideways stepping on a treadmill. Disturbances were elicited by placing a piece of cardboard under the foot and pulling the cardboard in different directions. In this way, the leg was displaced in a particular direction and simultaneously unloaded. We observed whether the swing phase was immediately initiated after the application of disturbances in various directions. Electromyography, vertical ground reaction forces, and hip motion in frontal and sagittal planes were recorded. The results showed that the most potent sensory input to initiate the swing phase depends on the direction of stepping. Although low load was always necessary to initiate swing for all directions of walking, the preferred hip position was always one directly opposite the direction of walking. The results indicated the presence of selective gating of sensory input from the legs as a function of the direction of stepping.
Zhang, Guobo; Chen, Min; Liu, Feng; Yuan, Xiaohui; Weng, Suming; Zheng, Jun; Ma, Yanyun; Shao, Fuqiu; Sheng, Zhengming; Zhang, Jie
2017-10-02
Relativistically intense laser solid target interaction has been proved to be a promising way to generate high-order harmonics, which can be used to diagnose ultrafast phenomena. However, their emission direction and spectra still lack tunability. Based upon two-dimensional particle-in-cell simulations, we show that directional enhancement of selected high-order-harmonics can be realized using blazed grating targets. Such targets can select harmonics with frequencies being integer times of the grating frequency. Meanwhile, the radiation intensity and emission area of the harmonics are increased. The emission direction is controlled by tailoring the local blazed structure. Theoretical and electron dynamics analysis for harmonics generation, selection and directional enhancement from the interaction between multi-cycle laser and grating target are carried out. These studies will benefit the generation and application of laser plasma-based high order harmonics.
Hayden, Eric J; Bratulic, Sinisa; Koenig, Iwo; Ferrada, Evandro; Wagner, Andreas
2014-02-01
The distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged.
Detecting consistent patterns of directional adaptation using differential selection codon models.
Parto, Sahar; Lartillot, Nicolas
2017-06-23
Phylogenetic codon models are often used to characterize the selective regimes acting on protein-coding sequences. Recent methodological developments have led to models explicitly accounting for the interplay between mutation and selection, by modeling the amino acid fitness landscape along the sequence. However, thus far, most of these models have assumed that the fitness landscape is constant over time. Fluctuations of the fitness landscape may often be random or depend on complex and unknown factors. However, some organisms may be subject to systematic changes in selective pressure, resulting in reproducible molecular adaptations across independent lineages subject to similar conditions. Here, we introduce a codon-based differential selection model, which aims to detect and quantify the fine-grained consistent patterns of adaptation at the protein-coding level, as a function of external conditions experienced by the organism under investigation. The model parameterizes the global mutational pressure, as well as the site- and condition-specific amino acid selective preferences. This phylogenetic model is implemented in a Bayesian MCMC framework. After validation with simulations, we applied our method to a dataset of HIV sequences from patients with known HLA genetic background. Our differential selection model detects and characterizes differentially selected coding positions specifically associated with two different HLA alleles. Our differential selection model is able to identify consistent molecular adaptations as a function of repeated changes in the environment of the organism. These models can be applied to many other problems, ranging from viral adaptation to evolution of life-history strategies in plants or animals.
Oh, Hyunjin; Uhm, Dong-Choon; Yoon, Young Joo
2016-01-01
Negative work environments influence the ability of nurses to provide optimal patient care in a safe environment. The purpose of the study was to test a model linking workplace bullying (WPB) and lateral violence (LV) with job stress, intent to leave, and, subsequently, nurse-assessed patient adverse outcomes (safety issues). This descriptive-correlational study examined the relationships between study variables and used a structural equation model to test the validity of the proposed theoretical framework. A convenience sample of 508 clinical nurses working in eight general hospitals in Daejeon, South Korea, completed a questionnaire on measures of WPB, LV, job stress, intent to leave, and nurse-assessed patient safety. Analysis of moment structures was used to estimate a set of three models with competing measurement structures for WPB and LV and the same structural model. Akaike Information Criterion was used for model selection. Among the three proposed models, the model with complex factor loadings was selected (WPB and LV were both associated with verbal abuse and physical threat). WPB directly and indirectly influenced nurse-assessed patient safety. Job stress directly influenced intent to leave, and intent to leave directly influenced nurse-assessed patient safety. The results of the study support the proposition that WPB, job stress, and intent to leave may be associated with nurse-perceived adverse outcomes (patient safety issues) in hospitals. Nurse perceptions of WPB were associated with nurse-assessed patient safety outcomes (adverse events) directly and through mediating job stress and intent to leave. LV was not associated with the mediators or nurse-assessed adverse outcomes (safety).
Azeem, Rubeena Abdul; Sureshbabu, Nivedhitha Malli
2018-01-01
Composite resin, serves as esthetic alternative to amalgam and cast restorations. Posterior teeth can be restored using direct or indirect composite restorations. The selection between direct and indirect technique is a clinically challenging decision-making process. Most important influencing factor is the amount of remaining tooth substance. The aim of this systematic review was to compare the clinical performance of direct versus indirect composite restorations in posterior teeth. The databases searched included PubMed CENTRAL (until July 2015), Medline, and Cochrane Database of Systematic Reviews. The bibliographies of clinical studies and reviews identified in the electronic search were analyzed to identify studies which were published outside the electronically searched journals. The primary outcome measure was evaluation of the survival of direct and indirect composite restorations in posterior teeth. This review included thirteen studies in which clinical performance of various types of direct and indirect composite restorations in posterior teeth were compared. Out of the thirteen studies which were included seven studies had a high risk of bias and five studies had a moderate risk of bias. One study having a low risk of bias, concluded that there was no significant difference between direct and indirect technique. However, the available evidence revealed inconclusive results. Further research should focus on randomized controlled trials with long term follow-up to give concrete evidence on the clinical performce of direct and indirect composite restorations.
Sharma, Manmohan D; Hunt, John; Hosken, David J
2012-03-01
Natural and sexual selection are classically thought to oppose one another, and although there is evidence for this, direct experimental demonstrations of this antagonism are largely lacking. Here, we assessed the effects of sexual and natural selection on the evolution of cuticular hydrocarbons (CHCs), a character subject to both modes of selection, in Drosophila simulans. Natural selection and sexual selection were manipulated in a fully factorial design, and after 27 generations of experimental evolution, the responses of male and female CHCs were assessed. The effects of natural and sexual selection differed greatly across the sexes. The responses of female CHCs were generally small, but CHCs evolved predominantly in the direction of natural selection. For males, profiles evolved via sexual and natural selection, as well as through the interaction between the two, with some male CHC components only evolving in the direction of natural selection when sexual selection was relaxed. These results indicate sex-specific responses to selection, and that sexual and natural selection act antagonistically for at least some combinations of CHCs. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.
Terra, Sandra M
2007-01-01
This research seeks to determine whether there is adequate evidence-based justification for selection of one acute care case management model over another. Acute Inpatient Hospital. This article presents a systematic review of published case management literature, resulting in classification specific to terms of level of evidence. This review examines the best available evidence in an effort to select an acute care case management model. Although no single case management model can be identified as preferred, it is clear that adequate evidence-based literature exists to acknowledge key factors driving the acute care model and to form a foundation for the efficacy of hospital case management practice. Although no single case management model can be identified as preferred, this systematic review demonstrates that adequate evidence-based literature exists to acknowledge key factors driving the acute care model and forming a foundation for the efficacy of hospital case management practice. Distinctive aspects of case management frameworks can be used to guide the development of an acute care case management model. The study illustrates: * The effectiveness of case management when there is direct patient contact by the case manager regardless of disease condition: not only does the quality of care increase but also length of stay (LOS) decreases, care is defragmented, and both patient and physician satisfaction can increase. * The preferred case management models result in measurable outcomes that can directly relate to, and demonstrate alignment with, organizational strategy. * Acute care management programs reduce cost and LOS, and improve outcomes. * An integrated case management program that includes social workers, as well as nursing, is the most effective acute care management model. * The successful case management model will recognize physicians, as well as patients, as valued customers with whom partnership can positively affect financial outcomes in terms of reduction in LOS, improvement in quality, and delivery of care.
Cowman, James G; Bakheet, Manuel
2017-01-01
Background A student-selected component (SSC) of the medical curriculum requires the student to be self-directed in locating and undertaking a placement in a clinical specialty of their choosing and completing a project. The clinical area for experience was an accident and emergency department, and our topic was a focused audit on the investigations and referral for paracetamol overdose. The purpose of this paper is twofold: to reflect on the education value to medical students of an SSC in a medical curriculum, and to highlight learning and understanding through completion of an audit. Materials and methods An audit approach was applied. The aim of the project study was to investigate the level of compliance with best-practice guidelines for investigations and psychiatric referral in paracetamol overdose. Results A total of 40 cases meeting the inclusion criteria were randomly selected. The sample had a mean age of 27 years, of whom 70.5% were female, and the ingested dose of paracetamol ranged from 0.864 to 80 g. Paracetamol abuse may present as intentional and unintentional overdose. In our study, 85% of cases were identified as intentional overdose and 76% had a history of psychiatric illness. Generally, medical management was compliant with guidelines, with some minor irregularities. The international normalized ratio was the most underperformed test. Conclusion Our choice of topic, paracetamol overdose, contributed to our understanding of the breadth of factors to be considered in the emergency medical management of a patient. In this regard, we had the benefit of understanding how the diagnostic and therapeutic factors, when applied in accordance with best-practice guidelines, work very effectively. The SSC impacted positively on our cognitive, personal, and professional development. In facilitating the student with choice, the SSC encouraged self-direction and proactivity. We gained experience in the discipline of research and acquired some skills in independent thinking and analysis. PMID:28883749
Analysis of pharmacy student motivators and deterrents for professional organization involvement.
Petersen, Erin; Wascher, Molly; Kier, Karen
2017-07-01
The purpose of this study was to determine motivators and deterrents impacting a student pharmacist's decision to join professional organizations. The goal was to create a list of meaningful factors that organizations can use for membership recruitment. This descriptive study utilized a blinded electronic survey sent to eight accredited pharmacy schools in Ohio, Michigan, Wisconsin, Indiana, Illinois, and Kentucky. The survey assessed motivating and hindering factors, as well as demographic data. Eight-hundred fifty-six students completed the survey, a 15.05% participation rate. Professional development and networking were the top two endorsed motivational factors, selected as significant by 88.0% and 87.5% respectively. Upon chi-square analysis, networking (p<0.001), involvement opportunities (p=0.01), and scholarships (p=0.02) were motivating factors with which membership was found to be significantly influenced. Networking and involvement opportunities were more significant for members while scholarships were a greater motivator among nonmembers. Time required for involvement and cost were the most commonly selected hindrances with 78% and 76% respectively identifying these as significant barriers. The hindering factor found to be significantly different between active members and nonmembers was bylaws/rules of the organization (p=0.032), with non-members rating this as a greater consideration than current members. Multiple factors contribute to a student's decision to join a professional organization. Those active members find greater significance in networking involvement opportunities. Non-member students found scholarships more motivating and recognize bylaws as a consideration for membership more than current members. These results emphasize the multifactorial nature of membership and may direct future membership initiatives. Copyright © 2017 Elsevier Inc. All rights reserved.
Human body area factors for radiation exchange analysis: standing and walking postures
NASA Astrophysics Data System (ADS)
Park, Sookuk; Tuller, Stanton E.
2011-09-01
Effective radiation area factors ( f eff) and projected area factors ( f p) of unclothed Caucasians' standing and walking postures used in estimating human radiation exchange with the surrounding environment were determined from a sample of adults in Canada. Several three-dimensional (3D) computer body models were created for standing and walking postures. Only small differences in f eff and f p values for standing posture were found between gender (male or female) and body type (normal- or over-weight). Differences between this study and previous studies were much larger: ≤0.173 in f p and ≤0.101 in f eff. Directionless f p values for walking posture also had only minor differences between genders and positions in a stride. However, the differences of mean directional f p values of the positions dependent on azimuth angles were large enough, ≤0.072, to create important differences in modeled radiation receipt. Differences in f eff values were small: 0.02 between the normal-weight male and female models and up to 0.033 between positions in a stride. Variations of directional f p values depending on solar altitudes for walking posture were narrower than those for standing posture. When both standing and walking postures are considered, the mean f eff value, 0.836, of standing (0.826) and walking (0.846) could be used. However, f p values should be selected carefully because differences between directional and directionless f p values were large enough that they could influence the estimated level of human thermal sensation.
STAT3 selectively interacts with Smad3 to antagonize TGF-β signaling
Wang, Gaohang; Yu, Yi; Sun, Chuang; Liu, Ting; Liang, Tingbo; Zhan, Lixing; Lin, Xia; Feng, Xin-Hua
2015-01-01
Smad and STAT proteins are critical signal transducers and transcription factors in controlling cell growth and tumorigenesis. Here we report that the STAT3 signaling pathway attenuates TGF-β-induced responses through a direct Smad3-STAT3 interplay. Activated STAT3 blunts TGF-β-mediated signaling. Depletion of STAT3 promotes TGF-β-mediated transcriptional and physiological responses, including cell cycle arrest, apoptosis and epithelial-to-mesenchymal transition. STAT3 directly interacts with Smad3 in vivo and in vitro, resulting in attenuation of the Smad3-Smad4 complex formation and suppression of DNA-binding ability of Smad3. The N-terminal region of DNA-binding domain of STAT3 is responsible for the STAT3-Smad3 interaction and also indispensable for STAT3-mediated inhibition of TGF-β signaling. Thus, our finding illustrates a direct crosstalk between the STAT3 and Smad3 signaling pathways that may contribute to tumor development and inflammation. PMID:26616859
Kaplan, Peter S; Asherin, Ryan M; Vogeli, Jo M; Fekri, Shiva M; Scheyer, Kathryn E; Everhart, Kevin D
2018-01-01
Face preferences for speakers of infant-directed and adult-directed speech (IDS and ADS) were investigated in 4- to 13.5-month-old infants of depressed and non-depressed mothers. Following 1-min of exposure to an ID or AD speaker (order counterbalanced), infants had an immediate paired-comparison test with a still, silent image of the familiarized versus a novel face. In the test phase, ID face preference ratios were significantly lower in infants of depressed than non-depressed mothers. Infants' ID face preference ratios, but not AD face preference ratios, correlated with their percentile scores on the cognitive ( Cog ) scale of the Bayley Scales of Infant & Toddler Development (3 rd Edition; BSID III), assessed concurrently. Regression analyses revealed that infant ID face preferences significantly predicted infant Cog percentiles even after demographic risk factors and maternal depression had been controlled. Infants may use IDS to select social partners who are likely to support and facilitate cognitive development.
Point-of-Care Coagulation Monitoring in Trauma Patients.
Stein, Philipp; Kaserer, Alexander; Spahn, Gabriela H; Spahn, Donat R
2017-06-01
Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-directed way based on point-of-care (POC) and routine laboratory measurements. Viscoelastic POC measurement of the developing clot in whole blood and POC platelet function testing allow rapid and tailored coagulation and transfusion treatment based on goal-directed, factor concentrate-based algorithms. The first studies have been published showing that this concept reduces the need for allogeneic blood transfusion and improves outcome. This review highlights the concept of goal-directed POC coagulation management in trauma patients, introduces a selection of POC devices, and presents algorithms which allow a reduction in allogeneic blood product transfusion and an improvement of trauma patient outcome. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Design Considerations of a Transverse Flux Machine for Direct-Drive Wind Turbine Applications
DOE Office of Scientific and Technical Information (OSTI.GOV)
Husain, Tausif; Hasan, Iftekhar; Sozer, Yilmaz
This paper presents the design considerations of a double-sided transverse flux machine (TFM) for direct-drive wind turbine applications. The proposed TFM has a modular structure with quasi-U stator cores and toroidal ring windings. The rotor is constructed with ferrite magnets in a flux-concentrating setup to achieve high air gap flux density. Pole number selection is critical in the design process of a TFM as it affects both the torque density and power factor under fixed magnetic and changing electrical loading. Several key design ratios are introduced to facilitate the initial design procedure. The effect of pole shaping on back-EMF andmore » inductance is also analyzed. These investigations provide guidance toward the required design of a TFM for direct-drive applications. The analyses are carried out using analytical and three-dimensional finite element analysis (FEA). A proof-of-concept prototype was developed to experimentally validate the FEA results.« less
Design Considerations of a Transverse Flux Machine for Direct-Drive Wind Turbine Applications
Husain, Tausif; Hasan, Iftekhar; Sozer, Yilmaz; ...
2018-03-12
This paper presents the design considerations of a double-sided transverse flux machine (TFM) for direct-drive wind turbine applications. The proposed TFM has a modular structure with quasi-U stator cores and toroidal ring windings. The rotor is constructed with ferrite magnets in a flux-concentrating setup to achieve high air gap flux density. Pole number selection is critical in the design process of a TFM as it affects both the torque density and power factor under fixed magnetic and changing electrical loading. Several key design ratios are introduced to facilitate the initial design procedure. The effect of pole shaping on back-EMF andmore » inductance is also analyzed. These investigations provide guidance toward the required design of a TFM for direct-drive applications. The analyses are carried out using analytical and three-dimensional finite element analysis (FEA). A proof-of-concept prototype was developed to experimentally validate the FEA results.« less
2013-01-01
Background Over the past decades site-directed mutagenesis (SDM) has become an indispensable tool for biological structure-function studies. In principle, SDM uses modified primer pairs in a PCR reaction to introduce a mutation in a cDNA insert. DpnI digestion of the reaction mixture is used to eliminate template copies before amplification in E. coli; however, this process is inefficient resulting in un-mutated clones which can only be distinguished from mutant clones by sequencing. Results We have developed a program – ‘SDM-Assist’ which creates SDM primers adding a specific identifier: through additional silent mutations a restriction site is included or a previous one removed which allows for highly efficient identification of ‘mutated clones’ by a simple restriction digest. Conclusions The direct identification of SDM clones will save time and money for researchers. SDM-Assist also scores the primers based on factors such as Tm, GC content and secondary structure allowing for simplified selection of optimal primer pairs. PMID:23522286
Influence Of Advertisments On Changes In The Urban Structure Of Cites On The Example Of Poznan
NASA Astrophysics Data System (ADS)
Bonenberg, Agata
2015-09-01
The article presents the results of studies on the influence of outdoor advertisements on the activation of selected areas in the spatial structure of the city of Poznań. The contents of advertisements were analyzed in terms of the places which advertisements placed on signs, billboards and advertising displays located in public spaces direct us to. The results of studies indicated that the majority of advertisements located in the city center of Poznań promote suburban locations, encouraging its inhabitants to make use of trade and services outside of the strict city center. At the same time, it was indicated that outside advertisements due to the content of the advertising message are a factor degrading the city center, directing potential customers away into the suburbs. In practice, it was noted that the phenomenon significantly decreases the effectiveness of actions directed towards revitalizing the city center and the urban activation of this region.
Psychosomatic factors in pruritus.
Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil
2013-01-01
Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). Copyright © 2013 Elsevier Inc. All rights reserved.
Consolidation & Factors Influencing Sintering Process in Polymer Powder Based Additive Manufacturing
NASA Astrophysics Data System (ADS)
Sagar, M. B.; Elangovan, K.
2017-08-01
Additive Manufacturing (AM) is two decade old technology; where parts are build layer manufacturing method directly from a CAD template. Over the years, AM techniques changes the future way of part fabrication with enhanced intricacy and custom-made features are aimed. Commercially polymers, metals, ceramic and metal-polymer composites are in practice where polymers enhanced the expectations in AM and are considered as a kind of next industrial revolution. Growing trend in polymer application motivated to study their feasibility and properties. Laser sintering, Heat sintering and Inhibition sintering are the most successful AM techniques for polymers but having least application. The presentation gives up selective sintering of powder polymers and listed commercially available polymer materials. Important significant factors for effective processing and analytical approaches to access them are discussed.
The moon illusion: II. A reference theory.
Baird, J C
1982-09-01
The present theory provides explanations for the moon illusion and related issues involving size and distance perception in natural, outdoor settings. Although some assumptions of previous theories are rejected, other pivotal aspects are retained in this formulation. In particular, the present theory states that both the sky and ground are important referents in judging the spatial extent of the moon. Neither factor alone can account for all the available data, but quantitative models incorporating both factors do quite well when applied to the parametric findings of Holway and Boring, as well as to the results obtained by Kaufman and Rock. The reference theory and its associated class of specific models suggest new theoretical directions and experimental tests to narrow yet further the selection of appropriate explanations for one of visual perception's oldest unsolved puzzles.
Spectral reflectance indices as a selection criterion for yield improvement in wheat
NASA Astrophysics Data System (ADS)
Babar, Md. Ali
2005-11-01
Scope and methods of study. Yield in wheat ( Triticum aestivum L.) is a complex trait and influenced by many environmental factors, and yield improvement is a daunting task for wheat breeders. Spectral reflectance indices (SRIs) have been used to study different physiological traits in wheat. SRIs have the potential to differentiate genotypes for grain yield. SRIs strongly associated with grain yield can be used to achieve effective genetic gain in wheat under different environments. Three experiments (15 adapted genotypes, 25 and 36 random sister lines derived from two different crosses) under irrigated conditions, and three experiments (each with 30 advanced genotypes) under water-limited conditions were conducted in three successive years in Northwest Mexico at the CIMMYT (International Maize and wheat Improvement Center) experimental station. SRIs and different agronomic data were collected for three years, and biomass was harvested for two years. Phenotypic and genetic correlations between SRIs and grain yield, between SRIs and biomass, realized and broad sense heritability, direct and correlated selection responses for grain yield, and SRIs were calculated. Findings and conclusion. Seven SRIs were calculated, and three near infrared based indices (WI, NWI-1 and NWI-2) showed higher level of genetic and phenotypic correlations with grain yield, yield components and biomass than other SRIs (PRI, RNDVI, GNDVI, and SR) under both irrigated and water limiting environments. Moderate to high realized and broad sense heritability, and selection response were demonstrated by the three NIR based indices. High efficiency of correlated response for yield estimation was demonstrated by the three NIR based indices. The ratio between the correlated response to grain yield based on the three NIR based indices and direct selection response for grain yield was very close to one. The NIR based indices showed very high accuracy in selecting superior genotypes for grain yield under both well-watered and water-limited conditions. These results demonstrated that effective genetic gain in grain yield improvement can be achieved by making selections with the three NIR based indices.
Media advertising effects on consumer perception of orthodontic treatment quality.
Edwards, Daenya T; Shroff, Bhavna; Lindauer, Steven J; Fowler, Chad E; Tufekci, Eser
2008-09-01
To determine the effect of media advertising on consumer perception of orthodontic treatment quality. A survey instrument was designed to evaluate factors influencing consumer selection of an orthodontist and consumer perception of different forms of media advertising (radio, television, newspaper, magazine, direct mail, and billboard) by orthodontic practices. The surveys were distributed by eight orthodontic offices in and around the Richmond, Virginia area. The survey return rate was 97%. Respondents most often cited dentist and patient referrals as how they learned of the orthodontic practices they visited (50% to 57%). A caring attitude and good practitioner reputation were the top reasons influencing actual selection of an orthodontist (53% and 49%, respectively). Of respondents, 14% to 24% felt that advertising orthodontists would offer a lower quality of care than nonadvertising orthodontists. Newspaper, magazine, and direct mail advertisements were viewed more favorably than radio, television, and billboard advertisements. Chi-square analyses revealed few statistically significant differences in perception between different income and education groups. The majority of patients do not perceive advertising to reflect poorly on the quality of orthodontic care. However, patients with different income and education levels perceive media advertising differently.
SAGA complex and Gcn5 are necessary for respiration in budding yeast.
Canzonetta, Claudia; Leo, Manuela; Guarino, Salvatore Rocco; Montanari, Arianna; Francisci, Silvia; Filetici, Patrizia
2016-12-01
In budding yeast, growth through fermentation and/or respiration is dependent on the type of carbon source present in the medium. SAGA complex is the main acetylation complex and is required, together with Rtg factors, for nucleus-mitochondria communication and transcriptional activation of specific nuclear genes. Even though acetylation is necessary for mitochondria activity and respiratory pathways the direct role of histone acetyltransferases and SAGA complex has never been investigated directly. In this study we demonstrate, for the first time, that Gcn5 and SAGA are needed for respiratory metabolism and oxygen consumption. According to a central role for acetylation in respiration we find that the Gcn5 inhibitor CPTH2 had higher efficacy on cells grown in glycerol containing media. We also demonstrated that the opposing activities of Gcn5 and Hda1 modify selectively H3-AcK18 and are essential for respiration. Taken together our results suggest a novel paradigm coupling acetyltransferase activity to respiratory metabolism. Correspondingly we propose the selective utilization of KAT inhibitor CPTH2, combined to the modulation of the respiratory metabolism of the cell, as a promising novel tool of intervention in cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.
Zinc starvation induces autophagy in yeast
Kawamata, Tomoko; Horie, Tetsuro; Matsunami, Miou; Sasaki, Michiko; Ohsumi, Yoshinori
2017-01-01
Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome. In this study, we investigated how autophagy functions under zinc starvation. Zinc depletion induced non-selective autophagy, which is important for zinc-limited growth. Induction of autophagy by zinc starvation was not directly related to transcriptional activation of Zap1. Instead, TORC1 inactivation directed zinc starvation-induced autophagy. Abundant zinc proteins, such as Adh1, Fba1, and ribosomal protein Rpl37, were degraded in an autophagy-dependent manner. But the targets of autophagy were not restricted to zinc-binding proteins. When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes. PMID:28264932
Source apportionment and location by selective wind sampling and Positive Matrix Factorization.
Venturini, Elisa; Vassura, Ivano; Raffo, Simona; Ferroni, Laura; Bernardi, Elena; Passarini, Fabrizio
2014-10-01
In order to determine the pollution sources in a suburban area and identify the main direction of their origin, PM2.5 was collected with samplers coupled with a wind select sensor and then subjected to Positive Matrix Factorization (PMF) analysis. In each sample, soluble ions, organic carbon, elemental carbon, levoglucosan, metals, and Polycyclic Aromatic Hydrocarbons (PAHs) were determined. PMF results identified six main sources affecting the area: natural gas home appliances, motor vehicles, regional transport, biomass combustion, manufacturing activities, and secondary aerosol. The connection of factor temporal trends with other parameters (i.e., temperature, PM2.5 concentration, and photochemical processes) confirms factor attributions. PMF analysis indicated that the main source of PM2.5 in the area is secondary aerosol. This should be mainly due to regional contributions, owing to both the secondary nature of the source itself and the higher concentration registered in inland air masses. The motor vehicle emission source contribution is also important. This source likely has a prevalent local origin. The most toxic determined components, i.e., PAHs, Cd, Pb, and Ni, are mainly due to vehicular traffic. Even if this is not the main source in the study area, it is the one of greatest concern. The application of PMF analysis to PM2.5 collected with this new sampling technique made it possible to obtain more detailed results on the sources affecting the area compared to a classical PMF analysis.
ERIC Educational Resources Information Center
Suleman, Qaiser; Gul, Rizwana
2015-01-01
The main objective of the study was to compare the teaching effectiveness of directly selected, in-service promoted and online selected subject specialists teaching at higher secondary school level in Kohat Division, Pakistan. The target population of the study was the higher secondary school students in Kohat Division, Pakistan. A sample of 600…
Cohen, Philip R
2017-04-01
Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors including female sex hormones, genetic predisposition and ultraviolet light exposure. The management of melasma is usually directed at more than one of the causative etiologic factors and often incorporates a combination of topical agents, with or without the addition of physical modalities. Estrogen and angiogenesis are significant factors in the etiology of melasma. A useful addition to the therapeutic armentarium for treating melasma would include a topical agent that could effect both of these causative factors. Specifically, a topical preparation consisting of an anti-estrogen and a vascular endothelial growth factor inhibitor would accomplish this goal. Suitable candidates that target estrogen receptors and vascular endothelial growth factor are currently used in medical oncology as systemic antineoplastic agents. The anti-estrogen could be either a selective estrogen receptor modulator (such as tamoxifen or raloxifene) or an aromatase inhibitor (such as anastrozole or letrozole or exemestane). The vascular endothelial growth factor inhibitor would be bevacizumab. In conclusion, a novel-topically administered-therapy for melasma would combine an anti-estrogen and a vascular endothelial growth factor inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.
Lewis, Jesse S.; Farnsworth, Matthew L.; Burdett, Chris L.; Theobald, David M.; Gray, Miranda; Miller, Ryan S.
2017-01-01
Biotic and abiotic factors are increasingly acknowledged to synergistically shape broad-scale species distributions. However, the relative importance of biotic and abiotic factors in predicting species distributions is unclear. In particular, biotic factors, such as predation and vegetation, including those resulting from anthropogenic land-use change, are underrepresented in species distribution modeling, but could improve model predictions. Using generalized linear models and model selection techniques, we used 129 estimates of population density of wild pigs (Sus scrofa) from 5 continents to evaluate the relative importance, magnitude, and direction of biotic and abiotic factors in predicting population density of an invasive large mammal with a global distribution. Incorporating diverse biotic factors, including agriculture, vegetation cover, and large carnivore richness, into species distribution modeling substantially improved model fit and predictions. Abiotic factors, including precipitation and potential evapotranspiration, were also important predictors. The predictive map of population density revealed wide-ranging potential for an invasive large mammal to expand its distribution globally. This information can be used to proactively create conservation/management plans to control future invasions. Our study demonstrates that the ongoing paradigm shift, which recognizes that both biotic and abiotic factors shape species distributions across broad scales, can be advanced by incorporating diverse biotic factors. PMID:28276519
Digital analysis of changes by Plasmodium vivax malaria in erythrocytes.
Edison, Maombi; Jeeva, J B; Singh, Megha
2011-01-01
Blood samples of malaria patients (n = 30), selected based on the severity of parasitemia, were divided into low (LP), medium (MP) and high (HP) parasitemia, which represent increasing levels of the disease severity. Healthy subjects (n = 10) without any history of disease were selected as a control group. By processing of erythrocytes images their contours were obtained and from these the shape parameters area, perimeter and form factor were obtained. The gray level intensity was determined by scanning of erythrocyte along its largest diameter. A comparison of these with that of normal cells showed a significant change in shape parameters. The gray level intensity decreases with the increase of severity of the disease. The changes in shape parameters directly and gray level intensity variation inversely are correlated with the increase in parasite density due to the disease.
The continuous end-state comfort effect: weighted integration of multiple biases.
Herbort, Oliver; Butz, Martin V
2012-05-01
The grasp orientation when grasping an object is frequently aligned in anticipation of the intended rotation of the object (end-state comfort effect). We analyzed grasp orientation selection in a continuous task to determine the mechanisms underlying the end-state comfort effect. Participants had to grasp a box by a circular handle-which allowed for arbitrary grasp orientations-and then had to rotate the box by various angles. Experiments 1 and 2 revealed both that the rotation's direction considerably determined grasp orientations and that end-postures varied considerably. Experiments 3 and 4 further showed that visual stimuli and initial arm postures biased grasp orientations if the intended rotation could be easily achieved. The data show that end-state comfort but also other factors determine grasp orientation selection. A simple mechanism that integrates multiple weighted biases can account for the data.
A regulatory role for TGF-β signaling in the establishment and function of the thymic medulla.
Hauri-Hohl, Mathias; Zuklys, Saulius; Holländer, Georg A; Ziegler, Steven F
2014-06-01
Medullary thymic epithelial cells (mTECs) are critical in establishing and maintaining the appropriate microenvironment for negative selection and maturation of immunocompetent T cells with a self-tolerant T cell antigen receptor repertoire. Cues that direct proliferation and maturation of mTECs are provided by members of the tumor necrosis factor (TNF) superfamily expressed on developing thymocytes. Here we demonstrate a negative role of the morphogen TGF-β in tempering these signals under physiological conditions, limiting both growth and function of the thymic medulla. Eliminating TGF-β signaling specifically in TECs or by pharmacological means increased the size of the mTEC compartment, enhanced negative selection and functional maturation of medullary thymocytes as well as the production of regulatory T cells, thus reducing the autoreactive potential of peripheral T cells.
Harmon-Jones, Eddie; Harmon-Jones, Cindy; Amodio, David M; Gable, Philip A
2011-12-01
The present work outlines a theory of attitudes toward emotions, provides a measure of attitudes toward emotions, and then tests several predictions concerning relationships between attitudes toward specific emotions and emotional situation selection, emotional traits, emotional reactivity, and emotion regulation. The present conceptualization of individual differences in attitudes toward emotions focuses on specific emotions and presents data indicating that 5 emotions (anger, sadness, joy, fear, and disgust) load on 5 separate attitude factors (Study 1). Attitudes toward emotions predicted emotional situation selection (Study 2). Moreover, attitudes toward approach emotions (e.g., anger, joy) correlated directly with the associated trait emotions, whereas attitudes toward withdrawal emotions (fear, disgust) correlated inversely with associated trait emotions (Study 3). Similar results occurred when attitudes toward emotions were used to predict state emotional reactivity (Study 4). Finally, attitudes toward emotions predicted specific forms of emotion regulation (Study 5).
Recent progress in the biology of multiple myeloma and future directions in the treatment.
Pico, J L; Castagna, L; Bourhis, J H
1998-04-01
A great amount of scientific information, accumulated over recent years on the biology of Multiple Myeloma (MM), has fuelled speculation about the origin of malignant plasma cells, about a purported critical role played by the bone marrow stroma, and further still, on cytokine interactions and in particular that of IL-6 and its relationship with the immune system. Among the growth factors secreted by stroma cells, IL-6 is a potent stimulator of myeloma cells in vitro but does not induce a malignant phenotype in normal plasma cells. Many efforts have been produced to identify the stem cell in MM and probably memory B lymphocytes are the best candidates. The demonstration of a Graft vs Myeloma effect in the allogeneic setting strongly supports the immunotherapy in MM. Recent data also suggest that a virus (Kaposi-associated herpes virus, HHV-8) may be significantly associated with the development of MM. In parallel, progress has been achieved in the treatment of this incurable disease with well defined prognostic factors, more efficient supportive care and its corollary, improved quality of life and dose-intensified chemo-radiotherapy followed by autologous hematopoietic stem cell support. Improving the quality of grafts with the selection of CD34 positive cells is another approach aimed at reducing plasma cell contamination without impairing haematological recovery. An EBMT randomized study assessing the role of CD34 selection has been initiated by our group Increasingly efficient first-line therapy, better quality autografts and improved post-remission treatment with, for example, anti-idiopathic vaccination are the most promising future directions.
Löfgren, Stefan; Fröberg, Mats; Yu, Jun; Nisell, Jakob; Ranneby, Bo
2014-12-01
From a policy perspective, it is important to understand forestry effects on surface waters from a landscape perspective. The EU Water Framework Directive demands remedial actions if not achieving good ecological status. In Sweden, 44 % of the surface water bodies have moderate ecological status or worse. Many of these drain catchments with a mosaic of managed forests. It is important for the forestry sector and water authorities to be able to identify where, in the forested landscape, special precautions are necessary. The aim of this study was to quantify the relations between forestry parameters and headwater stream concentrations of nutrients, organic matter and acid-base chemistry. The results are put into the context of regional climate, sulphur and nitrogen deposition, as well as marine influences. Water chemistry was measured in 179 randomly selected headwater streams from two regions in southwest and central Sweden, corresponding to 10 % of the Swedish land area. Forest status was determined from satellite images and Swedish National Forest Inventory data using the probabilistic classifier method, which was used to model stream water chemistry with Bayesian model averaging. The results indicate that concentrations of e.g. nitrogen, phosphorus and organic matter are related to factors associated with forest production but that it is not forestry per se that causes the excess losses. Instead, factors simultaneously affecting forest production and stream water chemistry, such as climate, extensive soil pools and nitrogen deposition, are the most likely candidates The relationships with clear-felled and wetland areas are likely to be direct effects.
Obesity studies in the circumpolar Inuit: a scoping review
Galloway, Tracey; Blackett, Hilary; Chatwood, Susan; Jeppesen, Charlotte; Kandola, Kami; Linton, Janice; Bjerregaard, Peter
2012-01-01
Background Among circumpolar populations, recent research has documented a significant increase in risk factors which are commonly associated with chronic disease, notably obesity. Objective The present study undertakes a scoping review of research on obesity in the circumpolar Inuit to determine the extent obesity research has been undertaken, how well all subpopulations and geographic areas are represented, the methodologies used and whether they are sufficient in describing risk factors, and the prevalence and health outcomes associated with obesity. Design Online databases were used to identify papers published 1992–2011, from which we selected 38 publications from Canada, the United States, and Greenland that used obesity as a primary or secondary outcome variable in 30 or more non-pregnant Inuit (“Eskimo”) participants aged 2 years or older. Results The majority of publications (92%) reported cross-sectional studies while 8% examined retrospective cohorts. All but one of the studies collected measured data. Overall 84% of the publications examined obesity in adults. Those examining obesity in children focused on early childhood or adolescence. While most (66%) reported 1 or more anthropometric indices, none incorporated direct measures of adiposity. Evaluated using a customized quality assessment instrument, 26% of studies achieved an “A” quality ranking, while 18 and 39% achieved quality rankings of “B” and “C”, respectively. Conclusions While the quality of studies is generally high, research on obesity among Inuit would benefit from careful selection of methods and reference standards, direct measures of adiposity in adults and children, studies of preadolescent children, and prospective cohort studies linking early childhood exposures with obesity outcomes throughout childhood and adolescence. PMID:22765938
Lee, Hyekyung; Kim, Junsuk; Kim, Hyeonsoo; Kim, Ho-Young; Lee, Hyomin; Kim, Sung Jae
2017-08-24
Over the past decade, nanofluidic diodes that rectify ionic currents (i.e. greater current in one direction than in the opposite direction) have drawn significant attention in biomolecular sensing, switching and energy harvesting devices. To obtain current rectification, conventional nanofluidic diodes have utilized complex nanoscale asymmetry such as nanochannel geometry, surface charge density, and reservoir concentration. Avoiding the use of sophisticated nano-asymmetry, micro/nanofluidic diodes using microscale asymmetry have been recently introduced; however, their diodic performance is still impeded by (i) low (even absent) rectification effects at physiological concentrations over 100 mM and strong dependency on the bulk concentration, and (ii) the fact that they possess only passive predefined rectification factors. Here, we demonstrated a new class of micro/nanofluidic diode with an ideal perm-selective nanoporous membrane based on ion concentration polarization (ICP) phenomenon. Thin side-microchannels installed near a nanojunction served as mitigators of the amplified electrokinetic flows generated by ICP and induced convective salt transfer to the nanoporous membrane, leading to actively controlled micro-scale asymmetry. Using this device, current rectifications were successfully demonstrated in a wide range of electrolytic concentrations (10 -5 M to 3 M) as a function of the fluidic resistance of the side-microchannels. Noteworthily, it was confirmed that the rectification factors were independent from the bulk concentration due to the ideal perm-selectivity. Moreover, the rectification of the presenting diode was actively controlled by adjusting the external convective flows, while that of the previous diode was passively determined by invariant nanoscale asymmetry.
The zinc fingers of YY1 bind single-stranded RNA with low sequence specificity.
Wai, Dorothy C C; Shihab, Manar; Low, Jason K K; Mackay, Joel P
2016-11-02
Classical zinc fingers (ZFs) are traditionally considered to act as sequence-specific DNA-binding domains. More recently, classical ZFs have been recognised as potential RNA-binding modules, raising the intriguing possibility that classical-ZF transcription factors are involved in post-transcriptional gene regulation via direct RNA binding. To date, however, only one classical ZF-RNA complex, that involving TFIIIA, has been structurally characterised. Yin Yang-1 (YY1) is a multi-functional transcription factor involved in many regulatory processes, and binds DNA via four classical ZFs. Recent evidence suggests that YY1 also interacts with RNA, but the molecular nature of the interaction remains unknown. In the present work, we directly assess the ability of YY1 to bind RNA using in vitro assays. Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to identify preferred RNA sequences bound by the YY1 ZFs from a randomised library over multiple rounds of selection. However, a strong motif was not consistently recovered, suggesting that the RNA sequence selectivity of these domains is modest. YY1 ZF residues involved in binding to single-stranded RNA were identified by NMR spectroscopy and found to be largely distinct from the set of residues involved in DNA binding, suggesting that interactions between YY1 and ssRNA constitute a separate mode of nucleic acid binding. Our data are consistent with recent reports that YY1 can bind to RNA in a low-specificity, yet physiologically relevant manner. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
Direction of Wording Effects in Balanced Scales.
ERIC Educational Resources Information Center
Miller, Timothy R.; Cleary, T. Anne
1993-01-01
The degree to which statistical item selection reduces direction-of-wording effects in balanced affective measures developed from relatively small item pools was investigated with 171 male and 228 female undergraduate and graduate students at 2 U.S. universities. Clearest direction-of-wording effects result from selection of items with high…
Network models of frequency modulated sweep detection.
Skorheim, Steven; Razak, Khaleel; Bazhenov, Maxim
2014-01-01
Frequency modulated (FM) sweeps are common in species-specific vocalizations, including human speech. Auditory neurons selective for the direction and rate of frequency change in FM sweeps are present across species, but the synaptic mechanisms underlying such selectivity are only beginning to be understood. Even less is known about mechanisms of experience-dependent changes in FM sweep selectivity. We present three network models of synaptic mechanisms of FM sweep direction and rate selectivity that explains experimental data: (1) The 'facilitation' model contains frequency selective cells operating as coincidence detectors, summing up multiple excitatory inputs with different time delays. (2) The 'duration tuned' model depends on interactions between delayed excitation and early inhibition. The strength of delayed excitation determines the preferred duration. Inhibitory rebound can reinforce the delayed excitation. (3) The 'inhibitory sideband' model uses frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections results in neurons responsive to sweeps in a single direction of sufficient sweep rate. Variations of these properties, can explain the diversity of rate-dependent direction selectivity seen across species. We show that the inhibitory sideband model can be trained using spike timing dependent plasticity (STDP) to develop direction selectivity from a non-selective network. These models provide a means to compare the proposed synaptic and spectrotemporal mechanisms of FM sweep processing and can be utilized to explore cellular mechanisms underlying experience- or training-dependent changes in spectrotemporal processing across animal models. Given the analogy between FM sweeps and visual motion, these models can serve a broader function in studying stimulus movement across sensory epithelia.
Effects of cytosine methylation on transcription factor binding sites
2014-01-01
Background DNA methylation in promoters is closely linked to downstream gene repression. However, whether DNA methylation is a cause or a consequence of gene repression remains an open question. If it is a cause, then DNA methylation may affect the affinity of transcription factors (TFs) for their binding sites (TFBSs). If it is a consequence, then gene repression caused by chromatin modification may be stabilized by DNA methylation. Until now, these two possibilities have been supported only by non-systematic evidence and they have not been tested on a wide range of TFs. An average promoter methylation is usually used in studies, whereas recent results suggested that methylation of individual cytosines can also be important. Results We found that the methylation profiles of 16.6% of cytosines and the expression profiles of neighboring transcriptional start sites (TSSs) were significantly negatively correlated. We called the CpGs corresponding to such cytosines “traffic lights”. We observed a strong selection against CpG “traffic lights” within TFBSs. The negative selection was stronger for transcriptional repressors as compared with transcriptional activators or multifunctional TFs as well as for core TFBS positions as compared with flanking TFBS positions. Conclusions Our results indicate that direct and selective methylation of certain TFBS that prevents TF binding is restricted to special cases and cannot be considered as a general regulatory mechanism of transcription. PMID:24669864
Erickson, Lucy C; Thiessen, Erik D; Godwin, Karrie E; Dickerson, John P; Fisher, Anna V
2015-10-01
Selective sustained attention is vital for higher order cognition. Although endogenous and exogenous factors influence selective sustained attention, assessment of the degree to which these factors influence performance and learning is often challenging. We report findings from the Track-It task, a paradigm that aims to assess the contribution of endogenous and exogenous factors to selective sustained attention within the same task. Behavioral accuracy and eye-tracking data on the Track-It task were correlated with performance on an explicit learning task. Behavioral accuracy and fixations to distractors during the Track-It task did not predict learning when exogenous factors supported selective sustained attention. In contrast, when endogenous factors supported selective sustained attention, fixations to distractors were negatively correlated with learning. Similarly, when endogenous factors supported selective sustained attention, higher behavioral accuracy was correlated with greater learning. These findings suggest that endogenously and exogenously driven selective sustained attention, as measured through different conditions of the Track-It task, may support different kinds of learning. Copyright © 2015 Elsevier Inc. All rights reserved.
EVOLUTION OF DIVERGENT FEMALE MATING PREFERENCE IN RESPONSE TO EXPERIMENTAL SEXUAL SELECTION
Debelle, Allan; Ritchie, Michael G; Snook, Rhonda R
2014-01-01
Sexual selection is predicted to drive the coevolution of mating signals and preferences (mating traits) within populations, and could play a role in speciation if sexual isolation arises due to mating trait divergence between populations. However, few studies have demonstrated that differences in mating traits between populations result from sexual selection alone. Experimental evolution is a promising approach to directly examine the action of sexual selection on mating trait divergence among populations. We manipulated the opportunity for sexual selection (low vs. high) in populations of Drosophila pseudoobscura. Previous studies on these experimental populations have shown that sexual selection manipulation resulted in the divergence between sexual selection treatments of several courtship song parameters, including interpulse interval (IPI) which markedly influences male mating success. Here, we measure female preference for IPI using a playback design to test for preference divergence between the sexual selection treatments after 130 generations of experimental sexual selection. The results suggest that female preference has coevolved with male signal, in opposite directions between the sexual selection treatments, providing direct evidence of the ability of sexual selection to drive the divergent coevolution of mating traits between populations. We discuss the implications in the context sexual selection and speciation. PMID:24931497
Wagner, Barry T; Jackson, Heather M
2006-02-01
This study examined the cognitive demands of 2 selection techniques in augmentative and alternative communication (AAC), direct selection, and visual linear scanning, by determining the memory retrieval abilities of typically developing children when presented with fixed communication displays. One hundred twenty typical children from kindergarten, 1st, and 3rd grades were randomly assigned to either a direct selection or visual linear scanning group. Memory retrieval was assessed through word span using Picture Communication Symbols (PCSs). Participants were presented various numbers and arrays of PCSs and asked to retrieve them by placing identical graphic symbols on fixed communication displays with grid layouts. The results revealed that participants were able to retrieve more PCSs during direct selection than scanning. Additionally, 3rd-grade children retrieved more PCSs than kindergarten and 1st-grade children. An analysis on the type of errors during retrieval indicated that children were more successful at retrieving the correct PCSs than the designated location of those symbols on fixed communication displays. AAC practitioners should consider using direct selection over scanning whenever possible and account for anticipatory monitoring and pulses when scanning is used in the service delivery of children with little or no functional speech. Also, researchers should continue to investigate AAC selection techniques in relationship to working memory resources.
A national UK survey of radiology trainees special interest choices: what and why?
Parvizi, Nassim; Bhuva, Shaheel
2017-11-01
A national survey was designed to better understand factors influencing special interest choices, future aspirations of UK radiology trainees and perceptions of breast radiology. A SurveyMonkey questionnaire was developed and distributed to all radiology trainees in the UK through the British Institute of Radiology, RCR Junior Radiologists Forum and by directly contacting UK training schemes as well as by social media between December 2015 and January 2016. From 21 training schemes across the UK, 232 responses were received. Over half entered radiology after foundation training and 62% were ST1-3; one-fifth of trainees intended to leave the NHS. The most popular special interests were musculoskeletal (18%), abdominal imaging (16%) and neuroradiology (13%). Gynaecological and oncological imaging proved to be the least popular. Strong personal interest, a successful rotation during training, a mix of imaging modalities, direct impact on patient care and job prospects were the most popular factors influencing career choice. Research and potential for private income were the least influential factors. Respondents detailed their perceptions of breast radiology, selecting an awareness of career prospects (41%) and a better trainee experience (36%) as factors that would increase their interest in pursuing it as a career. Understanding the factors that influence special interest choice is essential to addressing the alarming staffing shortfalls that will befall certain radiology special interests. Addressing trainee's preconceptions and improving the trainee experience are key to attracting trainees to breast radiology. Advances in knowledge: This is the first survey of its kind in the UK literature designed to evaluate special interest career choices and the factors that influence those among radiology trainees.
Niche construction, sources of selection and trait coevolution.
Laland, Kevin; Odling-Smee, John; Endler, John
2017-10-06
Organisms modify and choose components of their local environments. This 'niche construction' can alter ecological processes, modify natural selection and contribute to inheritance through ecological legacies. Here, we propose that niche construction initiates and modifies the selection directly affecting the constructor, and on other species, in an orderly, directed and sustained manner. By dependably generating specific environmental states, niche construction co-directs adaptive evolution by imposing a consistent statistical bias on selection. We illustrate how niche construction can generate this evolutionary bias by comparing it with artificial selection. We suggest that it occupies the middle ground between artificial and natural selection. We show how the perspective leads to testable predictions related to: (i) reduced variance in measures of responses to natural selection in the wild; (ii) multiple trait coevolution, including the evolution of sequences of traits and patterns of parallel evolution; and (iii) a positive association between niche construction and biodiversity. More generally, we submit that evolutionary biology would benefit from greater attention to the diverse properties of all sources of selection.
NASA Astrophysics Data System (ADS)
Byers, David Alan
The purpose of this study was to identify specific career development attributes of contemporary senior-level airport executives and to evaluate the relationship of these attributes to the level of satisfaction airport executives have in their career choice. Attribute sets that were examined included early aviation interests, health factors, psychological factors, demographic factors, formal education, and other aviation-related experiences. A hypothesized causal model that expressed direct and indirect effects among these attributes relative to airport executives' career satisfaction was tested using sample data collected from 708 airport executives from general aviation and commercial service airport throughout the United States. Applying a multiple regression analysis strategy to the model, the overall results revealed that 16% of the variability in airport executives' career satisfaction scores was due to the collective influence of the six research attribute sets, this was significant. The results of the path analysis also indicated that four attribute sets (early aviation interests, health factors, formal education, and other aviation-related experiences) had respective direct significant effects on participants' career satisfaction. Early aviation interests, health factors, and demographic factors had additional indirect effects on career satisfaction; all were mediated by formal education attitude. These results were inconsistent with the hypothesized path model and a revised model was developed to reflect the sample data. The findings suggest that airport executives, as a group, are satisfied with their career choice. Early aviation interests appear to play an important role for influencing the career field selection phase of career development. The study also suggests health factors, formal education, and other aviation-related experiences such as flight training or military experience influence the compromise phase of career development. Each of these four factors had significant effects on career satisfaction. In addition to its applicability to airport executives, the study provides a generalized path model for investigating factors influencing the career development, compromise, and satisfaction process in other vocations.
LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes
Singh, Parmit Kumar; Plumb, Matthew R.; Ferris, Andrea L.; Iben, James R.; Wu, Xiaolin; Fadel, Hind J.; Luke, Brian T.; Esnault, Caroline; Poeschla, Eric M.; Hughes, Stephen H.; Kvaratskhelia, Mamuka; Levin, Henry L.
2015-01-01
The host chromatin-binding factor LEDGF/p75 interacts with HIV-1 integrase and directs integration to active transcription units. To understand how LEDGF/p75 recognizes transcription units, we sequenced 1 million HIV-1 integration sites isolated from cultured HEK293T cells. Analysis of integration sites showed that cancer genes were preferentially targeted, raising concerns about using lentivirus vectors for gene therapy. Additional analysis led to the discovery that introns and alternative splicing contributed significantly to integration site selection. These correlations were independent of transcription levels, size of transcription units, and length of the introns. Multivariate analysis with five parameters previously found to predict integration sites showed that intron density is the strongest predictor of integration density in transcription units. Analysis of previously published HIV-1 integration site data showed that integration density in transcription units in mouse embryonic fibroblasts also correlated strongly with intron number, and this correlation was absent in cells lacking LEDGF. Affinity purification showed that LEDGF/p75 is associated with a number of splicing factors, and RNA sequencing (RNA-seq) analysis of HEK293T cells lacking LEDGF/p75 or the LEDGF/p75 integrase-binding domain (IBD) showed that LEDGF/p75 contributes to splicing patterns in half of the transcription units that have alternative isoforms. Thus, LEDGF/p75 interacts with splicing factors, contributes to exon choice, and directs HIV-1 integration to transcription units that are highly spliced. PMID:26545813
Network selection, Information filtering and Scalable computation
NASA Astrophysics Data System (ADS)
Ye, Changqing
This dissertation explores two application scenarios of sparsity pursuit method on large scale data sets. The first scenario is classification and regression in analyzing high dimensional structured data, where predictors corresponds to nodes of a given directed graph. This arises in, for instance, identification of disease genes for the Parkinson's diseases from a network of candidate genes. In such a situation, directed graph describes dependencies among the genes, where direction of edges represent certain causal effects. Key to high-dimensional structured classification and regression is how to utilize dependencies among predictors as specified by directions of the graph. In this dissertation, we develop a novel method that fully takes into account such dependencies formulated through certain nonlinear constraints. We apply the proposed method to two applications, feature selection in large margin binary classification and in linear regression. We implement the proposed method through difference convex programming for the cost function and constraints. Finally, theoretical and numerical analyses suggest that the proposed method achieves the desired objectives. An application to disease gene identification is presented. The second application scenario is personalized information filtering which extracts the information specifically relevant to a user, predicting his/her preference over a large number of items, based on the opinions of users who think alike or its content. This problem is cast into the framework of regression and classification, where we introduce novel partial latent models to integrate additional user-specific and content-specific predictors, for higher predictive accuracy. In particular, we factorize a user-over-item preference matrix into a product of two matrices, each representing a user's preference and an item preference by users. Then we propose a likelihood method to seek a sparsest latent factorization, from a class of over-complete factorizations, possibly with a high percentage of missing values. This promotes additional sparsity beyond rank reduction. Computationally, we design methods based on a ``decomposition and combination'' strategy, to break large-scale optimization into many small subproblems to solve in a recursive and parallel manner. On this basis, we implement the proposed methods through multi-platform shared-memory parallel programming, and through Mahout, a library for scalable machine learning and data mining, for mapReduce computation. For example, our methods are scalable to a dataset consisting of three billions of observations on a single machine with sufficient memory, having good timings. Both theoretical and numerical investigations show that the proposed methods exhibit significant improvement in accuracy over state-of-the-art scalable methods.
NASA Astrophysics Data System (ADS)
Mohammedshum, A. A.; Gebresilassie, M. A.; Rulinda, C. M.; Kahsay, G. H.; Tesfay, M. S.
2014-11-01
Identifying solid waste disposal sites and appropriately managing them is a challenging task to many developing countries. This is a critical problem too in Ethiopia in general and in Wukro town in particular. The existing site for Wukro town is not sufficient in its capacity and it is damaging the environment due to its location, and the type of waste dumped, while the surrounding area is being irrigated. Due to the swift expansion and urbanization developments in Wukro town, it badly needs to develop controlled solid waste dumping site to prevent several contamination problems. This study was conducted first, to assess the existing waste management strategies in Wukro town; and second, to find out the potential waste disposal sites for the town, using GIS and Remote Sensing techniques. The study exploited the Multi-Criteria Evaluation (MCE) methods to combine necessary factors considered for dumping site selection. The selected method also uses various geographical data including remote sensing data, with GIS spatial analysis tools. Accordingly, site suitability maps for each of the factors were developed in a GIS environment. Results indicate that 12 dumping sites were appropriate and they were further ranked against their suitability in terms of wind direction, proximity to settlement area and distance from the center of the town. Finally, two sites are the best suitable for dumping site. This study indicated that the application of Geographic Information System and Remote Sensing techniques are efficient and low cost tools to study and select appropriate dumping site so as to facilitate decision making processes.
Modality-specificity of Selective Attention Networks.
Stewart, Hannah J; Amitay, Sygal
2015-01-01
To establish the modality specificity and generality of selective attention networks. Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs. The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled "general attention." The third component was labeled "auditory attention," as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as "spatial orienting" and "spatial conflict," respectively-they were comprised of orienting and conflict resolution measures from the vANT, aANT, and TAiL attend-location task-all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location). These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific.
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
Giltrap, Donna L; Ausseil, Anne-Gaelle E; Thakur, Kailash P; Sutherland, M Anne
2013-11-01
In this study, we developed emission factor (EF) look-up tables for calculating the direct nitrous oxide (N2O) emissions from grazed pasture soils in New Zealand. Look-up tables of long-term average direct emission factors (and their associated uncertainties) were generated using multiple simulations of the NZ-DNDC model over a representative range of major soil, climate and management conditions occurring in New Zealand using 20 years of climate data. These EFs were then combined with national activity data maps to estimate direct N2O emissions from grazed pasture in New Zealand using 2010 activity data. The total direct N2O emissions using look-up tables were 12.7±12.1 Gg N2O-N (equivalent to using a national average EF of 0.70±0.67%). This agreed with the amount calculated using the New Zealand specific EFs (95% confidence interval 7.7-23.1 Gg N2O-N), although the relative uncertainty increased. The high uncertainties in the look-up table EFs were primarily due to the high uncertainty of the soil parameters within the selected soil categories. Uncertainty analyses revealed that the uncertainty in soil parameters contributed much more to the uncertainty in N2O emissions than the inter-annual weather variability. The effect of changes to fertiliser applications was also examined and it was found that for fertiliser application rates of 0-50 kg N/ha for sheep and beef and 60-240 kg N/ha for dairy the modelled EF was within ±10% of the value simulated using annual fertiliser application rates of 15 kg N/ha and 140 kg N/ha respectively. Copyright © 2013 Elsevier B.V. All rights reserved.
Evolution of genetic architecture under directional selection.
Hansen, Thomas F; Alvarez-Castro, José M; Carter, Ashley J R; Hermisson, Joachim; Wagner, Günter P
2006-08-01
We investigate the multilinear epistatic model under mutation-limited directional selection. We confirm previous results that only directional epistasis, in which genes on average reinforce or diminish each other's effects, contribute to the initial evolution of mutational effects. Thus, either canalization or decanalization can occur under directional selection, depending on whether positive or negative epistasis is prevalent. We then focus on the evolution of the epistatic coefficients themselves. In the absence of higher-order epistasis, positive pairwise epistasis will tend to weaken relative to additive effects, while negative pairwise epistasis will tend to become strengthened. Positive third-order epistasis will counteract these effects, while negative third-order epistasis will reinforce them. More generally, gene interactions of all orders have an inherent tendency for negative changes under directional selection, which can only be modified by higher-order directional epistasis. We identify three types of nonadditive quasi-equilibrium architectures that, although not strictly stable, can be maintained for an extended time: (1) nondirectional epistatic architectures; (2) canalized architectures with strong epistasis; and (3) near-additive architectures in which additive effects keep increasing relative to epistasis.
Sandring, Saskia; Agren, Jon
2009-05-01
The evolution of floral display and flowering time in animal-pollinated plants is commonly attributed to pollinator-mediated selection. Yet, the causes of selection on flowering phenology and traits contributing to floral display have rarely been tested experimentally in natural populations. We quantified phenotypic selection on morphological and phenological characters in the perennial, outcrossing herb Arabidopsis lyrata in two years using female reproductive success as a proxy of fitness. To determine whether selection on floral display and flowering phenology can be attributed to interactions with pollinators, selection was quantified both for open-pollinated controls and for plants receiving supplemental hand-pollination. We documented directional selection for many flowers, large petals, late start of flowering, and early end of flowering. Seed output was pollen-limited in both years and supplemental hand-pollination reduced the magnitude of selection on number of flowers, and reversed the direction of selection on end of flowering. The results demonstrate that interactions with pollinators may affect the strength of selection on floral display and the direction of selection on phenology of flowering in natural plant populations. They thus support the contention that pollinators can drive the evolution of both floral display and flowering time.
Ndwiga, Joshua Muriuki; Kikuvi, Gideon; Omolo, Jared Odhiambo
2016-01-01
The World Health Organization (WHO) promotes the Directly Observed Treatment (DOT) strategy as the standard to increase adherence to Tuberculosis (TB) medication. However, cases of retreatment and Multi Drug Resistant continue to be reported in many parts of Kenya. This study sought to determine the factors influencing the completion of tuberculosis medication among TB patients in Embu County, Kenya. A descriptive cross-sectional study was conducted on a population of tuberculosis patients under DOT attending selected TB treatment clinics in Embu County, in Kenya. One hundred and forty TB patients interviewed within a period of 3 months. Data were analyzed using SPSS version 17.0 and included Bivariate and Multivariate Analysis. The level of significance was p≤ 0.05. The male and female participants were 61.4% and 38.6% respectively. The mean age of the respondents was 35±31.34-39.3 years. For the majority (52%) of the participants, the highest level of education was primary education. The unemployed participants formed the highest number of the respondent in the study (73%). The majorities (91.4%0) of the respondents were under the home-based DOT strategy (91.4%, 95% C.I: 85.5-95.5). Bivariate analysis using Chi-square showed that the level of education (p=0.003), patients feeling uncomfortable during supervision (p=0.01), and knowledge regarding the frequency of taking medication (p=0.004) were all significantly associated with knowledge regarding the importance of completion of medication. However, none of these factors was significant after multivariate analysis. Most participants did not know the importance of completion of medication. TB programs should come up with better ways to educate TB patients on the importance of supervision and treatment completion during the treatment of TB. The education programs should focus on influencing the attitudes of patients and creating awareness about the importance of treatment completion. The TB programs should be designed towards eliminating the factors influencing the completion of TB medication.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rigsby, Matthew L.; Wasylenko, Derek J.; Pegis, Michael L.
2015-04-08
Several substituted iron porphyrin com-plexes were evaluated for oxygen reduction reaction (ORR) electrocatalysis in different homogeneous and heterogeneous media. The selectivity for 4-electron re-duction to H2O vs. 2-electron reduction to H2O2 varies substantially from one medium to another for a given catalyst. In many cases, the influence of the medium in which the catalyst is evaluated has a larger effect on the observed selectivity than the factors attributable to chemical modification of the catalyst. For instance, introduction of potential proton relays has variable effects depending on the catalyst medium. Thus, comparisons of ORR selectivity results need to be interpreted withmore » caution, as the catalysis is a property not just of the catalyst, but also of the larger mesoscale environment be-yond the catalyst. Still, in all the direct pairwise comparisons in the same medium, the catalysts with potential proton relays have similar or better selectivity for the preferred 4e– path. This work was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.« less
A new approach to modeling the influence of image features on fixation selection in scenes
Nuthmann, Antje; Einhäuser, Wolfgang
2015-01-01
Which image characteristics predict where people fixate when memorizing natural images? To answer this question, we introduce a new analysis approach that combines a novel scene-patch analysis with generalized linear mixed models (GLMMs). Our method allows for (1) directly describing the relationship between continuous feature value and fixation probability, and (2) assessing each feature's unique contribution to fixation selection. To demonstrate this method, we estimated the relative contribution of various image features to fixation selection: luminance and luminance contrast (low-level features); edge density (a mid-level feature); visual clutter and image segmentation to approximate local object density in the scene (higher-level features). An additional predictor captured the central bias of fixation. The GLMM results revealed that edge density, clutter, and the number of homogenous segments in a patch can independently predict whether image patches are fixated or not. Importantly, neither luminance nor contrast had an independent effect above and beyond what could be accounted for by the other predictors. Since the parcellation of the scene and the selection of features can be tailored to the specific research question, our approach allows for assessing the interplay of various factors relevant for fixation selection in scenes in a powerful and flexible manner. PMID:25752239
Hicks, Brian M; Johnson, Wendy; Durbin, C Emily; Blonigen, Daniel M; Iacono, William G; McGue, Matt
2014-01-01
Utilizing the large, longitudinal Minnesota Twin Family Study (N = 2510; 96 % European American ancestry), we examined the influence of several person-environment transactions on adolescent substance abuse. We focused on the two childhood personality traits found to be most predictive of substance abuse in this sample-socialization (willingness to follow rules and endorse conventional values) and boldness (social engagement and assurance, stress resilience, thrill seeking)-and the environmental variables of antisocial and prosocial peers, academic engagement, parent-child relationship quality, and stressful life events. Path analysis revealed that low socialization had a selection effect for each environmental risk factor, that is, socialization at age 11 predicted environmental risk at age 14, after controlling for the stability of the environmental variables from ages 11 to 14. Antisocial peers and academic engagement at age 14 then mediated some of the risk of low socialization on substance abuse at age 17, but the majority of risk for substance abuse was accounted for by the stability of socialization from age 11 to 14. Boldness at age 11 also increased risk for substance abuse, but did so primarily via a direct effect. The findings help to parse the nature of person-environment transactions across multiple personality traits and contextual risk factors that contribute to adolescent substance abuse.