Distributions of Mutational Effects and the Estimation of Directional Selection in Divergent Lineages of Arabidopsis thaliana.

PubMed

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.

Selected Issues in the Federal Direct Loan Program. A Collection of Commissioned Papers.

ERIC Educational Resources Information Center

Office of Postsecondary Education (ED), Washington, DC.

This document presents seven papers that address several aspects of the new direct lending federal loan program established by the Student Loan Reform Act of 1993. Among the topics examined are the following: (1) the experiences with implementing new student aid programs; (2) the policy questions involved in lending in proprietary (profit-making)…

Antagonistic responses to natural and sexual selection and the sex-specific evolution of cuticular hydrocarbons in Drosophila simulans.

PubMed

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.

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study, volume 1

NASA Technical Reports Server (NTRS)

Hanks, G. W.; Shomber, H. A.; Dethman, H. A.; Gratzer, L. B.; Maeshiro, A.; Gangsaas, D.; Blight, J. D.; Buchan, S. M.; Crumb, C. B.; Dorwart, R. J.

1981-01-01

An active controls technology (ACT) system architecture was selected based on current technology system elements and optimal control theory was evaluated for use in analyzing and synthesizing ACT multiple control laws. The system selected employs three redundant computers to implement all of the ACT functions, four redundant smaller computers to implement the crucial pitch-augmented stability function, and a separate maintenance and display computer. The reliability objective of probability of crucial function failure of less than 1 x 10 to the -9th power per flight of 1 hr can be met with current technology system components, if the software is assumed fault free and coverage approaching 1.0 can be provided. The optimal control theory approach to ACT control law synthesis yielded comparable control law performance much more systematically and directly than the classical s-domain approach. The ACT control law performance, although somewhat degraded by the inclusion of representative nonlinearities, remained quite effective. Certain high-frequency gust-load alleviation functions may require increased surface rate capability.

A behavioral perspective on fishing-induced evolution.

PubMed

Uusi-Heikkilä, Silva; Wolter, Christian; Klefoth, Thomas; Arlinghaus, Robert

2008-08-01

The potential for excessive and/or selective fishing to act as an evolutionary force has been emphasized recently. However, most studies have focused on evolution of life-history traits in response to size-selective harvesting. Here we draw attention to fishing-induced evolution of behavioral and underlying physiological traits. We contend that fishing-induced selection directly acting on behavioral rather than on life-history traits per se can be expected in all fisheries that operate with passive gears such as trapping, angling and gill-netting. Recent artificial selection experiments in the nest-guarding largemouth bass Micropterus salmoides suggest that fishing-induced evolution of behavioral traits that reduce exposure to fishing gear might be maladaptive, potentially reducing natural recruitment. To improve understanding and management of fisheries-induced evolution, we encourage greater application of methods from behavioral ecology, physiological ecology and behavioral genetics.

Models of microbiome evolution incorporating host and microbial selection.

PubMed

Zeng, Qinglong; Wu, Steven; Sukumaran, Jeet; Rodrigo, Allen

2017-09-25

Numerous empirical studies suggest that hosts and microbes exert reciprocal selective effects on their ecological partners. Nonetheless, we still lack an explicit framework to model the dynamics of both hosts and microbes under selection. In a previous study, we developed an agent-based forward-time computational framework to simulate the neutral evolution of host-associated microbial communities in a constant-sized, unstructured population of hosts. These neutral models allowed offspring to sample microbes randomly from parents and/or from the environment. Additionally, the environmental pool of available microbes was constituted by fixed and persistent microbial OTUs and by contributions from host individuals in the preceding generation. In this paper, we extend our neutral models to allow selection to operate on both hosts and microbes. We do this by constructing a phenome for each microbial OTU consisting of a sample of traits that influence host and microbial fitnesses independently. Microbial traits can influence the fitness of hosts ("host selection") and the fitness of microbes ("trait-mediated microbial selection"). Additionally, the fitness effects of traits on microbes can be modified by their hosts ("host-mediated microbial selection"). We simulate the effects of these three types of selection, individually or in combination, on microbiome diversities and the fitnesses of hosts and microbes over several thousand generations of hosts. We show that microbiome diversity is strongly influenced by selection acting on microbes. Selection acting on hosts only influences microbiome diversity when there is near-complete direct or indirect parental contribution to the microbiomes of offspring. Unsurprisingly, microbial fitness increases under microbial selection. Interestingly, when host selection operates, host fitness only increases under two conditions: (1) when there is a strong parental contribution to microbial communities or (2) in the absence of a strong parental contribution, when host-mediated selection acts on microbes concomitantly. We present a computational framework that integrates different selective processes acting on the evolution of microbiomes. Our framework demonstrates that selection acting on microbes can have a strong effect on microbial diversities and fitnesses, whereas selection on hosts can have weaker outcomes.

Selection for sex in finite populations.

PubMed

Roze, D

2014-07-01

Finite population size generates interference between selected loci, which has been shown to favour increased rates of recombination. In this article, I present different analytical models exploring selection acting on a 'sex modifier locus' (that affects the relative investment into asexual and sexual reproduction) in a finite population. Two forms of selective forces act on the modifier: direct selection due to intrinsic costs associated with sexual reproduction and indirect selection generated by one or two other loci affecting fitness. The results show that indirect selective forces differ from those acting on a recombination modifier even in the case of a haploid population: in particular, a single selected locus generates indirect selection for sex, while two loci are required in the case of a recombination modifier. This effect stems from the fact that modifier alleles increasing sex escape more easily from low-fitness genetic backgrounds than alleles coding for lower rates of sex. Extrapolating the results from three-locus models to a large number of loci at mutation-selection balance indicates that in the parameter range where indirect selection is strong enough to outweigh a substantial cost of sex, interactions between selected loci have a stronger effect than the sum of individual effects of each selected locus. Comparisons with multilocus simulation results show that such extrapolations may provide correct predictions for the evolutionarily stable rate of sex, unless the cost of sex is high. © 2014 The Author. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Convergent and divergent patterns of morphological differentiation provide more evidence for reproductive character displacement in a wood cricket Gryllus fultoni (Orthoptera: Gryllidae)

PubMed Central

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

Convergent and divergent patterns of morphological differentiation provide more evidence for reproductive character displacement in a wood cricket Gryllus fultoni (Orthoptera: Gryllidae).

PubMed

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.

Epidemic spreading through direct and indirect interactions.

PubMed

Ganguly, Niloy; Krueger, Tyll; Mukherjee, Animesh; Saha, Sudipta

2014-09-01

In this paper we study the susceptible-infected-susceptible epidemic dynamics, considering a specialized setting where popular places (termed passive entities) are visited by agents (termed active entities). We consider two types of spreading dynamics: direct spreading, where the active entities infect each other while visiting the passive entities, and indirect spreading, where the passive entities act as carriers and the infection is spread via them. We investigate in particular the effect of selection strategy, i.e., the way passive entities are chosen, in the spread of epidemics. We introduce a mathematical framework to study the effect of an arbitrary selection strategy and derive formulas for prevalence, extinction probabilities, and epidemic thresholds for both indirect and direct spreading. We also obtain a very simple relationship between the extinction probability and the prevalence. We pay special attention to preferential selection and derive exact formulas. The analysis reveals that an increase in the diversity in the selection process lowers the epidemic thresholds. Comparing the direct and indirect spreading, we identify regions in the parameter space where the prevalence of the indirect spreading is higher than the direct one.

Epidemic spreading through direct and indirect interactions

NASA Astrophysics Data System (ADS)

Ganguly, Niloy; Krueger, Tyll; Mukherjee, Animesh; Saha, Sudipta

2014-09-01

In this paper we study the susceptible-infected-susceptible epidemic dynamics, considering a specialized setting where popular places (termed passive entities) are visited by agents (termed active entities). We consider two types of spreading dynamics: direct spreading, where the active entities infect each other while visiting the passive entities, and indirect spreading, where the passive entities act as carriers and the infection is spread via them. We investigate in particular the effect of selection strategy, i.e., the way passive entities are chosen, in the spread of epidemics. We introduce a mathematical framework to study the effect of an arbitrary selection strategy and derive formulas for prevalence, extinction probabilities, and epidemic thresholds for both indirect and direct spreading. We also obtain a very simple relationship between the extinction probability and the prevalence. We pay special attention to preferential selection and derive exact formulas. The analysis reveals that an increase in the diversity in the selection process lowers the epidemic thresholds. Comparing the direct and indirect spreading, we identify regions in the parameter space where the prevalence of the indirect spreading is higher than the direct one.

Constraint, natural selection, and the evolution of human body form

PubMed Central

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.

PubMed

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.

Patients' understanding and use of advance directives.

PubMed Central

Jacobson, J A; White, B E; Battin, M P; Francis, L P; Green, D J; Kasworm, E S

1994-01-01

The Patient Self-Determination Act was implemented in December 1991. Before and after its implementation, we used a structured interview of 302 randomly selected patients to determine their awareness, understanding, and use of advance directives. Implementation of the Act did not have a major effect on these. Although more than 90% of patients were aware of the living will, only about a third selected the correct definition or the correct circumstances in which it applied, and less than 20% of patients had completed one. About a third of patients were aware of a Durable Power of Attorney for Health Care and chose the correct definition, and about half identified the correct circumstances in which it applies; less than 10% had completed such a document. Surprisingly, patients who said they had completed advance directives did not demonstrate better understanding of these documents. Our results indicate that many patients, including some who have completed advance directives, do not fully understand them. It may be unwise to regard these documents as carefully considered, compelling statements of patients' preferences. Appropriate responses to our findings include increased public education, revising state statutes to bring them into congruence with public perception, and expanding the dialogue between physicians and patients. PMID:8191755

Unravelling the effects of gene flow and selection in highly connected populations of the silver-lip pearl oyster (Pinctada maxima).

PubMed

Nayfa, Maria G; Zenger, Kyall R

2016-08-01

Many marine organisms often display weak levels of population genetic structuring as a result of both environmental characteristics (e.g., ocean currents) and life history traits (e.g., widely dispersed planktonic larval stages) maintaining high levels of gene flow. This can lead to the assumption that these organisms can be managed as a single stock based on high levels of population connectivity. However, this neglects to account for other micro-evolutionary forces such as selection, which also shape these populations. This study utilizes 1130 genome-wide SNP loci to unravel the effects of gene flow and selection shaping three highly connected populations of the silver-lip pearl oyster (Pinctada maxima) in the ecologically and economically important Indo-Pacific region (Aru, Bali, and West Papua). Twenty-two loci under directional selection were identified amongst the populations, providing further supporting evidence of strong local adaptation (i.e., G×E effects) among populations in this region. Global Fst values for directional outliers (0.348) were up to eight times greater than for neutral markers (0.043). Pairwise Fst comparisons between Aru and Bali revealed the largest directional differences (0.488), while Bali and West Papua had the least (0.062). Unrooted neighbour-joining (NJ) distance trees and genetic diversity indices of directional outliers revealed that individuals from Bali and West Papua had reduced allelic variation (MAFavg=0.144, Ho=0.238 and MAFavg=0.232, Ho=0.369, respectively) compared to Aru (MAFavg=0.292, Ho=0.412). This indicates that directional selection is most likely acting upon genetic variation within the Bali and West Papua populations. NJ distance trees, discriminant analysis of principal components, and Fst analyses of directional outliers revealed two divergent groups ("Bali/West Papua"; "Aru") that had previously gone unrecognized. This study not only illustrates that relatively strong local adaptive forces are occurring despite high gene flow, but identifies the populations that are most likely experiencing selection. Additionally, this study highlights the need to understand all micro-evolutionary forces acting on populations when resolving stock structure. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

5 CFR 315.401 - Reinstatement.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Compulsory service on work of national importance under civilian direction as required by the Military Selective Service Act; (8) Active military duty terminated under honorable conditions; (9) Service with the... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL...

5 CFR 315.401 - Reinstatement.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Compulsory service on work of national importance under civilian direction as required by the Military Selective Service Act; (8) Active military duty terminated under honorable conditions; (9) Service with the... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL...

5 CFR 315.401 - Reinstatement.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Compulsory service on work of national importance under civilian direction as required by the Military Selective Service Act; (8) Active military duty terminated under honorable conditions; (9) Service with the... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL...

5 CFR 315.401 - Reinstatement.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Compulsory service on work of national importance under civilian direction as required by the Military Selective Service Act; (8) Active military duty terminated under honorable conditions; (9) Service with the... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL...

Environment-dependent variation in selection on life history across small spatial scales.

PubMed

Lange, Rolanda; Monro, Keyne; J Marshall, Dustin

2016-10-01

Variation in life-history traits is ubiquitous, even though genetic variation is thought to be depleted by selection. One potential mechanism for the maintenance of trait variation is spatially variable selection. We explored spatial variation in selection in the field for a colonial marine invertebrate that shows phenotypic differences across a depth gradient of only 3 m. Our analysis included life-history traits relating to module size, colony growth, and phenology. Directional selection on colony growth varied in strength across depths, while module size was under directional selection at one depth but not the other. Differences in selection may explain some of the observed phenotypic differentiation among depths for one trait but not another: instead, selection should actually erode the differences observed for this trait. Our results suggest selection is not acting alone to maintain trait variation within and across environments in this system. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

PubMed

Ahmed, Asma; Felmlee, Daniel J

2015-12-18

There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

Trade Union Reform and Employment Rights Act 1993 [1 July 1993].

PubMed

1993-01-01

This document contains major provisions of the 1993 Trade Union Reform and Employment Rights Act. This Act contains many new and improved individual employment protection rights (many of which bring the UK in line with European Community directives). All pregnant employees have a new right to 14 weeks of maternity leave in addition to the existing right to return to work up to 29 weeks after child-birth. The law also strengthens the protection against dismissal or selection for redundancy on the grounds of pregnancy or child-birth. Additional protections cover sex discrimination in collective agreements.

AUTONOMIC AND BEHAVIORAL RESPONSES OF SELECTIVELY BRED HYPERCHOLINERGIC RATS TO OXOTREMORINE AND DIISOPROPYL FLUOROPHOSPHATE

EPA Science Inventory

The hypercholinergic Flinders Sensitive Line (FSL) rat was significantly more sensitive than the Flinders Resistant Line (FRL) rat to the biotelemetrically recorded hypothermic effects of oxotremorine, a directly acting muscarinic agonist, and diisopropyl fluorophosphate (DFP), a...

A Raven in a Coal Scuttle: Theodore Roosevelt & the Animal Coloration Controversy.

ERIC Educational Resources Information Center

Hendrick, Robert

1995-01-01

Recounts a debate between Theodore Roosevelt and Abbott Thayer in 1909-12 over whether animal coloration was an adaptation resulting from natural selection or whether the animal's environment acted directly on it to form its color patterns. (ZWH)

Color-selective attention need not be mediated by spatial attention.

PubMed

Andersen, Søren K; Müller, Matthias M; Hillyard, Steven A

2009-06-08

It is well-established that attention can select stimuli for preferential processing on the basis of non-spatial features such as color, orientation, or direction of motion. Evidence is mixed, however, as to whether feature-selective attention acts by increasing the signal strength of to-be-attended features irrespective of their spatial locations or whether it acts by guiding the spotlight of spatial attention to locations containing the relevant feature. To address this question, we designed a task in which feature-selective attention could not be mediated by spatial selection. Participants observed a display of intermingled dots of two colors, which rapidly and unpredictably changed positions, with the task of detecting brief intervals of reduced luminance of 20% of the dots of one or the other color. Both behavioral indices and electrophysiological measures of steady-state visual evoked potentials showed selectively enhanced processing of the attended-color items. The results demonstrate that feature-selective attention produces a sensory gain enhancement at early levels of the visual cortex that occurs without mediation by spatial attention.

Current spring warming as a driver of selection on reproductive timing in a wild passerine.

PubMed

Marrot, Pascal; Charmantier, Anne; Blondel, Jacques; Garant, Dany

2018-05-01

Evolutionary adaptation as a response to climate change is expected for fitness-related traits affected by climate and exhibiting genetic variance. Although the relationship between warmer spring temperature and earlier timing of reproduction is well documented, quantifications and predictions of the impact of global warming on natural selection acting on phenology in wild populations remain rare. If global warming affects fitness in a similar way across individuals within a population, or if fitness consequences are independent of phenotypic variation in key-adaptive traits, then no evolutionary response is expected for these traits. Here, we quantified the selection pressures acting on laying date during a 24-year monitoring of blue tits in southern Mediterranean France, a hot spot of climate warming. We explored the temporal fluctuation in annual selection gradients and we determined its temperature-related drivers. We first investigated the month-specific warming since 1970 in our study site and tested its influence on selection pressures, using a model averaging approach. Then, we quantified the selection strength associated with temperature anomalies experienced by the blue tit population. We found that natural selection acting on laying date significantly fluctuated both in magnitude and in sign across years. After identifying a significant warming in spring and summer, we showed that warmer daily maximum temperatures in April were significantly associated with stronger selection pressures for reproductive timing. Our results indicated an increase in the strength of selection by 46% for every +1°C anomaly. Our results confirm the general assumption that recent climate change translates into strong selection favouring earlier breeders in passerine birds. Our findings also suggest that differences in fitness among individuals varying in their breeding phenology increase with climate warming. Such climate-driven influence on the strength of directional selection acting on laying date could favour an adaptive response in this trait, since it is heritable. © 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society.

Processing and Integration of Contextual Information in Monkey Ventrolateral Prefrontal Neurons during Selection and Execution of Goal-Directed Manipulative Actions.

PubMed

Bruni, Stefania; Giorgetti, Valentina; Bonini, Luca; Fogassi, Leonardo

2015-08-26

The prefrontal cortex (PFC) is deemed to underlie the complexity, flexibility, and goal-directedness of primates' behavior. Most neurophysiological studies performed so far investigated PFC functions with arm-reaching or oculomotor tasks, thus leaving unclear whether, and to which extent, PFC neurons also play a role in goal-directed manipulative actions, such as those commonly used by primates during most of their daily activities. Here we trained two macaques to perform or withhold grasp-to-eat and grasp-to-place actions, depending on the combination of two subsequently presented cues: an auditory go/no-go cue (high/low tone) and a visually presented target (food/object). By varying the order of presentation of the two cues, we could segment and independently evaluate the processing and integration of contextual information allowing the monkey to make a decision on whether or not to act, and what action to perform. We recorded 403 task-related neurons from the ventrolateral prefrontal cortex (VLPFC): unimodal sensory-driven (37%), motor-related (21%), unimodal sensory-and-motor (23%), and multisensory (19%) neurons. Target and go/no-go selectivity characterized most of the recorded neurons, particularly those endowed with motor-related discharge. Interestingly, multisensory neurons appeared to encode a behavioral decision independently from the sensory modality of the stimulus allowing the monkey to make it: some of them reflected the decision to act or refraining from acting (56%), whereas others (44%) encoded the decision to perform (or withhold) a specific action (e.g., grasp-to-eat). Our findings indicate that VLPFC neurons play a role in the processing of contextual information underlying motor decision during goal-directed manipulative actions. We demonstrated that macaque ventrolateral prefrontal cortex (VLPFC) neurons show remarkable selectivity for different aspects of the contextual information allowing the monkey to select and execute goal-directed manipulative actions. Interestingly, a set of these neurons provide multimodal representations of the intended goal of a forthcoming action, encoding a behavioral decision (e.g., grasp-to-eat) independently from the sensory information allowing the monkey to make it. Our findings expand the available knowledge on prefrontal functions by showing that VLPFC neurons play a role in the selection and execution of goal-directed manipulative actions resembling those of common primates' foraging behaviors. On these bases, we propose that VLPFC may host an abstract "vocabulary" of the intended goals pursued by primates in their natural environment. Copyright © 2015 the authors 0270-6474/15/3511877-14$15.00/0.

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

Targeting the CACNA1A IRES as a Treatment for Spinocerebellar Ataxia Type 6.

PubMed

Pastor, Parviz Daniel Hejazi; Du, Xiaofei; Fazal, Sarah; Davies, Andre N; Gomez, Christopher M

2018-02-01

We have discovered that the P/Q-type voltage-gated Ca 2+ channel (VGCC) gene, CACNA1A, encodes both the α1A (Cav2.1) subunit and a newly recognized transcription factor, α1ACT, by means of a novel internal ribosomal entry site (IRES) within the α1A C-terminal coding region. α1ACT, when mutated with an expansion of the polyglutamine tract in the C-terminus, gives rise to spinocerebellar ataxia type 6 (SCA6). Because silencing of the entire CACNA1A gene would result in the loss of the essential Cav2.1 channel, the IRES controlling α1ACT expression is an excellent target for selective silencing of α1ACT as a therapeutic intervention for SCA6. We performed a high-throughput screen of FDA-approved small molecules using a dual luciferase reporter system and identified ten hits able to selectively inhibit the IRES. We identified four main candidates that showed selective suppression of α1ACT relative to α1A in HEK cells expressing a native CACNA1A vector. We previously pursued another avenue of molecular intervention through miRNA silencing. We studied three human miRNAs (miRNA-711, -3191-5p, -4786) that would potentially bind to sequences within the CACNA1A IRES region, based on an miRNA prediction program. Only miRNA-3191-5p was found to selectively inhibit the translation of α1ACT in cells. We developed a hyperacute model of SCA6 in mice by injecting a pathogenic form of the IRES-mediated α1ACT (AAV9-α1ACTQ33). Finally, we tested the effectiveness of the miRNA therapy by co-expressing either control miRNA or miRNA-3191-5p and found that miRNA-3191-5p decreased the levels of α1ACTQ33 and prevented the hyperacute disease in mice. These studies provide the proof of principle that a therapy directed at selectively preventing α1ACT expression could be used to treat SCA6.

Signatures of positive selection in the cis-regulatory sequences of the human oxytocin receptor (OXTR) and arginine vasopressin receptor 1a (AVPR1A) genes.

PubMed

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.

Highly selective fluorescence detection of Cu2+ in water by chiral dimeric Zn2+ complexes through direct displacement.

PubMed

Khatua, Snehadrinarayan; Choi, Shin Hei; Lee, Junseong; Huh, Jung Oh; Do, Youngkyu; Churchill, David G

2009-03-02

Fluorescent dinuclear chiral zinc complexes were synthesized in a "one-pot" method in which the lysine-based Schiff base ligand was generated in situ. This complex acts as a highly sensitive and selective fluorescent ON-OFF probe for Cu(2+) in water at physiological pH. Other metal ions such as Hg(2+), Cd(2+), and Pb(2+) gave little fluorescence change.

Do males pay for sex? Sex-specific selection coefficients suggest not.

PubMed

Prokop, Zofia M; Prus, Monika A; Gaczorek, Tomasz S; Sychta, Karolina; Palka, Joanna K; Plesnar-Bielak, Agata; Skarboń, Magdalena

2017-03-01

Selection acting on males can reduce mutation load of sexual relative to asexual populations, thus mitigating the twofold cost of sex, provided that it seeks and destroys the same mutations as selection acting on females, but with higher efficiency. This could happen due to sexual selection-a potent evolutionary force that in most systems predominantly affects males. We used replicate populations of red flour beetles (Tribolium castaneum) to study sex-specific selection against deleterious mutations introduced with ionizing radiation. We found no evidence for selection being stronger in males than in females; in fact, we observed a nonsignificant trend in the opposite direction. This suggests that selection on males does not reduce mutation load below the level expected under the (hypothetical) scenario of asexual reproduction. Additionally, we employed a novel approach, based on a simple model, to quantify the relative contributions of sexual and offspring viability selection to the overall selection observed in males. We found them to be similar in magnitude; however, only the offspring viability component was statistically significant. In summary, we found no support for the hypothesis that selection on males in general, and sexual selection in particular, contributes to the evolutionary maintenance of sex. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Geographical gradients in selection can reveal genetic constraints for evolutionary responses to ocean acidification

PubMed Central

Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D.; Bodrossy, Levente; Hobday, Alistair J.

2017-01-01

Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA. PMID:28148831

Natural Selection in Large Populations

NASA Astrophysics Data System (ADS)

Desai, Michael

2011-03-01

I will discuss theoretical and experimental approaches to the evolutionary dynamics and population genetics of natural selection in large populations. In these populations, many mutations are often present simultaneously, and because recombination is limited, selection cannot act on them all independently. Rather, it can only affect whole combinations of mutations linked together on the same chromosome. Methods common in theoretical population genetics have been of limited utility in analyzing this coupling between the fates of different mutations. In the past few years it has become increasingly clear that this is a crucial gap in our understanding, as sequence data has begun to show that selection appears to act pervasively on many linked sites in a wide range of populations, including viruses, microbes, Drosophila, and humans. I will describe approaches that combine analytical tools drawn from statistical physics and dynamical systems with traditional methods in theoretical population genetics to address this problem, and describe how experiments in budding yeast can help us directly observe these evolutionary dynamics.

Cognitive Science Program. Hierarchical Distributed Networks in the Neuropsychology of Selective Attention.

DTIC Science & Technology

1985-05-15

The -. . . . . . . . . . ..- L 12 example, Hughes & Zimba (1985) have argued that attention acts simply by inhibiting the hemifield to which one is...and control of attention. Brain 104, 1981, 861-872. Hughes, H.C. & Zimba , L.D. Spatial maps of directed attention. Paper presented to the Psychonmics

75 FR 75179 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-02

... of Federally-funded research and development. Foreign patent applications are filed on selected... and Its Reactivity to Human Tumors,'' HHS Reference No. E-272-2010/0-- Research Material. Patent... before they can act to kill the cell. As a result, research has generally been directed to overcoming MDR...

Environmental Epigenetics and a Unified Theory of the Molecular Aspects of Evolution: A Neo-Lamarckian Concept that Facilitates Neo-Darwinian Evolution.

PubMed

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.

Mapping Proteome-Wide Interactions of Reactive Chemicals Using Chemoproteomic Platforms

PubMed Central

Counihan, Jessica L.; Ford, Breanna; Nomura, Daniel K.

2015-01-01

A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these irreversible agents directly in complex biological systems. We review here several chemoproteomic strategies that have facilitated our understanding of specific protein interactions of irreversibly-acting pharmaceuticals, endogenous metabolites, and environmental electrophiles to reveal novel pharmacological, biological, and toxicological mechanisms. PMID:26647369

Tunnel effect measuring systems and particle detectors

NASA Technical Reports Server (NTRS)

Kaiser, William J. (Inventor); Waltman, Steven B. (Inventor); Kenny, Thomas W. (Inventor)

1994-01-01

Methods and apparatus for measuring gravitational and inertial forces, magnetic fields, or wave or radiant energy acting on an object or fluid in space provide an electric tunneling current through a gap between an electrode and that object or fluid in space and vary that gap with any selected one of such forces, magnetic fields, or wave or radiant energy acting on that object or fluid. These methods and apparatus sense a corresponding variation in an electric property of that gap and determine the latter force, magnetic fields, or wave or radiant energy in response to that corresponding variation, and thereby sense or measure such parameters as acceleration, position, particle mass, velocity, magnetic field strength, presence or direction, or wave or radiant energy intensity, presence or direction.

Tunnel effect measuring systems and particle detectors

NASA Technical Reports Server (NTRS)

Kaiser, William J. (Inventor); Waltman, Steven B. (Inventor); Kenny, Thomas W. (Inventor)

1993-01-01

Methods and apparatus for measuring gravitational and inertial forces, magnetic fields, or wave or radiant energy acting on an object or fluid in space provide an electric tunneling current through a gap between an electrode and that object or fluid in space and vary that gap with any selected one of such forces, magnetic fields, or wave or radiant energy acting on that object or fluid. These methods and apparatus sense a corresponding variation in an electric property of that gap and determine the latter force, magnetic fields, or wave or radiant energy in response to that corresponding variation, and thereby sense or measure such parameters as acceleration, position, particle mass, velocity, magnetic field strength, presence or direction, or wave or radiant energy intensity, presence or direction.

Tunnel effect wave energy detection

NASA Technical Reports Server (NTRS)

Kaiser, William J. (Inventor); Waltman, Steven B. (Inventor); Kenny, Thomas W. (Inventor)

1995-01-01

Methods and apparatus for measuring gravitational and inertial forces, magnetic fields, or wave or radiant energy acting on an object or fluid in space provide an electric tunneling current through a gap between an electrode and that object or fluid in space and vary that gap with any selected one of such forces, magnetic fields, or wave or radiant energy acting on that object or fluid. These methods and apparatus sense a corresponding variation in an electric property of that gap and determine the latter force, magnetic fields, or wave or radiant energy in response to that corresponding variation, and thereby sense or measure such parameters as acceleration, position, particle mass, velocity, magnetic field strength, presence or direction, or wave or radiant energy intensity, presence or direction.

Multilocus approaches for the measurement of selection on correlated genetic loci.

PubMed

Gompert, Zachariah; Egan, Scott P; Barrett, Rowan D H; Feder, Jeffrey L; Nosil, Patrik

2017-01-01

The study of ecological speciation is inherently linked to the study of selection. Methods for estimating phenotypic selection within a generation based on associations between trait values and fitness (e.g. survival) of individuals are established. These methods attempt to disentangle selection acting directly on a trait from indirect selection caused by correlations with other traits via multivariate statistical approaches (i.e. inference of selection gradients). The estimation of selection on genotypic or genomic variation could also benefit from disentangling direct and indirect selection on genetic loci. However, achieving this goal is difficult with genomic data because the number of potentially correlated genetic loci (p) is very large relative to the number of individuals sampled (n). In other words, the number of model parameters exceeds the number of observations (p ≫ n). We present simulations examining the utility of whole-genome regression approaches (i.e. Bayesian sparse linear mixed models) for quantifying direct selection in cases where p ≫ n. Such models have been used for genome-wide association mapping and are common in artificial breeding. Our results show they hold promise for studies of natural selection in the wild and thus of ecological speciation. But we also demonstrate important limitations to the approach and discuss study designs required for more robust inferences. © 2016 John Wiley & Sons Ltd.

Oversight Hearings Before the Select Subcommittee on Education of the Committee on Education and Labor. House of Representatives, Ninety-Third Congress, Second Session on Future Directions of the Rehabilitation Services Administration. Part 3.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

The document records a hearing held by the Select Subcommittee on Education on the application of technology in meeting the needs of handicapped Americans: The Rehabilitation Act of 1973 provides for research funds and requires that 25 percent of moneys appropriated for research in 1975 be expended to establish and support engineering research…

Nonmathematical concepts of selection, evolutionary energy, and levels of evolution.

PubMed

Darlington, P J

1972-05-01

The place of mathematics in hypotheticodeductive processes and in biological research is discussed. (Natural) Selection is defined and described as differential elimination of performed sets at any level. Sets and acting sets are groups of units (themselves sets of smaller units) at any level that may or do interact. A pseudomathematical equation describes directional change (evolution) in sets at any level. Selection is the ram of evolution; it cannot generate, but can only direct, evolutionary energy. The energy of evolution is derived from molecular or chemical levels, is transmitted upwards through the increasingly complex sets of sets that form living systems, and is turned in directions determined by the sum of selective processes, at different levels, which may either supplement or oppose each other. All evolutionary processes conform to the pseudomathematical equation referred to above, use energy as described above, and have a P/OE (ratio of programming to open-endedness) that cannot be measured, but can be related to other P/OE values. Phylogeny and ontogeny are compared as processes af directional change with set selection. Stages in the evolution of multi-cellular individuals are suggested, and are essentially the same as stages in the evolution of some multi-individual insect societies. Thinking is considered as a part of ontogeny involving an irreversible, nonrepetitive process of set selection in the brain.

The genetic consequences of selection in natural populations.

PubMed

Thurman, Timothy J; Barrett, Rowan D H

2016-04-01

The selection coefficient, s, quantifies the strength of selection acting on a genetic variant. Despite this parameter's central importance to population genetic models, until recently we have known relatively little about the value of s in natural populations. With the development of molecular genetic techniques in the late 20th century and the sequencing technologies that followed, biologists are now able to identify genetic variants and directly relate them to organismal fitness. We reviewed the literature for published estimates of natural selection acting at the genetic level and found over 3000 estimates of selection coefficients from 79 studies. Selection coefficients were roughly exponentially distributed, suggesting that the impact of selection at the genetic level is generally weak but can occasionally be quite strong. We used both nonparametric statistics and formal random-effects meta-analysis to determine how selection varies across biological and methodological categories. Selection was stronger when measured over shorter timescales, with the mean magnitude of s greatest for studies that measured selection within a single generation. Our analyses found conflicting trends when considering how selection varies with the genetic scale (e.g., SNPs or haplotypes) at which it is measured, suggesting a need for further research. Besides these quantitative conclusions, we highlight key issues in the calculation, interpretation, and reporting of selection coefficients and provide recommendations for future research. © 2016 John Wiley & Sons Ltd.

Ruling by California Judge Casts a Cloud over All University Agricultural Research.

ERIC Educational Resources Information Center

London, Herbert

1988-01-01

A court ruling that the University of California must ensure that all federal Hatch Act agricultural research funds go to projects benefiting primarily small family farms is seen as promoting special-interest politics, selective interpretation of federal legislation, and a romanticized view of farmers and may unduly influence research directions.…

The Missing Response to Selection in the Wild.

PubMed

Pujol, Benoit; Blanchet, Simon; Charmantier, Anne; Danchin, Etienne; Facon, Benoit; Marrot, Pascal; Roux, Fabrice; Scotti, Ivan; Teplitsky, Céline; Thomson, Caroline E; Winney, Isabel

2018-05-01

Although there are many examples of contemporary directional selection, evidence for responses to selection that match predictions are often missing in quantitative genetic studies of wild populations. This is despite the presence of genetic variation and selection pressures - theoretical prerequisites for the response to selection. This conundrum can be explained by statistical issues with accurate parameter estimation, and by biological mechanisms that interfere with the response to selection. These biological mechanisms can accelerate or constrain this response. These mechanisms are generally studied independently but might act simultaneously. We therefore integrated these mechanisms to explore their potential combined effect. This has implications for explaining the apparent evolutionary stasis of wild populations and the conservation of wildlife. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Population genetics inside a cell: Mutations and mitochondrial genome maintenance

NASA Astrophysics Data System (ADS)

Goyal, Sidhartha; Shraiman, Boris; Gottschling, Dan

2012-02-01

In realistic ecological and evolutionary systems natural selection acts on multiple levels, i.e. it acts on individuals as well as on collection of individuals. An understanding of evolutionary dynamics of such systems is limited in large part due to the lack of experimental systems that can challenge theoretical models. Mitochondrial genomes (mtDNA) are subjected to selection acting on cellular as well as organelle levels. It is well accepted that mtDNA in yeast Saccharomyces cerevisiae is unstable and can degrade over time scales comparable to yeast cell division time. We utilize a recent technology designed in Gottschling lab to extract DNA from populations of aged yeast cells and deep sequencing to characterize mtDNA variation in a population of young and old cells. In tandem, we developed a stochastic model that includes the essential features of mitochondrial biology that provides a null model for expected mtDNA variation. Overall, we find approximately 2% of the polymorphic loci that show significant increase in frequency as cells age providing direct evidence for organelle level selection. Such quantitative study of mtDNA dynamics is absolutely essential to understand the propagation of mtDNA mutations linked to a spectrum of age-related diseases in humans.

Genetic correlations and sex-specific adaptation in changing environments.

PubMed

Connallon, Tim; Hall, Matthew D

2016-10-01

Females and males have conflicting evolutionary interests. Selection favors the evolution of different phenotypes within each sex, yet divergence between the sexes is constrained by the shared genetic basis of female and male traits. Current theory predicts that such "sexual antagonism" should be common: manifesting rapidly during the process of adaptation, and slow in its resolution. However, these predictions apply in temporally stable environments. Environmental change has been shown empirically to realign the direction of selection acting on shared traits and thereby alleviate signals of sexually antagonistic selection. Yet there remains no theory for how common sexual antagonism should be in changing environments. Here, we analyze models of sex-specific evolutionary divergence under directional and cyclic environmental change, and consider the impact of genetic correlations on long-run patterns of sex-specific adaptation. We find that environmental change often aligns directional selection between the sexes, even when they have divergent phenotypic optima. Nevertheless, some forms of environmental change generate persistent sexually antagonistic selection that is difficult to resolve. Our results reinforce recent empirical observations that changing environmental conditions alleviate conflict between males and females. They also generate new predictions regarding the scope for sexually antagonistic selection and its resolution in changing environments. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Wing planform study and final configuration selection

NASA Technical Reports Server (NTRS)

1981-01-01

This report summarizes the Wing Planform Study Task and Final Configuration Selection of the Integrated Application of Active Controls (IAAC) Technology Project within the Energy Efficient Transport Program. Application of Active Controls Technology (ACT) in combination with increased wing span resulted in significant improvements over the Conventional Baseline Configuration (Baseline) and the Initial ACT Configuration previously established. The configurations use the same levels of technology (except for ACT), takeoff gross weight, and payload as the Baseline. The Final ACT Configuration (Model 768-107) incorporates pitch-augmented stability (which enabled an approximately 10% aft shift in cruise center of gravity and a 45% reduction in horizontal tail sizes), lateral/directional-augmented stability, an angle-of-attack limiter, and wing-load alleviation. Flutter-mode control was not beneficial for this configuration. This resulted in an 890 kg (1960 lb) reduction in airplane takeoff gross weight and a 9.8% improvement in cruise lift/drag. At the Baseline mission range (3590 km) (1938 nmi), this amounts to 10% block fuel reduction. Good takeoff performance at high-altitude airports on a hot day was also achieved. Results of this task strongly indicate that the IAAC Project should proceed with the Final ACT evaluation and begin the required control system development and testing.

Geographical gradients in selection can reveal genetic constraints for evolutionary responses to ocean acidification.

PubMed

Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D; Bodrossy, Levente; Hobday, Alistair J

2017-02-01

Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO 2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA. © 2017 The Author(s).

Flies and flowers in Darwin's race.

PubMed

Pauw, Anton; Stofberg, Jaco; Waterman, Richard J

2009-01-01

The idea of coevolution originated with Darwin's proposal that long-proboscid pollinators and long-tubed flowers might be engaged in reciprocal selection, but this has not been demonstrated. Here we test key aspects of Darwin's hypothesis of reciprocal selection in an experiment with naturally interacting populations of extremely long-proboscid flies (Moegistorhynchus longirostris: Nemestinidae) and long-tubed irises (Lapeirousia anceps: Iridaceae). We show that the benefit derived by both the fly (volume of nectar consumed) and the plant (number pollen grains received) depends on the relative length of their interacting organs. Each trait is shown to act both as agent and target in directional reciprocal selection, potentially leading to a race. This understanding of how fitness in both species varies in relation to the balance of their armament allows us to make tentative predictions about the nature of selection across multiple communities. We find that in each community a core group of long-tubed plant species might together be involved in diffuse coevolution with the fly. In poorly matched populations, the imbalance in armament is too great to allow reciprocal selection to act, and these species might instead experience one-sided selection that leads to convergence with the core species. Reciprocal selection drives the evolution of the community, then, additional species become attached to the network of interacting mutualists by convergence.

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Wing planform study and final configuration selection

NASA Technical Reports Server (NTRS)

1981-01-01

The Wing Planform Study and Final Configuration Selection Task of the Integrated Application of Active Controls (IAAC) Technology Project within the Energy Efficient Transport Program is documented. Application of Active Controls Technology (ACT) in combination with increased wing span resulted in significant improvements over the Conventional Baseline Configuration (Baseline) and the Initial ACT Configuration previously established. The configurations use the same levels of technology, takeoff gross weight, and payload as the Baseline. The Final ACT Configuration (Model 768-107) incorporates pitch-augmented stability (which enabled an approximately 10% aft shift in cruise center of gravity and a 44% reduction in horizontal tail size), lateral/directional-augmented stability, an angle-of-attack limiter, and wing-load alleviation. Flutter-mode control was not beneficial for this configuration. This resulted in an 890 kg (1960 lb) reduction in airplane takeoff gross weight and a 9.8% improvement in cruise lift/drag. At the Baseline mission range (3589 km 1938 nmi), this amounts to 10% block-fuel reduction. Results of this task strongly indicate that the IAAC Project should proceed with the Final ACT evaluation, and begin the required control system development and test.

Correlational selection leads to genetic integration of body size and an attractive plumage trait in dark-eyed juncos.

PubMed

McGlothlin, Joel W; Parker, Patricia G; Nolan, Val; Ketterson, Ellen D

2005-03-01

When a trait's effect on fitness depends on its interaction with other traits, the resultant selection is correlational and may lead to the integration of functionally related traits. In relation to sexual selection, when an ornamental trait interacts with phenotypic quality to determine mating success, correlational sexual selection should generate genetic correlations between the ornament and quality, leading to the evolution of honest signals. Despite its potential importance in the evolution of signal honesty, correlational sexual selection has rarely been measured in natural populations. In the dark-eyed junco (Junco hyemalis), males with experimentally elevated values of a plumage trait (whiteness in the tail or "tail white") are more attractive to females and dominant in aggressive encounters over resources. We used restricted maximum-likelihood analysis of a long-term dataset to measure the heritability of tail white and two components of body size (wing length and tail length), as well as genetic correlations between pairs of these traits. We then used multiple regression to assess directional, quadratic, and correlational selection as they acted on tail white and body size via four components of lifetime fitness (juvenile and adult survival, mating success, and fecundity). We found a positive genetic correlation between tail white and body size (as measured by wing length), which indicates past correlational selection. Correlational selection, which was largely due to sexual selection on males, was also found to be currently acting on the same pair of traits. Larger males with whiter tails sired young with more females, most likely due to a combination of female choice, which favors males with whiter tails, and male-male competition, which favors both tail white and larger body size. To our knowledge, this is the first study to show both genetic correlations between sexually selected traits and currently acting correlational sexual selection, and we suggest that correlational sexual selection frequently may be an important mechanism for maintaining the honesty of sexual signals.

20 CFR 30.411 - What happens if the opinion of the physician selected by OWCP differs from the opinion of the...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false What happens if the opinion of the physician... Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ENERGY EMPLOYEES... OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED Medical and Related Benefits Directed Medical...

Procedures for Making Grant Awards under Three Department of Education Discretionary Grant Programs. Report.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC.

Procedures are described for selecting field readers and awarding grants under the Women's Educational Equity Act Program, National Institute of Education, and Talent Search Programs. Information is provided for each on (1) the legislation, regulations, policy, and program directives that govern the grant award process; (2) how and by whom funding…

The Logic of Evaluative Argument. CSE Monograph Series in Evaluation, 7.

ERIC Educational Resources Information Center

House, Ernest R.

Evaluation is an act of persuasion directed to a specific audience concerning the solution of a problem. The process of evaluation is prescribed by the nature of knowledge--which is generally complex, always uncertain (in varying degrees), and not always propositional--and by the nature of logic, which is always selective. In the process of…

Selection on an extreme weapon in the frog-legged leaf beetle (Sagra femorata).

PubMed

O'Brien, Devin M; Katsuki, Masako; Emlen, Douglas J

2017-11-01

Biologists have been fascinated with the extreme products of sexual selection for decades. However, relatively few studies have characterized patterns of selection acting on ornaments and weapons in the wild. Here, we measure selection on a wild population of weapon-bearing beetles (frog-legged leaf beetles: Sagra femorata) for two consecutive breeding seasons. We consider variation in both weapon size (hind leg length) and in relative weapon size (deviations from the population average scaling relationship between hind leg length and body size), and provide evidence for directional selection on weapon size per se and stabilizing selection on a particular scaling relationship in this population. We suggest that whenever growth in body size is sensitive to external circumstance such as nutrition, then considering deviations from population-level scaling relationships will better reflect patterns of selection relevant to evolution of the ornament or weapon than will variation in trait size per se. This is because trait-size versus body-size scaling relationships approximate underlying developmental reaction norms relating trait growth with body condition in these species. Heightened condition-sensitive expression is a hallmark of the exaggerated ornaments and weapons favored by sexual selection, yet this plasticity is rarely reflected in the way we think about-and measure-selection acting on these structures in the wild. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

The origin and dynamic evolution of chemical information transfer

PubMed Central

Steiger, Sandra; Schmitt, Thomas; Schaefer, H. Martin

2011-01-01

Although chemical communication is the most widespread form of communication, its evolution and diversity are not well understood. By integrating studies of a wide range of terrestrial plants and animals, we show that many chemicals are emitted, which can unintentionally provide information (cues) and, therefore, act as direct precursors for the evolution of intentional communication (signals). Depending on the content, design and the original function of the cue, there are predictable ways that selection can enhance the communicative function of chemicals. We review recent progress on how efficacy-based selection by receivers leads to distinct evolutionary trajectories of chemical communication. Because the original function of a cue may channel but also constrain the evolution of functional communication, we show that a broad perspective on multiple selective pressures acting upon chemicals provides important insights into the origin and dynamic evolution of chemical information transfer. Finally, we argue that integrating chemical ecology into communication theory may significantly enhance our understanding of the evolution, the design and the content of signals in general. PMID:21177681

Evolutionary trends in directional hearing

PubMed Central

Carr, Catherine E.; Christensen-Dalsgaard, Jakob

2016-01-01

Tympanic hearing is a true evolutionary novelty that arose in parallel within early tetrapods. We propose that in these tetrapods, selection for sound localization in air acted upon pre-existing directionally sensitive brainstem circuits, similar to those in fishes. Auditory circuits in birds and lizards resemble this ancestral, directionally sensitive framework. Despite this anatomically similarity, coding of sound source location differs between birds and lizards. In birds, brainstem circuits compute sound location from interaural cues. Lizards, however, have coupled ears, and do not need to compute source location in the brain. Thus their neural processing of sound direction differs, although all show mechanisms for enhancing sound source directionality. Comparisons with mammals reveal similarly complex interactions between coding strategies and evolutionary history. PMID:27448850

Variation in pre- and post-copulatory sexual selection on male genital size in two species of lygaeid bug.

PubMed

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.

Characterization of the unique function of a reduced amide bond in a cytolytic peptide that acts on phospholipid membranes.

PubMed Central

Oh, J E; Lee, K H

2000-01-01

The incorporation of a reduced amide bond, psi(CH(2)NH), into peptide results in an increase in the net positive charge and the perturbation of alpha-helical structure. By using this characteristic of the reduced amide bond, we designed and synthesized novel pseudopeptides containing reduced amide bonds, which had a great selectivity between bacterial and mammalian cells. A structure-activity relationship study on pseudopeptides indicated that the decrease in alpha-helicity and the increase in net positive charge in the backbone, caused by the incorporation of a reduced amide bond into the peptide, both contributed to an improvement in the selectivity between lipid membranes with various surface charges. However, activity results in vitro indicated that a perturbation of alpha-helical structure rather than an increase in net positive charge in the backbone is more important in the selectivity between bacterial and mammalian cells. The present result revealed that the backbone of membrane-active peptides were important not only in maintaining the secondary structure for the interactions with lipid membranes but also in direct interactions with lipid membranes. The present study showed the unique function of a reduced amide bond in cytolytic peptides and a direction for developing novel anti-bacterial agents from cytolytic peptides that act on the lipid membrane of micro-organisms. PMID:11104671

Cell biology: scaling and the emergence of evolutionary cell biology.

PubMed

Phillips, Patrick C; Bowerman, Bruce

2015-03-16

A new study investigating the origins of diversity in the structure of the mitotic spindle in nematode embryos, at timescales spanning a few generations to hundreds of millions of years, finds that most features of the spindle evolve via a scaling relationship generated by natural selection acting directly upon embryo size. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using Systematic Item Selection Methods to Improve Universal Design of Assessments. Policy Directions. Number 18

ERIC Educational Resources Information Center

Johnstone, Christopher; Thurlow, Martha; Moore, Michael; Altman, Jason

2006-01-01

The No Child Left Behind Act of 2001 (NCLB) and other recent changes in federal legislation have placed greater emphasis on accountability in large-scale testing. Included in this emphasis are regulations that require assessments to be accessible. States are accountable for the success of all students, and tests should be designed in a way that…

Harming ourselves and defiling others: what determines a moral domain?

PubMed

Chakroff, Alek; Dungan, James; Young, Liane

2013-01-01

Recent work has distinguished "harm" from "purity" violations, but how does an act get classified as belonging to a domain in the first place? We demonstrate the impact of not only the kind of action (e.g., harmful versus impure) but also its target (e.g., oneself versus another). Across two experiments, common signatures of harm and purity tracked with other-directed and self-directed actions, respectively. First, participants judged self-directed acts as primarily impure and other-directed acts as primarily harmful. Second, conservatism predicted harsher judgments of self-directed but not other-directed acts. Third, while participants delivered harsher judgments of intentional versus accidental acts, this effect was smaller for self-directed than other-directed acts. Finally, participants judged self-directed acts more harshly when focusing on the actor's character versus the action itself; other-directed acts elicited the opposite pattern. These findings suggest that moral domains are defined not only by the kind of action but also by the target of the action.

Harming Ourselves and Defiling Others: What Determines a Moral Domain?

PubMed Central

Chakroff, Alek; Dungan, James; Young, Liane

2013-01-01

Recent work has distinguished “harm” from “purity” violations, but how does an act get classified as belonging to a domain in the first place? We demonstrate the impact of not only the kind of action (e.g., harmful versus impure) but also its target (e.g., oneself versus another). Across two experiments, common signatures of harm and purity tracked with other-directed and self-directed actions, respectively. First, participants judged self-directed acts as primarily impure and other-directed acts as primarily harmful. Second, conservatism predicted harsher judgments of self-directed but not other-directed acts. Third, while participants delivered harsher judgments of intentional versus accidental acts, this effect was smaller for self-directed than other-directed acts. Finally, participants judged self-directed acts more harshly when focusing on the actor’s character versus the action itself; other-directed acts elicited the opposite pattern. These findings suggest that moral domains are defined not only by the kind of action but also by the target of the action. PMID:24040245

Selective Packaging of Host tRNA's by Murine Leukemia Virus Particles Does Not Require Genomic RNA

PubMed Central

Levin, Judith G.; Seidman, J. G.

1979-01-01

The 4S RNA contained in RNA tumor virus particles consists of a selected population of host tRNA's. However, the mechanism by which virions select host tRNA's has not been elucidated. We have considered a model which specifies that 35S genomic RNA determines which tRNA's are to be encapsidated as well as the relative amounts of these tRNA's within the virion. The model was tested by comparing the free 4S RNA composition of normal murine leukemia virus (MuLV) particles and noninfectious virions from actinomycin D (ActD)-treated cells, which are deficient in genomic RNA (ActD virions). Viral 4S RNA was analyzed by two-dimensional polyacrylamide gel electrophoresis. Surprisingly, the patterns obtained for control and ActD 4S RNA were identical to each other and were clearly distinct from the cell 4S RNA pattern. The viral patterns had three prominent areas of radioactivity. One of the spots was identified on the basis of its oligonucleotide fingerprint as tRNA Pro, the primer for MuLV RNA-directed DNA synthesis. These results were obtained with two different MuLV strains, AKR and Moloney, each grown in SC-1 cells. The demonstration that ActD virions contain primer tRNA and in general exhibit the characteristic MuLV tRNA pattern rather than the complete representation of cell 4S RNA leads to the conclusion that genomic RNA is not the major determinant in selective packaging of host tRNA's. A possible role for one or more viral proteins, including reverse transcriptase, is suggested. Images PMID:219227

Stabilizing multicellularity through ratcheting

PubMed Central

Libby, Eric; Conlin, Peter L.; Kerr, Ben; Ratcliff, William C.

2016-01-01

The evolutionary transition to multicellularity probably began with the formation of simple undifferentiated cellular groups. Such groups evolve readily in diverse lineages of extant unicellular taxa, suggesting that there are few genetic barriers to this first key step. This may act as a double-edged sword: labile transitions between unicellular and multicellular states may facilitate the evolution of simple multicellularity, but reversion to a unicellular state may inhibit the evolution of increased complexity. In this paper, we examine how multicellular adaptations can act as evolutionary ‘ratchets’, limiting the potential for reversion to unicellularity. We consider a nascent multicellular lineage growing in an environment that varies between favouring multicellularity and favouring unicellularity. The first type of ratcheting mutations increase cell-level fitness in a multicellular context but are costly in a single-celled context, reducing the fitness of revertants. The second type of ratcheting mutations directly decrease the probability that a mutation will result in reversion (either as a pleiotropic consequence or via direct modification of switch rates). We show that both types of ratcheting mutations act to stabilize the multicellular state. We also identify synergistic effects between the two types of ratcheting mutations in which the presence of one creates the selective conditions favouring the other. Ratcheting mutations may play a key role in diverse evolutionary transitions in individuality, sustaining selection on the new higher-level organism by constraining evolutionary reversion. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431522

Response to Selection in Finite Locus Models with Nonadditive Effects.

PubMed

Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jørn Rind; Bijma, Piter; Sørensen, Anders Christian

2017-05-01

Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive variance can be sustained or even increased when nonadditive genetic effects are present. We tested the hypothesis that finite-locus models with both additive and nonadditive genetic effects maintain more additive genetic variance (VA) and realize larger medium- to long-term genetic gains than models with only additive effects when the trait under selection is subject to truncation selection. Four genetic models that included additive, dominance, and additive-by-additive epistatic effects were simulated. The simulated genome for individuals consisted of 25 chromosomes, each with a length of 1 M. One hundred bi-allelic QTL, 4 on each chromosome, were considered. In each generation, 100 sires and 100 dams were mated, producing 5 progeny per mating. The population was selected for a single trait (h2 = 0.1) for 100 discrete generations with selection on phenotype or BLUP-EBV. VA decreased with directional truncation selection even in presence of nonadditive genetic effects. Nonadditive effects influenced long-term response to selection and among genetic models additive gene action had highest response to selection. In addition, in all genetic models, BLUP-EBV resulted in a greater fixation of favorable and unfavorable alleles and higher response than phenotypic selection. In conclusion, for the schemes we simulated, the presence of nonadditive genetic effects had little effect in changes of additive variance and VA decreased by directional selection. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pathogen-driven selection in the human genome.

PubMed

Cagliani, Rachele; Sironi, Manuela

2013-01-01

Infectious diseases and epidemics have always accompanied and characterized human history, representing one of the main causes of death. Even today, despite progress in sanitation and medical research, infections are estimated to account for about 15% of deaths. The hypothesis whereby infectious diseases have been acting as a powerful selective pressure was formulated long ago, but it was not until the availability of large-scale genetic data and the development of novel methods to study molecular evolution that we could assess how pervasively infectious agents have shaped human genetic diversity. Indeed, recent evidences indicated that among the diverse environmental factors that acted as selective pressures during the evolution of our species, pathogen load had the strongest influence. Beside the textbook example of the major histocompatibility complex, selection signatures left by pathogen-exerted pressure can be identified at several human loci, including genes not directly involved in immune response. In the future, high-throughput technologies and the availability of genetic data from different populations are likely to provide novel insights into the evolutionary relationships between the human host and its pathogens. Hopefully, this will help identify the genetic determinants modulating the susceptibility to infectious diseases and will translate into new treatment strategies.

Chaos and unpredictability in evolution.

PubMed

Doebeli, Michael; Ispolatov, Iaroslav

2014-05-01

The possibility of complicated dynamic behavior driven by nonlinear feedbacks in dynamical systems has revolutionized science in the latter part of the last century. Yet despite examples of complicated frequency dynamics, the possibility of long-term evolutionary chaos is rarely considered. The concept of "survival of the fittest" is central to much evolutionary thinking and embodies a perspective of evolution as a directional optimization process exhibiting simple, predictable dynamics. This perspective is adequate for simple scenarios, when frequency-independent selection acts on scalar phenotypes. However, in most organisms many phenotypic properties combine in complicated ways to determine ecological interactions, and hence frequency-dependent selection. Therefore, it is natural to consider models for evolutionary dynamics generated by frequency-dependent selection acting simultaneously on many different phenotypes. Here we show that complicated, chaotic dynamics of long-term evolutionary trajectories in phenotype space is very common in a large class of such models when the dimension of phenotype space is large, and when there are selective interactions between the phenotypic components. Our results suggest that the perspective of evolution as a process with simple, predictable dynamics covers only a small fragment of long-term evolution. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

The evolution of sexual size dimorphism in the house finch. II. Population divergence in relation to local selection.

PubMed

Badyaev, A V; Hill, G E; Stoehr, A M; Nolan, P M; McGraw, K J

2000-12-01

Recent colonization of ecologically distinct areas in North America by the house finch (Carpodacus mexicanus) was accompanied by strong population divergence in sexual size dimorphism. Here we examined whether this divergence was produced by population differences in local selection pressures acting on each sex. In a long-term study of recently established populations in Alabama, Michigan, and Montana, we examined three selection episodes for each sex: selection for pairing success, overwinter survival, and within-season fecundity. Populations varied in intensity of these selection episodes, the contribution of each episode to the net selection, and in the targets of selection. Direction and intensity of selection strongly differed between sexes, and different selection episodes often favored opposite changes in morphological traits. In each population, current net selection for sexual dimorphism was highly concordant with observed sexual dimorphism--in each population, selection for dimorphism was the strongest on the most dimorphic traits. Strong directional selection on sexually dimorphic traits, and similar intensities of selection in both sexes, suggest that in each of the recently established populations, both males and females are far from their local fitness optimum, and that sexual dimorphism has arisen from adaptive responses in both sexes. Population differences in patterns of selection on dimorphism, combined with both low levels of ontogenetic integration in heritable sexually dimorphic traits and sexual dimorphism in growth patterns, may account for the close correspondence between dimorphism in selection and observed dimorphism in morphology across house finch populations.

Reconstructing the Origin of Helianthus deserticola: Survival and Selection on the Desert Floor

PubMed Central

Gross, Briana L.; Kane, Nolan C.; Lexer, Christian; Ludwig, Fulco; Rosenthal, David M.; Donovan, Lisa A.; Rieseberg, Loren H.

2008-01-01

The diploid hybrid species Helianthus deserticola inhabits the desert floor, an extreme environment relative to its parental species Helianthus annuus and Helianthus petiolaris. Adaptation to the desert floor may have occurred via selection acting on transgressive, or extreme, traits in early hybrids between the parental species. We explored this possibility through a field experiment in the hybrid species’ native habitat using H. deserticola, H. annuus, H. petiolaris, and two populations of early-generation (BC2) hybrids between the parental species, which served as proxies for the ancestral genotype of the ancient hybrid species. Character expression was evaluated for each genotypic class. Helianthus deserticola was negatively transgressive for stem diameter, leaf area, and flowering date, and the latter two traits are likely to be advantageous in a desert environment. The BC2 hybrids contained a range of variation that overlapped these transgressive trait means, and an analysis of phenotypic selection revealed that some of the selective pressures on leaf size and flowering date, but not stem diameter, would move the BC2 population toward the H. deserticola phenotype. Thus, H. deserticola may have originated from habitat-mediated directional selection acting on hybrids between H. annuus and H. petiolaris in a desert environment. PMID:15278840

Herbivores modify selection on plant functional traits in a temperate rainforest understory.

PubMed

Salgado-Luarte, Cristian; Gianoli, Ernesto

2012-08-01

There is limited evidence regarding the adaptive value of plant functional traits in contrasting light environments. It has been suggested that changes in these traits in response to light availability can increase herbivore susceptibility. We tested the adaptive value of plant functional traits linked with carbon gain in contrasting light environments and also evaluated whether herbivores can modify selection on these traits in each light environment. In a temperate rainforest, we examined phenotypic selection on functional traits in seedlings of the pioneer tree Aristotelia chilensis growing in sun (canopy gap) and shade (forest understory) and subjected to either natural herbivory or herbivore exclusion. We found differential selection on functional traits depending on light environment. In sun, there was positive directional selection on photosynthetic rate and relative growth rate (RGR), indicating that selection favors competitive ability in a high-resource environment. Seedlings with high specific leaf area (SLA) and intermediate RGR were selected in shade, suggesting that light capture and conservative resource use are favored in the understory. Herbivores reduced the strength of positive directional selection acting on SLA in shade. We provide the first demonstration that natural herbivory rates can change the strength of selection on plant ecophysiological traits, that is, attributes whose main function is resource uptake. Research addressing the evolution of shade tolerance should incorporate the selective role of herbivores.

Gene expression allelic imbalance in ovine brown adipose tissue impacts energy homeostasis

PubMed Central

Ghazanfar, Shila; Vuocolo, Tony; Morrison, Janna L.; Nicholas, Lisa M.; McMillen, Isabella C.; Yang, Jean Y. H.; Buckley, Michael J.

2017-01-01

Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects. Allele specific gene expression or allelic imbalance in gene expression (AI) occurring at heterozygous loci provides an opportunity to identify genes directly impacted by cis-acting genetic variants as indirect trans-acting effects equally impact the expression of both alleles. However, the identification of genes showing AI in the context of the expression of all genes remains a challenge due to a variety of technical and statistical issues. The current study focuses on the discovery of genes showing AI using single nucleotide polymorphisms as allelic reporters. By developing a computational and statistical process that addressed multiple analytical challenges, we ranked 5,809 genes for evidence of AI using RNA-Seq data derived from brown adipose tissue samples from a cohort of late gestation fetal lambs and then identified a conservative subgroup of 1,293 genes. Thus, AI was extensive, representing approximately 25% of the tested genes. Genes associated with AI were enriched for multiple Gene Ontology (GO) terms relating to lipid metabolism, mitochondrial function and the extracellular matrix. These functions suggest that cis-acting genetic variations causing AI in the population are preferentially impacting genes involved in energy homeostasis and tissue remodelling. These functions may contribute to production traits likely to be under genetic selection in the population. PMID:28665992

Crowd of individuals walking in opposite directions. A toy model to study the segregation of the group into lanes of individuals moving in the same direction

NASA Astrophysics Data System (ADS)

Goldsztein, Guillermo H.

2017-08-01

Consider a corridor, street or bridge crowded with pedestrians walking in both directions. The individuals do not walk in a completely straight line. They adjust their path to avoid colliding with incoming pedestrians. As a result of these adjustments, the whole group sometimes end up split into lanes of individuals moving in the same direction. While this formation of lanes facilitates the flow and benefits the whole group, it is believed that results from the actions of the individuals acting only on their behalf, without considering others. This phenomenon is an example of self-organization. We analyze a simple model. We assume that individuals move around a two-lane circular track. All of them at the same speed. Half of them in one direction and the rest in the opposite direction. Each time two individuals collide, one of them moves to the other lane. The individual changing lanes is selected randomly. The system self-organizes. Eventually each lane is occupied with individuals moving in only one direction. We show that the time required for the system to self-organize is bounded by a linear function on the number of individuals. This toy model provides an example where global self-organization occurs even though each member of the group acts without considering the rest.

Preparatory attention in visual cortex.

PubMed

Battistoni, Elisa; Stein, Timo; Peelen, Marius V

2017-05-01

Top-down attention is the mechanism that allows us to selectively process goal-relevant aspects of a scene while ignoring irrelevant aspects. A large body of research has characterized the effects of attention on neural activity evoked by a visual stimulus. However, attention also includes a preparatory phase before stimulus onset in which the attended dimension is internally represented. Here, we review neurophysiological, functional magnetic resonance imaging, magnetoencephalography, electroencephalography, and transcranial magnetic stimulation (TMS) studies investigating the neural basis of preparatory attention, both when attention is directed to a location in space and when it is directed to nonspatial stimulus attributes (content-based attention) ranging from low-level features to object categories. Results show that both spatial and content-based attention lead to increased baseline activity in neural populations that selectively code for the attended attribute. TMS studies provide evidence that this preparatory activity is causally related to subsequent attentional selection and behavioral performance. Attention thus acts by preactivating selective neurons in the visual cortex before stimulus onset. This appears to be a general mechanism that can operate on multiple levels of representation. We discuss the functional relevance of this mechanism, its limitations, and its relation to working memory, imagery, and expectation. We conclude by outlining open questions and future directions. © 2017 New York Academy of Sciences.

Sexy sons: a dead end for cytoplasmic genes.

PubMed

Zeh, Jeanne A

2004-08-07

Critics of sexual conflict theory argue that females may gain a net reproductive benefit from mating with manipulative males because the direct costs that they suffer may be offset by the production of sexy, i.e. manipulative, sons. However, this exclusive focus on nuclear gene effects represents an incomplete view of female fitness. Females differ fundamentally from males in transmitting not only nuclear genes but also a wide range of cytoplasmic genetic elements (CGEs) that can have profound effects, from male killing to influencing development of the nervous system and cognitive ability. Maternal transmission of CGEs has two major implications for sexual selection. First, the evolution of male fitness traits, such as sperm competitive ability, may be constrained because response to selection on mitochondrial genomes can occur only through the female line. Second, CGEs bear the direct costs of male manipulation but gain no indirect benefits when females produce sexy sons. This should result in perpetual antagonistic coevolution between nuclear genes involved in male manipulation and CGEs that promote female resistance to male sexually selected traits. Explicit consideration of the consequences of selection acting on CGEs is therefore necessary for a better understanding of the relationship between sexual selection and sexual conflict.

Sexy sons: a dead end for cytoplasmic genes.

PubMed Central

Zeh, Jeanne A

2004-01-01

Critics of sexual conflict theory argue that females may gain a net reproductive benefit from mating with manipulative males because the direct costs that they suffer may be offset by the production of sexy, i.e. manipulative, sons. However, this exclusive focus on nuclear gene effects represents an incomplete view of female fitness. Females differ fundamentally from males in transmitting not only nuclear genes but also a wide range of cytoplasmic genetic elements (CGEs) that can have profound effects, from male killing to influencing development of the nervous system and cognitive ability. Maternal transmission of CGEs has two major implications for sexual selection. First, the evolution of male fitness traits, such as sperm competitive ability, may be constrained because response to selection on mitochondrial genomes can occur only through the female line. Second, CGEs bear the direct costs of male manipulation but gain no indirect benefits when females produce sexy sons. This should result in perpetual antagonistic coevolution between nuclear genes involved in male manipulation and CGEs that promote female resistance to male sexually selected traits. Explicit consideration of the consequences of selection acting on CGEs is therefore necessary for a better understanding of the relationship between sexual selection and sexual conflict. PMID:15504002

Direct Synthesis of Silicon Nanowires, Silica Nanospheres, Wire-Like Nanosphere Agglomerates, and Silica-Based Nanotubes and Nanofiber Arrays

DTIC Science & Technology

2001-01-01

decades, the vapor-liquid-solid (VLS) process, ’ 2 where gold particles act as a mediating solvent on a silicon substrate, forming a molten alloy, has...34Nanocatalysis: Selective Conversion of Ethanol to Acetaldehyde Using Monoatomically Dispersed Copper on Silica Nanospheres", Journal of Catalysis, submitted. 7.Sales literature, Cabot Corporation. C5.9.8 Nanoparticles in Biology

Toward an integrated account of object and action selection: A computational analysis and empirical findings from reaching-to-grasp and tool-use

PubMed Central

Botvinick, Matthew M.; Buxbaum, Laurel J.; Bylsma, Lauren M.; Jax, Steven A.

2014-01-01

The act of reaching for and acting upon an object involves two forms of selection: selection of the object as a target, and selection of the action to be performed. While these two forms of selection are logically dissociable, and are evidently subserved by separable neural pathways, they must also be closely coordinated. We examine the nature of this coordination by developing and analyzing a computational model of object and action selection first proposed by Ward [Ward, R. (1999). Interactions between perception and action systems: a model for selective action. In G. W. Humphreys, J. Duncan, & A. Treisman (Eds.), Attention, Space and Action: Studies in Cognitive Neuroscience. Oxford: Oxford University Press]. An interesting tenet of this account, which we explore in detail, is that the interplay between object and action selection depends critically on top-down inputs representing the current task set or plan of action. A concrete manifestation of this, established through a series of simulations, is that the impact of distractor objects on reaching times can vary depending on the nature of the current action plan. In order to test the model's predictions in this regard, we conducted two experiments, one involving direct object manipulation, the other involving tool-use. In both experiments we observed the specific interaction between task set and distractor type predicted by the model. Our findings provide support for the computational model, and more broadly for an interactive account of object and action selection. PMID:19100758

Agonist-Directed Desensitization of the β2-Adrenergic Receptor

PubMed Central

Goral, Vasiliy; Jin, Yan; Sun, Haiyan; Ferrie, Ann M.; Wu, Qi; Fang, Ye

2011-01-01

The β2-adrenergic receptor (β2AR) agonists with reduced tachyphylaxis may offer new therapeutic agents with improved tolerance profile. However, receptor desensitization assays are often inferred at the single signaling molecule level, thus ligand-directed desensitization is poorly understood. Here we report a label-free biosensor whole cell assay with microfluidics to determine ligand-directed desensitization of the β2AR. Together with mechanistic deconvolution using small molecule inhibitors, the receptor desensitization and resensitization patterns under the short-term agonist exposure manifested the long-acting agonism of salmeterol, and differentiated the mechanisms of agonist-directed desensitization between a full agonist epinephrine and a partial agonist pindolol. This study reveals the cellular mechanisms of agonist-selective β2AR desensitization at the whole cell level. PMID:21541288

Pragmatic Study of Directive Speech Acts in Stories in Alquran

ERIC Educational Resources Information Center

Santosa, Rochmat Budi; Nurkamto, Joko; Baidan, Nashruddin; Sumarlam

2016-01-01

This study aims at describing the directive speech acts in the verses that contain the stories in the Qur'an. Specifically, the objectives of this study are to assess the sub directive speech acts contained in the verses of the stories and the dominant directive speech acts. The research target is the verses ("ayat") containing stories…

Demographic noise can reverse the direction of deterministic selection

PubMed Central

Constable, George W. A.; Rogers, Tim; McKane, Alan J.; Tarnita, Corina E.

2016-01-01

Deterministic evolutionary theory robustly predicts that populations displaying altruistic behaviors will be driven to extinction by mutant cheats that absorb common benefits but do not themselves contribute. Here we show that when demographic stochasticity is accounted for, selection can in fact act in the reverse direction to that predicted deterministically, instead favoring cooperative behaviors that appreciably increase the carrying capacity of the population. Populations that exist in larger numbers experience a selective advantage by being more stochastically robust to invasions than smaller populations, and this advantage can persist even in the presence of reproductive costs. We investigate this general effect in the specific context of public goods production and find conditions for stochastic selection reversal leading to the success of public good producers. This insight, developed here analytically, is missed by the deterministic analysis as well as by standard game theoretic models that enforce a fixed population size. The effect is found to be amplified by space; in this scenario we find that selection reversal occurs within biologically reasonable parameter regimes for microbial populations. Beyond the public good problem, we formulate a general mathematical framework for models that may exhibit stochastic selection reversal. In this context, we describe a stochastic analog to r−K theory, by which small populations can evolve to higher densities in the absence of disturbance. PMID:27450085

Facility siting as a decision process at the Savannah River Site

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

Wike, L.D.

1995-12-31

Site selection for new facilities at Savannah River Site (SRS) historically has been a process dependent only upon specific requirements of the facility. While this approach is normally well suited to engineering and operational concerns, it can have serious deficiencies in the modern era of regulatory oversight and compliance requirements. There are many issues related to the site selection for a facility that are not directly related to engineering or operational requirements; such environmental concerns can cause large schedule delays and budget impact,s thereby slowing or stopping the progress of a project. Some of the many concerns in locating amore » facility include: waste site avoidance, National Environmental Policy Act requirements, Clean Water Act, Clean Air Act, wetlands conservation, US Army Corps of Engineers considerations, US Fish and Wildlife Service statutes including threatened and endangered species issues, and State of South Carolina regulations, especially those of the Department of Health and Environmental Control. In addition, there are SRS restrictions on research areas set aside for National Environmental Research Park (NERP), Savannah River Ecology Laboratory, Savannah River Forest Station, University of South Carolina Institute of Archaeology and Anthropology, Southeastern Forest Experimental Station, and Savannah River Technology Center (SRTC) programs. As with facility operational needs, all of these siting considerations do not have equal importance. The purpose of this document is to review recent site selection exercises conducted for a variety of proposed facilities, develop the logic and basis for the methods employed, and standardize the process and terminology for future site selection efforts.« less

An Approach to Greater Specificity for Glucocorticoids

PubMed Central

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

TRIM-directed selective autophagy regulates immune activation.

PubMed

Kimura, Tomonori; Jain, Ashish; Choi, Seong Won; Mandell, Michael A; Johansen, Terje; Deretic, Vojo

2017-05-04

Selectivity of autophagy is achieved by target recognition; however, the number of autophagy receptors identified so far is limited. In this study we demonstrate that a subset of tripartite motif (TRIM) proteins mediate selective autophagy of key regulators of inflammatory signaling. MEFV/TRIM20, and TRIM21 act as autophagic receptors recognizing their cognate targets and delivering them for autophagic degradation. MEFV recognizes the inflammasome components NLRP3, CASP1 and NLRP1, whereas TRIM21 specifically recognizes the activated, dimeric from of IRF3 inducing type I interferon gene expression. MEFV and TRIM21 have a second activity, whereby they act not only as receptors but also recruit and organize key components of autophagic machinery consisting of ULK1, BECN1, ATG16L1, and mammalian homologs of Atg8, with a preference for GABARAP. MEFV capacity to organize the autophagy apparatus is affected by common mutations causing familial Mediterranean fever. These findings reveal a general mode of action of TRIMs as autophagic receptor-regulators performing a highly-selective type of autophagy (precision autophagy), with MEFV specializing in the suppression of inflammasome and CASP1 activation engendering IL1B/interleukin-1β production and implicated in the form of cell death termed pyroptosis, whereas TRIM21 dampens type I interferon responses.

Heritability, covariation and natural selection on 24 traits of common evening primrose (Oenothera biennis) from a field experiment.

PubMed

Johnson, M T J; Agrawal, A A; Maron, J L; Salminen, J-P

2009-06-01

This study explored genetic variation and co-variation in multiple functional plant traits. Our goal was to characterize selection, heritabilities and genetic correlations among different types of traits to gain insight into the evolutionary ecology of plant populations and their interactions with insect herbivores. In a field experiment, we detected significant heritable variation for each of 24 traits of Oenothera biennis and extensive genetic covariance among traits. Traits with diverse functions formed several distinct groups that exhibited positive genetic covariation with each other. Genetic variation in life-history traits and secondary chemistry together explained a large proportion of variation in herbivory (r(2) = 0.73). At the same time, selection acted on lifetime biomass, life-history traits and two secondary compounds of O. biennis, explaining over 95% of the variation in relative fitness among genotypes. The combination of genetic covariances and directional selection acting on multiple traits suggests that adaptive evolution of particular traits is constrained, and that correlated evolution of groups of traits will occur, which is expected to drive the evolution of increased herbivore susceptibility. As a whole, our study indicates that an examination of genetic variation and covariation among many different types of traits can provide greater insight into the evolutionary ecology of plant populations and plant-herbivore interactions.

75 FR 44724 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Reorganization of the Select Agent and Toxin List AGENCY: Animal and Plant Health Inspection Service, USDA... Agricultural Bioterrorism Protection Act of 2002, we are soliciting public comment regarding the list of select...

The Effects of Direct and Indirect Speech Acts on Native English and ESL Speakers' Perception of Teacher Written Feedback

ERIC Educational Resources Information Center

Baker, Wendy; Hansen Bricker, Rachel

2010-01-01

This study explores how second language (L2) learners perceive indirect (hedging or indirect speech acts) and direct written teacher feedback. Though research suggests that indirect speech acts may be more difficult to interpret than direct speech acts ([Champagne, 2001] and [Holtgraves, 1999]), using indirect speech acts is often encouraged in…

Laser additive manufacturing of 3D meshes for optical applications.

PubMed

Essa, Khamis; Sabouri, Aydin; Butt, Haider; Basuny, Fawzia Hamed; Ghazy, Mootaz; El-Sayed, Mahmoud Ahmed

2018-01-01

Selective laser melting (SLM) is a widely used additive manufacturing process that can be used for printing of intricate three dimensional (3D) metallic structures. Here we demonstrate the fabrication of titanium alloy Ti-6Al-4V alloy based 3D meshes with nodally-connected diamond like unit cells, with lattice spacing varying from 400 to 1000 microns. A Concept Laser M2 system equipped with laser that has a wavelength of 1075 nm, a constant beam spot size of 50μm and maximum power of 400W was used to manufacture the 3D meshes. These meshes act as optical shutters / directional transmitters and display interesting optical properties. A detailed optical characterisation was carried out and it was found that these structures can be optimised to act as scalable rotational shutters with high efficiencies and as angle selective transmission screens for protection against unwanted and dangerous radiations. The efficiency of fabricated lattice structures can be increased by enlarging the meshing size.

Laser additive manufacturing of 3D meshes for optical applications

PubMed Central

Essa, Khamis; Sabouri, Aydin; Butt, Haider; Basuny, Fawzia Hamed; Ghazy, Mootaz

2018-01-01

Selective laser melting (SLM) is a widely used additive manufacturing process that can be used for printing of intricate three dimensional (3D) metallic structures. Here we demonstrate the fabrication of titanium alloy Ti–6Al–4V alloy based 3D meshes with nodally-connected diamond like unit cells, with lattice spacing varying from 400 to 1000 microns. A Concept Laser M2 system equipped with laser that has a wavelength of 1075 nm, a constant beam spot size of 50μm and maximum power of 400W was used to manufacture the 3D meshes. These meshes act as optical shutters / directional transmitters and display interesting optical properties. A detailed optical characterisation was carried out and it was found that these structures can be optimised to act as scalable rotational shutters with high efficiencies and as angle selective transmission screens for protection against unwanted and dangerous radiations. The efficiency of fabricated lattice structures can be increased by enlarging the meshing size. PMID:29414982

Noseleaf pit in Egyptian slit-faced bat as a doubly curved reflector

NASA Astrophysics Data System (ADS)

Zhuang, Qiao; Wang, Xiao-Min; Li, Ming-Xuan; Mao, Jie; Wang, Fu-Xun

2012-02-01

Noseleaves in slit-faced bats have been hypothesized to affect the sonar beam. Using numerical methods, we show that the pit in the noseleaf of an Egyptian slit-faced bat has an effect on focusing the acoustic near field as well as shaping the radiation patterns and hence enhancing the directionality. The underlying physical mechanism suggested by the properties of the effect is that the pit acts as a doubly curved reflector. Thanks to the pit the beam shape is overall directional and more selectively widened at the high end of the biosonar frequency range to improve spatial coverage and detectability of targets.

δ-Conotoxins synthesized using an acid-cleavable solubility tag approach reveal key structural determinants for NaV subtype selectivity.

PubMed

Peigneur, Steve; Paolini-Bertrand, Marianne; Gaertner, Hubert; Biass, Daniel; Violette, Aude; Stöcklin, Reto; Favreau, Philippe; Tytgat, Jan; Hartley, Oliver

2014-12-19

Conotoxins are venom peptides from cone snails with multiple disulfide bridges that provide a rigid structural scaffold. Typically acting on ion channels implicated in neurotransmission, conotoxins are of interest both as tools for pharmacological studies and as potential new medicines. δ-Conotoxins act by inhibiting inactivation of voltage-gated sodium channels (Nav). Their pharmacology has not been extensively studied because their highly hydrophobic character makes them difficult targets for chemical synthesis. Here we adopted an acid-cleavable solubility tag strategy that facilitated synthesis, purification, and directed disulfide bridge formation. Using this approach we readily produced three native δ-conotoxins from Conus consors plus two rationally designed hybrid peptides. We observed striking differences in Nav subtype selectivity across this group of compounds, which differ in primary structure at only three positions: 12, 23, and 25. Our results provide new insights into the structure-activity relationships underlying the Nav subtype selectivity of δ-conotoxins. Use of the acid-cleavable solubility tag strategy should facilitate synthesis of other hydrophobic peptides with complex disulfide bridge patterns. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Propagative selection of tilted array patterns in directional solidification

NASA Astrophysics Data System (ADS)

Song, Younggil; Akamatsu, Silvère; Bottin-Rousseau, Sabine; Karma, Alain

2018-05-01

We investigate the dynamics of tilted cellular/dendritic array patterns that form during directional solidification of a binary alloy when a preferred-growth crystal axis is misoriented with respect to the temperature gradient. In situ experimental observations and phase-field simulations in thin samples reveal the existence of a propagative source-sink mechanism of array spacing selection that operates on larger space and time scales than the competitive growth at play during the initial solidification transient. For tilted arrays, tertiary branching at the diverging edge of the sample acts as a source of new cells with a spacing that can be significantly larger than the initial average spacing. A spatial domain of large spacing then invades the sample propagatively. It thus yields a uniform spacing everywhere, selected independently of the initial conditions, except in a small region near the converging edge of the sample, which acts as a sink of cells. We propose a discrete geometrical model that describes the large-scale evolution of the spatial spacing profile based on the local dependence of the cell drift velocity on the spacing. We also derive a nonlinear advection equation that predicts the invasion velocity of the large-spacing domain, and sheds light on the fundamental nature of this process. The models also account for more complex spacing modulations produced by an irregular dynamics at the source, in good quantitative agreement with both phase-field simulations and experiments. This basic knowledge provides a theoretical basis to improve the processing of single crystals or textured polycrystals for advanced materials.

77 FR 24373 - International Services Surveys and Direct Investment Surveys Reporting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

.... 111012619-2230-03] RIN 0691-AA81 International Services Surveys and Direct Investment Surveys Reporting... services and direct investment surveys, which are provided for by the International Investment and Trade in Services Survey Act (the Act). In addition to the Act, the Omnibus Trade and Competitiveness Act of 1988...

Impact of treatment and re-treatment with artemether-lumefantrine and artesunate-amodiaquine on selection of Plasmodium falciparum multidrug resistance gene-1 polymorphisms in the Democratic Republic of Congo and Uganda

PubMed Central

Mavoko, Hypolite Muhindo; Nabasumba, Carolyn; Francis, Filbert; Lutumba, Pascal; Alifrangis, Michael; Van geertruyden, Jean-Pierre

2018-01-01

Background The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings. Methods P. falciparum positive samples were collected from children aged 12–59 months in a clinical trial in DR Congo and Uganda. Pfmdr1 single nucleotide polymorphisms (SNPs) analysis at codons N86Y, Y184F, and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism (RFLP) assays. Results The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites, (p>0.001) and (p = 0.013), respectively. There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment with AL in Uganda site (p = 0.05). Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ. Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86, D1246 alleles in the pre-RCT, RCT and post-RCT phases in both AL and ASAQ treatment arms. Pfmdr1 86Y was significantly associated with reduced risk of AL treatment failure (RR = 0.34, 95% CI:0.11–1.05, p = 0.04) while no evidence for D1246 allele (RR = 1.02; 95% CI: 0.42–2.47, p = 1.0). Survival estimates showed that the Pfmdr1 alleles had comparable mean-time to PCR-corrected recrudescence and new infections in both AL and ASAQ treatment arms. Conclusion We found limited impact of (re-)treatment with AL or ASAQ on selection for Pfmdr1 variants and haplotypes associated with resistance to partner drugs. These findings further supplement the evidence use of same or alternative ACTs as a rescue therapy for recurrent P.falciparum infections. Continued monitoring of genetic signatures of resistance is warranted to timely inform malaria (re-)treatment policies and guidelines. PMID:29390014

Testing for the Occurrence of Selective Episodes During the Divergence of Otophysan Fishes: Insights from Mitogenomics.

PubMed

D'Anatro, Alejandro; Giorello, Facundo; Feijoo, Matías; Lessa, Enrique P

2017-04-01

How natural selection shapes biodiversity constitutes a topic of renewed interest during the last few decades. The division Otophysi comprises approximately two-thirds of freshwater fish diversity and probably underwent an extensive adaptive radiation derived from a single invasion of the supercontinent Pangaea, giving place to the evolution of the main five Otophysan lineages during a short period of time. Little is known about the factors involved in the processes that lead to lineage diversification among this group of fishes and identifying directional selection acting over protein-coding genes could offer clues about the processes acting on species diversification. The main objective of this study was to explore the otophysan mitochondrial genome evolution, in order to account for the possible signatures of selective events in this lineage, and to explore for the functional connotations of these molecular substitutions. Mainly, three different approaches were used: the "ω-based" BS-REL and MEME methods, implemented in the DATAMONKEY web server, and analysis of selection on amino acid properties, implemented in the software TreeSAAP. We found evidence of selective episodes along several branches of the evolutionary history of othophysan fishes. Analyses carried out using the BS-REL algorithm suggest episodic diversifying selection at basal branches of the otophysan lineage, which was also supported by analyses implemented in MEME and TreeSAAP. These results suggest that throughout the Siluriformes radiation, an important number of adaptive changes occurred in their mitochondrial genome. The metabolic consequences and ecological correlates of these molecular substitutions should be addressed in future studies.

Selection on female behaviour fluctuates with offspring environment.

PubMed

Taylor, R W; Boutin, S; Humphries, M M; McAdam, A G

2014-11-01

Temporal variation in selection has long been proposed as a mechanism by which genetic variation could be maintained despite short-term strong directional selection and has been invoked to explain the maintenance of consistent individual differences in behaviour. We tested the hypothesis that ecological changes through time lead to fluctuating selection, which could promote the maintenance of variation in female behavioural traits in a wild population of North American red squirrels. As predicted, linear selection gradients on female aggression and activity significantly fluctuated across years depending on the level of competition among juveniles for vacant territories. This selection acted primarily through juvenile overwinter survival rather than maternal fecundity. Incorporating uncertainty in individual measures of behaviour reduced the magnitude of annual selection gradients and increased uncertainty in these estimates, but did not affect the overall pattern of temporal fluctuations in natural selection that coincided with the intensity of competition for vacant territories. These temporal fluctuations in selection might, therefore, promote the maintenance of heritable individual differences in behaviour in this wild red squirrel population. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

The Creativity of Natural Selection? Part I: Darwin, Darwinism, and the Mutationists.

PubMed

Beatty, John

2016-12-01

This is the first of a two-part essay on the history of debates concerning the creativity of natural selection, from Darwin through the evolutionary synthesis and up to the present. Here I focus on the mid-late nineteenth century to the early twentieth, with special emphasis on early Darwinism and its critics, the self-styled "mutationists." The second part focuses on the evolutionary synthesis and some of its critics, especially the "neutralists" and "neo-mutationists." Like Stephen Gould, I consider the creativity of natural selection to be a key component of what has traditionally counted as "Darwinism." I argue that the creativity of natural selection is best understood in terms of (1) selection initiating evolutionary change, and (2) selection being responsible for the presence of the variation it acts upon, for example by directing the course of variation. I consider the respects in which both of these claims sound non-Darwinian, even though they have long been understood by supporters and critics alike to be virtually constitutive of Darwinism.

Differences in selection drive olfactory receptor genes in different directions in dogs and wolf.

PubMed

Chen, Rui; Irwin, David M; Zhang, Ya-Ping

2012-11-01

The olfactory receptor (OR) gene family is the largest gene family found in mammalian genomes. It is known to evolve through a birth-and-death process. Here, we characterized the sequences of 16 segregating OR pseudogenes in the samples of the wolf and the Chinese village dog (CVD) and compared them with the sequences from dogs of different breeds. Our results show that the segregating OR pseudogenes in breed dogs are under strong purifying selection, while evolving neutrally in the CVD, and show a more complicated pattern in the wolf. In the wolf, we found a trend to remove deleterious polymorphisms and accumulate nondeleterious polymorphisms. On the basis of protein structure of the ORs, we found that the distribution of different types of polymorphisms (synonymous, nonsynonymous, tolerated, and untolerated) varied greatly between the wolf and the breed dogs. In summary, our results suggest that different forms of selection have acted on the segregating OR pseudogenes in the CVD since domestication, breed dogs after breed formation, and ancestral wolf population, which has driven the evolution of these genes in different directions.

Fluctuating selection: the perpetual renewal of adaptation in variable environments

PubMed Central

Bell, Graham

2010-01-01

Darwin insisted that evolutionary change occurs very slowly over long periods of time, and this gradualist view was accepted by his supporters and incorporated into the infinitesimal model of quantitative genetics developed by R. A. Fisher and others. It dominated the first century of evolutionary biology, but has been challenged in more recent years both by field surveys demonstrating strong selection in natural populations and by quantitative trait loci and genomic studies, indicating that adaptation is often attributable to mutations in a few genes. The prevalence of strong selection seems inconsistent, however, with the high heritability often observed in natural populations, and with the claim that the amount of morphological change in contemporary and fossil lineages is independent of elapsed time. I argue that these discrepancies are resolved by realistic accounts of environmental and evolutionary changes. First, the physical and biotic environment varies on all time-scales, leading to an indefinite increase in environmental variance over time. Secondly, the intensity and direction of natural selection are also likely to fluctuate over time, leading to an indefinite increase in phenotypic variance in any given evolving lineage. Finally, detailed long-term studies of selection in natural populations demonstrate that selection often changes in direction. I conclude that the traditional gradualist scheme of weak selection acting on polygenic variation should be supplemented by the view that adaptation is often based on oligogenic variation exposed to commonplace, strong, fluctuating natural selection. PMID:20008388

Proanthocyanidins from the bark of Hamamelis virginiana exhibit antimutagenic properties against nitroaromatic compounds.

PubMed

Dauer, A; Metzner, P; Schimmer, O

1998-05-01

The antimutagenic activity of Hamamelis virginiana bark was examined in the Ames assay. A commercial tincture and a methanolic extract showed dose-dependent inhibitory effects on mutagenicity induced by 2-nitrofluorene. Tannin-free samples did not display any inhibition. Bioassay-guided fractionation resulted in the isolation of two active fractions which were shown to contain oligomeric, proanthocyanidins. They were capable of inhibiting the mutagenicity of selected nitroaromatic compounds. The mechanism of antimutagenic action was also studied. The proanthocyanidins did not act as bioantimutagens, but rather as direct-acting desmutagens. The antimutagenic effect increased with an increasing degree of polymerisation in the proanthocyanidins. The most active fraction consisted of catechin and gallocatechin oligomers with an average polymerisation degree of 9.2.

Consistent Selection towards Low Activity Phenotypes When Catchability Depends on Encounters among Human Predators and Fish

PubMed Central

Alós, Josep; Palmer, Miquel; Arlinghaus, Robert

2012-01-01

Together with life-history and underlying physiology, the behavioural variability among fish is one of the three main trait axes that determines the vulnerability to fishing. However, there are only a few studies that have systematically investigated the strength and direction of selection acting on behavioural traits. Using in situ fish behaviour revealed by telemetry techniques as input, we developed an individual-based model (IBM) that simulated the Lagrangian trajectory of prey (fish) moving within a confined home range (HR). Fishers exhibiting various prototypical fishing styles targeted these fish in the model. We initially hypothesised that more active and more explorative individuals would be systematically removed under all fished conditions, in turn creating negative selection differentials on low activity phenotypes and maybe on small HR. Our results partly supported these general predictions. Standardised selection differentials were, on average, more negative on HR than on activity. However, in many simulation runs, positive selection pressures on HR were also identified, which resulted from the stochastic properties of the fishes’ movement and its interaction with the human predator. In contrast, there was a consistent negative selection on activity under all types of fishing styles. Therefore, in situations where catchability depends on spatial encounters between human predators and fish, we would predict a consistent selection towards low activity phenotypes and have less faith in the direction of the selection on HR size. Our study is the first theoretical investigation on the direction of fishery-induced selection of behaviour using passive fishing gears. The few empirical studies where catchability of fish was measured in relation to passive fishing techniques, such as gill-nets, traps or recreational fishing, support our predictions that fish in highly exploited situations are, on average, characterised by low swimming activity, stemming, in part, from negative selection on swimming activity. PMID:23110164

Genetic architecture of hybrid male sterility in Drosophila: analysis of intraspecies variation for interspecies isolation.

PubMed

Reed, Laura K; LaFlamme, Brooke A; Markow, Therese A

2008-08-27

The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. Isofemale strains of D. mojavensis vary significantly in their production of sterile F(1) sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL) mapping analyses directly on F(1) hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS) in the F(1) is complex, involving multiple QTL, epistasis, and cytoplasmic effects. The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation.

Did template-directed nucleation precede molecular replication?

NASA Technical Reports Server (NTRS)

Orgel, Leslie E.

1986-01-01

It is proposed that mononucleotides incorporated into the surfaces of microcrystals of inorganic phosphates such as hydroxyapatite can act as templates to assemble complementary mononucleotides from solution, and that the phosphate groups of the assembled nucleotides can facilitate nucleation of a second hydroxyapatite crystal. This would provide a mechanism of replication that is subject to natural selection. The possible role of a replicating system of this kind in the origins of life on the earth is discussed.

Mixed infections and the competitive fitness of faster-acting genetically modified viruses

PubMed Central

Zwart, Mark P; Van Der Werf, Wopke; Van Oers, Monique M; Hemerik, Lia; Van Lent, Jan M V; De Visser, J Arjan G M; Vlak, Just M; Cory, Jenny S

2009-01-01

Faster-acting recombinant baculoviruses have shown potential for improved suppression of insect pests, but their ecological impact on target and nontarget hosts and naturally occurring pathogens needs to be assessed. Previous studies have focused on the fitness of recombinants at the between-hosts level. However, the population structure of the transmission stages will also be decided by within-host selection. Here we have experimentally quantified the within-host competitive fitness of a fast-acting recombinant Autographa californica multicapsid nucleopolyhedrovirus missing the endogenous egt gene (vEGTDEL), by means of direct competition in single- and serial-passage experiments with its parental virus. Quantitative real-time PCR was employed to determine the ratio of these two viruses in passaged mixtures. We found that vEGTDEL had reduced within-host fitness: per passage the ratio of wild type to vEGTDEL was on average enhanced by a factor of 1.53 (single passage) and 1.68 (serial passage). There is also frequency-dependence: the higher the frequency of vEGTDEL, the stronger the selection against it is. Additionally, the virus ratio is a predictor of time to host death and virus yield. Our results show that egt is important to within-host fitness and allow for a more complete assessment of the ecological impact of recombinant baculovirus release. PMID:25567862

A Model-Based Approach for Identifying Signatures of Ancient Balancing Selection in Genetic Data

PubMed Central

DeGiorgio, Michael; Lohmueller, Kirk E.; Nielsen, Rasmus

2014-01-01

While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates. PMID:25144706

A model-based approach for identifying signatures of ancient balancing selection in genetic data.

PubMed

DeGiorgio, Michael; Lohmueller, Kirk E; Nielsen, Rasmus

2014-08-01

While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates.

Antibody-mediated delivery of therapeutics for cancer therapy.

PubMed

Parakh, Sagun; Parslow, Adam C; Gan, Hui K; Scott, Andrew M

2016-01-01

Antibody-conjugated therapies (ACTs) combine the specificity of monoclonal antibodies to target cancer cells directly with highly potent payloads, often resulting in superior efficacy and/or reduced toxicity. This represents a new approach to the treatment of cancer. There have been highly promising clinical trial results using this approach with improvements in linker and payload technology. The breadth of current trials examining ACTs in haematological malignancies and solid tumours indicate the potential for clinical impact. This review will provide an overview of ACTs currently in clinical development as well as the principles of antibody delivery and types of payloads used, including cytotoxic drugs, radiolabelled isotopes, nanoparticle-based siRNA particles and immunotoxins. The focus of much of the clinical activity in ACTs has, understandably, been on their use as a monotherapy or in combination with standard of care drugs. This will continue, as will the search for better targets, linkers and payloads. Increasingly, as these drugs enter routine clinical care, important questions will arise regarding how to optimise ACT treatment approaches, including investigation of resistance mechanisms, biomarker and patient selection strategies, understanding of the unique toxicities of these drugs, and combinatorial approaches with standard therapies as well as emerging therapeutic agents like immunotherapy.

Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

PubMed

Virlogeux, Victor; Pradat, Pierre; Hartig-Lavie, Kerstin; Bailly, François; Maynard, Marianne; Ouziel, Guillaume; Poinsot, Domitille; Lebossé, Fanny; Ecochard, Marie; Radenne, Sylvie; Benmakhlouf, Samir; Koffi, Joseph; Lack, Philippe; Scholtes, Caroline; Uhres, Anne-Claire; Ducerf, Christian; Mabrut, Jean-Yves; Rode, Agnès; Levrero, Massimo; Combet, Christophe; Merle, Philippe; Zoulim, Fabien

2017-08-01

Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; P<.001). Hepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors affecting embryo viability and uterine receptivity: insights from an analysis of the UK registry data.

PubMed

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.

20 CFR 670.420 - Are there any special requirements for enrollment related to the Military Selective Service Act?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Are there any special requirements for enrollment related to the Military Selective Service Act? 670.420 Section 670.420 Employees' Benefits... INVESTMENT ACT Recruitment, Eligibility, Screening, Selection and Assignment, and Enrollment § 670.420 Are...

75 FR 42363 - Public Health Security and Bioterrorism Preparedness and Response Act of 2002; Biennial Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... Bioterrorism Preparedness and Response Act of 2002; Biennial Review and Republication of the Select Agent and... Act) requires the biennial review and republication of the HHS list of select agents and toxins. Accordingly, we are soliciting public comment on the current HHS list of select agents and toxins, including...

Natural selection and inheritance of breeding time and clutch size in the collared flycatcher.

PubMed

Sheldon, B C; Kruuk, L E B; Merilä, J

2003-02-01

Many characteristics of organisms in free-living populations appear to be under directional selection, possess additive genetic variance, and yet show no evolutionary response to selection. Avian breeding time and clutch size are often-cited examples of such characters. We report analyses of inheritance of, and selection on, these traits in a long-term study of a wild population of the collared flycatcher Ficedula albicollis. We used mixed model analysis with REML estimation ("animal models") to make full use of the information in complex multigenerational pedigrees. Heritability of laying date, but not clutch size, was lower than that estimated previously using parent-offspring regressions, although for both traits there was evidence of substantial additive genetic variance (h2 = 0.19 and 0.29, respectively). Laying date and clutch size were negatively genetically correlated (rA = -0.41 +/- 0.09), implying that selection on one of the traits would cause a correlated response in the other, but there was little evidence to suggest that evolution of either trait would be constrained by correlations with other phenotypic characters. Analysis of selection on these traits in females revealed consistent strong directional fecundity selection for earlier breeding at the level of the phenotype (beta = -0.28 +/- 0.03), but little evidence for stabilising selection on breeding time. We found no evidence that clutch size was independently under selection. Analysis of fecundity selection on breeding values for laying date, estimated from an animal model, indicated that selection acts directly on additive genetic variance underlying breeding time (beta = -0.20 +/- 0.04), but not on clutch size (beta = 0.03 +/- 0.05). In contrast, selection on laying date via adult female survival fluctuated in sign between years, and was opposite in sign for selection on phenotypes (negative) and breeding values (positive). Our data thus suggest that any evolutionary response to selection on laying date is partially constrained by underlying life-history trade-offs, and illustrate the difficulties in using purely phenotypic measures and incomplete fitness estimates to assess evolution of life-history trade-offs. We discuss some of the difficulties associated with understanding the evolution of laying date and clutch size in natural populations.

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Test act system validation

NASA Technical Reports Server (NTRS)

1985-01-01

The primary objective of the Test Active Control Technology (ACT) System laboratory tests was to verify and validate the system concept, hardware, and software. The initial lab tests were open loop hardware tests of the Test ACT System as designed and built. During the course of the testing, minor problems were uncovered and corrected. Major software tests were run. The initial software testing was also open loop. These tests examined pitch control laws, wing load alleviation, signal selection/fault detection (SSFD), and output management. The Test ACT System was modified to interface with the direct drive valve (DDV) modules. The initial testing identified problem areas with DDV nonlinearities, valve friction induced limit cycling, DDV control loop instability, and channel command mismatch. The other DDV issue investigated was the ability to detect and isolate failures. Some simple schemes for failure detection were tested but were not completely satisfactory. The Test ACT System architecture continues to appear promising for ACT/FBW applications in systems that must be immune to worst case generic digital faults, and be able to tolerate two sequential nongeneric faults with no reduction in performance. The challenge in such an implementation would be to keep the analog element sufficiently simple to achieve the necessary reliability.

The transition to modernity and chronic disease: mismatch and natural selection.

PubMed

Corbett, Stephen; Courtiol, Alexandre; Lummaa, Virpi; Moorad, Jacob; Stearns, Stephen

2018-05-09

The Industrial Revolution and the accompanying nutritional, epidemiological and demographic transitions have profoundly changed human ecology and biology, leading to major shifts in life history traits, which include age and size at maturity, age-specific fertility and lifespan. Mismatch between past adaptations and the current environment means that gene variants linked to higher fitness in the past may now, through antagonistic pleiotropic effects, predispose post-transition populations to non-communicable diseases, such as Alzheimer disease, cancer and coronary artery disease. Increasing evidence suggests that the transition to modernity has also altered the direction and intensity of natural selection acting on many traits, with important implications for public and global health.

Sexual selection on cuticular hydrocarbons in the Australian field cricket, Teleogryllus oceanicus

PubMed Central

Thomas, Melissa L; Simmons, Leigh W

2009-01-01

Background Females in a wide range of taxa have been shown to base their choice of mates on pheromone signals. However, little research has focussed specifically on the form and intensity of selection that mate choice imposes on the pheromone signal. Using multivariate selection analysis, we characterise directly the form and intensity of sexual selection acting on cuticular hydrocarbons, chemical compounds widely used in the selection of mates in insects. Using the Australian field cricket Teleogryllus oceanicus as a model organism, we use three measures of male attractiveness to estimate fitness; mating success, the duration of courtship required to elicit copulation, and subsequent spermatophore attachment duration. Results We found that all three measures of male attractiveness generated sexual selection on male cuticular hydrocarbons, however there were differences in the form and intensity of selection among these three measures. Mating success was the only measure of attractiveness that imposed both univariate linear and quadratic selection on cuticular hydrocarbons. Although we found that all three attractiveness measures generated nonlinear selection, again only mating success was found to exert statistically significant stabilizing selection. Conclusion This study shows that sexual selection plays an important role in the evolution of male cuticular hydrocarbon signals. PMID:19594896

Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro

NASA Technical Reports Server (NTRS)

Phelan, K. D.; Gallagher, J. P.

1992-01-01

We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

Prevention and Treatment of Child Abuse and Neglect: Policy Directions for the Future. Hearing before the Subcommittee on Select Education of the Committee on Education and the Workforce. House of Representatives, One Hundred Seventh Congress, First Session (October 17, 2001).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and the Workforce.

These transcripts present testimony from the second hearing held on the reauthorization of the Child Abuse Prevention and Treatment Act (CAPTA). Discussed at this hearing were total financial costs of child abuse and neglect, cost savings from prevention programs, the role of infant safe havens, and parents' rights. Representative Robert Scott…

Precision Manipulation with Cooperative Robots

NASA Technical Reports Server (NTRS)

Stroupe, Ashley; Huntsberger, Terry; Okon, Avi; Aghzarian, Hrand

2005-01-01

This work addresses several challenges of cooperative transportThis work addresses several challenges of cooperative transport and precision manipulation. Precision manipulation requires a rigid grasp, which places a hard constraint on the relative rover formation that must be accommodated, even though the rovers cannot directly observe their relative poses. Additionally, rovers must jointly select appropriate actions based on all available sensor information. Lastly, rovers cannot act on independent sensor information, but must fuse information to move jointly; the methods for fusing information must be determined.

[Modes of action of agrochemicals against plant pathogenic organisms].

PubMed

Leroux, Pierre

2003-01-01

The chemical control of plant pathogens concerns mainly fungal diseases of crops. Most of the available fungicides act directly on essential fungal functions such as respiration, sterol biosynthesis or cell division. Consequently, these compounds can exhibit undesirable toxicological and environmental effects and sometimes select fungal resistant strains. Plant activators are expected to provide sustainable disease management in several crops because the development of resistance is not expected. Considering the future, the discovery of novel antifungal molecules will reap advantage from throughput screening methodologies and functional genomics.

78 FR 63218 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment... antiviral (DAA) drugs for the treatment of chronic hepatitis C. This guidance revises and replaces a...

Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency changes in polygenic adaptation.

PubMed

Stephan, Wolfgang

2016-01-01

In the past 15 years, numerous methods have been developed to detect selective sweeps underlying adaptations. These methods are based on relatively simple population genetic models, including one or two loci at which positive directional selection occurs, and one or two marker loci at which the impact of selection on linked neutral variation is quantified. Information about the phenotype under selection is not included in these models (except for fitness). In contrast, in the quantitative genetic models of adaptation, selection acts on one or more phenotypic traits, such that a genotype-phenotype map is required to bridge the gap to population genetics theory. Here I describe the range of population genetic models from selective sweeps in a panmictic population of constant size to evolutionary traffic when simultaneous sweeps at multiple loci interfere, and I also consider the case of polygenic selection characterized by subtle allele frequency shifts at many loci. Furthermore, I present an overview of the statistical tests that have been proposed based on these population genetics models to detect evidence for positive selection in the genome. © 2015 John Wiley & Sons Ltd.

76 FR 26948 - Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

...] Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting AGENCY: U.S... series of public meetings on the implementation of provisions of the Small Business Jobs Act of 2010... INFORMATION CONTACT: Richard L. Miller, Small Business Job's Act Tour-Office of Government Contracting and...

Bt: mode of action and use.

PubMed

Whalon, Mark E; Wingerd, Byron A

2003-12-01

The insecticidal toxins from Bacillus thuringiensis (Bt) represent a class of biopesticides that are attractive alternatives to broad-spectrum "hard" chemistries. The U.S. Food Quality Protection Act and the European Economic Council directives aimed at reducing the use of carbamate and organophosphate insecticides were expected to increase the use of narrowly targeted, "soft" compounds like Bt. Here we summarize the unique mode of action of Bt, which contributes to pest selectivity. We also review the patterns of Bt use in general agriculture and in specific niche markets. Despite continued predictions of dramatic growth for biopesticides due to US Food Quality Protection Act-induced cancellations of older insecticides, Bt use has remained relatively constant, even in niche markets where Bt has traditionally been relatively high. Copyright 2003 Wiley-Liss, Inc.

Explaining negative kin discrimination in a cooperative mammal society

PubMed Central

Cant, Michael A.; Sanderson, Jennifer L.; Gilchrist, Jason S.; Bell, Matthew B. V.; Hodge, Sarah J.; Johnstone, Rufus A.

2017-01-01

Kin selection theory predicts that, where kin discrimination is possible, animals should typically act more favorably toward closer genetic relatives and direct aggression toward less closely related individuals. Contrary to this prediction, we present data from an 18-y study of wild banded mongooses, Mungos mungo, showing that females that are more closely related to dominant individuals are specifically targeted for forcible eviction from the group, often suffering severe injury, and sometimes death, as a result. This pattern cannot be explained by inbreeding avoidance or as a response to more intense local competition among kin. Instead, we use game theory to show that such negative kin discrimination can be explained by selection for unrelated targets to invest more effort in resisting eviction. Consistent with our model, negative kin discrimination is restricted to eviction attempts of older females capable of resistance; dominants exhibit no kin discrimination when attempting to evict younger females, nor do they discriminate between more closely or less closely related young when carrying out infanticidal attacks on vulnerable infants who cannot defend themselves. We suggest that in contexts where recipients of selfish acts are capable of resistance, the usual prediction of positive kin discrimination can be reversed. Kin selection theory, as an explanation for social behavior, can benefit from much greater exploration of sequential social interactions. PMID:28439031

77 FR 772 - International Services Surveys and Direct Investment Surveys Reporting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-06

....: 111012619-1619-01] RIN 0691-AA81 International Services Surveys and Direct Investment Surveys Reporting... international trade in services and direct investment surveys provided for by the International Investment and Trade in Services Survey Act (22 U.S.C. 3101 to 3108, (the Act)). In addition to the Act, the Omnibus...

DIRECT-ACTING, DNA-DAMAGING AS (III)-METHYLATED SPECIES: IMPLICATIONS FOR A CARCINOGENIC MECHANISM OF ACTION OF ARSENICALS

EPA Science Inventory

Direct-acting, DNA-damaging As (III)-methylated species: implications for a carcinogenic . mechanism of action of arsenicals

Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a carcinogen without reacting directly with DNA; neither iAs nor the As(...

75 FR 55797 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-14

...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment... antiviral agents (DAAs), defined as agents that interfere with specific steps in the hepatitis C virus (HCV...

Impairment of actions chains in autism and its possible role in intention understanding

PubMed Central

Cattaneo, Luigi; Fabbri-Destro, Maddalena; Boria, Sonia; Pieraccini, Cinzia; Monti, Annalisa; Cossu, Giuseppe; Rizzolatti, Giacomo

2007-01-01

Experiments in monkeys demonstrated that many parietal and premotor neurons coding a specific motor act (e.g., grasping) show a markedly different activation when this act is part of actions that have different goals (e.g., grasping for eating vs. grasping for placing). Many of these “action-constrained” neurons have mirror properties firing selectively to the observation of the initial motor act of the actions to which they belong motorically. By activating a specific action chain from its very outset, this mechanism allows the observers to have an internal copy of the whole action before its execution, thus enabling them to understand directly the agent's intention. Using electromyographic recordings, we show that a similar chained organization exists in typically developing children, whereas it is impaired in children with autism. We propose that, as a consequence of this functional impairment, high-functioning autistic children may understand the intentions of others cognitively but lack the mechanism for understanding them experientially. PMID:17965234

Impairment of actions chains in autism and its possible role in intention understanding.

PubMed

Cattaneo, Luigi; Fabbri-Destro, Maddalena; Boria, Sonia; Pieraccini, Cinzia; Monti, Annalisa; Cossu, Giuseppe; Rizzolatti, Giacomo

2007-11-06

Experiments in monkeys demonstrated that many parietal and premotor neurons coding a specific motor act (e.g., grasping) show a markedly different activation when this act is part of actions that have different goals (e.g., grasping for eating vs. grasping for placing). Many of these "action-constrained" neurons have mirror properties firing selectively to the observation of the initial motor act of the actions to which they belong motorically. By activating a specific action chain from its very outset, this mechanism allows the observers to have an internal copy of the whole action before its execution, thus enabling them to understand directly the agent's intention. Using electromyographic recordings, we show that a similar chained organization exists in typically developing children, whereas it is impaired in children with autism. We propose that, as a consequence of this functional impairment, high-functioning autistic children may understand the intentions of others cognitively but lack the mechanism for understanding them experientially.

Footprints of Directional Selection in Wild Atlantic Salmon Populations: Evidence for Parasite-Driven Evolution?

PubMed Central

Zueva, Ksenia J.; Lumme, Jaakko; Veselov, Alexey E.; Kent, Matthew P.; Lien, Sigbjørn; Primmer, Craig R.

2014-01-01

Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved. PMID:24670947

Footprints of directional selection in wild Atlantic salmon populations: evidence for parasite-driven evolution?

PubMed

Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Lien, Sigbjørn; Primmer, Craig R

2014-01-01

Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved.

Ecological neighborhoods as a framework for umbrella species selection

USGS Publications Warehouse

Stuber, Erica F.; Fontaine, Joseph J.

2018-01-01

Umbrella species are typically chosen because they are expected to confer protection for other species assumed to have similar ecological requirements. Despite its popularity and substantial history, the value of the umbrella species concept has come into question because umbrella species chosen using heuristic methods, such as body or home range size, are not acting as adequate proxies for the metrics of interest: species richness or population abundance in a multi-species community for which protection is sought. How species associate with habitat across ecological scales has important implications for understanding population size and species richness, and therefore may be a better proxy for choosing an umbrella species. We determined the spatial scales of ecological neighborhoods important for predicting abundance of 8 potential umbrella species breeding in Nebraska using Bayesian latent indicator scale selection in N-mixture models accounting for imperfect detection. We compare the conservation value measured as collective avian abundance under different umbrella species selected following commonly used criteria and selected based on identifying spatial land cover characteristics within ecological neighborhoods that maximize collective abundance. Using traditional criteria to select an umbrella species resulted in sub-maximal expected collective abundance in 86% of cases compared to selecting an umbrella species based on land cover characteristics that maximized collective abundance directly. We conclude that directly assessing the expected quantitative outcomes, rather than ecological proxies, is likely the most efficient method to maximize the potential for conservation success under the umbrella species concept.

Fluid-dynamic design optimization of hydraulic proportional directional valves

NASA Astrophysics Data System (ADS)

Amirante, Riccardo; Catalano, Luciano Andrea; Poloni, Carlo; Tamburrano, Paolo

2014-10-01

This article proposes an effective methodology for the fluid-dynamic design optimization of the sliding spool of a hydraulic proportional directional valve: the goal is the minimization of the flow force at a prescribed flow rate, so as to reduce the required opening force while keeping the operation features unchanged. A full three-dimensional model of the flow field within the valve is employed to accurately predict the flow force acting on the spool. A theoretical analysis, based on both the axial momentum equation and flow simulations, is conducted to define the design parameters, which need to be properly selected in order to reduce the flow force without significantly affecting the flow rate. A genetic algorithm, coupled with a computational fluid dynamics flow solver, is employed to minimize the flow force acting on the valve spool at the maximum opening. A comparison with a typical single-objective optimization algorithm is performed to evaluate performance and effectiveness of the employed genetic algorithm. The optimized spool develops a maximum flow force which is smaller than that produced by the commercially available valve, mainly due to some major modifications occurring in the discharge section. Reducing the flow force and thus the electromagnetic force exerted by the solenoid actuators allows the operational range of direct (single-stage) driven valves to be enlarged.

Selective autophagy mediated by autophagic adapter proteins

PubMed Central

Lamark, Trond

2011-01-01

Mounting evidence suggests that autophagy is a more selective process than originally anticipated. The discovery and characterization of autophagic adapters, like p62 and NBR1, has provided mechanistic insight into this process. p62 and NBR1 are both selectively degraded by autophagy and able to act as cargo receptors for degradation of ubiquitinated substrates. A direct interaction between these autophagic adapters and the autophagosomal marker protein LC3, mediated by a so-called LIR (LC3-interacting region) motif, their inherent ability to polymerize or aggregate as well as their ability to specifically recognize substrates are required for efficient selective autophagy. These three required features of autophagic cargo receptors are evolutionarily conserved and also employed in the yeast cytoplasm-to-vacuole targeting (Cvt) pathway and in the degradation of P granules in C. elegans. Here, we review the mechanistic basis of selective autophagy in mammalian cells discussing the degradation of misfolded proteins, p62 bodies, aggresomes, mitochondria and invading bacteria. The emerging picture of selective autophagy affecting the regulation of cell signaling with consequences for oxidative stress responses, tumorigenesis and innate immunity is also addressed. PMID:21189453

Work required for selective quantum measurement

NASA Astrophysics Data System (ADS)

Konishi, Eiji

2018-06-01

In quantum mechanics, we define the measuring system M in a selective measurement by two conditions. Firstly, when we define the measured system S as the system in which the non-selective measurement part acts, M is independent from the measured system S as a quantum system in the sense that any time-dependent process in the total system S  +  M is divisible into parts for S and M. Secondly, when we can separate S and M from each other without changing the unitary equivalence class of the state of S from that obtained by the partial trace of M, the eigenstate selection in the selective measurement cannot be realized. In order for such a system M to exist, we show that in one selective measurement of an observable of a quantum system S 0 of particles in S, there exists a negative entropy transfer from M to S that can be directly transformed into an amount of Helmholtz free energy of where T is the thermodynamic temperature of the system S. Equivalently, an extra amount of work, , is required to be done by the system M.

Phenotypic selection varies with pollination intensity across populations of Sabatia angularis.

PubMed

Emel, Sarah L; Franks, Steven J; Spigler, Rachel B

2017-07-01

Pollinators are considered primary selective agents acting on plant traits, and thus variation in the strength of the plant-pollinator interaction might drive variation in the opportunity for selection and selection intensity across plant populations. Here, we examine whether these critical evolutionary parameters covary with pollination intensity across wild populations of the biennial Sabatia angularis. We quantified pollination intensity in each of nine S. angularis populations as mean stigmatic pollen load per population. For female fitness and three components, fruit number, fruit set (proportion of flowers setting fruit) and number of seeds per fruit, we evaluated whether the opportunity for selection varied with pollination intensity. We used phenotypic selection analyses to test for interactions between pollination intensity and selection gradients for five floral traits, including flowering phenology. The opportunity for selection via fruit set and seeds per fruit declined significantly with increasing pollen receipt, as expected. We demonstrated significant directional selection on multiple traits across populations. We also found that selection intensity for all traits depended on pollination intensity. Consistent with general theory about the relationship between biotic interaction strength and the intensity of selection, our study suggests that variation in pollination intensity drives variation in selection across S. angularis populations. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Drosophila Heartless Acts with Heartbroken/Dof in Muscle Founder Differentiation

PubMed Central

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

Changes in Neuronal Signaling and Cell Stress Response Pathways are Associated with a Multigenic Response of Drosophila melanogaster to DDT Selection

PubMed Central

Coates, Brad S; Sun, Weilin; Clark, John M; Pittendrigh, Barry R

2017-01-01

Abstract The adaptation of insect populations to insecticidal control is a continual threat to human health and sustainable agricultural practices, but many complex genomic mechanisms involved in this adaption remain poorly understood. This study applied a systems approach to investigate the interconnections between structural and functional variance in response to dichlorodiphenyltrichloroethane (DDT) within the Drosophila melanogaster strain 91-R. Directional selection in 6 selective sweeps coincided with constitutive gene expression differences in DDT resistant flies, including the most highly upregulated transcript, Unc-115 b, which plays a central role in axon guidance, and the most highly downregulated transcript, the angiopoietin-like CG31832, which is involved in directing vascular branching and dendrite outgrowth but likely may be under trans-regulatory control. Direct functions and protein–protein interactions mediated by differentially expressed transcripts control changes in cell migration, signal transduction, and gene regulatory cascades that impact the nervous system. Although changes to cellular stress response pathways involve 8 different cytochrome P450s, stress response, and apoptosis is controlled by a multifacetted regulatory mechanism. These data demonstrate that DDT selection in 91-R may have resulted in genome-wide adaptations that impacts genetic and signal transduction pathways that converge to modify stress response, cell survival, and neurological functions. This study implicates the involvement of a multigenic mechanism in the adaptation to a chemical insecticide, which impact interconnected regulatory cascades. We propose that DDT selection within 91-R might act systemically, wherein pathway interactions function to reinforce the epistatic effects of individual adaptive changes on an additive or nonadditive basis. PMID:29211847

Genetic Architecture of Hybrid Male Sterility in Drosophila: Analysis of Intraspecies Variation for Interspecies Isolation

PubMed Central

Reed, Laura K.; LaFlamme, Brooke A.; Markow, Therese A.

2008-01-01

Background The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. Methodology/Principal Findings Isofemale strains of D. mojavensis vary significantly in their production of sterile F1 sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL) mapping analyses directly on F1 hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS) in the F1 is complex, involving multiple QTL, epistasis, and cytoplasmic effects. Conclusions/Significance The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation. PMID:18728782

Energy transport corridors: the potential role of Federal lands in states identified by the Energy Policy Act of 2005, section 368(b).

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

Krummel, J.; Hlohowskyj, I.; Kuiper, J.

2011-09-01

On August 8, 2005, the President signed the Energy Policy Act of 2005 (EPAct) into law. In Subtitle F of EPAct, Congress set forth various provisions that would change the way certain federal agencies (Agencies) coordinate to authorize the use of land for a variety of energy-related purposes. As part of Subtitle F of EPAct, Section 368 addresses the issue of energy transportation corridors on federal land for oil, gas, and hydrogen pipelines, as well as electricity transmission and distribution facilities. Because of the critical importance of improving the nation's electrical transmission grid, Congress recognized that electricity transmission issues shouldmore » receive added attention when the Agencies address corridor location and analysis issues. In Section 368, Congress specifically directed the Agencies to consider the need for upgraded and new facilities to deliver electricity: In carrying out [Section 368], the Secretaries shall take into account the need for upgraded and new electricity transmission and distribution facilities to (1) improve reliability; (2) relieve congestion; and (3) enhance capability of the national grid to deliver electricity. Section 368 does not require the Agencies to consider or approve specific projects, applications for rights-of-way (ROWs), or other permits within designated energy corridors. Importantly, Section 368 does not direct, license, or otherwise permit any on-the-ground activity of any sort. If an applicant is interested in obtaining an authorization to develop a project within any corridor designated under Section 368, the applicant would have to apply for a ROW authorization and applicable permits. The Agencies would consider each application by applying appropriate project-specific reviews under requirements of laws and related regulations, including, but not limited to, the National Environmental Policy Act (NEPA), the Clean Water Act, the Clean Air Act, Section 7 of the Endangered Species Act (ESA), and Section 106 of the National Historic Preservation Act (NHPA). Under Section 368, Congress divided the United States into two groups of states: the 11 contiguous western states and the remaining states. Direction for energy transportation corridor analysis and selection in the 11 western states was addressed in Section 368(a) of EPAct, while direction for energy transportation corridor analysis and selection in all other states was addressed under Section 368(b) of EPAct. It was clearly the priority of Congress to conduct corridor location studies and designation first on federal lands in the western states. Under Section 368(a), the Agencies produced a programmatic environmental impact statement (EIS), Designation of Energy Corridors on Federal Land in the 11 Western States (DOE and DOI 2008), that was used in part as the basis for designating more than 6,000 mi (9,656 km) of energy transportation corridors on federal land in 11 western states. Under Section 368(a) of EPAct, Congress clearly stated the Agencies needed to (1) designate energy transportation corridors on federal land, (2) conduct the necessary environmental review of the designated corridors, and (3) incorporate the designated corridors into the appropriate land use plans. Congressional direction under Section 368(b) of EPAct differs from that provided under Section 368(a). Specifically, Section 368(b) requires the secretaries of the Agencies, in consultation with the Federal Energy Regulatory Commission (FERC), affected utility industries, and other interested persons, to jointly: (1) Identify corridors for oil, gas, and hydrogen pipelines and electricity transmission and distribution facilities on federal land in states other than the 11 western states identified under Section 368(a) of EPAct, and (2) Schedule prompt action to identify, designate, and incorporate the corridors into the applicable land use plans. While Section 368(a) clearly directs designation as a necessary first step for energy transportation corridors in the 11 western states, Section 368(b) directs the Agencies to first identify corridors and then schedule prompt action to identify, designate, and incorporate the corridors into applicable land use plans. To comply with the congressional direction provided in Section 368(b), the Agencies investigated corridor identification issues in the Section 368(b) states; this report to Congress provides information that could be relevant to possible future designation of energy corridors. Future designations, if appropriate and necessary, would occur when the Agencies undertake revisions and/or updates to land use plans that guide management decisions on lands located within individual administrative units, such as specific National Forests, National Parks, or Wildlife Refuges. At this time, the Agencies are not proposing any actions or decisions related directly or indirectly to designating energy corridors on federal land under Section 368(b) of EPAct.« less

To lie or not to lie: to whom and under what circumstances.

PubMed

Perkins, Serena A; Turiel, Elliot

2007-01-01

This research examined adolescents' judgments about lying to circumvent directives from parents or friends in the moral, personal, and prudential domains. One hundred and twenty-eight adolescents (12.1-17.3 years) were presented with situations in which an adolescent avoids a directive through deception. The majority of adolescents judged some acts as acceptable, including deception regarding parental directives to engage in moral violations and to restrict personal activities. Other acts of deception were judged as unacceptable, including deception of parents regarding prudential acts, as well as deception of friends in each domain. In addition, lying to conceal a misdeed was negatively evaluated. Most adolescents thought that directives from parents and friends to engage in moral violations or to restrict personal acts were not legitimate, whereas parental directives concerning prudential acts were seen as legitimate. Results indicate that adolescents value honesty, but sometimes subordinate it to moral and personal concerns in relationships of inequality.

Selective reaching in macaques: evidence for action-centred attention.

PubMed

Bulgheroni, Maria; Camperio-Ciani, Andrea; Straulino, Elisa; Sartori, Luisa; D'Amico, Enrico; Castiello, Umberto

2017-03-01

When a monkey selects a piece of food lying on the ground from among other viable objects in the near vicinity, only the desired item governs the particular pattern and direction of the animal's reaching action. It would seem then that selection is an important component controlling the animal's action. But, we may ask, is the selection process in such cases impervious to the presence of other objects that could constitute potential obstacles to or constraints on movement execution? And if it is, in fact, pervious to other objects, do they have a direct influence on the organization of the response? The kinematics of macaques' reaching movements were examined by the current study that analysed some exemplars as they selectively reached to grasp a food item in the absence as well as in the presence of potential obstacles (i.e., stones) that could affect the arm trajectory. Changes in movement parameterization were noted in temporal measures, such as movement time, as well as in spatial ones, such as paths of trajectory. Generally speaking, the presence of stones in the vicinity of the acting hand stalled the reaching movement and affected the arm trajectory as the hand veered away from the stone even when it was not a physical obstacle. We concluded that nearby objects evoke a motor response in macaques, and the attentional mechanisms that allow for a successful action selection are revealed in the reaching path. The data outlined here concur with human studies indicating that potential obstacles are internally represented, a finding implying basic cognitive operations allowing for action selection in macaques.

Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent Dolutegravir or Abacavir plus Lamivudine.

PubMed

Khatri, Amit; Trinh, Roger; Zhao, Weihan; Podsadecki, Thomas; Menon, Rajeev

2016-10-01

The direct-acting antiviral regimen of 25 mg ombitasvir-150 mg paritaprevir-100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (n = 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (Cmax) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean Cmax and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean Cmax and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally well tolerated, with no evidence of increased rates of adverse events during combination administration. These data indicate that the 3-direct-acting-antiviral regimen can be administered with dolutegravir or abacavir plus lamivudine without dose adjustment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Sequence selection by dynamical symmetry breaking in an autocatalytic binary polymer model

NASA Astrophysics Data System (ADS)

Fellermann, Harold; Tanaka, Shinpei; Rasmussen, Steen

2017-12-01

Template-directed replication of nucleic acids is at the essence of all living beings and a major milestone for any origin of life scenario. We present an idealized model of prebiotic sequence replication, where binary polymers act as templates for their autocatalytic replication, thereby serving as each others reactants and products in an intertwined molecular ecology. Our model demonstrates how autocatalysis alters the qualitative and quantitative system dynamics in counterintuitive ways. Most notably, numerical simulations reveal a very strong intrinsic selection mechanism that favors the appearance of a few population structures with highly ordered and repetitive sequence patterns when starting from a pool of monomers. We demonstrate both analytically and through simulation how this "selection of the dullest" is caused by continued symmetry breaking through random fluctuations in the transient dynamics that are amplified by autocatalysis and eventually propagate to the population level. The impact of these observations on related prebiotic mathematical models is discussed.

Patterns and Mechanisms of Evolutionary Transitions between Genetic Sex-Determining Systems

PubMed Central

Sander van Doorn, G.

2014-01-01

The diversity and patchy phylogenetic distribution of genetic sex-determining mechanisms observed in some taxa is thought to have arisen by the addition, modification, or replacement of regulators at the upstream end of the sex-determining pathway. Here, I review the various evolutionary forces acting on upstream regulators of sexual development that can cause transitions between sex-determining systems. These include sex-ratio selection and pleiotropic benefits, as well as indirect selection mechanisms involving sex-linked sexually antagonistic loci or recessive deleterious mutations. Most of the current theory concentrates on the population–genetic aspects of sex-determination transitions, using models that do not reflect the developmental mechanisms involved in sex determination. However, the increasing availability of molecular data creates opportunities for the development of mechanistic models that can clarify how selection and developmental architecture interact to direct the evolution of sex-determination genes. PMID:24993578

Surface stability and the selection rules of substrate orientation for optimal growth of epitaxial II-VI semiconductors

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

Yin, Wan-Jian; Department of Physics & Astronomy, and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo, Ohio 43606; Yang, Ji-Hui

2015-10-05

The surface structures of ionic zinc-blende CdTe (001), (110), (111), and (211) surfaces are systematically studied by first-principles density functional calculations. Based on the surface structures and surface energies, we identify the detrimental twinning appearing in molecular beam epitaxy (MBE) growth of II-VI compounds as the (111) lamellar twin boundaries. To avoid the appearance of twinning in MBE growth, we propose the following selection rules for choosing optimal substrate orientations: (1) the surface should be nonpolar so that there is no large surface reconstructions that could act as a nucleation center and promote the formation of twins; (2) the surfacemore » structure should have low symmetry so that there are no multiple equivalent directions for growth. These straightforward rules, in consistent with experimental observations, provide guidelines for selecting proper substrates for high-quality MBE growth of II-VI compounds.« less

Analysis of differential selective forces acting on the coat protein (P3) of the plant virus family Luteoviridae.

PubMed

Torres, Marina W; Corrêa, Régis L; Schrago, Carlos G

2005-12-30

The coat protein (CP) of the family Luteoviridae is directly associated with the success of infection. It participates in various steps of the virus life cycle, such as virion assembly, stability, systemic infection, and transmission. Despite its importance, extensive studies on the molecular evolution of this protein are lacking. In the present study, we investigate the action of differential selective forces on the CP coding region using maximum likelihood methods. We found that the protein is subjected to heterogeneous selective pressures and some sites may be evolving near neutrality. Based on the proposed 3-D model of the CP S-domain, we showed that nearly neutral sites are predominantly located in the region of the protein that faces the interior of the capsid, in close contact with the viral RNA, while highly conserved sites are mainly part of beta-strands, in the protein's major framework.

Continuous in vitro evolution of a ribozyme ligase: a model experiment for the evolution of a biomolecule.

PubMed

Ledbetter, Michael P; Hwang, Tony W; Stovall, Gwendolyn M; Ellington, Andrew D

2013-01-01

Evolution is a defining criterion of life and is central to understanding biological systems. However, the timescale of evolutionary shifts in phenotype limits most classroom evolution experiments to simple probability simulations. In vitro directed evolution (IVDE) frequently serves as a model system for the study of Darwinian evolution but produces noticeable phenotypic shifts in a matter of hours. An IVDE demonstration lab would serve to both directly demonstrate how Darwinian selection can act on a pool of variants and introduce students to an essential method of modern molecular biology. To produce an IVDE demonstration lab, continuous IVDE of a T500 ribozyme ligase population has been paired with a fluorescent strand displacement reporter system to visualize the selection of improved catalytic function. A ribozyme population is taken through rounds of isothermal amplification dependent on the self-ligation of a T7 promoter. As the population is selectively enriched with better ligase activity, the strand displacement system allows for the monitoring of the population's ligation rate. The strand displacement reporter system permits the detection of ligated ribozyme. Once ligated with the T7 promoter, the 5' end of the ribozyme displaces paired fluorophore-quencher oligonucleotides, in turn, generating visible signal upon UV light excitation. As the ligation rate of the population increases, due to the selection for faster ligating species, the fluorescent signal develops more rapidly. The pairing of the continuous isothermal system with the fluorescent reporting scheme allows any user, provided with minimal materials, to model the continuous directed evolution of a biomolecule. Copyright © 2013 Wiley-Liss, Inc.

Water resources planning under the Fish and Wildlife Coordination Act

USGS Publications Warehouse

Stutzman, Karl F.

1980-01-01

This paper briefly discusses the more significant provisions of the Fish and Wildlife Coordination Act (1958). It covers pertinent aspects of legislative history, the development and current status (April 1980) of certain policies relevant to administering the Act, and other matters. It is directed primarily to practicing fish and wildlife agency field biologists, planners, and decisionmakers engaged in water resources development activities under the Act. It is not intended to be exhaustive in its treatment. The Fish and Wildlife Coordination Act provides a basic procedural framework for the orderly consideration of fish and wildlife conservation measures to be incorporated into Federal and Federally permitted or licensed water development projects. The principal provisions of the Act include: 1. a statement of Congressional purpose that fish and wildlife conservation shall receive equal consideration with other project features; 2. mandatory consultation with wildlife agencies with a view to achieving such conservation; 3. full consideration by action of the recommendations stemming from consultation; 4. authority for action agencies to implement such recommendations as they find acceptable. The FWCA in effect amends, conditions, or supplements other Federal laws and is thus closely linked in its application and interpretation. It is similarly linked to Federal planning standards and procedures. Because of this, interpretations tend to be flexible and evolve, adapting to changing situations. The following reference matrix outlines selected sections of the Fish and Wildlife Coordination Act which are of particular relevance to planners.

Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

PubMed

Schachter, Michael J; Oesch, Nicholas; Smith, Robert G; Taylor, W Rowland

2010-08-19

The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.

76 FR 77914 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Amendments to the Select Agent and Toxin Regulations AGENCY: Animal and Plant Health Inspection Service, USDA... proposed rule that would amend and republish the list of select agents and toxins that have the potential...

77 FR 57017 - Privacy Act; Implementation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... Act; Implementation AGENCY: Defense Intelligence Agency, DoD. ACTION: Direct final rule with request for comments. SUMMARY: Defense Intelligence Agency (DIA) is proposing to update the DIA Privacy Act... Records. This direct final rule makes nonsubstantive changes to the Defense Intelligence Agency Program...

Superfund Site Information

EPA Pesticide Factsheets

This asset includes a number of individual data sets related to site-specific information for Superfund, which is governed under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) of 1980, which was amended by the Superfund Amendments and Reauthorization Act (SARA) in 1986. The Superfund Enterprise Management System (SEMS) contains basic site description, location, schedule of activities, enforcement and settlement data, contaminants and selected remedy and much more, as well as the records that clearly document site decisions. This asset also includes sampling data and lab results (CLPSS, EDDs), redevelopment and technical assistance case studies, site reuse and land revitalization information, EPAOSC.net information, Superfund Technical Assistance Grants information, site management information records (RODs, Remediation plans, cleanup directives), contract management information, and more.Superfund site management information can also be found in agency wide systems such as EAS and COMPASS.

Commercial Orbital Transportation Services (COTS) Demonstrations

NASA Technical Reports Server (NTRS)

Lindenmoyer, Allan

2006-01-01

U.S. space policy directs pursuit of commercial opportunities for providing transportation and other services low Earth orbit and beyond. COTS Project established to implement policy. COTS strategy: Phase 1) Assist industry with system development/demonstrations (COTS Demos); Phase 2) Procure commercial services for ISS logistics support. COTS Demonstrations competition completed in 10 months. Two industry partners selected for funded Space Act Agreements: 1) SpaceX & Rocketplane-Kistler; and 2) Unfunded Space Act Agreements in work with other competitors. COTS budget of $500 M thru 2010, with pay for performance milestone approach. Cargo flight demonstrations planned for 2008 and 2009: Crew flight demonstration options for 2011-2012. Commercial cargo transportation services potentially available as early as 2009-2010. Successful COTS partners may open new space markets and provide reliable, cost effective cargo and crew transportation services, a new era for commercial space.

The Strange Case of CDK4/6 Inhibitors: Mechanisms, Resistance, and Combination Strategies

PubMed Central

Knudsen, Erik S.; Witkiewicz, Agnieszka K.

2016-01-01

CDK4/6 inhibitors have emerged as a powerful class of agents with clinical activity in a number of malignancies. Targeting the cell cycle represents a core attack on a defining feature of cancer. However, the mechanisms through which selective CDK4/6 targeted agents act has few parallels in the current pharmaceutical armamentarium against cancer. Notably, CDK4/6 inhibitors act downstream of most mitogenic signaling cascades, which have implications both related to clinical efficacy and resistance. Core knowledge of cell cycle processes has provided insights into mechanisms of intrinsic resistance to CDK4/6 inhibitors; however, the basis of acquired resistance versus durable response is only beginning to emerge. This review focuses on the mechanism of action and biomarkers to direct the precision use of CDK4/6 inhibitors and rationally-developed combination therapies. PMID:28303264

The Selection of a Marine Artillery Battery Fire Direction Computer System.

DTIC Science & Technology

1982-12-01

yhsical Characteristics: Tbe VI provi-ds s h gen er al physical characteri-sti-cs of the BCS. The total weight of the BCS is based on ti,: eg’±ipment...twenty special fanc -tion keys. Six of the special function keys arc- currently spares and will be programmed -o support the P31 software aiditions...close to the weapon or mounted on the weapon. Phs- ga C aacteri sti cs: Table XIV provides the gen e ral physical charactaristics of the FCC. The act

Introgression of a Block of Genome Under Infinitesimal Selection.

PubMed

Sachdeva, Himani; Barton, Nicholas H

2018-06-12

Adaptive introgression is common in nature and can be driven by selection acting on multiple, linked genes. We explore the effects of polygenic selection on introgression under the infinitesimal model with linkage. This model assumes that the introgressing block has an effectively infinite number of loci, each with an infinitesimal effect on the trait under selection. The block is assumed to introgress under directional selection within a native population that is genetically homogeneous. We use individual-based simulations and a branching process approximation to compute various statistics of the introgressing block, and explore how these depend on parameters such as the map length and initial trait value associated with the introgressing block, the genetic variability along the block, and the strength of selection. Our results show that the introgression dynamics of a block under infinitesimal selection are qualitatively different from the dynamics of neutral introgression. We also find that in the long run, surviving descendant blocks are likely to have intermediate lengths, and clarify how their length is shaped by the interplay between linkage and infinitesimal selection. Our results suggest that it may be difficult to distinguish the long-term introgression of a block of genome with a single strongly selected locus from the introgression of a block with multiple, tightly linked and weakly selected loci. Copyright © 2018, Genetics.

Synergism and Antagonism of Proximate Mechanisms Enable and Constrain the Response to Simultaneous Selection on Body Size and Development Time: An Empirical Test Using Experimental Evolution.

PubMed

Davidowitz, Goggy; Roff, Derek; Nijhout, H Frederik

2016-11-01

Natural selection acts on multiple traits simultaneously. How mechanisms underlying such traits enable or constrain their response to simultaneous selection is poorly understood. We show how antagonism and synergism among three traits at the developmental level enable or constrain evolutionary change in response to simultaneous selection on two focal traits at the phenotypic level. After 10 generations of 25% simultaneous directional selection on all four combinations of body size and development time in Manduca sexta (Sphingidae), the changes in the three developmental traits predict 93% of the response of development time and 100% of the response of body size. When the two focal traits were under synergistic selection, the response to simultaneous selection was enabled by juvenile hormone and ecdysteroids and constrained by growth rate. When the two focal traits were under antagonistic selection, the response to selection was due primarily to change in growth rate and constrained by the two hormonal traits. The approach used here reduces the complexity of the developmental and endocrine mechanisms to three proxy traits. This generates explicit predictions for the evolutionary response to selection that are based on biologically informed mechanisms. This approach has broad applicability to a diverse range of taxa, including algae, plants, amphibians, mammals, and insects.

Sound localization in the alligator.

PubMed

Bierman, Hilary S; Carr, Catherine E

2015-11-01

In early tetrapods, it is assumed that the tympana were acoustically coupled through the pharynx and therefore inherently directional, acting as pressure difference receivers. The later closure of the middle ear cavity in turtles, archosaurs, and mammals is a derived condition, and would have changed the ear by decoupling the tympana. Isolation of the middle ears would then have led to selection for structural and neural strategies to compute sound source localization in both archosaurs and mammalian ancestors. In the archosaurs (birds and crocodilians) the presence of air spaces in the skull provided connections between the ears that have been exploited to improve directional hearing, while neural circuits mediating sound localization are well developed. In this review, we will focus primarily on directional hearing in crocodilians, where vocalization and sound localization are thought to be ecologically important, and indicate important issues still awaiting resolution. Copyright © 2015 Elsevier B.V. All rights reserved.

Vertical and lateral forces when a permanent magnet above a superconductor traverses in arbitrary directions

NASA Astrophysics Data System (ADS)

Yang, Yong

2008-12-01

In an actual levitation system composed of high temperature superconductors (HTSs) and permanent magnets (PMs), the levitating bodies may traverse in arbitrary directions. Many previous researchers assumed that the levitating bodies moved in a vertical direction or a lateral direction in order to simplify the problem. In this paper, the vertical and lateral forces acting on the PM are calculated by the modified frozen-image method when a PM above an HTS traverses in arbitrary directions. In order to study the effects of the movement directions on the vertical and lateral forces, comparisons of the forces that act on a PM traversing in a tilted direction with those that act on a PM traversing in a vertical direction or a lateral direction have been presented.

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

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

Lolicato, Marco; Arrigoni, Cristina; Mori, Takahiro

Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK1 subfamily generate ‘leak’ currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses1, 2, 3. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit4, 5, 6. In contrast to other potassium channels, K2P channels use a selectivity filter ‘C-type’ gate7, 8, 9, 10 as the principal gating site. Despite recent advances3, 11, 12, poor pharmacological profiles of K2P channels limit mechanistic and biological studies. Here we describe a classmore » of small-molecule TREK activators that directly stimulate the C-type gate by acting as molecular wedges that restrict interdomain interface movement behind the selectivity filter. Structures of K2P2.1 (also known as TREK-1) alone and with two selective K2P2.1 (TREK-1) and K2P10.1 (TREK-2) activators—an N-aryl-sulfonamide, ML335, and a thiophene-carboxamide, ML402—define a cryptic binding pocket unlike other ion channel small-molecule binding sites and, together with functional studies, identify a cation–π interaction that controls selectivity. Together, our data reveal a druggable K2P site that stabilizes the C-type gate ‘leak mode’ and provide direct evidence for K2P selectivity filter gating.« less

Attentional Gain Control of Ongoing Cortical Speech Representations in a “Cocktail Party”

PubMed Central

Kerlin, Jess R.; Shahin, Antoine J.; Miller, Lee M.

2010-01-01

Normal listeners possess the remarkable perceptual ability to select a single speech stream among many competing talkers. However, few studies of selective attention have addressed the unique nature of speech as a temporally extended and complex auditory object. We hypothesized that sustained selective attention to speech in a multi-talker environment would act as gain control on the early auditory cortical representations of speech. Using high-density electroencephalography and a template-matching analysis method, we found selective gain to the continuous speech content of an attended talker, greatest at a frequency of 4–8 Hz, in auditory cortex. In addition, the difference in alpha power (8–12 Hz) at parietal sites across hemispheres indicated the direction of auditory attention to speech, as has been previously found in visual tasks. The strength of this hemispheric alpha lateralization, in turn, predicted an individual’s attentional gain of the cortical speech signal. These results support a model of spatial speech stream segregation, mediated by a supramodal attention mechanism, enabling selection of the attended representation in auditory cortex. PMID:20071526

Unequal Opportunities: The Recruitment, Selection and Promotion Prospects for Black Teachers.

ERIC Educational Resources Information Center

Brar, Harbhajan Singh

1991-01-01

The 1988 Education Reform Act greatly impacted equal opportunities in recruitment and selection of black teachers in the United Kingdom. A case study examines recruitment and selection in London, noting that ad hoc practices (encouraged by the 1988 Act) perpetuates the poor position of black teachers. (SM)

Principles of biofouling protection in marine sponges: a model for the design of novel biomimetic and bio-inspired coatings in the marine environment?

PubMed

Müller, Werner E G; Wang, Xiaohong; Proksch, Peter; Perry, Carole C; Osinga, Ronald; Gardères, Johan; Schröder, Heinz C

2013-08-01

The process of biofouling of marine structures and substrates, such as platforms or ship hulls, proceeds in multiple steps. Soon after the formation of an initial conditioning film, formed via the adsorption of organic particles to natural or man-made substrates, a population of different bacterial taxa associates under the formation of a biofilm. These microorganisms communicate through a complex quorum sensing network. Macro-foulers, e.g., barnacles, then settle and form a fouling layer on the marine surfaces, a process that globally has severe impacts both on the economy and on the environment. Since the ban of tributyltin, an efficient replacement of this antifouling compound by next-generation antifouling coatings that are environmentally more acceptable and also showing longer half-lives has not yet been developed. The sponges, as sessile filter-feeder animals, have evolved antifouling strategies to protect themselves against micro- and subsequent macro-biofouling processes. Experimental data are summarized and suggest that coating of the sponge surface with bio-silica contributes to the inhibition of the formation of a conditioning film. A direct adsorption of the surfaces by microorganisms can be impaired through poisoning the organisms with direct-acting secondary metabolites or toxic peptides. In addition, first, compounds from sponges have been identified that interfere with the anti-quorum sensing network. Sponge secondary metabolites acting selectively on diatom colonization have not yet been identified. Finally, it is outlined that direct-acting secondary metabolites inhibiting the growth of macro-fouling animals and those that poison the multidrug resistance pump are available. It is concluded that rational screening programs for inhibitors of the complex and dynamic problem of biofilm production, based on multidisciplinary studies and using sponges as a model, are required in the future.

Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: Data from the Veterans administration.

PubMed

Fox, D Steven; McGinnis, Justin J; Tonnu-Mihara, Ivy Q; McCombs, Jeffrey S

2017-06-01

Data addressing real world effectiveness of direct acting antiviral agents in hepatitis C infected patients are now emerging. This study compared the sustained virologic response rates achieved 12 weeks post-treatment in patients treated with three such agents by the Veterans Health Administration. A retrospective cohort study was conducted using patients who terminated treatment by July 1, 2015. Data were retrieved from the Veterans Health Administration electronic medical records system. Patients were included if sufficient viral load laboratory data were available to determine sustained virologic response. Applying an intention to treat approach and logistic regression analysis, the sustained virologic response rates achieved were compared across drug regimens. A total of 11 464 patients met study selection criteria. Without controlling for other risk factors, sustained virologic response at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients. After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate sustained virologic response. Human immunodeficiency virus, hepatitis B infection, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact sustained virologic response rates. Sustained virologic response rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a sustained virologic response. All three direct acting antiviral regimens appear highly effective in achieving sustained virologic response. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Evolution of haploid selection in predominantly diploid organisms

PubMed Central

Otto, Sarah P.; Scott, Michael F.; Immler, Simone

2015-01-01

Diploid organisms manipulate the extent to which their haploid gametes experience selection. Animals typically produce sperm with a diploid complement of most proteins and RNA, limiting selection on the haploid genotype. Plants, however, exhibit extensive expression in pollen, with actively transcribed haploid genomes. Here we analyze models that track the evolution of genes that modify the strength of haploid selection to predict when evolution intensifies and when it dampens the “selective arena” within which male gametes compete for fertilization. Considering deleterious mutations, evolution leads diploid mothers to strengthen selection among haploid sperm/pollen, because this reduces the mutation load inherited by their diploid offspring. If, however, selection acts in opposite directions in haploids and diploids (“ploidally antagonistic selection”), mothers evolve to reduce haploid selection to avoid selectively amplifying alleles harmful to their offspring. Consequently, with maternal control, selection in the haploid phase either is maximized or reaches an intermediate state, depending on the deleterious mutation rate relative to the extent of ploidally antagonistic selection. By contrast, evolution generally leads diploid fathers to mask mutations in their gametes to the maximum extent possible, whenever masking (e.g., through transcript sharing) increases the average fitness of a father’s gametes. We discuss the implications of this maternal–paternal conflict over the extent of haploid selection and describe empirical studies needed to refine our understanding of haploid selection among seemingly diploid organisms. PMID:26669442

Conflict between biotic and climatic selective pressures acting on an extended phenotype in a subarctic, but not temperate, environment.

PubMed

Rohwer, V G; Bonier, F; Martin, P R

2015-10-22

Climatic selective pressures are thought to dominate biotic selective pressures at higher latitudes. However, few studies have experimentally tested how these selective pressures differentially act on traits across latitudes because traits can rarely be manipulated independently of the organism in nature. We overcame this challenge by using an extended phenotype-active bird nests-and conducted reciprocal transplant experiments between a subarctic and temperate site, separated by 14° of latitude. At the subarctic site, biotic selective pressures (nest predation) favoured smaller, non-local temperate nests, whereas climatic selective pressures (temperature) favoured larger local nests, particularly at colder temperatures. By contrast, at the temperate site, climatic and biotic selective pressures acted similarly on temperate and subarctic nests. Our results illustrate a functional trade-off in the subarctic between nest morphologies favoured by biotic versus climatic selective pressures, with climate favouring local nest morphologies. At our temperate site, however, allocative trade-offs in the time and effort devoted to nest construction favour smaller, local nests. Our findings illustrate a conflict between biotic and climatic selective pressures at the northern extremes of a species geographical range, and suggest that trade-offs between trait function and trait elaboration act differentially across latitude to create broad geographic variation in traits. © 2015 The Author(s).

Conflict between biotic and climatic selective pressures acting on an extended phenotype in a subarctic, but not temperate, environment

PubMed Central

Rohwer, V. G.; Bonier, F.; Martin, P. R.

2015-01-01

Climatic selective pressures are thought to dominate biotic selective pressures at higher latitudes. However, few studies have experimentally tested how these selective pressures differentially act on traits across latitudes because traits can rarely be manipulated independently of the organism in nature. We overcame this challenge by using an extended phenotype—active bird nests—and conducted reciprocal transplant experiments between a subarctic and temperate site, separated by 14° of latitude. At the subarctic site, biotic selective pressures (nest predation) favoured smaller, non-local temperate nests, whereas climatic selective pressures (temperature) favoured larger local nests, particularly at colder temperatures. By contrast, at the temperate site, climatic and biotic selective pressures acted similarly on temperate and subarctic nests. Our results illustrate a functional trade-off in the subarctic between nest morphologies favoured by biotic versus climatic selective pressures, with climate favouring local nest morphologies. At our temperate site, however, allocative trade-offs in the time and effort devoted to nest construction favour smaller, local nests. Our findings illustrate a conflict between biotic and climatic selective pressures at the northern extremes of a species geographical range, and suggest that trade-offs between trait function and trait elaboration act differentially across latitude to create broad geographic variation in traits. PMID:26490789

Linking brains and brawn: exercise and the evolution of human neurobiology.

PubMed

Raichlen, David A; Polk, John D

2013-01-07

The hunting and gathering lifestyle adopted by human ancestors around 2 Ma required a large increase in aerobic activity. High levels of physical activity altered the shape of the human body, enabling access to new food resources (e.g. animal protein) in a changing environment. Recent experimental work provides strong evidence that both acute bouts of exercise and long-term exercise training increase the size of brain components and improve cognitive performance in humans and other taxa. However, to date, researchers have not explored the possibility that the increases in aerobic capacity and physical activity that occurred during human evolution directly influenced the human brain. Here, we hypothesize that proximate mechanisms linking physical activity and neurobiology in living species may help to explain changes in brain size and cognitive function during human evolution. We review evidence that selection acting on endurance increased baseline neurotrophin and growth factor signalling (compounds responsible for both brain growth and for metabolic regulation during exercise) in some mammals, which in turn led to increased overall brain growth and development. This hypothesis suggests that a significant portion of human neurobiology evolved due to selection acting on features unrelated to cognitive performance.

Moving without a purpose: an experimental study of swarm guidance in the Western honey bee, Apis mellifera.

PubMed

Makinson, James C; Beekman, Madeleine

2014-06-01

During reproductive swarming, honey bee scouts perform two very important functions. Firstly, they find new nesting locations and return to the swarm cluster to communicate their discoveries. Secondly, once the swarm is ready to depart, informed scout bees act as guides, leading the swarm to its final destination. We have previously hypothesised that the two processes, selecting a new nest site and swarm guidance, are tightly linked in honey bees. When swarms can be laissez faire about where they nest, reaching directional consensus prior to lift off seems unnecessary. If, in contrast, it is essential that the swarm reaches a precise location, either directional consensus must be near unanimous prior to swarm departure or only a select subgroup of the scouts guide the swarm. Here, we tested experimentally whether directional consensus is necessary for the successful guidance of swarms of the Western honey bee Apis mellifera by forcing swarms into the air prior to the completion of the decision-making process. Our results show that swarms were unable to guide themselves prior to the swarm reaching the pre-flight buzzing phase of the decision-making process, even when directional consensus was high. We therefore suggest that not all scouts involved in the decision-making process attempt to guide the swarm. © 2014. Published by The Company of Biologists Ltd.

Done Wrong or Said Wrong? Young Children Understand the Normative Directions of Fit of Different Speech Acts

ERIC Educational Resources Information Center

Rakoczy, Hannes; Tomasello, Michael

2009-01-01

Young children use and comprehend different kinds of speech acts from the beginning of their communicative development. But it is not clear how they understand the conventional and normative structure of such speech acts. In particular, imperative speech acts have a world-to-word direction of fit, such that their fulfillment means that the world…

Quantitative genetic models of sexual selection by male choice.

PubMed

Nakahashi, Wataru

2008-09-01

There are many examples of male mate choice for female traits that tend to be associated with high fertility. I develop quantitative genetic models of a female trait and a male preference to show when such a male preference can evolve. I find that a disagreement between the fertility maximum and the viability maximum of the female trait is necessary for directional male preference (preference for extreme female trait values) to evolve. Moreover, when there is a shortage of available male partners or variance in male nongenetic quality, strong male preference can evolve. Furthermore, I also show that males evolve to exhibit a stronger preference for females that are more feminine (less resemblance to males) than the average female when there is a sexual dimorphism caused by fertility selection which acts only on females.

31 CFR 543.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (50 U... adjustment pursuant to the Federal Civil Penalties Inflation Adjustment Act of 1990 (Pub. L. 101-410, as... pursuant to 18 U.S.C. 3571. (c) Attention is directed to section 5 of the United Nations Participation Act...

Naturally acidified habitat selects for ocean acidification–tolerant mussels

PubMed Central

Thomsen, Jörn; Stapp, Laura S.; Haynert, Kristin; Schade, Hanna; Danelli, Maria; Lannig, Gisela; Wegner, K. Mathias; Melzner, Frank

2017-01-01

Ocean acidification severely affects bivalves, especially their larval stages. Consequently, the fate of this ecologically and economically important group depends on the capacity and rate of evolutionary adaptation to altered ocean carbonate chemistry. We document successful settlement of wild mussel larvae (Mytilus edulis) in a periodically CO2-enriched habitat. The larval fitness of the population originating from the CO2-enriched habitat was compared to the response of a population from a nonenriched habitat in a common garden experiment. The high CO2–adapted population showed higher fitness under elevated Pco2 (partial pressure of CO2) than the non-adapted cohort, demonstrating, for the first time, an evolutionary response of a natural mussel population to ocean acidification. To assess the rate of adaptation, we performed a selection experiment over three generations. CO2 tolerance differed substantially between the families within the F1 generation, and survival was drastically decreased in the highest, yet realistic, Pco2 treatment. Selection of CO2-tolerant F1 animals resulted in higher calcification performance of F2 larvae during early shell formation but did not improve overall survival. Our results thus reveal significant short-term selective responses of traits directly affected by ocean acidification and long-term adaptation potential in a key bivalve species. Because immediate response to selection did not directly translate into increased fitness, multigenerational studies need to take into consideration the multivariate nature of selection acting in natural habitats. Combinations of short-term selection with long-term adaptation in populations from CO2-enriched versus nonenriched natural habitats represent promising approaches for estimating adaptive potential of organisms facing global change. PMID:28508039

Naturally acidified habitat selects for ocean acidification-tolerant mussels.

PubMed

Thomsen, Jörn; Stapp, Laura S; Haynert, Kristin; Schade, Hanna; Danelli, Maria; Lannig, Gisela; Wegner, K Mathias; Melzner, Frank

2017-04-01

Ocean acidification severely affects bivalves, especially their larval stages. Consequently, the fate of this ecologically and economically important group depends on the capacity and rate of evolutionary adaptation to altered ocean carbonate chemistry. We document successful settlement of wild mussel larvae ( Mytilus edulis ) in a periodically CO 2 -enriched habitat. The larval fitness of the population originating from the CO 2 -enriched habitat was compared to the response of a population from a nonenriched habitat in a common garden experiment. The high CO 2 -adapted population showed higher fitness under elevated P co 2 (partial pressure of CO 2 ) than the non-adapted cohort, demonstrating, for the first time, an evolutionary response of a natural mussel population to ocean acidification. To assess the rate of adaptation, we performed a selection experiment over three generations. CO 2 tolerance differed substantially between the families within the F 1 generation, and survival was drastically decreased in the highest, yet realistic, P co 2 treatment. Selection of CO 2 -tolerant F 1 animals resulted in higher calcification performance of F 2 larvae during early shell formation but did not improve overall survival. Our results thus reveal significant short-term selective responses of traits directly affected by ocean acidification and long-term adaptation potential in a key bivalve species. Because immediate response to selection did not directly translate into increased fitness, multigenerational studies need to take into consideration the multivariate nature of selection acting in natural habitats. Combinations of short-term selection with long-term adaptation in populations from CO 2 -enriched versus nonenriched natural habitats represent promising approaches for estimating adaptive potential of organisms facing global change.

Dissociating interference-control processes between memory and response.

PubMed

Bissett, Patrick G; Nee, Derek Evan; Jonides, John

2009-09-01

The ability to mitigate interference is of central importance to cognition. Previous research has provided conflicting accounts about whether operations that resolve interference are singular in character or form a family of functions. Here, the authors examined the relationship between interference-resolution processes acting on working memory representations versus responses. The authors combined multiple forms of interference into a single paradigm by merging a directed-forgetting task, which induces proactive interference, with a stop-signal task, which taps response inhibition processes. The results demonstrated that proactive interference and response inhibition produced distinct behavioral signatures that did not interact. By contrast, combining two different measures of response inhibition by merging a go/no-go task variant and a stop signal produced overadditive behavioral interference, demonstrating that different forms of response inhibition tap the same processes. However, not all forms of response conflict interacted, suggesting that inhibition-related functions acting on response selection are dissociable from those acting on response inhibition. These results suggest that inhibition-related functions for memory and responses are dissociable. (c) 2009 APA, all rights reserved.

The Atacama Cosmology Telescope (ACT): Beam Profiles and First SZ Cluster Maps

NASA Technical Reports Server (NTRS)

Hincks, A. D.; Acquaviva, V.; Ade, P. A.; Aguirre, P.; Amiri, M.; Appel, J. W.; Barrientos, L. F.; Battistelli, E. S.; Bond, J. R.; Brown, B.;

Goal-directed, habitual and Pavlovian prosocial behavior

PubMed Central

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

Armament Imbalances: Match and Mismatch in Plant-Pollinator Traits of Highly Specialized Long-Spurred Orchids

PubMed Central

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

Evolutionary rates for multivariate traits: the role of selection and genetic variation

PubMed Central

Pitchers, William; Wolf, Jason B.; Tregenza, Tom; Hunt, John; Dworkin, Ian

2014-01-01

A fundamental question in evolutionary biology is the relative importance of selection and genetic architecture in determining evolutionary rates. Adaptive evolution can be described by the multivariate breeders' equation (), which predicts evolutionary change for a suite of phenotypic traits () as a product of directional selection acting on them (β) and the genetic variance–covariance matrix for those traits (G). Despite being empirically challenging to estimate, there are enough published estimates of G and β to allow for synthesis of general patterns across species. We use published estimates to test the hypotheses that there are systematic differences in the rate of evolution among trait types, and that these differences are, in part, due to genetic architecture. We find some evidence that sexually selected traits exhibit faster rates of evolution compared with life-history or morphological traits. This difference does not appear to be related to stronger selection on sexually selected traits. Using numerous proposed approaches to quantifying the shape, size and structure of G, we examine how these parameters relate to one another, and how they vary among taxonomic and trait groupings. Despite considerable variation, they do not explain the observed differences in evolutionary rates. PMID:25002697

Speeding Up Microevolution: The Effects of Increasing Temperature on Selection and Genetic Variance in a Wild Bird Population

PubMed Central

Husby, Arild; Visser, Marcel E.; Kruuk, Loeske E. B.

2011-01-01

The amount of genetic variance underlying a phenotypic trait and the strength of selection acting on that trait are two key parameters that determine any evolutionary response to selection. Despite substantial evidence that, in natural populations, both parameters may vary across environmental conditions, very little is known about the extent to which they may covary in response to environmental heterogeneity. Here we show that, in a wild population of great tits (Parus major), the strength of the directional selection gradients on timing of breeding increased with increasing spring temperatures, and that genotype-by-environment interactions also predicted an increase in additive genetic variance, and heritability, of timing of breeding with increasing spring temperature. Consequently, we therefore tested for an association between the annual selection gradients and levels of additive genetic variance expressed each year; this association was positive, but non-significant. However, there was a significant positive association between the annual selection differentials and the corresponding heritability. Such associations could potentially speed up the rate of micro-evolution and offer a largely ignored mechanism by which natural populations may adapt to environmental changes. PMID:21408101

One-pot deposition of palladium on hybrid TiO2 nanoparticles and catalytic applications in hydrogenation.

PubMed

Mehri, Afef; Kochkar, Hafedh; Daniele, Stéphane; Mendez, Violaine; Ghorbel, Abdelhamid; Berhault, Gilles

2012-03-01

One-pot deposition of Pd onto TiO(2) has been achieved through directly contacting palladium(II) salt with nanosized functionalized TiO(2) support initially obtained by sol-gel process using titanium isopropoxide and citric acid. Citrate groups act as functional moieties able to directly reduce the Pd salt avoiding any further reducing treatment. Various palladium salts (Na(2)PdCl(4) and Pd(NH(3))(4)Cl(2)·H(2)O) and titanium to citrate (Ti/CA) ratios (20, 50, and 100) were used in order to study the effect of the nature of the precursor and of the citrate content on the final Pd particle size and catalytic properties of the as-obtained Pd/TiO(2) systems. Characterization was performed using N(2) adsorption-desorption isotherms, ICP-AES, FTIR, XRD, XPS, and TEM. The as-obtained hybrid Pd/TiO(2) catalysts were tested in the selective hydrogenation (HYD) of an α,β-unsaturated aldehyde, i.e. cinnamaldehyde. Citrate-free Pd/TiO(2)-based catalysts present lower selectivity into saturated alcohol. However, citrate-functionalized Pd/TiO(2) catalyst seems to control the selectivity, the particle size and dispersion of Pd NPs leading to high intrinsic activity. Copyright © 2011 Elsevier Inc. All rights reserved.

Exogenous selection rather than cytonuclear incompatibilities shapes asymmetrical fitness of reciprocal Arabidopsis hybrids.

PubMed

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.

Interactions between Human Liver Fatty Acid Binding Protein and Peroxisome Proliferator Activated Receptor Selective Drugs

PubMed Central

Velkov, Tony

2013-01-01

Fatty acid binding proteins (FABPs) act as intracellular shuttles for fatty acids as well as lipophilic xenobiotics to the nucleus, where these ligands are released to a group of nuclear receptors called the peroxisome proliferator activated receptors (PPARs). PPAR mediated gene activation is ultimately involved in maintenance of cellular homeostasis through the transcriptional regulation of metabolic enzymes and transporters that target the activating ligand. Here we show that liver- (L-) FABP displays a high binding affinity for PPAR subtype selective drugs. NMR chemical shift perturbation mapping and proteolytic protection experiments show that the binding of the PPAR subtype selective drugs produces conformational changes that stabilize the portal region of L-FABP. NMR chemical shift perturbation studies also revealed that L-FABP can form a complex with the PPAR ligand binding domain (LBD) of PPARα. This protein-protein interaction may represent a mechanism for facilitating the activation of PPAR transcriptional activity via the direct channeling of ligands between the binding pocket of L-FABP and the PPARαLBD. The role of L-FABP in the delivery of ligands directly to PPARα via this channeling mechanism has important implications for regulatory pathways that mediate xenobiotic responses and host protection in tissues such as the small intestine and the liver where L-FABP is highly expressed. PMID:23476633

Selection of Shared and Neoantigen-Reactive T Cells for Adoptive Cell Therapy Based on CD137 Separation.

PubMed

Seliktar-Ofir, Sivan; Merhavi-Shoham, Efrat; Itzhaki, Orit; Yunger, Sharon; Markel, Gal; Schachter, Jacob; Besser, Michal J

2017-01-01

Adoptive cell therapy (ACT) of autologous tumor infiltrating lymphocytes (TIL) is an effective immunotherapy for patients with solid tumors, yielding objective response rates of around 40% in refractory patients with metastatic melanoma. Most clinical centers utilize bulk, randomly isolated TIL from the tumor tissue for ex vivo expansion and infusion. Only a minor fraction of the administered T cells recognizes tumor antigens, such as shared and mutation-derived neoantigens, and consequently eliminates the tumor. Thus, there are many ongoing effects to identify and select tumor-specific TIL for therapy; however, those approaches are very costly and require months, which is unreasonable for most metastatic patients. CD137 (4-1BB) has been identified as a co-stimulatory marker, which is induced upon the specific interaction of T cells with their target cell. Therefore, CD137 can be a useful biomarker and an important tool for the selection of tumor-reactive T cells. Here, we developed and validated a simple and time efficient method for the selection of CD137-expressing T cells for therapy based on magnetic bead separation. CD137 selection was performed with clinical grade compliant reagents, and TIL were expanded in a large-scale manner to meet cell numbers required for the patient setting in a GMP facility. For the first time, the methodology was designed to comply with both clinical needs and limitations, and its feasibility was assessed. CD137-selected TIL demonstrated significantly increased antitumor reactivity and were enriched for T cells recognizing neoantigens as well as shared tumor antigens. CD137-based selection enabled the enrichment of tumor-reactive T cells without the necessity of knowing the epitope specificity or the antigen type. The direct implementation of the CD137 separation method to the cell production of TIL may provide a simple way to improve the clinical efficiency of TIL ACT.

Selection of Shared and Neoantigen-Reactive T Cells for Adoptive Cell Therapy Based on CD137 Separation

PubMed Central

Seliktar-Ofir, Sivan; Merhavi-Shoham, Efrat; Itzhaki, Orit; Yunger, Sharon; Markel, Gal; Schachter, Jacob; Besser, Michal J.

2017-01-01

Adoptive cell therapy (ACT) of autologous tumor infiltrating lymphocytes (TIL) is an effective immunotherapy for patients with solid tumors, yielding objective response rates of around 40% in refractory patients with metastatic melanoma. Most clinical centers utilize bulk, randomly isolated TIL from the tumor tissue for ex vivo expansion and infusion. Only a minor fraction of the administered T cells recognizes tumor antigens, such as shared and mutation-derived neoantigens, and consequently eliminates the tumor. Thus, there are many ongoing effects to identify and select tumor-specific TIL for therapy; however, those approaches are very costly and require months, which is unreasonable for most metastatic patients. CD137 (4-1BB) has been identified as a co-stimulatory marker, which is induced upon the specific interaction of T cells with their target cell. Therefore, CD137 can be a useful biomarker and an important tool for the selection of tumor-reactive T cells. Here, we developed and validated a simple and time efficient method for the selection of CD137-expressing T cells for therapy based on magnetic bead separation. CD137 selection was performed with clinical grade compliant reagents, and TIL were expanded in a large-scale manner to meet cell numbers required for the patient setting in a GMP facility. For the first time, the methodology was designed to comply with both clinical needs and limitations, and its feasibility was assessed. CD137-selected TIL demonstrated significantly increased antitumor reactivity and were enriched for T cells recognizing neoantigens as well as shared tumor antigens. CD137-based selection enabled the enrichment of tumor-reactive T cells without the necessity of knowing the epitope specificity or the antigen type. The direct implementation of the CD137 separation method to the cell production of TIL may provide a simple way to improve the clinical efficiency of TIL ACT. PMID:29067023

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection.

PubMed

Mendes-Junior, C T; Castelli, E C; Meyer, D; Simões, A L; Donadi, E A

2013-12-01

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3'UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.

Interferon-free therapy of chronic hepatitis C with direct-acting antivirals does not change the short-term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis.

PubMed

Mettke, F; Schlevogt, B; Deterding, K; Wranke, A; Smith, A; Port, K; Manns, M P; Vogel, A; Cornberg, M; Wedemeyer, H

2018-02-01

Hepatitis C virus (HCV) clearance with IFN-based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN-free therapy with direct-acting antivirals alters the risk for HCC. To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct-acting antivirals vs untreated controls. We prospectively monitored 373 patients with chronic hepatitis C who received IFN-free therapies with direct-acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols. 158 direct-acting antiviral-treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91-908) and 592 (range 90-1000) days. HCCs developed in 6 and 14 patients during follow-up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person-years. In the direct-acting antiviral-treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD-Scores and AFP-levels were independently associated with HCC development. Transplant-free patient survival was similar in both groups. IFN-free direct-acting antiviral therapy of chronic hepatitis C does not alter the short-term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5 years of follow-up. © 2017 John Wiley & Sons Ltd.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

PubMed

Yoo, S H; Kwon, J H; Nam, S W; Kim, H Y; Kim, C W; You, C R; Choi, S W; Cho, S H; Han, J-Y; Song, D S; Chang, U I; Yang, J M; Lee, H L; Lee, S W; Han, N I; Kim, S-H; Song, M J; Hwang, S; Sung, P S; Jang, J W; Bae, S H; Choi, J Y; Yoon, S K

2018-04-16

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response. © 2018 John Wiley & Sons Ltd.

75 FR 50730 - Public Health Security and Bioterrorism Preparedness and Response Act of 2002: Biennial Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-17

... Bioterrorism Preparedness and Response Act of 2002: Biennial Review and Republication of the Select Agent and... public comment on the current HHS list of select agents and toxins. This document is extending the... changes to the list of select agents and toxins'' and mailed to: Centers for Disease Control and...

75 FR 76039 - Di-Pro, Inc., a Subsidiary of Bendix-Spicer/Knorr-Bremse Bendix-Spicer Foundation Brake Including...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... From Select, Act-1 and Pridestaff Fresno, CA; Amended Certification Regarding Eligibility To Apply for...-Spicer/Knorr-Bremse, including on-site leased workers from Select, Fresno, California. The notice was... Foundation Brake, including on-site leased workers from Select, Act-1 and PrideStaff, Fresno, California, who...

76 FR 23876 - Clarifications to Indian Tribes' Clean Air Act Regulatory Requirements; Direct Final Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... Clarifications to Indian Tribes' Clean Air Act Regulatory Requirements; Direct Final Amendments AGENCY... to amend certain Clean Air Act regulations pertaining to Indian tribes. This action changes the title... Subpart L, which includes provisions specific to implementation plans for tribes located in EPA Region IX...

31 CFR 546.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Attention is directed to section 206 of the International Emergency Economic Powers Act (50 U.S.C. 1705... adjustment pursuant to the Federal Civil Penalties Inflation Adjustment Act of 1990 (Pub. L. 101-410, as... pursuant to 18 U.S.C. 3571. (c) Attention is directed to section 5 of the United Nations Participation Act...

Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

PubMed

Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

2015-09-16

Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be genotype-specific or geographically tailored.

Cheminformatics-aided discovery of small-molecule Protein-Protein Interaction (PPI) dual inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL).

PubMed

Melagraki, Georgia; Ntougkos, Evangelos; Rinotas, Vagelis; Papaneophytou, Christos; Leonis, Georgios; Mavromoustakos, Thomas; Kontopidis, George; Douni, Eleni; Afantitis, Antreas; Kollias, George

2017-04-01

We present an in silico drug discovery pipeline developed and applied for the identification and virtual screening of small-molecule Protein-Protein Interaction (PPI) compounds that act as dual inhibitors of TNF and RANKL through the trimerization interface. The cheminformatics part of the pipeline was developed by combining structure-based with ligand-based modeling using the largest available set of known TNF inhibitors in the literature (2481 small molecules). To facilitate virtual screening, the consensus predictive model was made freely available at: http://enalos.insilicotox.com/TNFPubChem/. We thus generated a priority list of nine small molecules as candidates for direct TNF function inhibition. In vitro evaluation of these compounds led to the selection of two small molecules that act as potent direct inhibitors of TNF function, with IC50 values comparable to those of a previously-described direct inhibitor (SPD304), but with significantly reduced toxicity. These molecules were also identified as RANKL inhibitors and validated in vitro with respect to this second functionality. Direct binding of the two compounds was confirmed both for TNF and RANKL, as well as their ability to inhibit the biologically-active trimer forms. Molecular dynamics calculations were also carried out for the two small molecules in each protein to offer additional insight into the interactions that govern TNF and RANKL complex formation. To our knowledge, these compounds, namely T8 and T23, constitute the second and third published examples of dual small-molecule direct function inhibitors of TNF and RANKL, and could serve as lead compounds for the development of novel treatments for inflammatory and autoimmune diseases.

Notification: Evaluation of Enforcement Decree Compliance for Selected Clean Air Act Sources

EPA Pesticide Factsheets

Project #OPE-FY14-0016, May 22, 2014. The Office of Inspector General (OIG) plans to begin the preliminary research phase of an evaluation of enforcement decree compliance for selected Clean Air Act (CAA) sources.

Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

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

Xiang, Jin; Wang, Ying; Su, Ke

Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist formore » E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER.« less

The evolution of recombination in a heterogeneous environment.

PubMed Central

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

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

Sehgal, Neelima; Hlozek, Renee; Addison, Graeme

We present the measured Sunyaev-Zel'dovich (SZ) flux from 474 optically selected MaxBCG clusters that fall within the Atacama Cosmology Telescope (ACT) Equatorial survey region. The ACT Equatorial region used in this analysis covers 510 deg{sup 2} and overlaps Stripe 82 of the Sloan Digital Sky Survey. We also present the measured SZ flux stacked on 52 X-ray-selected MCXC clusters that fall within the ACT Equatorial region and an ACT Southern survey region covering 455 deg{sup 2}. We find that the measured SZ flux from the X-ray-selected clusters is consistent with expectations. However, we find that the measured SZ flux frommore » the optically selected clusters is both significantly lower than expectations and lower than the recovered SZ flux measured by the Planck satellite. Since we find a lower recovered SZ signal than Planck, we investigate the possibility that there is a significant offset between the optically selected brightest cluster galaxies (BCGs) and the SZ centers, to which ACT is more sensitive due to its finer resolution. Such offsets can arise due to either an intrinsic physical separation between the BCG and the center of the gas concentration or from misidentification of the cluster BCG. We find that the entire discrepancy for both ACT and Planck can be explained by assuming that the BCGs are offset from the SZ maxima with a uniform random distribution between 0 and 1.5 Mpc. Such large offsets between gas peaks and BCGs for optically selected cluster samples seem unlikely given that we find the physical separation between BCGs and X-ray peaks for an X-ray-selected subsample of MaxBCG clusters to have a much narrower distribution that peaks within 0.2 Mpc. It is possible that other effects are lowering the ACT and Planck signals by the same amount, with offsets between BCGs and SZ peaks explaining the remaining difference between ACT and Planck measurements. Several effects that can lower the SZ signal equally for both ACT and Planck, but not explain the difference in measured signals, include a larger percentage of false detections in the MaxBCG sample, a lower normalization of the mass-richness relation, radio or infrared galaxy contamination of the SZ flux, and a low intrinsic SZ signal. In the latter two cases, the effects would need to be preferentially more significant in the optically selected MaxBCG sample than in the MCXC X-ray sample.« less

Tube and column agglutination technology for autocontrol testing.

PubMed

Courtney, J E; Vincent, J L; Indrikovs, A J

2001-01-01

The incidence of positive autocontrol test results with column agglutination technology is a concern. This study investigates the incidence and significance of positive autocontrols in the ID Micro Typing System (gel) and the Gamma ReACT (ReACT). The study encompassed a total of 1021 randomly selected samples from patients and 95 samples from donors collected during 1 month. The autocontrol testing was carried out according to the manufacturer's instructions for the column agglutination tests. The tube method was carried out using low-ionic-strength solution (LISS). The direct antiglobulin test (DAT) was performed using the tube method, and further investigated with elution studies if warranted. Seventy-nine patient's samples (7.74%) had a positive autocontrol: the gel test, 72 (91.13%); ReACT, 21 (26.58%); and the tube method, 27 (34.18%). Of the 79 positive autocontrols, 44 samples had a negative DAT. Of the samples with positive DAT results, only one possessed a clinically significant antibody, anti-D. Moreover, the same sample also tested positive in all three methods. Column agglutination techniques have increased sensitivity for a positive autocontrol beyond the conventional tube method. However, ReACT and gel tests differ significantly in their frequency of positives. Investigation of the significance of a positive autocontrol in column agglutination technology when the conventional tube method is also positive is suggested.

Development of an iron nitrate resistant injector valve for the Space Shuttle orbiter primary thruster

NASA Technical Reports Server (NTRS)

Wichmann, Horst; Marquardt, Kaiser; Goforth, Alyssa

1993-01-01

Design of a direct-acting valve (DAV) for a primary thruster which is fully interchangeable with a thruster equipped with pilot-operated valves is described. The DAV is based on a bellows to isolate propellants form the actuator for maximum resistance to iron nitrate and other contamination and to select optimum materials for the actuator. It provides improved seal performance under all operating conditions and insensitivity to pressure transients. As compared with the existing pilot-operated valve, the DAV design is much simpler, consists of fewer parts, and will be lower in cost.

Emerging roles for neurosteroids in sexual behavior and function.

PubMed

King, Steven R

2008-01-01

Although gonadal and adrenal steroids heavily impact sexual function at the level of the brain, the nervous system also produces its own steroids de novo that may regulate sexual behavior and reproduction. Current evidence points to important roles for neurosteroids in sexual and gender-typical behaviors, control of ovulation, and behaviors that strongly influence sexual interest and motivation like aggression, anxiety and depression. At the cellular level, neurosteroids act through stimulating rapid changes in excitability and direct activation of membrane receptors in neurons. Thus, unlike peripheral steroids, neurosteroids can have immediate and specific effects on select neuronal pathways to regulate sexual function.

Emerging Treatment Mechanisms for Depression: Focus on Glutamate and Synaptic Plasticity

PubMed Central

Gerhard, Danielle M.; Wohleb, Eric S.; Duman, Ronald S.

2016-01-01

Major depression is a chronic and debilitating illness that effects approximately 1 in 5 people, but currently available treatments are limited by low rates of efficacy, therapeutic time lag, and undesirable side effects. Recent efforts have been directed towards investigating rapid-acting agents that reverse the behavioral and neuronal deficits of chronic stress and depression, notably the glutamate NMDA receptor antagonist ketamine. The cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are discussed, as well as novel, selective glutamatergic receptor targets that are safer and have fewer side effects. PMID:26854424

77 FR 49721 - International Services Surveys and Direct Investment Surveys Reporting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

...] RIN 0691-AA81 International Services Surveys and Direct Investment Surveys Reporting AGENCY: Bureau of... BEA will follow to collect data on international trade in services and direct investment surveys. The surveys are provided for by the International Investment and Trade in Services Survey Act (the Act) and...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 2 2013-04-01 2013-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 2 2011-04-01 2011-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 2 2012-04-01 2012-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 2 2014-04-01 2014-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

31 CFR 560.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 537.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 538.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 560.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 541.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 537.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 541.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 595.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 595.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 538.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

When bigger is not better: selection against large size, high condition and fast growth in juvenile lemon sharks.

PubMed

Dibattista, J D; Feldheim, K A; Gruber, S H; Hendry, A P

2007-01-01

Selection acting on large marine vertebrates may be qualitatively different from that acting on terrestrial or freshwater organisms, but logistical constraints have thus far precluded selection estimates for the former. We overcame these constraints by exhaustively sampling and repeatedly recapturing individuals in six cohorts of juvenile lemon sharks (450 age-0 and 255 age-1 fish) at an enclosed nursery site (Bimini, Bahamas). Data on individual size, condition factor, growth rate and inter-annual survival were used to test the 'bigger is better', 'fatter is better' and 'faster is better' hypotheses of life-history theory. For age-0 sharks, selection on all measured traits was weak, and generally acted against large size and high condition. For age-1 sharks, selection was much stronger, and consistently acted against large size and fast growth. These results suggest that selective pressures at Bimini may be constraining the evolution of large size and fast growth, an observation that fits well with the observed small size and low growth rate of juveniles at this site. Our results support those of some other recent studies in suggesting that bigger/fatter/faster is not always better, and may often be worse.

Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAA Receptor Modulators.

PubMed

Forkuo, Gloria S; Nieman, Amanda N; Yuan, Nina Y; Kodali, Revathi; Yu, Olivia B; Zahn, Nicolas M; Jahan, Rajwana; Li, Guanguan; Stephen, Michael Rajesh; Guthrie, Margaret L; Poe, Michael M; Hartzler, Benjamin D; Harris, Ted W; Yocum, Gene T; Emala, Charles W; Steeber, Douglas A; Stafford, Douglas C; Cook, James M; Arnold, Leggy A

2017-06-05

We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α 4 β 3 γ 2 GABA A R selective compound 1 and acidic α 5 β 3 γ 2 selective GABA A R positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compounds 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties. Additionally, compound 1 reduced the number of lung CD4 + T lymphocytes and directly modulated their transmembrane currents by acting on GABA A Rs. Excellent pharmacokinetic properties were observed, including long plasma half-life (up to 15 h), oral availability, and extremely low brain distribution. In conclusion, we report the selective targeting of GABA A Rs expressed outside the brain and demonstrate reduction of AHR and airway inflammation with two novel orally available GABA A R ligands.

Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9.

PubMed

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.

Recovery Act: Planned Efforts and Challenges in Evaluating Compliance with Maintenance of Effort and Similar Provisions. Report to the Republican Leader, U.S. Senate. GAO-10-247

ERIC Educational Resources Information Center

Dodaro, Gene L.

2009-01-01

To help prevent the substitution of federal funds for state, local, or private funds, the American Recovery and Reinvestment Act of 2009 (Recovery Act) contains maintenance of effort and similar provisions requiring that recipients maintain certain levels of spending for selected programs. This report provides information on selected programs in…

Endocrine phenotype, reproductive success and survival in the great tit, Parus major.

PubMed

Ouyang, J Q; Sharp, P; Quetting, M; Hau, M

2013-09-01

A central goal in evolutionary ecology is to characterize and identify selection patterns on the optimal phenotype in different environments. Physiological traits, such as hormonal responses, provide important mechanisms by which individuals can adapt to fluctuating environmental conditions. It is therefore expected that selection shapes hormonal traits, but the strength and the direction of selection on plastic hormonal signals are still under investigation. Here, we determined whether, and in which way, selection is acting on the hormones corticosterone and prolactin by characterizing endocrine phenotypes and their relationship with fitness in free-living great tits, Parus major. We quantified variation in circulating concentrations of baseline and stress-induced corticosterone and in prolactin during the prebreeding (March) and the breeding season (May) for two consecutive years, and correlated these with reproductive success (yearly fledgling number) and overwinter survival in female and male individuals. In both years, individuals with high baseline corticosterone concentrations in March had the highest yearly fledgling numbers; while in May, individuals with low baseline corticosterone had the highest yearly reproductive success. Likewise, individuals that displayed strong seasonal plasticity in baseline corticosterone concentrations (high in March and low in May) had the highest reproductive success in each year. Prolactin concentrations were not related to reproductive success, but were positively correlated to the proximity to lay. Between-year plasticity in stress-induced corticosterone concentrations of males was related to yearly variation in food abundance, but not to overall reproductive success. These findings suggest that seasonally alternating directional selection is operating on baseline corticosterone concentrations in both sexes. The observed between-year consistency in selection patterns indicates that a one-time hormone sample in a given season can allow the prediction of individual fitness. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

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.

Evidence for strong intralocus sexual conflict in the Indian meal moth, Plodia interpunctella.

PubMed

Lewis, Zenobia; Wedell, Nina; Hunt, John

2011-07-01

Males and females share a genome and express many shared phenotypic traits, which are often selected in opposite directions. This generates intralocus sexual conflict that may constrain trait evolution by preventing the sexes from reaching their optimal phenotype. Furthermore, if present across multiple loci, intralocus sexual conflict can result in a gender load that may diminish the benefits of sexual selection and help maintain genetic variation for fitness. Despite the importance of intralocus sexual conflict, surprisingly few empirical studies conclusively demonstrate its operation. We show that the pattern of multivariate selection acting on three sexually dimorphic life-history traits (development time, body size, and longevity) in the Indian meal moth, Plodia interpunctella, is opposing for the sexes. Moreover, we combined our estimates of selection with the additive genetic variance-covariance matrix (G) to predict the evolutionary response of the life-history traits in the sexes and showed that the angle between the vector of responses and the vector of sexually antagonistic selection was almost orthogonal at 84.70°. Thus, G biases the predicted response of life-history traits in the sexes away from the direction of sexually antagonistic selection, confirming the presence of strong intralocus sexual conflict in this species. Despite this, sexual dimorphism has evolved in all of the life-history traits examined suggesting that mechanism(s) have evolved to resolve this conflict and allow the sexes to reach their life-history optima. We argue that intralocus sexual conflict is likely to play an important role in the evolution of divergent life-history strategies between the sexes in this species. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Phylodynamics of H1N1/2009 influenza reveals the transition from host adaptation to immune-driven selection

PubMed Central

Su, Yvonne C. F.; Bahl, Justin; Joseph, Udayan; Butt, Ka Man; Peck, Heidi A.; Koay, Evelyn S. C.; Oon, Lynette L. E.; Barr, Ian G.; Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.

2015-01-01

Influenza A H1N1/2009 virus that emerged from swine rapidly replaced the previous seasonal H1N1 virus. Although the early emergence and diversification of H1N1/2009 is well characterized, the ongoing evolutionary and global transmission dynamics of the virus remain poorly investigated. To address this we analyse >3,000 H1N1/2009 genomes, including 214 full genomes generated from our surveillance in Singapore, in conjunction with antigenic data. Here we show that natural selection acting on H1N1/2009 directly after introduction into humans was driven by adaptation to the new host. Since then, selection has been driven by immunological escape, with these changes corresponding to restricted antigenic diversity in the virus population. We also show that H1N1/2009 viruses have been subject to regular seasonal bottlenecks and a global reduction in antigenic and genetic diversity in 2014. PMID:26245473

Selection of Person of the Year from Public Health Perspective: Promotion of Mass Clusters of Copycat Self-immolation

PubMed Central

Zarghami, Mehran

2012-01-01

Suicide is a complex phenomenon with multiple diverse causes. It is obvious that if the media give rewards to the suicides directly or indirectly, they will have more copycat effect. It seems that political means in the mainstream media, particularly in the Western world overshadow public health- especially mental health- issues. Selection of a Tunisian fruit vendor who set himself on fire in a public square as the person of the year by Time Magazine is a good example in this domain. Mass clusters of copycat altruistic self-burning promotion in the Middle East and North Africa obviously demonstrate the importance of the dilemma and its relevance in terms of public health, and the need to develop efficacious interruptive strategies able to prevent people from committing a dramatic fatal act. PMID:24644463

Ploidally antagonistic selection maintains stable genetic polymorphism.

PubMed

Immler, Simone; Arnqvist, Göran; Otto, Sarah Perin

2012-01-01

Understanding the maintenance of genetic variation in the face of selection remains a key issue in evolutionary biology. One potential mechanism for the maintenance of genetic variation is opposing selection during the diploid and haploid stages of biphasic life cycles universal among eukaryotic sexual organisms. If haploid and diploid gene expression both occur, selection can act in each phase, potentially in opposing directions. In addition, sex-specific selection during haploid phases is likely simply because male and female gametophytes/gametes tend to have contrasting life histories. We explored the potential for the maintenance of a stable polymorphism under ploidally antagonistic as well as sex-specific selection. Furthermore, we examined the role of the chromosomal location of alleles (autosomal or sex-linked). Our analyses show that the most permissible conditions for the maintenance of polymorphism occur under negative ploidy-by-sex interactions, where stronger selection for an allele in female than male diploids is coupled with weaker selection against the allele in female than male haploids. Such ploidy-by-sex interactions also promote allele frequency differences between the sexes. With constant fitness, ploidally antagonistic selection can maintain stable polymorphisms for autosomal and X-linked genes but not for Y-linked genes. We discuss the implications of our results and outline a number of biological settings where the scenarios modeled may apply. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution.

20 CFR 661.310 - Under what limited conditions may a Local Board directly be a provider of core services...

Code of Federal Regulations, 2011 CFR

2011-04-01

... Board directly be a provider of core services, intensive services, or training services, or act as a One... Board directly be a provider of core services, intensive services, or training services, or act as a One-Stop Operator? (a) A Local Board may not directly provide core services, or intensive services, or be...

20 CFR 661.310 - Under what limited conditions may a Local Board directly be a provider of core services...

Code of Federal Regulations, 2010 CFR

2010-04-01

... Board directly be a provider of core services, intensive services, or training services, or act as a One... Board directly be a provider of core services, intensive services, or training services, or act as a One-Stop Operator? (a) A Local Board may not directly provide core services, or intensive services, or be...

Survival of female Lesser Scaup: Effects of body size, age, and reproductive effort

USGS Publications Warehouse

Rotella, J.J.; Clark, R.G.; Afton, A.D.

2003-01-01

In birds, larger females generally have greater breeding propensity, reproductive investment, and success than do smaller females. However, optimal female body size also depends on how natural selection acts during other parts of the life cycle. Larger female Lesser Scaup (Aythya affinis) produce larger eggs than do smaller females, and ducklings from larger eggs survive better than those hatching from smaller eggs. Accordingly, we examined patterns of apparent annual survival for female scaup and tested whether natural selection on female body size primarily was stabilizing, a frequent assumption in studies of sexually dimorphic species in which males are the larger sex, or was directional, counter-acting reproductive advantages of large size. We estimated survival using mark-recapture methods for individually marked females from two study sites in Canada (Erickson, Manitoba; St. Denis, Saskatchewan). Structurally larger (adults) and heavier (ducklings) females had lower survival than did smaller individuals in Manitoba; no relationship was detected in adults from Saskatchewan. Survival of adult females declined with indices of increasing reproductive effort at both sites; consequently, the cost of reproduction could explain age-related patterns of breeding propensity in scaup. Furthermore, if larger females are more likely to breed than are smaller females, then cost of reproduction also may help explain why survival was lower for larger females. Overall, we found that advantages of large body size of female scaup during breeding or as young ducklings apparently were counteracted by natural selection favoring lightweight juveniles and structurally smaller adult females through higher annual survival.

The effects of selection and genetic drift on the genomic distribution of sexually antagonistic alleles.

PubMed

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.

78 FR 41199 - Telemarketing Sales Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

... telemarketing acts or practices.''). The Telemarketing Act directs the Commission to include in the TSR... amendments to the general media and direct mail exemptions in sections 310.6(b)(5) and (6)). \\31\\ 16 CFR 310... begin with a paper item. However, they are similar to RCCs in that they . . . bear no direct evidence of...

Believer-Skeptic Meets Actor-Critic: Rethinking the Role of Basal Ganglia Pathways during Decision-Making and Reinforcement Learning

PubMed Central

Dunovan, Kyle; Verstynen, Timothy

2016-01-01

The flexibility of behavioral control is a testament to the brain's capacity for dynamically resolving uncertainty during goal-directed actions. This ability to select actions and learn from immediate feedback is driven by the dynamics of basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with the traditional view that these pathways act as independent levers for facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor output, suggesting instead that they engage in a dynamic competition during action decisions that computationally captures action uncertainty. Here we discuss the utility of encoding action uncertainty as a dynamic competition between opposing control pathways and provide evidence that this simple mechanism may have powerful implications for bridging neurocomputational theories of decision making and reinforcement learning. PMID:27047328

Believer-Skeptic Meets Actor-Critic: Rethinking the Role of Basal Ganglia Pathways during Decision-Making and Reinforcement Learning.

PubMed

Dunovan, Kyle; Verstynen, Timothy

2016-01-01

The flexibility of behavioral control is a testament to the brain's capacity for dynamically resolving uncertainty during goal-directed actions. This ability to select actions and learn from immediate feedback is driven by the dynamics of basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with the traditional view that these pathways act as independent levers for facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor output, suggesting instead that they engage in a dynamic competition during action decisions that computationally captures action uncertainty. Here we discuss the utility of encoding action uncertainty as a dynamic competition between opposing control pathways and provide evidence that this simple mechanism may have powerful implications for bridging neurocomputational theories of decision making and reinforcement learning.

78 FR 12221 - National School Lunch Program: Direct Certification Continuous Improvement Plans Required by the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

..., Hunger-Free Kids Act of 2010 AGENCY: Food and Nutrition Service, USDA. ACTION: Final rule. SUMMARY: This... Healthy, Hunger-Free Kids Act of 2010 designed to encourage States to improve direct certification efforts.../CNP/cnp.htm .) Section 101(b) of Public Law 111-296, the Healthy, Hunger-Free Kids Act of 2010 (HHFKA...

Direct protein interaction underlies gene-for-gene specificity and coevolution of the flax resistance genes and flax rust avirulence genes

PubMed Central

Dodds, Peter N.; Lawrence, Gregory J.; Catanzariti, Ann-Maree; Teh, Trazel; Wang, Ching-I. A.; Ayliffe, Michael A.; Kobe, Bostjan; Ellis, Jeffrey G.

2006-01-01

Plant resistance proteins (R proteins) recognize corresponding pathogen avirulence (Avr) proteins either indirectly through detection of changes in their host protein targets or through direct R–Avr protein interaction. Although indirect recognition imposes selection against Avr effector function, pathogen effector molecules recognized through direct interaction may overcome resistance through sequence diversification rather than loss of function. Here we show that the flax rust fungus AvrL567 genes, whose products are recognized by the L5, L6, and L7 R proteins of flax, are highly diverse, with 12 sequence variants identified from six rust strains. Seven AvrL567 variants derived from Avr alleles induce necrotic responses when expressed in flax plants containing corresponding resistance genes (R genes), whereas five variants from avr alleles do not. Differences in recognition specificity between AvrL567 variants and evidence for diversifying selection acting on these genes suggest they have been involved in a gene-specific arms race with the corresponding flax R genes. Yeast two-hybrid assays indicate that recognition is based on direct R–Avr protein interaction and recapitulate the interaction specificity observed in planta. Biochemical analysis of Escherichia coli-produced AvrL567 proteins shows that variants that escape recognition nevertheless maintain a conserved structure and stability, suggesting that the amino acid sequence differences directly affect the R–Avr protein interaction. We suggest that direct recognition associated with high genetic diversity at corresponding R and Avr gene loci represents an alternative outcome of plant–pathogen coevolution to indirect recognition associated with simple balanced polymorphisms for functional and nonfunctional R and Avr genes. PMID:16731621

A Toolbox for Corrective Action: Resource Conservation and Recovery Act Facilities Investigation Remedy Selection Track

EPA Pesticide Factsheets

The purpose of this toolbox is to help EPA Regional staff and their partners to take advantage of the efficiency and quality gains from the Resource Conservation and Recovery Act (RCRA) Facilities Investigation Remedy Selection Track (FIRST) approach.

Gravity-directed calcium current in germinating spores of Ceratopteris richardii

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Porterfield, D. M.; Smith, P. S.; Roux, S. J.

2000-01-01

Gravity directs the early polar development in single cells of Ceratopteris richardii Brogn. It acts over a limited period of time during which it irreversibly determines the axis of the spore cell's development. A self-referencing calcium selective electrode was utilized to record the net movement of calcium across the cell membrane at different positions around the periphery of the spore during the period in which gravity orients the polarity of the spore. A movement of calcium into the cell along the bottom and out of the cell along the top was detected. This movement was specific, polarized, and strongest in a direction that opposed the vector of gravity. Treatment with nifedipine, a calcium-channel blocker, diminished the calcium current and caused the cell to lose its responsiveness to the orienting influence of gravity. Results shown suggest that calcium plays a crucial role in the ability of a single cell to respond to gravity and in the subsequent establishment of its polarity.

The Atacama Cosmology Telescope: Relation Between Galaxy Cluster Optical Richness and Sunyaev-Zel'dovich Effect

NASA Technical Reports Server (NTRS)

Sehgal, Neelima; Addison, Graeme; Battaglia, Nick; Battistelli, Elia S.; Bond, J. Richard; Das, Sudeep; Devlin, Mark J.; Dunkley, Joanna; Duenner, Rolando; Gralla, Megan;

The selective reversible FAAH inhibitor, SSR411298, restores the development of maladaptive behaviors to acute and chronic stress in rodents.

PubMed

Griebel, Guy; Stemmelin, Jeanne; Lopez-Grancha, Mati; Fauchey, Valérie; Slowinski, Franck; Pichat, Philippe; Dargazanli, Gihad; Abouabdellah, Ahmed; Cohen, Caroline; Bergis, Olivier E

2018-02-05

Enhancing endogenous cannabinoid (eCB) signaling has been considered as a potential strategy for the treatment of stress-related conditions. Fatty acid amide hydrolase (FAAH) represents the primary degradation enzyme of the eCB anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). This study describes a potent reversible FAAH inhibitor, SSR411298. The drug acts as a selective inhibitor of FAAH, which potently increases hippocampal levels of AEA, OEA and PEA in mice. Despite elevating eCB levels, SSR411298 did not mimic the interoceptive state or produce the behavioral side-effects (memory deficit and motor impairment) evoked by direct-acting cannabinoids. When SSR411298 was tested in models of anxiety, it only exerted clear anxiolytic-like effects under highly aversive conditions following exposure to a traumatic event, such as in the mouse defense test battery and social defeat procedure. Results from experiments in models of depression showed that SSR411298 produced robust antidepressant-like activity in the rat forced-swimming test and in the mouse chronic mild stress model, restoring notably the development of inadequate coping responses to chronic stress. This preclinical profile positions SSR411298 as a promising drug candidate to treat diseases such as post-traumatic stress disorder, which involves the development of maladaptive behaviors.

The Tn7 transposition regulator TnsC interacts with the transposase subunit TnsB and target selector TnsD

PubMed Central

Choi, Ki Young; Spencer, Jeanelle M.; Craig, Nancy L.

2014-01-01

The excision of transposon Tn7 from a donor site and its insertion into its preferred target site, attachment site attTn7, is mediated by four Tn7-encoded transposition proteins: TnsA, TnsB, TnsC, and TnsD. Transposition requires the assembly of a nucleoprotein complex containing all four Tns proteins and the DNA substrates, the donor site containing Tn7, and the preferred target site attTn7. TnsA and TnsB together form the heteromeric Tn7 transposase, and TnsD is a target-selecting protein that binds specifically to attTn7. TnsC is the key regulator of transposition, interacting with both the TnsAB transposase and TnsD-attTn7. We show here that TnsC interacts directly with TnsB, and identify the specific region of TnsC involved in the TnsB–TnsC interaction during transposition. We also show that a TnsC mutant defective in interaction with TnsB is defective for Tn7 transposition both in vitro and in vivo. Tn7 displays cis-acting target immunity, which blocks Tn7 insertion into a target DNA that already contains Tn7. We provide evidence that the direct TnsB–TnsC interaction that we have identified also mediates cis-acting Tn7 target immunity. We also show that TnsC interacts directly with the target selector protein TnsD. PMID:24982178

A murine monoclonal antibody directed against the carboxyl-terminal domain of GRP78 suppresses melanoma growth in mice.

PubMed

de Ridder, Gustaaf G; Ray, Rupa; Pizzo, Salvatore V

2012-06-01

The HSP70 family member GRP78 is a selective tumor marker upregulated on the surface of many tumor cell types, including melanoma, where it acts as a growth factor receptor-like protein. Receptor-recognized forms of the proteinase inhibitor α2-macroglobulin (α2M*) are the best-characterized ligands for GRP78, but in melanoma and other cancer patients, autoantibodies arise against the NH2-terminal domain of GRP78 that react with tumor cell-surface GRP78. This causes the activation of signaling cascades that are proproliferative and antiapoptotic. Antibodies directed against the COOH-terminal domain of GRP78, however, upregulate p53-mediated proapoptotic signaling, leading to cell death. Here, we describe the binding characteristics, cell signaling properties, and downstream cellular effects of three novel murine monoclonal antibodies. The NH2-terminal domain-reactive antibody, N88, mimics α2M* as a ligand and drives PI 3-kinase-dependent activation of Akt and the subsequent stimulation of cellular proliferation in vitro. The COOH-terminal domain-reactive antibody, C38, acts as an antagonist of both α2M* and N88, whereas another, C107, directly induces apoptosis in vitro. In a murine B16F1 melanoma flank tumor model, we demonstrate the acceleration of tumor growth by treatment with N88, whereas C107 significantly slowed tumor growth whether administered before (P<0.005) or after (P<0.05) tumor implantation.

77 FR 16888 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-22

... Change To Delete Certain Select Symbols From the Rebates and Fees for Adding and Removing Liquidity in Select Symbols March 15, 2012. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act... [[Page 16889

Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.

PubMed

Henriques, Gisela; Hallett, Rachel L; Beshir, Khalid B; Gadalla, Nahla B; Johnson, Rachel E; Burrow, Rebekah; van Schalkwyk, Donelly A; Sawa, Patrick; Omar, Sabah A; Clark, Taane G; Bousema, Teun; Sutherland, Colin J

2014-12-15

The efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment was associated with subsequent microscopically detected parasitemia at days 28 or 42. DNA sequences of resistance-associated parasite loci pfcrt, pfmdr1, pfubp1, and pfap2mu were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment, and on the day of treatment failure. Parasites surviving ACT on day 2 or day 3 posttreatment were significantly more likely than the baseline population to carry the wild-type haplotypes of pfcrt (CVMNK at codons 72-76; P < .001) and pfmdr1 (NFD at codons 86, 184, 1246; P < .001). In contrast, variant alleles of the novel candidate resistance genes pfap2mu (S160N/T; P = .006) and pfubp-1 (E1528D; P < .001) were significantly more prevalent posttreatment. No genetic similarities were found to artemisinin-tolerant parasites recently described in Cambodia. Among treated children in western Kenya, certain P. falciparum genotypes defined at pfcrt, pfmdr1, pfap2mu, and pfubp1 more often survive ACT at the submicroscopic level, and contribute to onward transmission and subsequent patent recrudescence. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Evolution of resistance to a multiple-herbivore community: genetic correlations, diffuse coevolution, and constraints on the plant's response to selection.

PubMed

Wise, Michael J; Rausher, Mark D

2013-06-01

Although plants are generally attacked by a community of several species of herbivores, relatively little is known about the strength of natural selection for resistance in multiple-herbivore communities-particularly how the strength of selection differs among herbivores that feed on different plant organs or how strongly genetic correlations in resistance affect the evolutionary responses of the plant. Here, we report on a field study measuring natural selection for resistance in a diverse community of herbivores of Solanum carolinense. Using linear phenotypic-selection analyses, we found that directional selection acted to increase resistance to seven species. Selection was strongest to increase resistance to fruit feeders, followed by flower feeders, then leaf feeders. Selection favored a decrease in resistance to a stem borer. Bootstrapping analyses showed that the plant population contained significant genetic variation for each of 14 measured resistance traits and significant covariances in one-third of the pairwise combinations of resistance traits. These genetic covariances reduced the plant's overall predicted evolutionary response for resistance against the herbivore community by about 60%. Diffuse (co)evolution was widespread in this community, and the diffuse interactions had an overwhelmingly constraining (rather than facilitative) effect on the plant's evolution of resistance. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Sexual selection in hermaphrodites, sperm and broadcast spawners, plants and fungi

PubMed Central

Ortiz-Barrientos, Daniel

2016-01-01

Darwin was the first to recognize that sexual selection is a strong evolutionary force. Exaggerated traits allow same-sex individuals to compete over access to mates and provide a mechanism by which mates are selected. It is relatively easy to appreciate how inter- and intrasexual selection work in organisms with the sensory capabilities to perceive physical or behavioural traits that signal mate quality or mate compatibility, and to assess the relative quality of competitors. It is therefore not surprising that most studies of sexual selection have focused on animals with separate sexes and obvious adaptations that function in the context of reproductive competition. Yet, many sexual organisms are both male and female at the same time, often lack sexual dimorphism and never come into direct contact at mating. How does sexual selection act in such species, and what can we learn from them? Here, we address these questions by exploring the potential for sexual selection in simultaneous hermaphrodites, sperm- and broadcast spawners, plants and fungi. Our review reveals a range of mechanisms of sexual selection, operating primarily after gametes have been released, which are common in many of these groups and also quite possibly in more familiar (internally fertilizing and sexually dimorphic) organisms. This article is part of the themed issue ‘Weird sex: the underappreciated diversity of sexual reproduction’. PMID:27619704

Sexual selection in hermaphrodites, sperm and broadcast spawners, plants and fungi.

PubMed

Beekman, Madeleine; Nieuwenhuis, Bart; Ortiz-Barrientos, Daniel; Evans, Jonathan P

2016-10-19

Darwin was the first to recognize that sexual selection is a strong evolutionary force. Exaggerated traits allow same-sex individuals to compete over access to mates and provide a mechanism by which mates are selected. It is relatively easy to appreciate how inter- and intrasexual selection work in organisms with the sensory capabilities to perceive physical or behavioural traits that signal mate quality or mate compatibility, and to assess the relative quality of competitors. It is therefore not surprising that most studies of sexual selection have focused on animals with separate sexes and obvious adaptations that function in the context of reproductive competition. Yet, many sexual organisms are both male and female at the same time, often lack sexual dimorphism and never come into direct contact at mating. How does sexual selection act in such species, and what can we learn from them? Here, we address these questions by exploring the potential for sexual selection in simultaneous hermaphrodites, sperm- and broadcast spawners, plants and fungi. Our review reveals a range of mechanisms of sexual selection, operating primarily after gametes have been released, which are common in many of these groups and also quite possibly in more familiar (internally fertilizing and sexually dimorphic) organisms.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'. © 2016 The Author(s).

18 CFR 367.4581 - Account 458.1, Direct costs charged to non-associate companies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Account 458.1, Direct... Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE PUBLIC UTILITY..., FEDERAL POWER ACT AND NATURAL GAS ACT Operating Revenue Chart of Accounts § 367.4581 Account 458.1, Direct...

18 CFR 367.4571 - Account 457.1, Direct costs charged to associate companies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Account 457.1, Direct... Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE PUBLIC UTILITY..., FEDERAL POWER ACT AND NATURAL GAS ACT Operating Revenue Chart of Accounts § 367.4571 Account 457.1, Direct...

Directive Speech Act of Imamu in Katoba Discourse of Muna Ethnic

NASA Astrophysics Data System (ADS)

Ardianto, Ardianto; Hadirman, Hardiman

2018-05-01

One of the traditions of Muna ethnic is katoba ritual. Katoba ritual is one tradition that values local knowledge maintained its existence for generations until today. Katoba ritual is a ritual to be Islamic person, repentance, and the formation of a child's character (male/female) who will enter adulthood (6-11 years) using directive speech. In katoba ritual, a child who is in-katoba introduced to the teaching of the Islamic religion, customs, manners to parents and his brother and behaviour towards others which is expected to be implemented in daily life. This study aims to describe and explain the directive speech acts of the imamu in the katoba discourse of Muna ethnic. This research uses a qualitative approach. Data are collected from a natural setting, namely katoba speech discourses. The data consist of two types, namely: (a) speech data, and (b) field note data. Data are analyzed using an interactive model with four stages: (1) data collection, (2) data reduction, (3) data display, and (4) conclusion and verification. The result shows, firstly, the form of directive speech acts includes declarative and imperative form; secondly, the function of directive speech acts includes functions of teaching, explaining, suggesting, and expecting; and thirdly, the strategy of directive speech acts includes both direct and indirect strategy. The results of this study could be implied in the development of character learning materials at schools. It also can be one of the contents of local content (mulok) at school.

The effect of sexual selection on adaptation and extinction under increasing temperatures.

PubMed

Parrett, Jonathan M; Knell, Robert J

2018-04-25

Strong sexual selection has been reported to both enhance and hinder the adaptive capacity and persistence of populations when exposed to novel environments. Consequently, how sexual selection influences population adaption and persistence under stress remains widely debated. Here, we present two empirical investigations of the fitness consequences of sexual selection on populations of the Indian meal moth, Plodia interpunctella, exposed to stable or gradually increasing temperatures. When faced with increasing temperatures, strong sexual selection was associated with both increased fecundity and offspring survival compared with populations experiencing weak sexual selection, suggesting sexual selection acts to drive adaptive evolution by favouring beneficial alleles. Strong sexual selection did not, however, delay extinction when the temperature became excessively high. By manipulating individuals' mating opportunities during fitness assays, we were able to assess the effect of multiple mating independently from the effect of population-level sexual selection, and found that polyandry has a positive effect on both fecundity and offspring survival under increasing temperatures in those populations evolving with weak sexual selection. Within stable temperatures, there were some benefits from strong sexual selection but these were not consistent across the entire experiment, possibly reflecting changing costs and benefits of sexual selection under stabilizing and directional selection. These results indicate that sexual selection can provide a buffer against climate change and increase adaptation rates within a continuously changing environment. These positive effects of sexual selection may, however, be too small to protect populations and delay extinction when environmental changes are relatively rapid. © 2018 The Author(s).

Attention selectively modifies the representation of individual faces in the human brain

PubMed Central

Gratton, Caterina; Sreenivasan, Kartik K.; Silver, Michael A.; D’Esposito, Mark

2013-01-01

Attention modifies neural tuning for low-level features, but it is unclear how attention influences tuning for complex stimuli. We investigated this question in humans using fMRI and face stimuli. Participants were shown six faces (F1-F6) along a morph continuum, and selectivity was quantified by constructing tuning curves for individual voxels. Face-selective voxels exhibited greater responses to their preferred face than to non-preferred faces, particularly in posterior face areas. Anterior face areas instead displayed tuning for face categories: voxels in these areas preferred either the first (F1-F3) or second (F4-F6) half of the morph continuum. Next, we examined the effects of attention on voxel tuning by having subjects direct attention to one of the superimposed images of F1 and F6. We found that attention selectively enhanced responses in voxels preferring the attended face. Taken together, our results demonstrate that single voxels carry information about individual faces and that the nature of this information varies across cortical face areas. Additionally, we found that attention selectively enhances these representations. Our findings suggest that attention may act via a unitary principle of selective enhancement of responses to both simple and complex stimuli across multiple stages of the visual hierarchy. PMID:23595755

Evolutionary rates for multivariate traits: the role of selection and genetic variation.

PubMed

Pitchers, William; Wolf, Jason B; Tregenza, Tom; Hunt, John; Dworkin, Ian

2014-08-19

A fundamental question in evolutionary biology is the relative importance of selection and genetic architecture in determining evolutionary rates. Adaptive evolution can be described by the multivariate breeders' equation (Δz(-)=Gβ), which predicts evolutionary change for a suite of phenotypic traits (Δz(-)) as a product of directional selection acting on them (β) and the genetic variance-covariance matrix for those traits (G ). Despite being empirically challenging to estimate, there are enough published estimates of G and β to allow for synthesis of general patterns across species. We use published estimates to test the hypotheses that there are systematic differences in the rate of evolution among trait types, and that these differences are, in part, due to genetic architecture. We find some evidence that sexually selected traits exhibit faster rates of evolution compared with life-history or morphological traits. This difference does not appear to be related to stronger selection on sexually selected traits. Using numerous proposed approaches to quantifying the shape, size and structure of G, we examine how these parameters relate to one another, and how they vary among taxonomic and trait groupings. Despite considerable variation, they do not explain the observed differences in evolutionary rates. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Guidance on the Use of Best Available Science under the U.S. Endangered Species Act

NASA Astrophysics Data System (ADS)

Murphy, Dennis D.; Weiland, Paul S.

2016-07-01

The Endangered Species Act's best available science mandate has been widely emulated and reflects a Congressional directive to ensure that decisions made under the Act are informed by reliable knowledge applied using a structured approach. We build on a standing literature by describing the role of the best science directive in the Act's implementation and best practices that can be employed to realize the directive. Next we describe recurring impediments to realizing determinations by the federal wildlife agencies that are based on the best available science. We then identify the types of data, analyses, and modeling efforts that can serve as best science. Finally, we consider the role and application of best available science in effects analysis and adaptive management. We contend that more rigorous adherence by the wildlife agencies to the best available science directive and more assiduous judicial oversight of agency determinations and actions is essential for effective implementation of the Act, particularly where it has substantial ramifications for listed species, stakeholder segments of society, or both.

Guidance on the Use of Best Available Science under the U.S. Endangered Species Act.

PubMed

Murphy, Dennis D; Weiland, Paul S

2016-07-01

The Endangered Species Act's best available science mandate has been widely emulated and reflects a Congressional directive to ensure that decisions made under the Act are informed by reliable knowledge applied using a structured approach. We build on a standing literature by describing the role of the best science directive in the Act's implementation and best practices that can be employed to realize the directive. Next we describe recurring impediments to realizing determinations by the federal wildlife agencies that are based on the best available science. We then identify the types of data, analyses, and modeling efforts that can serve as best science. Finally, we consider the role and application of best available science in effects analysis and adaptive management. We contend that more rigorous adherence by the wildlife agencies to the best available science directive and more assiduous judicial oversight of agency determinations and actions is essential for effective implementation of the Act, particularly where it has substantial ramifications for listed species, stakeholder segments of society, or both.

Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats

PubMed Central

Baladi, Michelle G.; Newman, Amy H.

2010-01-01

The discriminative stimulus effects of dopamine (DA) D3/D2 receptor agonists are thought to be mediated by D2 receptors. To maintain responding, access to food is often restricted, which can alter neurochemical and behavioral effects of drugs acting on DA systems. This study established stimulus control with quinpirole in free-feeding rats and tested the ability of agonists to mimic and antagonists to attenuate the effects of quinpirole. The same antagonists were studied for their ability to attenuate quinpirole-induced yawning and hypothermia. DA receptor agonists apomorphine and lisuride, but not amphetamine and morphine, occasioned responding on the quinpirole lever. The discriminative stimulus effects of quinpirole were attenuated by the D3 receptor-selective antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl (PG01037) and the nonselective D3/D2 receptor antagonist raclopride, but not by the D2 receptor-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl-1H-indole (L-741,626); the potencies of PG01037 and raclopride to antagonize this effect of quinpirole paralleled their potencies to antagonize the ascending limb of the quinpirole yawning dose-response curve (thought to be mediated by D3 receptors). L-741,626 selectively antagonized the descending limb of the quinpirole yawning dose-response curve, and both L-741,626 and raclopride, but not PG01037, antagonized the hypothermic effects of quinpirole (thought to be mediated by D2 receptors). Food restriction (10 g/day/7 days) significantly decreased quinpirole-induced yawning without affecting the quinpirole discrimination. Many discrimination studies on DA receptor agonists use food-restricted rats; together with those studies, the current experiment using free-feeding rats suggests that feeding conditions affecting the behavioral effects of direct-acting DA receptor agonists might also have an impact on the effects of indirect-acting agonists such as cocaine and amphetamine. PMID:19797621

Dopamine D3 receptors mediate the discriminative stimulus effects of quinpirole in free-feeding rats.

PubMed

Baladi, Michelle G; Newman, Amy H; France, Charles P

2010-01-01

The discriminative stimulus effects of dopamine (DA) D3/D2 receptor agonists are thought to be mediated by D2 receptors. To maintain responding, access to food is often restricted, which can alter neurochemical and behavioral effects of drugs acting on DA systems. This study established stimulus control with quinpirole in free-feeding rats and tested the ability of agonists to mimic and antagonists to attenuate the effects of quinpirole. The same antagonists were studied for their ability to attenuate quinpirole-induced yawning and hypothermia. DA receptor agonists apomorphine and lisuride, but not amphetamine and morphine, occasioned responding on the quinpirole lever. The discriminative stimulus effects of quinpirole were attenuated by the D3 receptor-selective antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl (PG01037) and the nonselective D3/D2 receptor antagonist raclopride, but not by the D2 receptor-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl-1H-indole (L-741,626); the potencies of PG01037 and raclopride to antagonize this effect of quinpirole paralleled their potencies to antagonize the ascending limb of the quinpirole yawning dose-response curve (thought to be mediated by D3 receptors). L-741,626 selectively antagonized the descending limb of the quinpirole yawning dose-response curve, and both L-741,626 and raclopride, but not PG01037, antagonized the hypothermic effects of quinpirole (thought to be mediated by D2 receptors). Food restriction (10 g/day/7 days) significantly decreased quinpirole-induced yawning without affecting the quinpirole discrimination. Many discrimination studies on DA receptor agonists use food-restricted rats; together with those studies, the current experiment using free-feeding rats suggests that feeding conditions affecting the behavioral effects of direct-acting DA receptor agonists might also have an impact on the effects of indirect-acting agonists such as cocaine and amphetamine.

Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs.

PubMed

Millan, Mark J

2009-01-01

The past decade of efforts to find improved treatment for major depression has been dominated by genome-driven programs of rational drug discovery directed toward highly selective ligands for nonmonoaminergic agents. Selective drugs may prove beneficial for specific symptoms, for certain patient subpopulations, or both. However, network analyses of the brain and its dysfunction suggest that agents with multiple and complementary modes of action are more likely to show broad-based efficacy against core and comorbid symptoms of depression. Strategies for improved multitarget exploitation of monoaminergic mechanisms include triple inhibitors of dopamine, serotonin (5-HT) and noradrenaline reuptake, and drugs interfering with feedback actions of monoamines at inhibitory 5-HT(1A), 5-HT(1B) and possibly 5-HT(5A) and 5-HT(7) receptors. Specific subsets of postsynaptic 5-HT receptors mediating antidepressant actions are under study (e.g., 5-HT(4) and 5-HT(6)). Association of a clinically characterized antidepressant mechanism with a nonmonoaminergic component of activity is an attractive strategy. For example, agomelatine (a melatonin agonist/5-HT(2C) antagonist) has clinically proven activity in major depression. Dual neurokinin(1) antagonists/5-HT reuptake inhibitors (SRIs) and melanocortin(4) antagonists/SRIs should display advantages over their selective counterparts, and histamine H(3) antagonists/SRIs, GABA(B) antagonists/SRIs, glutamatergic/SRIs, and cholinergic agents/SRIs may counter the compromised cognitive function of depression. Finally, drugs that suppress 5-HT reuptake and blunt hypothalamo-pituitary-adrenocorticotrophic axis overdrive, or that act at intracellular proteins such as GSK-3beta, may abrogate the negative effects of chronic stress on mood and neuronal integrity. This review discusses the discovery and development of dual- and triple-acting antidepressants, focusing on novel concepts and new drugs disclosed over the last 2 to 3 years.

The anticonvulsant stiripentol acts directly on the GABAA receptor as a positive allosteric modulator

PubMed Central

Fisher, Janet L.

2009-01-01

SUMMARY Stiripentol(STP) has been used as co-therapy for treatment of epilepsy for many years. Its mechanism of action has long been considered to be indirect, as it inhibits the enzymes responsible for metabolism of other anticonvulsant agents. However, a recent report suggested that STP might also act at the neuronal level, increasing inhibitory GABAergic neurotransmission. We examined the effect of STP on the functional properties of recombinant GABAA receptors (GABARs) and found that it was a positive allosteric modulator of these ion channels. Its activity showed some dependence on subunit composition, with greater potentiation of α3-containing receptors and reduced potentiation when the β1 or ε subunits were present. STP caused a leftward shift in the GABA concentration-response relationship, but did not increase the peak response of the receptors to a maximal GABA concentration. Although STP shares some functional characteristics with the neurosteroids, its activity was not inhibited by a neurosteroid site antagonist and was unaffected by a mutation in the α3 subunit that reduced positive modulation by neurosteroids. The differential effect of STP on β1- and β2/β3-containing receptors was not altered by mutations within the second transmembrane domain that affect modulation by loreclezole. These findings suggest that STP acts as a direct allosteric modulator of the GABAR at a site distinct from many commonly used anti-convulsant, sedative and anxiolytic drugs. Its higher activity at α3-containing receptors as well as its activity at δ-containing receptors may provide a unique opportunity to target selected populations of GABARs. PMID:18585399

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2012 CFR

2012-07-01

... always stay in a “fire safe” facility. This is a facility that meets the fire safety requirements of the Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a...

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2013 CFR

2013-07-01

... always stay in a “fire safe” facility. This is a facility that meets the fire safety requirements of the Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a...

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2014 CFR

2014-07-01

... always stay in a “fire safe” facility. This is a facility that meets the fire safety requirements of the Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a...

20 CFR 670.420 - Are there any special requirements for enrollment related to the Military Selective Service Act?

Code of Federal Regulations, 2011 CFR

2011-04-01

..., each male applicant 18 years of age or older must present evidence that he has complied with section 3 of the Military Selective Service Act (50 U.S.C. App. 451 et seq.) if required; and (b) When a male...

Precision autophagy directed by receptor regulators - emerging examples within the TRIM family.

PubMed

Kimura, Tomonori; Mandell, Michael; Deretic, Vojo

2016-03-01

Selective autophagy entails cooperation between target recognition and assembly of the autophagic apparatus. Target recognition is conducted by receptors that often recognize tags, such as ubiquitin and galectins, although examples of selective autophagy independent of these tags are emerging. It is less known how receptors cooperate with the upstream autophagic regulators, beyond the well-characterized association of receptors with Atg8 or its homologs, such as LC3B (encoded by MAP1LC3B), on autophagic membranes. The molecular details of the emerging role in autophagy of the family of proteins called TRIMs shed light on the coordination between cargo recognition and the assembly and activation of the principal autophagy regulators. In their autophagy roles, TRIMs act both as receptors and as platforms ('receptor regulators') for the assembly of the core autophagy regulators, such as ULK1 and Beclin 1 in their activated state. As autophagic receptors, TRIMs can directly recognize endogenous or exogenous targets, obviating a need for intermediary autophagic tags, such as ubiquitin and galectins. The receptor and regulatory features embodied within the same entity allow TRIMs to govern cargo degradation in a highly exact process termed 'precision autophagy'. © 2016. Published by The Company of Biologists Ltd.

Phenotypic selection in natural populations: what limits directional selection?

PubMed

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.

Stabilizing Selection, Purifying Selection, and Mutational Bias in Finite Populations

PubMed Central

Charlesworth, Brian

2013-01-01

Genomic traits such as codon usage and the lengths of noncoding sequences may be subject to stabilizing selection rather than purifying selection. Mutations affecting these traits are often biased in one direction. To investigate the potential role of stabilizing selection on genomic traits, the effects of mutational bias on the equilibrium value of a trait under stabilizing selection in a finite population were investigated, using two different mutational models. Numerical results were generated using a matrix method for calculating the probability distribution of variant frequencies at sites affecting the trait, as well as by Monte Carlo simulations. Analytical approximations were also derived, which provided useful insights into the numerical results. A novel conclusion is that the scaled intensity of selection acting on individual variants is nearly independent of the effective population size over a wide range of parameter space and is strongly determined by the logarithm of the mutational bias parameter. This is true even when there is a very small departure of the mean from the optimum, as is usually the case. This implies that studies of the frequency spectra of DNA sequence variants may be unable to distinguish between stabilizing and purifying selection. A similar investigation of purifying selection against deleterious mutations was also carried out. Contrary to previous suggestions, the scaled intensity of purifying selection with synergistic fitness effects is sensitive to population size, which is inconsistent with the general lack of sensitivity of codon usage to effective population size. PMID:23709636

29 CFR 4.102 - Administration of the Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

...'Hara Service Contract Act Introductory § 4.102 Administration of the Act. As provided by section 4 of the Act and under provisions of sections 4 and 5 of the Walsh-Healey Public Contracts Act (49 Stat... authorized and directed to administer and enforce the provisions of the McNamara-O'Hara Service Contract Act...

Viscous/Inviscid Interaction Analysis of the Aerodynamic Performance of the NACA 65-213 Airfoil.

DTIC Science & Technology

1987-03-01

flows . The principal forces that act on the body are those which act directly on the mass of the fluid element, the bodi’ forces , and those which act...shall again consider a 2-D flow , as indicated in Figure.2-. The resultant force in the x- direction, for one unit length in z is F= ph.r~u + a(𔃼.10...x,+.a. Where fx is the body force per-unit mass in the x direction. The most conmmon body force for the flow fields is that of gravity. Equation 2.10

Promoted Iron Nanocrystals Obtained via Ligand Exchange as Active and Selective Catalysts for Synthesis Gas Conversion

PubMed Central

2017-01-01

Colloidal synthesis routes have been recently used to fabricate heterogeneous catalysts with more controllable and homogeneous properties. Herein a method was developed to modify the surface composition of colloidal nanocrystal catalysts and to purposely introduce specific atoms via ligands and change the catalyst reactivity. Organic ligands adsorbed on the surface of iron oxide catalysts were exchanged with inorganic species such as Na2S, not only to provide an active surface but also to introduce controlled amounts of Na and S acting as promoters for the catalytic process. The catalyst composition was optimized for the Fischer–Tropsch direct conversion of synthesis gas into lower olefins. At industrially relevant conditions, these nanocrystal-based catalysts with controlled composition were more active, selective, and stable than catalysts with similar composition but synthesized using conventional methods, possibly due to their homogeneity of properties and synergic interaction of iron and promoters. PMID:28824820

Joint attention in parent-child dyads involving children with selective mutism: a comparison between anxious and typically developing children.

PubMed

Nowakowski, Matilda E; Tasker, Susan L; Cunningham, Charles E; McHolm, Angela E; Edison, Shannon; Pierre, Jeff St; Boyle, Michael H; Schmidt, Louis A

2011-02-01

Although joint attention processes are known to play an important role in adaptive social behavior in typical development, we know little about these processes in clinical child populations. We compared early school age children with selective mutism (SM; n = 19) versus mixed anxiety (MA; n = 18) and community controls (CC; n = 26) on joint attention measures coded from direct observations with their parent during an unstructured free play task and two structured tasks. As predicted, the SM dyads established significantly fewer episodes of joint attention through parental initiation acts than the MA and CC dyads during the structured tasks. Findings suggest that children with SM may withdraw from their parents during stressful situations, thus missing out on opportunities for learning other coping skills. We discuss the implications of the present findings for understanding the maintenance and treatment of SM.

Neural Correlates of Intentional Communication

PubMed Central

Noordzij, Matthijs L.; Newman-Norlund, Sarah E.; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C.; Toni, Ivan

2010-01-01

We know a great deal about the neurophysiological mechanisms supporting instrumental actions, i.e., actions designed to alter the physical state of the environment. In contrast, little is known about our ability to select communicative actions, i.e., actions directly designed to modify the mental state of another agent. We have recently provided novel empirical evidence for a mechanism in which a communicator selects his actions on the basis of a prediction of the communicative intentions that an addressee is most likely to attribute to those actions. The main novelty of those findings was that this prediction of intention recognition is cerebrally implemented within the intention recognition system of the communicator, is modulated by the ambiguity in meaning of the communicative acts, and not by their sensorimotor complexity. The characteristics of this predictive mechanism support the notion that human communicative abilities are distinct from both sensorimotor and linguistic processes. PMID:21151781

Sneaker Males Affect Fighter Male Body Size and Sexual Size Dimorphism in Salmon.

PubMed

Weir, Laura K; Kindsvater, Holly K; Young, Kyle A; Reynolds, John D

2016-08-01

Large male body size is typically favored by directional sexual selection through competition for mates. However, alternative male life-history phenotypes, such as "sneakers," should decrease the strength of sexual selection acting on body size of large "fighter" males. We tested this prediction with salmon species; in southern populations, where sneakers are common, fighter males should be smaller than in northern populations, where sneakers are rare, leading to geographical clines in sexual size dimorphism (SSD). Consistent with our prediction, fighter male body size and SSD (fighter male∶female size) increase with latitude in species with sneaker males (Atlantic salmon Salmo salar and masu salmon Oncorhynchus masou) but not in species without sneakers (chum salmon Oncorhynchus keta and pink salmon Oncorhynchus gorbuscha). This is the first evidence that sneaker males affect SSD across populations and species, and it suggests that alternative male mating strategies may shape the evolution of body size.

Implementation of the Tribally Controlled Community Colleges Assistance Act. Hearing Before the Select Committee on Indian Affairs, United States Senate, Ninety-Sixth Congress, Second Session on P.L. 95-471, The Tribally Controlled Community Colleges Assistance Act, June 10, 1980.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Indian Affairs.

Meeting on June 10, 1980, the Select Committee on Indian Affairs heard testimony on the first-year implementation of Public Law 95-471, the Tribally Controlled Community Colleges Assistance Act of 1978. Testimony consisted of problems encountered during the first year, expectations for next year, and recommendations for change. The director of the…

Expression level, cellular compartment and metabolic network position all influence the average selective constraint on mammalian enzymes

PubMed Central

2011-01-01

Background A gene's position in regulatory, protein interaction or metabolic networks can be predictive of the strength of purifying selection acting on it, but these relationships are neither universal nor invariably strong. Following work in bacteria, fungi and invertebrate animals, we explore the relationship between selective constraint and metabolic function in mammals. Results We measure the association between selective constraint, estimated by the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions, and several, primarily metabolic, measures of gene function. We find significant differences between the selective constraints acting on enzyme-coding genes from different cellular compartments, with the nucleus showing higher constraint than genes from either the cytoplasm or the mitochondria. Among metabolic genes, the centrality of an enzyme in the metabolic network is significantly correlated with Ka/Ks. In contrast to yeasts, gene expression magnitude does not appear to be the primary predictor of selective constraint in these organisms. Conclusions Our results imply that the relationship between selective constraint and enzyme centrality is complex: the strength of selective constraint acting on mammalian genes is quite variable and does not appear to exclusively follow patterns seen in other organisms. PMID:21470417

Selective Moral Disengagement in the Exercise of Moral Agency.

ERIC Educational Resources Information Center

Bandura, Albert

2002-01-01

Addresses the issue of selective moral disengagement in the exercise of moral agency. Argues that moral functioning is governed by self-reactive selfhood rather than by dispassionate abstract reasoning. Concludes that the massive threats to human welfare stem mainly from deliberate acts of principle rather than from unrestrained acts of impulse.…

36 CFR 292.41 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Earth's crust prior to the Holocene epoch. Selective cutting means single tree or group selection... equipment means any contrivance which travels over ground, snow or water on wheels, tracks, skids, or by... the Mining Act of 1872, 30 U.S.C. 22 et seq., and the Mineral Leasing Act of 1920, 30 U.S.C. 181 et...

36 CFR 292.41 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Earth's crust prior to the Holocene epoch. Selective cutting means single tree or group selection... equipment means any contrivance which travels over ground, snow or water on wheels, tracks, skids, or by... the Mining Act of 1872, 30 U.S.C. 22 et seq., and the Mineral Leasing Act of 1920, 30 U.S.C. 181 et...

36 CFR 292.41 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Earth's crust prior to the Holocene epoch. Selective cutting means single tree or group selection... equipment means any contrivance which travels over ground, snow or water on wheels, tracks, skids, or by... the Mining Act of 1872, 30 U.S.C. 22 et seq., and the Mineral Leasing Act of 1920, 30 U.S.C. 181 et...

Reauthorization of the Higher Education Act by the 96th Congress--Selected Issues.

ERIC Educational Resources Information Center

Stedman, Jim

Selected issues to be considered by the 96th Congress regarding the Higher Education Act reauthorization are examined. Recently funded at approximately $5 billion, the programs of this legislation serve over 3 million students through financial assistance and nearly the full range of traditional higher education institutions and many proprietary…

Photonic spin Hall effect in hyperbolic metamaterials for polarization-controlled routing of subwavelength modes.

PubMed

Kapitanova, Polina V; Ginzburg, Pavel; Rodríguez-Fortuño, Francisco J; Filonov, Dmitry S; Voroshilov, Pavel M; Belov, Pavel A; Poddubny, Alexander N; Kivshar, Yuri S; Wurtz, Gregory A; Zayats, Anatoly V

2014-01-01

The routing of light in a deep subwavelength regime enables a variety of important applications in photonics, quantum information technologies, imaging and biosensing. Here we describe and experimentally demonstrate the selective excitation of spatially confined, subwavelength electromagnetic modes in anisotropic metamaterials with hyperbolic dispersion. A localized, circularly polarized emitter placed at the boundary of a hyperbolic metamaterial is shown to excite extraordinary waves propagating in a prescribed direction controlled by the polarization handedness. Thus, a metamaterial slab acts as an extremely broadband, nearly ideal polarization beam splitter for circularly polarized light. We perform a proof of concept experiment with a uniaxial hyperbolic metamaterial at radio-frequencies revealing the directional routing effect and strong subwavelength λ/300 confinement. The proposed concept of metamaterial-based subwavelength interconnection and polarization-controlled signal routing is based on the photonic spin Hall effect and may serve as an ultimate platform for either conventional or quantum electromagnetic signal processing.

Oxygen vacancies promoted interfacial charge carrier transfer of CdS/ZnO heterostructure for photocatalytic hydrogen generation.

PubMed

Xie, Ying Peng; Yang, Yongqiang; Wang, Guosheng; Liu, Gang

2017-10-01

The solid-state Z-scheme trinary/binary heterostructures show the advantage of utilizing the high-energy photogenerated charge carriers in photocatalysis. However, the key factors controlling such Z-scheme in the binary heterostructures are still unclear. In this paper, we showed that oxygen vacancies could act as an interface electron transfer mediator to promote the direct Z-scheme charge transfer process in binary semiconductor heterostructures of CdS/ZnS. Increasing the concentration of surface oxygen vacancies of ZnO crystal can greatly enhance photocatalytic hydrogen generation of CdS/ZnO heterostructure. This was attributed to the strengthened direct Z-scheme charge transfer process in CdS/ZnO, as evidenced by steady-state/time-resolved photoluminescence spectroscopy and selective photodeposition of metal particles on the heterostructure. Copyright © 2017 Elsevier Inc. All rights reserved.

Wastewater treatment and biodiesel production by Scenedesmus obliquus in a two-stage cultivation process.

PubMed

Álvarez-Díaz, P D; Ruiz, J; Arbib, Z; Barragán, J; Garrido-Pérez, M C; Perales, J A

2015-04-01

The microalga Scenedesmus obliquus was cultured in two cultivation stages: (1) in batch with real wastewater; (2) maintaining the stationary phase with different conditions of CO2, light and salinity according to a factorial design in order to improve the lipid content. The presence of the three factors increased lipid content from 35.8% to 49% at the end of the second stage; CO2 presence presented the highest direct effect increasing lipid content followed by light presence and salt presence. The ω-3 fatty acids content increased with CO2 and light presence acting in isolation, nevertheless, when both factors acted together the interaction effect was negative. The ω-3 eicosapentaenoic acid content of the oil from S. obliquus slightly exceeded the 1% maximum to be used as biodiesel source (EU normative). Therefore, it is suggested the blend with other oils or the selective extraction of the ω-3 fatty acids from S. obliquus oil. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detecting consistent patterns of directional adaptation using differential selection codon models.

PubMed

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.

Low level of polyandry constrains phenotypic plasticity of male body size in mites.

PubMed

Schausberger, Peter; Walzer, Andreas; Murata, Yasumasa; Osakabe, Masahiro

2017-01-01

Polyandry, i.e. females mating with multiple males, is more common than previously anticipated and potentially provides both direct and indirect fitness benefits to females. The level of polyandry (defined by the lifetime number of male mates of a female) is an important determinant of the occurrence and intensity of sexual selection acting on male phenotypes. While the forces of sexual selection acting on phenotypic male traits such as body size are relatively well understood, sexual selection acting on phenotypic plasticity of these traits is unexplored. We tackled this issue by scrutinizing the link between polyandry and phenotypic plasticity of male body size in two sympatric plant-inhabiting predatory mite species, Phytoseiulus persimilis and Neoseiulus californicus. These two species are similar in life history, ecological niche requirements, mating behavior, polygyny and female body size plasticity but strikingly differ in the level of both polyandry and phenotypic plasticity of male body size (both lower in P. persimilis). We hypothesized that deviations from standard body size, i.e. the size achieved under favorable conditions, incur higher costs for males in the less polyandrous P. persimilis. To test our hypotheses, we conducted two experiments on (i) the effects of male body size on spermatophore transfer in singly mating females and (ii) the effects of mate sequence (switching the order of standard-sized and small males) on mating behavior and paternity success in doubly mating females. In P. persimilis but not N. californicus, small males transferred fewer but larger spermatophores to the females; in both species, females re-mated more likely with standard-sized following small than small following standard-sized males; in P. persimilis, first standard-sized males sired a higher proportion of offspring produced after re-mating by the female than first small males, whereas in N. californicus the paternity success of small and standard-sized males was independent of the mating sequence. Based on our results and pertinent previous studies, which showed that females of P. persimilis, but not N. californicus, prefer mating with standard-sized over small males and allow them fertilizing more eggs, the lack of interspecific difference in female body size plasticity, and the absence of any clue pointing at a role of natural selection, we suggest that the interspecific difference in male body size plasticity is sexually selected. Our study provides an indication of sexual selection constraining plasticity of male phenotypes, suggesting that the level of polyandry may be an important co-determinant of the level of phenotypic plasticity of male body size.

Low level of polyandry constrains phenotypic plasticity of male body size in mites

PubMed Central

Walzer, Andreas; Murata, Yasumasa; Osakabe, Masahiro

2017-01-01

Polyandry, i.e. females mating with multiple males, is more common than previously anticipated and potentially provides both direct and indirect fitness benefits to females. The level of polyandry (defined by the lifetime number of male mates of a female) is an important determinant of the occurrence and intensity of sexual selection acting on male phenotypes. While the forces of sexual selection acting on phenotypic male traits such as body size are relatively well understood, sexual selection acting on phenotypic plasticity of these traits is unexplored. We tackled this issue by scrutinizing the link between polyandry and phenotypic plasticity of male body size in two sympatric plant-inhabiting predatory mite species, Phytoseiulus persimilis and Neoseiulus californicus. These two species are similar in life history, ecological niche requirements, mating behavior, polygyny and female body size plasticity but strikingly differ in the level of both polyandry and phenotypic plasticity of male body size (both lower in P. persimilis). We hypothesized that deviations from standard body size, i.e. the size achieved under favorable conditions, incur higher costs for males in the less polyandrous P. persimilis. To test our hypotheses, we conducted two experiments on (i) the effects of male body size on spermatophore transfer in singly mating females and (ii) the effects of mate sequence (switching the order of standard-sized and small males) on mating behavior and paternity success in doubly mating females. In P. persimilis but not N. californicus, small males transferred fewer but larger spermatophores to the females; in both species, females re-mated more likely with standard-sized following small than small following standard-sized males; in P. persimilis, first standard-sized males sired a higher proportion of offspring produced after re-mating by the female than first small males, whereas in N. californicus the paternity success of small and standard-sized males was independent of the mating sequence. Based on our results and pertinent previous studies, which showed that females of P. persimilis, but not N. californicus, prefer mating with standard-sized over small males and allow them fertilizing more eggs, the lack of interspecific difference in female body size plasticity, and the absence of any clue pointing at a role of natural selection, we suggest that the interspecific difference in male body size plasticity is sexually selected. Our study provides an indication of sexual selection constraining plasticity of male phenotypes, suggesting that the level of polyandry may be an important co-determinant of the level of phenotypic plasticity of male body size. PMID:29190832

45 CFR 89.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... person. Leadership Act means the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act... Leadership Act funds for HIV/AIDS programs directly or indirectly from HHS. Sex trafficking means the...

45 CFR 89.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... person. Leadership Act means the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act... Leadership Act funds for HIV/AIDS programs directly or indirectly from HHS. Sex trafficking means the...

45 CFR 89.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... person. Leadership Act means the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act... Leadership Act funds for HIV/AIDS programs directly or indirectly from HHS. Sex trafficking means the...

45 CFR 89.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... person. Leadership Act means the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act... Leadership Act funds for HIV/AIDS programs directly or indirectly from HHS. Sex trafficking means the...

Evolution of resistance and tolerance to herbivores: testing the trade-off hypothesis.

PubMed

Kariñho-Betancourt, Eunice; Núñez-Farfán, Juan

2015-01-01

Background. To cope with their natural enemies, plants rely on resistance and tolerance as defensive strategies. Evolution of these strategies among natural population can be constrained by the absence of genetic variation or because of the antagonistic genetic correlation (trade-off) between them. Also, since plant defenses are integrated by several traits, it has been suggested that trade-offs might occur between specific defense traits. Methodology/Principal Findings. We experimentally assessed (1) the presence of genetic variance in tolerance, total resistance, and leaf trichome density as specific defense trait, (2) the extent of natural selection acting on plant defenses, and (3) the relationship between total resistance and leaf trichome density with tolerance to herbivory in the annual herb Datura stramonium. Full-sib families of D. stramonium were either exposed to natural herbivores (control) or protected from them by a systemic insecticide. We detected genetic variance for leaf trichome density, and directional selection acting on this character. However, we did not detect a negative significant correlation between tolerance and total resistance, or between tolerance and leaf trichome density. We argue that low levels of leaf damage by herbivores precluded the detection of a negative genetic correlation between plant defense strategies. Conclusions/Significance. This study provides empirical evidence of the independent evolution of plant defense strategies, and a defensive role of leaf trichomes. The pattern of selection should favor individuals with high trichomes density. Also, because leaf trichome density reduces damage by herbivores and possess genetic variance in the studied population, its evolution is not constrained.

Evolution of resistance and tolerance to herbivores: testing the trade-off hypothesis

PubMed Central

Kariñho-Betancourt, Eunice

2015-01-01

Background. To cope with their natural enemies, plants rely on resistance and tolerance as defensive strategies. Evolution of these strategies among natural population can be constrained by the absence of genetic variation or because of the antagonistic genetic correlation (trade-off) between them. Also, since plant defenses are integrated by several traits, it has been suggested that trade-offs might occur between specific defense traits. Methodology/Principal Findings. We experimentally assessed (1) the presence of genetic variance in tolerance, total resistance, and leaf trichome density as specific defense trait, (2) the extent of natural selection acting on plant defenses, and (3) the relationship between total resistance and leaf trichome density with tolerance to herbivory in the annual herb Datura stramonium. Full-sib families of D. stramonium were either exposed to natural herbivores (control) or protected from them by a systemic insecticide. We detected genetic variance for leaf trichome density, and directional selection acting on this character. However, we did not detect a negative significant correlation between tolerance and total resistance, or between tolerance and leaf trichome density. We argue that low levels of leaf damage by herbivores precluded the detection of a negative genetic correlation between plant defense strategies. Conclusions/Significance. This study provides empirical evidence of the independent evolution of plant defense strategies, and a defensive role of leaf trichomes. The pattern of selection should favor individuals with high trichomes density. Also, because leaf trichome density reduces damage by herbivores and possess genetic variance in the studied population, its evolution is not constrained. PMID:25780756

Genetic evidence for extreme polyandry and extraordinary sex-role reversal in a pipefish.

PubMed

Jones, A G; Walker, D; Avise, J C

2001-12-22

Due to the phenomenon of male pregnancy, the fish family Syngnathidae (seahorses and pipefishes) has historically been considered an archetypal example of a group in which sexual selection should act more strongly on females than on males. However, more recent work has called into question the idea that all species with male pregnancy are sex-role reversed with respect to the intensity of sexual selection. Furthermore, no studies have formally quantified the opportunity for sexual selection in any natural breeding assemblage of pipefishes or seahorses in order to demonstrate conclusively that sexual selection acts most strongly on females. Here, we use a DNA-based study of parentage in the Gulf pipefish Syngnathus scovelli in order to show that sexual selection indeed acts more strongly on females than on males in this species. Moreover, the Gulf pipefish exhibits classical polyandry with the greatest asymmetry in reproductive roles (as quantified by variances in mating success) between males and females yet documented in any system. Thus, the intensity of sexual selection on females in pipefish rivals that of any other taxon yet studied.

Genetic evidence for extreme polyandry and extraordinary sex-role reversal in a pipefish.

PubMed Central

Jones, A. G.; Walker, D.; Avise, J. C.

2001-01-01

Due to the phenomenon of male pregnancy, the fish family Syngnathidae (seahorses and pipefishes) has historically been considered an archetypal example of a group in which sexual selection should act more strongly on females than on males. However, more recent work has called into question the idea that all species with male pregnancy are sex-role reversed with respect to the intensity of sexual selection. Furthermore, no studies have formally quantified the opportunity for sexual selection in any natural breeding assemblage of pipefishes or seahorses in order to demonstrate conclusively that sexual selection acts most strongly on females. Here, we use a DNA-based study of parentage in the Gulf pipefish Syngnathus scovelli in order to show that sexual selection indeed acts more strongly on females than on males in this species. Moreover, the Gulf pipefish exhibits classical polyandry with the greatest asymmetry in reproductive roles (as quantified by variances in mating success) between males and females yet documented in any system. Thus, the intensity of sexual selection on females in pipefish rivals that of any other taxon yet studied. PMID:11749706

77 FR 62283 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... using a Nasdaq Workstation or Weblink ACT 2.0 user account. Member firms subscribing to the ACT Reject... Workstation and Weblink ACT 2.0 user account selected for subscription to the ACT Reject Scan service. Nasdaq..., per month. Use of the ACT Reject Scan service is voluntary and the subscription fee will be imposed on...

Refinery siting workbook: appendices C to O

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

Not Available

Applicable laws and permits available for the selection and building of petroleum refineries are enclosed. A glossary of pertinent terms is also included. References related to the National Environmental Policy Act, the Clean Air Act, the Federal Water Pollution Control Act, Resource Conservation and Recovery Act, Toxic Substance Control Act, and Wetlands and Coastal Zone are included. Permit information is also presented. (DC)

The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations.

PubMed

Achilla, Evanthia; McCrone, Paul

2013-04-01

Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation. The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint. Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, 'long-acting injection', 'economic evaluation', 'cost-effectiveness' and 'cost-utility'. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia. After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long-acting injectable drugs, was associated with cost savings and additional clinical benefits and was the dominant strategy in terms of cost effectiveness. However, olanzapine in either oral or long-acting injectable formulation dominated risperidone long-acting injection in a Slovenian and a US study. Furthermore, in two UK studies, the use of long-acting risperidone increased the hospitalization days and overall healthcare costs, relative to other atypical or typical long-acting antipsychotics. Finally, paliperidone extended-release was the most cost-effective treatment compared with atypical oral or typical long-acting formulations. From a methodological viewpoint, most studies employed decision analytic models, presented results using average cost-effectiveness ratios and conducted comprehensive sensitivity analyses to test the robustness of the results. Variations in study methodologies restrict consistent and direct comparisons across countries. The exclusion of a large body of potentially relevant conference abstracts as well as some papers being unobtainable may have increased the likelihood of misrepresenting the overall cost effectiveness of long-acting antipsychotics. Finally, the review process was restricted to qualitative assessment rather than a quantitative synthesis of results, which could provide more robust conclusions. Atypical long-acting (especially risperidone)/extended-release antipsychotic medication is likely to be a cost-effective, first-line strategy for managing schizophrenia, compared with long-acting haloperidol and other oral or depot formulations, irrespective of country-specific differences. However, inconsistencies in study methodologies and in the reporting of study findings suggest caution needs to be applied in interpreting these findings.

The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases

PubMed Central

Orchard, Sandra; Ammari, Mais; Aranda, Bruno; Breuza, Lionel; Briganti, Leonardo; Broackes-Carter, Fiona; Campbell, Nancy H.; Chavali, Gayatri; Chen, Carol; del-Toro, Noemi; Duesbury, Margaret; Dumousseau, Marine; Galeota, Eugenia; Hinz, Ursula; Iannuccelli, Marta; Jagannathan, Sruthi; Jimenez, Rafael; Khadake, Jyoti; Lagreid, Astrid; Licata, Luana; Lovering, Ruth C.; Meldal, Birgit; Melidoni, Anna N.; Milagros, Mila; Peluso, Daniele; Perfetto, Livia; Porras, Pablo; Raghunath, Arathi; Ricard-Blum, Sylvie; Roechert, Bernd; Stutz, Andre; Tognolli, Michael; van Roey, Kim; Cesareni, Gianni; Hermjakob, Henning

2014-01-01

IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org). PMID:24234451

Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family[W][OPEN

PubMed Central

Ren, Lin-Ling; Liu, Yan-Jing; Liu, Hai-Jing; Qian, Ting-Ting; Qi, Li-Wang; Wang, Xiao-Ru; Zeng, Qing-Yin

2014-01-01

Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families. PMID:24934172

The geography of sex-specific selection, local adaptation, and sexual dimorphism.

PubMed

Connallon, Tim

2015-09-01

Local adaptation and sexual dimorphism are iconic evolutionary scenarios of intraspecific adaptive differentiation in the face of gene flow. Although theory has traditionally considered local adaptation and sexual dimorphism as conceptually distinct processes, emerging data suggest that they often act concurrently during evolutionary diversification. Here, I merge theories of local adaptation in space and sex-specific adaptation over time, and show that their confluence yields several new predictions about the roles of context-specific selection, migration, and genetic correlations, in adaptive diversification. I specifically revisit two influential predictions from classical studies of clinal adaptation and sexual dimorphism: (1) that local adaptation should decrease with distance from the species' range center and (2) that opposing directional selection between the sexes (sexual antagonism) should inevitably accompany the evolution of sexual dimorphism. I show that both predictions can break down under clinally varying selection. First, the geography of local adaptation can be sexually dimorphic, with locations of relatively high local adaptation differing profoundly between the sexes. Second, the intensity of sexual antagonism varies across the species' range, with subpopulations near the range center representing hotspots for antagonistic selection. The results highlight the context-dependent roles of migration versus sexual conflict as primary constraints to adaptive diversification. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Interactions of attention, emotion and motivation.

PubMed

Raymond, Jane

2009-01-01

Although successful visually guided action begins with sensory processes and ends with motor control, the intervening processes related to the appropriate selection of information for processing are especially critical because of the brain's limited capacity to handle information. Three important mechanisms--attention, emotion and motivation--contribute to the prioritization and selection of information. In this chapter, the interplay between these systems is discussed with emphasis placed on interactions between attention (or immediate task relevance of stimuli) and emotion (or affective evaluation of stimuli), and between attention and motivation (or the predicted value of stimuli). Although numerous studies have shown that emotional stimuli modulate mechanisms of selective attention in humans, little work has been directed at exploring whether such interactions can be reciprocal, that is, whether attention can influence emotional response. Recent work on this question (showing that distracting information is typically devalued upon later encounters) is reviewed in the first half of the chapter. In the second half, some recent experiments exploring how prior value-prediction learning (i.e., learning to associate potential outcomes, good or bad, with specific stimuli) plays a role in visual selection and conscious perception. The results indicate that some aspects of motivation act on selection independently of traditionally defined attention and other aspects interact with it.

Information security for compliance with select agent regulations.

PubMed

Lewis, Nick; Campbell, Mark J; Baskin, Carole R

2015-01-01

The past decade has seen a significant rise in research on high-consequence human and animal pathogens, many now known as "select agents." While physical security around these agents is tightly regulated, information security standards are still lagging. The understanding of the threats unique to the academic and research environment is still evolving, in part due to poor communication between the various stakeholders. Perhaps as a result, information security guidelines published by select agent regulators lack the critical details and directives needed to achieve even the lowest security level of the Federal Information Security Management Act (FISMA). While only government agencies are currently required to abide by the provisions of FISMA (unless specified as preconditions for obtaining government grants or contracts--still a relatively rare or narrowly scoped occurrence), the same strategies were recently recommended by executive order for others. We propose that information security guidelines for select agent research be updated to promulgate and detail FISMA standards and processes and that the latter be ultimately incorporated into select agent regulations. We also suggest that information security in academic and research institutions would greatly benefit from active efforts to improve communication among the biosecurity, security, and information technology communities, and from a secure venue for exchange of timely information on emerging threats and solutions in the research environment.

Information Security for Compliance with Select Agent Regulations

PubMed Central

Lewis, Nick; Campbell, Mark J.

2015-01-01

The past decade has seen a significant rise in research on high-consequence human and animal pathogens, many now known as “select agents.” While physical security around these agents is tightly regulated, information security standards are still lagging. The understanding of the threats unique to the academic and research environment is still evolving, in part due to poor communication between the various stakeholders. Perhaps as a result, information security guidelines published by select agent regulators lack the critical details and directives needed to achieve even the lowest security level of the Federal Information Security Management Act (FISMA). While only government agencies are currently required to abide by the provisions of FISMA (unless specified as preconditions for obtaining government grants or contracts—still a relatively rare or narrowly scoped occurrence), the same strategies were recently recommended by executive order for others. We propose that information security guidelines for select agent research be updated to promulgate and detail FISMA standards and processes and that the latter be ultimately incorporated into select agent regulations. We also suggest that information security in academic and research institutions would greatly benefit from active efforts to improve communication among the biosecurity, security, and information technology communities, and from a secure venue for exchange of timely information on emerging threats and solutions in the research environment. PMID:26042864

Path analysis of risk factors leading to premature birth.

PubMed

Fields, S J; Livshits, G; Sirotta, L; Merlob, P

1996-01-01

The present study tested whether various sociodemographic, anthropometric, behavioral, and medical/physiological factors act in a direct or indirect manner on the risk of prematurity using path analysis on a sample of Israeli births. The path model shows that medical complications, primarily toxemia, chorioammionitis, and a previous low birth weight delivery directly and significantly act on the risk of prematurity as do low maternal pregnancy weight gain and ethnicity. Other medical complications, including chronic hypertension, preclampsia, and placental abruption, although significantly correlated with prematurity, act indirectly on prematurity through toxemia. The model further shows that the commonly accepted sociodemographic, anthropometric, and behavioral risk factors act by modifying the development of medical complications that lead to prematurity as opposed to having a direct effect on premature delivery. © 1996 Wiley-Liss, Inc. Copyright © 1996 Wiley-Liss, Inc.

76 FR 16703 - Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... or cooperative research and development set aside for small business concerns shall be deemed an... SMALL BUSINESS ADMINISTRATION 13 CFR Parts 121, 124, 125, 126, and 127 [Docket No. SBA-2011-0006] Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting AGENCY: U.S...

The sources of adaptive variation

PubMed Central

2017-01-01

The role of natural selection in the evolution of adaptive phenotypes has undergone constant probing by evolutionary biologists, employing both theoretical and empirical approaches. As Darwin noted, natural selection can act together with other processes, including random changes in the frequencies of phenotypic differences that are not under strong selection, and changes in the environment, which may reflect evolutionary changes in the organisms themselves. As understanding of genetics developed after 1900, the new genetic discoveries were incorporated into evolutionary biology. The resulting general principles were summarized by Julian Huxley in his 1942 book Evolution: the modern synthesis. Here, we examine how recent advances in genetics, developmental biology and molecular biology, including epigenetics, relate to today's understanding of the evolution of adaptations. We illustrate how careful genetic studies have repeatedly shown that apparently puzzling results in a wide diversity of organisms involve processes that are consistent with neo-Darwinism. They do not support important roles in adaptation for processes such as directed mutation or the inheritance of acquired characters, and therefore no radical revision of our understanding of the mechanism of adaptive evolution is needed. PMID:28566483

The sources of adaptive variation.

PubMed

Charlesworth, Deborah; Barton, Nicholas H; Charlesworth, Brian

2017-05-31

The role of natural selection in the evolution of adaptive phenotypes has undergone constant probing by evolutionary biologists, employing both theoretical and empirical approaches. As Darwin noted, natural selection can act together with other processes, including random changes in the frequencies of phenotypic differences that are not under strong selection, and changes in the environment, which may reflect evolutionary changes in the organisms themselves. As understanding of genetics developed after 1900, the new genetic discoveries were incorporated into evolutionary biology. The resulting general principles were summarized by Julian Huxley in his 1942 book Evolution: the modern synthesis Here, we examine how recent advances in genetics, developmental biology and molecular biology, including epigenetics, relate to today's understanding of the evolution of adaptations. We illustrate how careful genetic studies have repeatedly shown that apparently puzzling results in a wide diversity of organisms involve processes that are consistent with neo-Darwinism. They do not support important roles in adaptation for processes such as directed mutation or the inheritance of acquired characters, and therefore no radical revision of our understanding of the mechanism of adaptive evolution is needed. © 2017 The Author(s).

Spatial heterogeneity and the evolution of sex in diploids.

PubMed

Agrawal, Aneil F

2009-07-01

Much of the theoretical work on the evolution of sex has focused on the effects of recombination. In diploids, segregation also occurs during sexual reproduction. Segregation breaks down some types of genetic associations that are not affected by recombination and thus influences the evolution of sex in ways that are not apparent from studying the evolution of recombination as a surrogate for sex. Here I examine the evolution of sex in diploids experiencing spatially heterogeneous selection. If divergent selection causes genetic differentiation, then migration can be a powerful force generating genetic associations that may not be favored by selection. An advantage to sex can arise from breaking down these associations. By examining modifiers of both sex and recombination, the model allows for a direct comparison of the forces acting on these related but different processes, illuminating the role of segregation. The model also includes inbreeding, which has been shown to be important for both segregation and recombination. I find that inbreeding affects the evolution of sex through segregation, not recombination. Several suggestions for empirical experiments are given.

Evidence of Natural Selection Acting on a Polymorphic Hybrid Incompatibility Locus in Mimulus

PubMed Central

Sweigart, Andrea L.; Flagel, Lex E.

2015-01-01

As a common cause of reproductive isolation in diverse taxa, hybrid incompatibilities are fundamentally important to speciation. A key question is which evolutionary forces drive the initial substitutions within species that lead to hybrid dysfunction. Previously, we discovered a simple genetic incompatibility that causes nearly complete male sterility and partial female sterility in hybrids between the two closely related yellow monkeyflower species Mimulus guttatus and M. nasutus. In this report, we fine map the two major incompatibility loci—hybrid male sterility 1 (hms1) and hybrid male sterility 2 (hms2)—to small nuclear genomic regions (each <70 kb) that include strong candidate genes. With this improved genetic resolution, we also investigate the evolutionary dynamics of hms1 in a natural population of M. guttatus known to be polymorphic at this locus. Using classical genetic crosses and population genomics, we show that a 320-kb region containing the hms1 incompatibility allele has risen to intermediate frequency in this population by strong natural selection. This finding provides direct evidence that natural selection within plant species can lead to hybrid dysfunction between species. PMID:25428983

Loss of Mhc and Neutral Variation in Peary Caribou: Genetic Drift Is Not Mitigated by Balancing Selection or Exacerbated by Mhc Allele Distributions

PubMed Central

Taylor, Sabrina S.; Jenkins, Deborah A.; Arcese, Peter

2012-01-01

Theory and empirical results suggest that the rate of loss of variation at Mhc and neutral microsatellite loci may differ because selection influences Mhc genes, and because a high proportion of rare alleles at Mhc loci may result in high rates of loss via drift. Most published studies compare Mhc and microsatellite variation in various contemporary populations to infer the effects of population size on genetic variation, even though different populations are likely to have different demographic histories that may also affect contemporary genetic variation. We directly compared loss of variation at Mhc and microsatellite loci in Peary caribou by comparing historical and contemporary samples. We observed that similar proportions of genetic variation were lost over time at each type of marker despite strong evidence for selection at Mhc genes. These results suggest that microsatellites can be used to estimate genome-wide levels of variation, but also that adaptive potential is likely to be lost following population bottlenecks. However, gene conversion and recombination at Mhc loci may act to increase variation following bottlenecks. PMID:22655029

25 CFR 273.36 - Eligible subcontractors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ACT PROGRAM EDUCATION CONTRACTS UNDER JOHNSON-O'MALLEY ACT Funding Provisions § 273.36 Eligible subcontractors. No contract funds under the Johnson-O'Malley Act shall be made available by the Bureau directly...

25 CFR 273.36 - Eligible subcontractors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ACT PROGRAM EDUCATION CONTRACTS UNDER JOHNSON-O'MALLEY ACT Funding Provisions § 273.36 Eligible subcontractors. No contract funds under the Johnson-O'Malley Act shall be made available by the Bureau directly...

25 CFR 273.36 - Eligible subcontractors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ACT PROGRAM EDUCATION CONTRACTS UNDER JOHNSON-O'MALLEY ACT Funding Provisions § 273.36 Eligible subcontractors. No contract funds under the Johnson-O'Malley Act shall be made available by the Bureau directly...

Tribally Controlled Community Colleges Assistance Act Amendment. Hearing Before the United States Senate Select Committee on Indian Affairs, Ninety-Sixth Congress, First Session on S. 1855 to Amend Public Law 95-471, The Tribally Controlled Community Colleges Assistance Act of 1978.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Indian Affairs.

The Senate Select Committee on Indian Affairs conducted a November 26, 1979, hearing regarding proposed amendment S. 1855 to the Tribally Controlled Community Colleges Assistance Act (PL 95-471), which would increase the authorization level for technical assistance grants from $3.2 million in fiscal 1981 and 1982 to $10 million for each year. At…

Acceptance and Commitment Therapy (ACT) as a Career Counselling Strategy

ERIC Educational Resources Information Center

Hoare, P. Nancey; McIlveen, Peter; Hamilton, Nadine

2012-01-01

Acceptance and commitment therapy (ACT) has potential to contribute to career counselling. In this paper, the theoretical tenets of ACT and a selection of its counselling techniques are overviewed along with a descriptive case vignette. There is limited empirical research into ACT's application in career counselling. Accordingly, a research agenda…

15 CFR 700.8 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... approved programs. Defense Production Act. the Defense Production Act of 1950, as amended (50 U.S.C. App... its integrity as a capital item. Rated order. A prime contract, a subcontract, or a purchase order in... Service Act and related statutes—Section 18 of the Selective Service Act of 1948 (50 U.S.C. app. 468), 10...

15 CFR 700.8 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... approved programs. Defense Production Act. the Defense Production Act of 1950, as amended (50 U.S.C. App... its integrity as a capital item. Rated order. A prime contract, a subcontract, or a purchase order in... Service Act and related statutes—Section 18 of the Selective Service Act of 1948 (50 U.S.C. app. 468), 10...

Direct observation of outpatient management of malaria in a rural Ghanaian district.

PubMed

Ameme, Donne Kofi; Afari, Edwin Andrews; Nyarko, Kofi Mensah; Malm, Keziah Laurencia; Sackey, Samuel; Wurapa, Fred

2014-01-01

In Ghana, malaria continues to top outpatient morbidities; accounting for about 40% of all attendances. Effective case-management is key to its control. We evaluated case-management practices of uncomplicated malaria in Kwahu South District (KSD) health facilities to determine their conformity to guidelines. We conducted a cross sectional survey at all public health facilities in three randomly selected sub-districts in KSD. A non-participatory observation of suspected malaria consultations was conducted. Suspected malaria was defined as any person with fever (by history or measured axillary temperature > or equal 37.5 oC) presenting at the selected health facilities between 19th and 29th April 2013. Findings were expressed as frequencies, relative frequencies, mean (± standard deviation) and median. Of 70 clinical observations involving 10 prescribers in six health facilities, 40 (57.1%) were females and 16 (22.9%) were below five years. Median age was 18 years (interquartile range: 5-33). Overall, 63 (90.0%) suspected case-patients had diagnostic tests. Two (3.6%) were treated presumptively. All 31 confirmed and 10 (33.3%) of the test negative case-patients received Artemisinin-based Combination Therapies (ACTs). However, only 12 (27.9%) of the 43 case-patients treated with ACT received Artesunate-Amodiaquine (AA). Only three (18.8%) of the under-fives were examined for non-malarial causes of fever. Mean number of drugs per patient was 3.7 drugs (± 1.1). Only 45 (64.3%) patients received at least one counseling message. Conformity of malaria case-management practices to guidelines in KSD was suboptimal. Apart from high rate of diagnostic testing and ACT use, prescription of AA, physical examination and counseling needed improvement.

Effect of school wellness policies and the Healthy, Hunger-Free Kids Act on food-consumption behaviors of students, 2006-2016: a systematic review.

PubMed

Mansfield, Jennifer L; Savaiano, Dennis A

2017-07-01

Federal regulation mandates that the US National School Lunch Program nutrition standards align with the Dietary Guidelines for Americans. As students consume a substantial proportion of their nutrition during school lunch, increasing access to healthy foods is proposed to improve student dietary outcomes. The purpose of this review is to assess whether policy changes impacted food-consumption behaviors of students during periods when (1) school wellness policies were implemented (2006-2007); (2) the Healthy, Hunger-Free Kids Act was passed (2010-2012); and (3) the Healthy, Hunger-Free Kids Act was implemented (2012-present). PubMed, Web of Science, and Science Direct were searched for primary research studies. Policy evaluations and interventions implemented from 2006 to 2016 were included. A total of 31 studies evaluating plate waste, dietary intake, food selection, and/or purchasing patterns were identified and reviewed. Fourteen of 19 intervention and longitudinal observation studies reported improved food-consumption behaviors (increased selection, intake, and sales of healthy foods, and decreased plate waste). Only 2 of 12 one-time observation studies reported food-consumption behaviors meeting target nutrition standards. The majority of studies indicated that increasing access to healthy foods during school lunch improved students' dietary intakes. Challenges related to study design, adaptation period, quality of foods, and policy implementation likely affect a school lunch program's ability to impact students' food-consumption behaviors. Ongoing evaluation of these programs is warranted. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Retinal Origin of Direction Selectivity in the Superior Colliculus

PubMed Central

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

76 FR 9361 - Exemptions From Certain Prohibited Transaction Restrictions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-17

... Participant Directed Plans on the Record Date resulted from an independent act of Citigroup as a corporate...), at the direction of an Independent Fiduciary (in the case of the Citigroup Pension Plan), or in... Pension Plan by an Independent Fiduciary acting as an investment manager. Such Independent Fiduciary will...

31 CFR 501.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Enemy Act (TWEA) Penalties § 501.701 Penalties. (a) Attention is directed to section 16 of the TWEA, as adjusted pursuant to the Federal Civil Penalties Inflation Adjustment Act of 1990 (Pub. L. 101... loss from the violation. (c) Attention is directed to 18 U.S.C. 1001, which provides that whoever, in...

Compliance of Postsecondary Institutions with Provisions for Disabled Students Mandated by the Architectural Barriers Act of 1968 and the Rehabilitation Act of 1973.

ERIC Educational Resources Information Center

Williams, Joan M.; Hodinko, Bernard A.

Perceptions were obtained from 480 college student services officers concerning compliance of their employing institutions with selected provisions of the Architectural Barriers Act of 1968 and the Rehabilitation Act of 1973 (specifically Section 504). The survey instrument presented a statement from each of 24 provisions of the two Acts.…

Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies

PubMed Central

2013-01-01

Background The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed. The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection. Methods A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included. Results Of 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study. Conclusions Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation. No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment. For patients achieving suboptimal symptom control, switching long-acting MPH formulations may be beneficial. When switching formulations, it is usually appropriate to titrate the immediate-release component of the formulation; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components. Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response. PMID:24074240

Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies.

PubMed

Coghill, David; Banaschewski, Tobias; Zuddas, Alessandro; Pelaz, Antonio; Gagliano, Antonella; Doepfner, Manfred

2013-09-27

The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed.The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection. A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included. Of 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study. Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation. No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment. For patients achieving suboptimal symptom control, switching long-acting MPH formulations may be beneficial. When switching formulations, it is usually appropriate to titrate the immediate-release component of the formulation; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components. Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response.

Ritonavir binds to and downregulates estrogen receptors: molecular mechanism of promoting early atherosclerosis.

PubMed

Xiang, Jin; Wang, Ying; Su, Ke; Liu, Min; Hu, Peng-Chao; Ma, Tian; Li, Jia-Xi; Wei, Lei; Zheng, Zhongliang; Yang, Fang

2014-10-01

Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.

The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model.

PubMed

McEvoy, Brian; Beleza, Sandra; Shriver, Mark D

2006-10-15

Skin pigmentation varies substantially across human populations in a manner largely coincident with ultraviolet radiation intensity. This observation suggests that natural selection in response to sunlight is a major force in accounting for pigmentation variability. We review recent progress in identifying the genes controlling this variation with a particular focus on the trait's evolutionary past and the potential role of testing for signatures of selection in aiding the discovery of functionally important genes. We have analyzed SNP data from the International HapMap project in 77 pigmentation candidate genes for such signatures. On the basis of these results and other similar work, we provide a tentative three-population model (West Africa, East Asia and North Europe) of the evolutionary-genetic architecture of human pigmentation. These results suggest a complex evolutionary history, with selection acting on different gene targets at different times and places in the human past. Some candidate genes may have been selected in the ancestral human population, others in the 'out of Africa' proto European-Asian population, whereas most appear to have selectively evolved solely in either Europeans or East Asians separately despite the pigmentation similarities between these two populations. Selection signatures can provide important clues to aid gene discovery. However, these should be viewed as complements, rather than replacements of, functional studies including linkage and association analyses, which can directly refine our understanding of the trait.

A multivariate analysis of genetic variation in the advertisement call of the gray treefrog, Hyla versicolor.

PubMed

Welch, Allison M; Smith, Michael J; Gerhardt, H Carl

2014-06-01

Genetic variation in sexual displays is crucial for an evolutionary response to sexual selection, but can be eroded by strong selection. Identifying the magnitude and sources of additive genetic variance underlying sexually selected traits is thus an important issue in evolutionary biology. We conducted a quantitative genetics experiment with gray treefrogs (Hyla versicolor) to investigate genetic variances and covariances among features of the male advertisement call. Two energetically expensive traits showed significant genetic variation: call duration, expressed as number of pulses per call, and call rate, represented by its inverse, call period. These two properties also showed significant genetic covariance, consistent with an energetic constraint to call production. Combining the genetic variance-covariance matrix with previous estimates of directional sexual selection imposed by female preferences predicts a limited increase in call duration but no change in call rate despite significant selection on both traits. In addition to constraints imposed by the genetic covariance structure, an evolutionary response to sexual selection may also be limited by high energetic costs of long-duration calls and by preferences that act most strongly against very short-duration calls. Meanwhile, the persistence of these preferences could be explained by costs of mating with males with especially unattractive calls. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

45 CFR 89.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... IMPLEMENTING PROGRAMS AND ACTIVITIES UNDER THE LEADERSHIP ACT § 89.2 Definitions. For the purposes of this part... person. Leadership Act means the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act... Leadership Act funds for HIV/AIDS programs directly or indirectly from HHS. Sex trafficking means the...

Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars.

PubMed

Cavanagh, Colin R; Chao, Shiaoman; Wang, Shichen; Huang, Bevan Emma; Stephen, Stuart; Kiani, Seifollah; Forrest, Kerrie; Saintenac, Cyrille; Brown-Guedira, Gina L; Akhunova, Alina; See, Deven; Bai, Guihua; Pumphrey, Michael; Tomar, Luxmi; Wong, Debbie; Kong, Stephan; Reynolds, Matthew; da Silva, Marta Lopez; Bockelman, Harold; Talbert, Luther; Anderson, James A; Dreisigacker, Susanne; Baenziger, Stephen; Carter, Arron; Korzun, Viktor; Morrell, Peter Laurent; Dubcovsky, Jorge; Morell, Matthew K; Sorrells, Mark E; Hayden, Matthew J; Akhunov, Eduard

2013-05-14

Domesticated crops experience strong human-mediated selection aimed at developing high-yielding varieties adapted to local conditions. To detect regions of the wheat genome subject to selection during improvement, we developed a high-throughput array to interrogate 9,000 gene-associated single-nucleotide polymorphisms (SNP) in a worldwide sample of 2,994 accessions of hexaploid wheat including landraces and modern cultivars. Using a SNP-based diversity map we characterized the impact of crop improvement on genomic and geographic patterns of genetic diversity. We found evidence of a small population bottleneck and extensive use of ancestral variation often traceable to founders of cultivars from diverse geographic regions. Analyzing genetic differentiation among populations and the extent of haplotype sharing, we identified allelic variants subjected to selection during improvement. Selective sweeps were found around genes involved in the regulation of flowering time and phenology. An introgression of a wild relative-derived gene conferring resistance to a fungal pathogen was detected by haplotype-based analysis. Comparing selective sweeps identified in different populations, we show that selection likely acts on distinct targets or multiple functionally equivalent alleles in different portions of the geographic range of wheat. The majority of the selected alleles were present at low frequency in local populations, suggesting either weak selection pressure or temporal variation in the targets of directional selection during breeding probably associated with changing agricultural practices or environmental conditions. The developed SNP chip and map of genetic variation provide a resource for advancing wheat breeding and supporting future population genomic and genome-wide association studies in wheat.

Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars

PubMed Central

Cavanagh, Colin R.; Chao, Shiaoman; Wang, Shichen; Huang, Bevan Emma; Stephen, Stuart; Kiani, Seifollah; Forrest, Kerrie; Saintenac, Cyrille; Brown-Guedira, Gina L.; Akhunova, Alina; See, Deven; Bai, Guihua; Pumphrey, Michael; Tomar, Luxmi; Wong, Debbie; Kong, Stephan; Reynolds, Matthew; da Silva, Marta Lopez; Bockelman, Harold; Talbert, Luther; Anderson, James A.; Dreisigacker, Susanne; Baenziger, Stephen; Carter, Arron; Korzun, Viktor; Morrell, Peter Laurent; Dubcovsky, Jorge; Morell, Matthew K.; Sorrells, Mark E.; Hayden, Matthew J.; Akhunov, Eduard

2013-01-01

Domesticated crops experience strong human-mediated selection aimed at developing high-yielding varieties adapted to local conditions. To detect regions of the wheat genome subject to selection during improvement, we developed a high-throughput array to interrogate 9,000 gene-associated single-nucleotide polymorphisms (SNP) in a worldwide sample of 2,994 accessions of hexaploid wheat including landraces and modern cultivars. Using a SNP-based diversity map we characterized the impact of crop improvement on genomic and geographic patterns of genetic diversity. We found evidence of a small population bottleneck and extensive use of ancestral variation often traceable to founders of cultivars from diverse geographic regions. Analyzing genetic differentiation among populations and the extent of haplotype sharing, we identified allelic variants subjected to selection during improvement. Selective sweeps were found around genes involved in the regulation of flowering time and phenology. An introgression of a wild relative-derived gene conferring resistance to a fungal pathogen was detected by haplotype-based analysis. Comparing selective sweeps identified in different populations, we show that selection likely acts on distinct targets or multiple functionally equivalent alleles in different portions of the geographic range of wheat. The majority of the selected alleles were present at low frequency in local populations, suggesting either weak selection pressure or temporal variation in the targets of directional selection during breeding probably associated with changing agricultural practices or environmental conditions. The developed SNP chip and map of genetic variation provide a resource for advancing wheat breeding and supporting future population genomic and genome-wide association studies in wheat. PMID:23630259

Direct-Current Monitor With Flux-Reset Transformer Coupling

NASA Technical Reports Server (NTRS)

Canter, Stanley

1993-01-01

Circuit measures constant or slowly-varying unidirectional electrical current using flux-reset transformer coupling. Measurement nonintrusive in sense that no need for direct contact with wire that carries load current to be measured, and no need to install series resistive element in load-current path. Toroidal magnetic core wrapped with coil of wire placed around load-current-carrying wire, acts as transformer core, load-current-carrying wire acts as primary winding of transformer, and coil wrapped on core acts as secondary winding.

Direct binding of Toll-like receptor 4 to ionotropic glutamate receptor N-methyl-D-aspartate subunit 1 induced by lipopolysaccharide in microglial cells N9 and EOC 20.

PubMed

Cui, Jie; Yu, Siyuan; Li, Yihui; Li, Pan; Liu, Feng

2018-03-01

Microglia, the primary immune cells in the brain, are the predominant cells regulating inflammation-mediated neuronal damage. In response to immunological challenges, such as lipopolysaccharide (LPS), microglia are activated and the inflammatory process is subsequently initiated. The aim of the present study was to determine whether LPS induces interactions between the Toll-like receptor 4 (TLR4) and the ionotropic glutamate receptor N-methyl-D‑aspartate subunit 1 (GluN1) in N9 and EOC 20 microglial cells. Immunocytochemistry demonstrated co-localization of TLR4 and GluN1 in response to LPS, and the direct binding of TLR4 and GluN1 was further validated by antibody-based Fluorescence Resonance Energy Transfer technology. Inhibition of the group I metabotropic glutamate receptor 5 with its selective antagonist, MTEP, abolished LPS-induced direct binding of TLR4 to GluN1. Therefore, these data demonstrated that GluN1 and TLR4 act reciprocally in response to LPS in N9 and EOC 20 microglial cells.

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2013 CFR

2013-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2014 CFR

2014-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2011 CFR

2011-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2012 CFR

2012-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.46 - Which Tribes/Consortia may be selected to receive a negotiation grant?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Which Tribes/Consortia may be selected to receive a negotiation grant? 1000.46 Section 1000.46 Indians OFFICE OF THE ASSISTANT SECRETARY, INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ANNUAL FUNDING AGREEMENTS UNDER THE TRIBAL SELF-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT...

Mosaic microecological differential stress causes adaptive microsatellite divergence in wild barley, Hordeum spontaneum, at Neve Yaar, Israel.

PubMed

Huang, Qingyang; Beharav, Alex; Li, Youchun; Kirzhner, Valery; Nevo, Eviatar

2002-12-01

Genetic diversity at 38 microsatellite (short sequence repeats (SSRs)) loci was studied in a sample of 54 plants representing a natural population of wild barley, Hordeum spontaneum, at the Neve Yaar microsite in Israel. Wild barley at the microsite was organized in a mosaic pattern over an area of 3180 m2 in the open Tabor oak forest, which was subdivided into four microniches: (i) sun-rock (11 genotypes), (ii) sun-soil (18 genotypes), (iii) shade-soil (11 genotypes), and (iv) shade-rock (14 genotypes). Fifty-four genotypes were tested for ecological-genetic microniche correlates. Analysis of 36 loci showed that allele distributions at SSR loci were nonrandom but structured by ecological stresses (climatic and edaphic). Sixteen (45.7%) of 35 polymorphic loci varied significantly (p < 0.05) in allele frequencies among the microniches. Significant genetic divergence and diversity were found among the four subpopulations. The soil and shade subpopulations showed higher genetic diversities at SSR loci than the rock and sun subpopulations, and the lowest genetic diversity was observed in the sun-rock subpopulation, in contrast with the previous allozyme and RAPD studies. On average, of 36 loci, 88.75% of the total genetic diversity exists within the four microniches, while 11.25% exists between the microniches. In a permutation test, G(ST) was lower for 4999 out of 5000 randomized data sets (p < 0.001) when compared with real data (0.1125). The highest genetic distance was between shade-soil and sun-rock (D = 0.222). Our results suggest that diversifying natural selection may act upon some regulatory regions, resulting in adaptive SSR divergence. Fixation of some loci (GMS61, GMS1, and EBMAC824) at a specific microniche seems to suggest directional selection. The pattern of other SSR loci suggests the operation of balancing selection. SSRs may be either direct targets of selection or markers of selected haplotypes (selective sweep).

The Patient Self-Determination Act. A matter of life and death.

PubMed

Kelley, K

1995-03-01

The Patient Self-Determination Act (PSDA) is a federal law, and compliance is mandatory. It is the purpose of this act to ensure that a patient's right to self-determination in health care decisions be communicated and protected. Through advance directives--the living will and the durable power of attorney--the right to accept or reject medical or surgical treatment is available to adults while competent, so that in the event that such adults become incompetent to make decisions, they would more easily continue to control decisions affecting their health care. Without advance directives and the proper adherence to such directives, former President Richard Nixon and former First Lady Jacqueline Kennedy Onassis might still be alive today, in persistent vegetative states. This article examines the history of the act, its importance to each individual, the clinical, ethical and legal issues, and the role of health care professionals in effectively implementing and ensuring compliance of the PSDA.

Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b.

PubMed

Kanda, Tatsuo; Nirei, Kazushige; Matsumoto, Naoki; Higuchi, Teruhisa; Nakamura, Hitomi; Yamagami, Hiroaki; Matsuoka, Shunichi; Moriyama, Mitsuhiko

2017-12-14

The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

32 CFR 1602.21 - Selective Service Law.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Selective Service Law. 1602.21 Section 1602.21 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM DEFINITIONS § 1602.21 Selective Service Law. The term Selective Service Law includes the Military Selective Service Act...

Multimodal Encoding of Goal-Directed Actions in Monkey Ventral Premotor Grasping Neurons.

PubMed

Bruni, Stefania; Giorgetti, Valentina; Fogassi, Leonardo; Bonini, Luca

2017-01-01

Visuo-motor neurons of the ventral premotor area F5 encode "pragmatic" representations of object in terms of the potential motor acts (e.g., precision grip) afforded by it. Likewise, objects with identical pragmatic features (e.g., small spheres) but different behavioral value (e.g., edible or inedible) convey different "semantic" information and thus afford different goal-directed behaviors (e.g., grasp-to-eat or grasp-to-place). However, whether F5 neurons can extract distinct behavioral affordances from objects with similar pragmatic features is unknown. We recorded 134 F5 visuo-motor neurons in 2 macaques during a contextually cued go/no-go task in which the monkey grasped, or refrained from grasping, a previously presented edible or inedible target to eat it or placing it, respectively. Sixty-nine visuo-motor neurons showed motor selectivity for the target (35 food and 34 object), and about half of them (N = 35) exhibited congruent visual preference. Interestingly, when the monkey grasped in complete darkness and could identify the target only based on haptic feedback, visuo-motor neurons lost their precontact selectivity, but most of them (80%) showed it again 60 ms after hand-target contact. These findings suggest that F5 neurons possess a multimodal access to semantic information on objects, which are transformed into motor representations of the potential goal-directed actions afforded by them. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

2'-O-methyl-modified RNAs act as TLR7 antagonists.

PubMed

Robbins, Marjorie; Judge, Adam; Liang, Lisa; McClintock, Kevin; Yaworski, Ed; MacLachlan, Ian

2007-09-01

RNA molecules such as single-stranded RNA (ssRNA) and small interfering RNA (siRNA) duplexes induce Toll-like receptor (TLR)-mediated immune stimulation after intracellular delivery. We have previously shown that selective incorporation of 2'-O-methyl (2'OMe) residues into siRNA abrogates cytokine production without reduction of gene silencing activity. Here we show that 2'OMe-modified RNA acts as a potent inhibitor of RNA-mediated cytokine induction in both human and murine systems. This activity does not require the direct incorporation of 2'OMe nucleotides into the immunostimulatory RNA or that the 2'OMe nucleotide-containing RNA be annealed as a complementary strand to form a duplex. Our results indicate that 2'OMe RNA acts as a potent antagonist of immunostimulatory RNA. We further show that 2'OMe RNA is able significantly to reduce both interferon-alpha (IFN-alpha) and interleukin-6 (IL-6) induction by the small-molecule TLR7 agonist loxoribine in human peripheral blood mononuclear cells (human PBMCs), in murine Flt3L dendritic cells (Flt3L DCs), and in vivo in mice. These results indicate that 2'OMe-modified RNA may have utility as an inhibitor of TLR7 with potential applications in the treatment of inflammatory and autoimmune diseases that involve TLR7-mediated immune stimulation.

31 CFR 548.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (50 U.S.C... adjustment pursuant to the Federal Civil Penalties Inflation Adjustment Act of 1990 (Pub. L. 101-410, as... pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S.C. 1001, which provides that whoever...

31 CFR 594.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is directed to section 5...

31 CFR 588.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 535.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 536.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

....701 Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers... Act of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 592.601 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Penalties. (a) Attention is directed to section 8 of the Clean Diamond Trade Act (the “Act”) (Pub. L. 108-19...) of this section, section 8(a) of the Clean Diamond Trade Act (Pub. L. 108-19) establishes penalties...) Attention is also directed to 18 U.S.C. 1001, which provides that whoever, in any matter within the...

31 CFR 549.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (50 U.S.C... adjustment pursuant to the Federal Civil Penalties Inflation Adjustment Act of 1990 (Pub. L. 101-410, as... pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S.C. 1001, which provides that “whoever...

31 CFR 545.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

....701 Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers... Act of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 535.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (the... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 548.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Attention is directed to section 206 of the International Emergency Economic Powers Act (50 U.S.C... adjustment pursuant to the Federal Civil Penalties Inflation Adjustment Act of 1990 (Pub. L. 101-410, as... pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S.C. 1001, which provides that whoever...

31 CFR 536.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

....701 Penalties. (a) Attention is directed to section 206 of the International Emergency Economic Powers... Act of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

PubMed

Ingley, Spencer J; Johnson, Jerald B

2016-03-01

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

Federal Aviation Administration Acquisition Management System (Rev.)

DOT National Transportation Integrated Search

1997-06-02

The Department of Transportation and Related Agencies Appropriations Act of 1996, : Public Law 104-50 (the "1996 DOT Appropriations Act"), was enacted November 15, : 1995. Section 348 of this Act directed the Administrator to develop and : implement ...

The Atacama Cosmology Telescope: Calibration with the Wilkinson Microwave Anisotropy Probe Using Cross-Correlations

NASA Technical Reports Server (NTRS)

Hajian, Amir; Acquaviva, Viviana; Ade, Peter A. R.; Aguirre, Paula; Amiri, Mandana; Appel, John William; Barrientos, L. Felipe; Battistelli, Elia S.; Bond, John R.; Brown, Ben;

Research on the porous flow of the mechanism of viscous-elastic fluids displacing residual oil droplets in micro pores

NASA Astrophysics Data System (ADS)

Dong, Guanyu

2018-03-01

In order to analyze the microscopic stress field acting on residual oil droplets in micro pores, calculate its deformation, and explore the hydrodynamic mechanism of viscous-elastic fluids displacing oil droplets, the viscous-elastic fluid flow equations in micro pores are established by choosing the Upper Convected Maxwell constitutive equation; the numerical solutions of the flow field are obtained by volume control and Alternate Direction Implicit methods. From the above, the velocity field and microscopic stress field; the forces acting on residual oil droplets; the deformations of residual oil droplets by various viscous-elastic displacing fluids and at various Wiesenberg numbers are calculated and analyzed. The result demonstrated that both the normal stress and horizontal force acting on the residual oil droplets by viscous-elastic fluids are much larger compared to that of inelastic fluid; the distribution of normal stress changes abruptly; under the condition of the same pressure gradient in the system under investigation, the ratio of the horizontal forces acting on the residual oil droplets by different displacing fluids is about 1:8:20, which means that under the above conditions, the driving force on a oil droplet is 20 times higher for a viscous-elastic fluid compared to that of a Newtonian Fluid. The conclusions are supportive of the mechanism that viscous-elastic driving fluids can increase the Displacement Efficiency. This should be of help in designing new chemicals and selecting Enhanced Oil Recovery systems.

A new metric of inclusive fitness predicts the human mortality profile.

PubMed

Newman, Saul J; Easteal, Simon

2015-01-01

Biological species have evolved characteristic patterns of age-specific mortality across their life spans. If these mortality profiles are shaped by natural selection they should reflect underlying variation in the fitness effect of mortality with age. Direct fitness models, however, do not accurately predict the mortality profiles of many species. For several species, including humans, mortality rates vary considerably before and after reproductive ages, during life-stages when no variation in direct fitness is possible. Variation in mortality rates at these ages may reflect indirect effects of natural selection acting through kin. To test this possibility we developed a new two-variable measure of inclusive fitness, which we term the extended genomic output or EGO. Using EGO, we estimate the inclusive fitness effect of mortality at different ages in a small hunter-gatherer population with a typical human mortality profile. EGO in this population predicts 90% of the variation in age-specific mortality. This result represents the first empirical measurement of inclusive fitness of a trait in any species. It shows that the pattern of human survival can largely be explained by variation in the inclusive fitness cost of mortality at different ages. More generally, our approach can be used to estimate the inclusive fitness of any trait or genotype from population data on birth dates and relatedness.

Mind the gap: genetic manipulation of basicranial growth within synchondroses modulates calvarial and facial shape in mice through epigenetic interactions.

PubMed

Parsons, Trish E; Downey, Charlene M; Jirik, Frank R; Hallgrimsson, Benedikt; Jamniczky, Heather A

2015-01-01

Phenotypic integration patterns in the mammalian skull have long been a focus of intense interest as a result of their suspected influence on the trajectory of hominid evolution. Here we test the hypothesis that perturbation of cartilage growth, which directly affects only the chondrocranium during development, will produce coordinated shape changes in the adult calvarium and face regardless of mechanism. Using two murine models of cartilage undergrowth that target two very different mechanisms, we show that strong reduction in cartilage growth produces a short, wide, and more flexed cranial base. This in turn produces a short, wide face in both models. Cranial base and face are already correlated early in ontogeny, and the relationship between these modules gains structure through postnatal growth and development. These results provide further evidence that there exist physical interactions between developing parts of the phenotype that produce variation at a distance from the actual locus upon which a particular selective pressure is acting. Phenotypic changes observed over the course of evolution may not all require adaptationist explanations; rather, it is likely that a substantial portion of observed phenotypic variation over the history of a clade is not directly adaptive but rather a secondary consequence of some local response to selection.

Pre- Versus Posttransplant Treatment of Hepatitis C Virus With Direct-Acting Antivirals in Liver Transplant Recipients: More Issues to be Solved.

PubMed

Abdelqader, Abdelhai; Kabacam, Gokhan; Woreta, Tinsay A; Hamilton, James P; Luu, Harry; Al Khalloufi, Kawtar; Saberi, Behnam; Philosophe, Benjamin; Cameron, Andrew M; Gurakar, Ahmet

2017-02-01

Our goal was to investigate wait times related to hepatitis C virus treatment with direct acting antivirals before versus after liver transplant at a single center as well as wait times for insurance approval for preemptive treatment with these agents after liver transplant. We retrospectively evaluated hepatitis C virus infections in transplant recipients of deceased liver donations in 2014 and 2015. Demographics, hepatocellular carcinoma incidence, Model for End-Stage Liver Disease scores, and transplant wait times were compared between patients treated before or after liver transplant. Wait times to approval of direct-acting antiviral treatment were evaluated in those untreated before transplant. During our study period, of 67 deceased-donor liver transplants, 21 patients received hepatitis C virus treatment pretransplant (treated group) and 46 patients were not treated pretransplant (untreated group). Twenty-five patients in the untreated group received hepatitis C virus-positive donations, with all in this group treated with direct-acting antivirals. We found no statistically significant differences regarding age, sex, race, donation after cardiac death, or incidence of hepatocellular carcinoma between groups. The treated group had a longer median wait time (287 vs 172 days; P = .02). Twelve of the 46 untreated patients (26.1%) developed biopsy-proven hepatitis C virus-related relapse (median 87 days; range, 55-383 days). Preemptive direct-acting antiviral therapy was initiated at a median of 81 days in the untreated group. Although treatment of hepatitis C virus before liver transplant is an attractive option to eliminate the risk of complications, it can limit the donor pool for recipients to uninfected donors, significantly increasing wait times in regions with large hepatitis C virus-positive donor pools. Allocation of Model for End-Stage Liver Disease score was not different between the treated and untreated groups. Insurance companies should revise their policies for rapid approval of preemptive direct-acting antiviral treatment after liver transplant.

Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal

PubMed Central

Risso, Davide S.; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

2016-01-01

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes. PMID:27138342

Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal.

PubMed

Risso, Davide S; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

2016-05-03

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment.

PubMed

Cropley, Jennifer E; Dang, Thurston H Y; Martin, David I K; Suter, Catherine M

2012-06-22

Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic A(vy) mice, in which the epigenetic state of the A(vy) allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent A(vy) allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations.

The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment

PubMed Central

Cropley, Jennifer E.; Dang, Thurston H. Y.; Martin, David I. K.; Suter, Catherine M.

2012-01-01

Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic Avy mice, in which the epigenetic state of the Avy allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent Avy allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations. PMID:22319121

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a... room cancellation deadline is 4 p.m. (or later) on the day of arrival; (4) Most hotels offer last... hotel reservation call centers). The FedRooms® rate code (XVU) must be entered to get the program...

Genetic basis and fitness correlates of dynamic carotenoid-based ornamental coloration in male and female common kestrels Falco tinnunculus.

PubMed

Vergara, P; Fargallo, J A; Martínez-Padilla, J

2015-01-01

Knowledge of the genetic basis of sexual ornaments is essential to understand their evolution through sexual selection. Although carotenoid-based ornaments have been instrumental in the study of sexual selection, given the inability of animals to synthesize carotenoids de novo, they are generally assumed to be influenced solely by environmental variation. However, very few studies have directly estimated the role of genes and the environment in shaping variation in carotenoid-based traits. Using long-term individual-based data, we here explore the evolutionary potential of a dynamic, carotenoid-based ornament (namely skin coloration), in male and female common kestrels. We first estimate the amount of genetic variation underlying variation in hue, chroma and brightness. After correcting for sex differences, the chroma of the orange-yellow eye ring coloration was significantly heritable (h2±SE=0.40±0.17), whereas neither hue (h2=0) nor brightness (h2=0.02) was heritable. Second, we estimate the strength and shape of selection acting upon chromatic (hue and chroma) and achromatic (brightness) variation and show positive and negative directional selection on female but not male chroma and hue, respectively, whereas brightness was unrelated to fitness in both sexes. This suggests that different components of carotenoid-based signals traits may show different evolutionary dynamics. Overall, we show that carotenoid-based coloration is a complex and multifaceted trait. If we are to gain a better understanding of the processes responsible for the generation and maintenance of variation in carotenoid-based coloration, these complexities need to be taken into account. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

Career Readiness in the United States 2015. ACT Insights in Education and Work

ERIC Educational Resources Information Center

LeFebvre, Mary

2015-01-01

ACT has conducted over 20,000 job analyses for occupations across a diverse array of industries and occupations since 1993. This report highlights the levels of career readiness for various subgroups of ACT Work Keys® examinees in the United States and provides career readiness benchmarks for selected ACT WorkKeys cognitive skills by career…

Male-male competition, female mate choice and their interaction: determining total sexual selection.

PubMed

Hunt, John; Breuker, Casper J; Sadowski, Jennifer A; Moore, Allen J

2009-01-01

Empirical studies of sexual selection typically focus on one of the two mechanisms of sexual selection without integrating these into a description of total sexual selection, or study total sexual selection without quantifying the contributions of all of the mechanisms of sexual selection. However, this can provide an incomplete or misleading view of how sexually selected traits evolve if the mechanisms of sexual selection are opposing or differ in form. Here, we take a two-fold approach to advocate a direction for future studies of sexual selection. We first show how a quantitative partitioning and examination of sexual selection mechanisms can inform by identifying illustrative studies that describe both male-male competition and female mate choice acting on the same trait. In our sample, the most common trait where this occurred was body size, and selection was typically linear. We found that male-male competition and female mate choice can be reinforcing or opposing, although the former is most common in the literature. The mechanisms of sexual selection can occur simultaneously or sequentially, and we found they were more likely to be opposing when the mechanisms operated sequentially. The degree and timing that these mechanisms interact have important implications for the operation of sexual selection and needs to be considered in designing studies. Our examples highlight where empirical data are needed. We especially lack standardized measures of the form and strength of selection imposed by each mechanism of sexual selection and how they combine to determine total sexual selection. Secondly, using quantitative genetic principles, we outline how the selection imposed by individual mechanisms can be measured and combined to estimate the total strength and form of sexual selection. We discuss the evolutionary consequences of combining the mechanisms of sexual selection and interpreting total sexual selection. We suggest how this approach may result in empirical progress in the field of sexual selection.

29 CFR 4.121 - Contracts for individual services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... McNamara-O'Hara Service Contract Act Specific Exclusions § 4.121 Contracts for individual services. The Act... to an “employment contract” for “direct services,” makes it clear that the Act's application to... contract service, the exemption applies and the contract will not be subject to the Act's provisions. The...

48 CFR 3052.209-74 - Limitations on contractors acting as lead system integrators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... acting as lead system integrators. 3052.209-74 Section 3052.209-74 Federal Acquisition Regulations System... contractors acting as lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(a), use the following provision: LIMITATIONS ON CONTRACTORS ACTING AS LEAD SYSTEM INTEGRATORS (JUL 2010) (a) Definitions. “Direct...

48 CFR 3052.209-74 - Limitations on contractors acting as lead system integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... acting as lead system integrators. 3052.209-74 Section 3052.209-74 Federal Acquisition Regulations System... contractors acting as lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(a), use the following provision: LIMITATIONS ON CONTRACTORS ACTING AS LEAD SYSTEM INTEGRATORS (JUL 2010) (a) Definitions. “Direct...

Module 4: Work-Family Policy in the United States. Work-Family Curriculum Guide

ERIC Educational Resources Information Center

Kossek, Ellen Ernst; Leana, Carrie; MacDermid, Shelley; Pitt-Catsouphes, Marcie; Raskin, Patricia; Secret, Mary; Shulkin, Sandee; Sweet, Stephen

2006-01-01

Public policy affects the experiences of workers and their families, both directly and indirectly. For example, employment-focused statutes such as the Fair Labor Standards Act (FLSA), the Employment Retirement and Income Security Act, the Occupational Health and Safety Act, and the Age Discrimination in Employment Act establish frameworks for…

Inference of Evolutionary Forces Acting on Human Biological Pathways

PubMed Central

Daub, Josephine T.; Dupanloup, Isabelle; Robinson-Rechavi, Marc; Excoffier, Laurent

2015-01-01

Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald–Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures. PMID:25971280

Modeling HIV-1 Drug Resistance as Episodic Directional Selection

PubMed Central

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.

PubMed

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.

The ACT Vision Mission Study Simulation Effort

NASA Astrophysics Data System (ADS)

Wunderer, C. B.; Kippen, R. M.; Bloser, P. F.; Boggs, S. E.; McConnell, M. L.; Hoover, A.; Oberlack, U.; Sturner, S.; Tournear, D.; Weidenspointner, G.; Zoglauer, A.

2004-12-01

The Advanced Compton Telescope (ACT) has been selected by NASA for a one-year "Vision Mission" study. The main goal of this study is to determine feasible instrument configurations to achieve ACT's sensitivity requirements, and to give recommendations for technology development. Space-based instruments operating in the energy range of nuclear lines are subject to complex backgrounds generated by cosmic-ray interactions and diffuse gamma rays; typically measurements are significantly background-dominated. Therefore accurate, detailed simulations of the background induced in different ACT configurations, and exploration of event selection and reconstruction techniques for reducing these backgrounds, are crucial to determining both the capabilities of a given instrument configuration and the technology enhancements that would result in the most significant performance improvements. The ACT Simulation team has assembled a complete suite of tools that allows the generation of particle backgrounds for a given orbit (based on CREME96), their propagation through any instrument and spacecraft geometry (using MGGPOD) - including delayed photon emission from instrument activation - as well as the event selection and reconstruction of Compton-scatter events in the given detectors (MEGAlib). The package can deal with polarized photon beams as well as e.g. anticoincidence shields. We will report on the progress of the ACT simulation effort and the suite of tools used. We thank Elena Novikova at NRL for her contributions, and NASA for support of this research.

31 CFR 542.701 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act”) (50 U.S... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

31 CFR 542.701 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Attention is directed to section 206 of the International Emergency Economic Powers Act (the “Act”) (50 U.S... of 1990 (Pub. L. 101-410, as amended, 28 U.S.C. 2461 note). (2) The criminal penalties provided in the Act are subject to adjustment pursuant to 18 U.S.C. 3571. (c) Attention is also directed to 18 U.S...

75 FR 34196 - Self-Regulatory Organizations; Notice of Filing of Proposed Rule Change by EDGX Exchange, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... Edge, Inc. June 10, 2010. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act... its corporate structure to provide that it will be a wholly-owned subsidiary of Direct Edge, Inc. (``DEI'') instead of Direct Edge Holdings, LLC (``DE Holdings''). The proposed Certificate of...

75 FR 34189 - Self-Regulatory Organizations; Notice of Filing of Proposed Rule Change by EDGA Exchange, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... Edge, Inc. June 10, 2010. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act... its corporate structure to provide that it will be a wholly-owned subsidiary of Direct Edge, Inc. (``DEI'') instead of Direct Edge Holdings, LLC (``DE Holdings''). The proposed Certificate of...

CONTROL SYSTEM FOR NEUTRONIC REACTORS

DOEpatents

Crever, F.E.

1962-05-01

BS>A slow-acting shim rod for control of major variations in reactor neutron flux and a fast-acting control rod to correct minor flux variations are employed to provide a sensitive, accurate control system. The fast-acting rod is responsive to an error signal which is produced by changes in the neutron flux from a predetermined optimum level. When the fast rod is thus actuated in a given direction, means is provided to actuate the slow-moving rod in that direction to return the fast rod to a position near the midpoint of its control range. (AEC)

Rhodium-Catalyzed C-C Bond Formation via Heteroatom-Directed C-H Bond Activation

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

Colby, Denise; Bergman, Robert; Ellman, Jonathan

2010-05-13

Once considered the 'holy grail' of organometallic chemistry, synthetically useful reactions employing C-H bond activation have increasingly been developed and applied to natural product and drug synthesis over the past decade. The ubiquity and relative low cost of hydrocarbons makes C-H bond functionalization an attractive alternative to classical C-C bond forming reactions such as cross-coupling, which require organohalides and organometallic reagents. In addition to providing an atom economical alternative to standard cross - coupling strategies, C-H bond functionalization also reduces the production of toxic by-products, thereby contributing to the growing field of reactions with decreased environmental impact. In the areamore » of C-C bond forming reactions that proceed via a C-H activation mechanism, rhodium catalysts stand out for their functional group tolerance and wide range of synthetic utility. Over the course of the last decade, many Rh-catalyzed methods for heteroatom-directed C-H bond functionalization have been reported and will be the focus of this review. Material appearing in the literature prior to 2001 has been reviewed previously and will only be introduced as background when necessary. The synthesis of complex molecules from relatively simple precursors has long been a goal for many organic chemists. The ability to selectively functionalize a molecule with minimal pre-activation can streamline syntheses and expand the opportunities to explore the utility of complex molecules in areas ranging from the pharmaceutical industry to materials science. Indeed, the issue of selectivity is paramount in the development of all C-H bond functionalization methods. Several groups have developed elegant approaches towards achieving selectivity in molecules that possess many sterically and electronically similar C-H bonds. Many of these approaches are discussed in detail in the accompanying articles in this special issue of Chemical Reviews. One approach that has seen widespread success involves the use of a proximal heteroatom that serves as a directing group for the selective functionalization of a specific C-H bond. In a survey of examples of heteroatom-directed Rh catalysis, two mechanistically distinct reaction pathways are revealed. In one case, the heteroatom acts as a chelator to bind the Rh catalyst, facilitating reactivity at a proximal site. In this case, the formation of a five-membered metallacycle provides a favorable driving force in inducing reactivity at the desired location. In the other case, the heteroatom initially coordinates the Rh catalyst and then acts to stabilize the formation of a metal-carbon bond at a proximal site. A true test of the utility of a synthetic method is in its application to the synthesis of natural products or complex molecules. Several groups have demonstrated the applicability of C-H bond functionalization reactions towards complex molecule synthesis. Target-oriented synthesis provides a platform to test the effectiveness of a method in unique chemical and steric environments. In this respect, Rh-catalyzed methods for C-H bond functionalization stand out, with several syntheses being described in the literature that utilize C-H bond functionalization in a key step. These syntheses are highlighted following the discussion of the method they employ.« less

48 CFR 926.7002 - Responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SOCIOECONOMIC PROGRAMS Implementation of Section 3021 of the Energy Policy Act of 1992 926.7002 Responsibilities... requirements falling within the scope of section 3021 of the Energy Policy Act. Identification shall occur at... award that directly satisfies an Energy Policy Act program or requirement. ...

48 CFR 926.7002 - Responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SOCIOECONOMIC PROGRAMS Implementation of Section 3021 of the Energy Policy Act of 1992 926.7002 Responsibilities... requirements falling within the scope of section 3021 of the Energy Policy Act. Identification shall occur at... award that directly satisfies an Energy Policy Act program or requirement. ...

48 CFR 926.7002 - Responsibilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SOCIOECONOMIC PROGRAMS Implementation of Section 3021 of the Energy Policy Act of 1992 926.7002 Responsibilities... requirements falling within the scope of section 3021 of the Energy Policy Act. Identification shall occur at... award that directly satisfies an Energy Policy Act program or requirement. ...

48 CFR 926.7002 - Responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SOCIOECONOMIC PROGRAMS Implementation of Section 3021 of the Energy Policy Act of 1992 926.7002 Responsibilities... requirements falling within the scope of section 3021 of the Energy Policy Act. Identification shall occur at... award that directly satisfies an Energy Policy Act program or requirement. ...

48 CFR 926.7002 - Responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SOCIOECONOMIC PROGRAMS Implementation of Section 3021 of the Energy Policy Act of 1992 926.7002 Responsibilities... requirements falling within the scope of section 3021 of the Energy Policy Act. Identification shall occur at... award that directly satisfies an Energy Policy Act program or requirement. ...

40 CFR 503.3 - Permits and direct enforceability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... with 40 CFR part 123 or 40 CFR part 501 or (2) Issued under subtitle C of the Solid Waste Disposal Act; part C of the Safe Drinking Water Act; the Marine Protection, Research, and Sanctuaries Act of 1972; or...

47 CFR 32.4 - Communications Act.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Communications Act. 32.4 Section 32.4 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Preface § 32.4 Communications Act. Attention is directed to the...

47 CFR 32.4 - Communications Act.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Communications Act. 32.4 Section 32.4 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Preface § 32.4 Communications Act. Attention is directed to the...

47 CFR 32.4 - Communications Act.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Communications Act. 32.4 Section 32.4 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Preface § 32.4 Communications Act. Attention is directed to the...

47 CFR 32.4 - Communications Act.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Communications Act. 32.4 Section 32.4 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Preface § 32.4 Communications Act. Attention is directed to the...

Finding Direction in the Search for Selection.

PubMed

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.

32 CFR 1665.2 - Requests for access.

Code of Federal Regulations, 2010 CFR

2010-07-01

... National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM PRIVACY ACT... description of such system of records. The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of specifying solely the Privacy Act of 1974 and, if the request may be...

32 CFR 1665.2 - Requests for access.

Code of Federal Regulations, 2011 CFR

2011-07-01

... National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM PRIVACY ACT... description of such system of records. The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of specifying solely the Privacy Act of 1974 and, if the request may be...

Formoterol versus short-acting beta-agonists as relief medication for adults and children with asthma

PubMed Central

Welsh, Emma J; Cates, Christopher J

2014-01-01

Background Formoterol is a long-acting beta2-agonist but because it has a fast onset of action it can also be used as a relief medication. Objectives To asses the efficacy and safety of formoterol as reliever therapy in comparison to short-acting beta2-agonists in adults and children with asthma. Search methods We searched the Cochrane Airways Group Specialised Register and websites of clinical trial registers (for unpublished trial data), and we checked the Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was February 2010. Selection criteria Randomised, parallel-arm trials of at least 12 weeks duration in patients of any age and severity of asthma. Studies randomised patients to any dose of as-needed formoterol versus short-acting beta2-agonist. Concomitant use of inhaled corticosteroids or other maintenance medication was allowed, as long as this was not part of the randomised treatment regimen. Data collection and analysis Two authors independently selected trials for inclusion in the review. Outcome data were extracted by one author and checked by the second author. We sought unpublished data on primary outcomes. Main results This review includes eight studies conducted in 22,604 participants (mostly adults). Six studies compared formoterol as-needed to terbutaline whilst two studies compared formoterol with salbutamol as-needed. Background maintenance therapy varied across the trials. Asthma exacerbations and serious adverse events showed a direction of treatment effect favouring formoterol, of which one outcome reached statistical significance (exacerbations requiring a course of oral corticosteroids). In patients on short-acting beta2-agonists, 117 people out of 1000 had exacerbations requiring oral corticosteroids over 30 weeks, compared to 101 (95% CI 93 to 108) out of 1000 for patients on formoterol as-needed. In patients on maintenance inhaled corticosteroids there were also significantly fewer exacerbations requiring a course of oral corticosteroids on formoterol as-needed (Peto OR 0.75; 95% CI 0.62 to 0.91). There was one death per 1000 people on formoterol or on short-acting beta2-agonists. Authors’ conclusions In adults, formoterol was similar to short-acting beta2-agonists when used as a reliever, and showed a reduction in the number of exacerbations requiring a course of oral corticosteroids. Clinicians should weigh the relatively modest benefits of formoterol as-needed against the benefits of single inhaler therapy and the potential danger of long-term use of long-acting beta2-agonists in some patients. We did not find evidence to recommend changes to guidelines that suggest that long-acting beta2-agonists should be given only to patients already taking inhaled corticosteroids. There was insufficient information reported from children in the included trials to come to any conclusion on the safety or efficacy of formoterol as relief medication for children with asthma. PMID:20824877

Capacitance-level/density monitor for fluidized-bed combustor

DOEpatents

Fasching, George E.; Utt, Carroll E.

1982-01-01

A multiple segment three-terminal type capacitance probe with segment selection, capacitance detection and compensation circuitry and read-out control for level/density measurements in a fluidized-bed vessel is provided. The probe is driven at a high excitation frequency of up to 50 kHz to sense quadrature (capacitive) current related to probe/vessel capacitance while being relatively insensitive to the resistance current component. Compensation circuitry is provided for generating a negative current of equal magnitude to cancel out only the resistive component current. Clock-operated control circuitry separately selects the probe segments in a predetermined order for detecting and storing this capacitance measurement. The selected segment acts as a guarded electrode and is connected to the read-out circuitry while all unselected segments are connected to the probe body, which together form the probe guard electrode. The selected probe segment capacitance component signal is directed to a corresponding segment channel sample and hold circuit dedicated to that segment to store the signal derived from that segment. This provides parallel outputs for display, computer input, etc., for the detected capacitance values. The rate of segment sampling may be varied to either monitor the dynamic density profile of the bed (high sampling rate) or monitor average bed characteristics (slower sampling rate).

A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli*

PubMed Central

Urfer, Matthias; Bogdanovic, Jasmina; Lo Monte, Fabio; Moehle, Kerstin; Zerbe, Katja; Omasits, Ulrich; Ahrens, Christian H.; Pessi, Gabriella; Eberl, Leo; Robinson, John A.

2016-01-01

Increasing antibacterial resistance presents a major challenge in antibiotic discovery. One attractive target in Gram-negative bacteria is the unique asymmetric outer membrane (OM), which acts as a permeability barrier that protects the cell from external stresses, such as the presence of antibiotics. We describe a novel β-hairpin macrocyclic peptide JB-95 with potent antimicrobial activity against Escherichia coli. This peptide exhibits no cellular lytic activity, but electron microscopy and fluorescence studies reveal an ability to selectively disrupt the OM but not the inner membrane of E. coli. The selective targeting of the OM probably occurs through interactions of JB-95 with selected β-barrel OM proteins, including BamA and LptD as shown by photolabeling experiments. Membrane proteomic studies reveal rapid depletion of many β-barrel OM proteins from JB-95-treated E. coli, consistent with induction of a membrane stress response and/or direct inhibition of the Bam folding machine. The results suggest that lethal disruption of the OM by JB-95 occurs through a novel mechanism of action at key interaction sites within clusters of β-barrel proteins in the OM. These findings open new avenues for developing antibiotics that specifically target β-barrel proteins and the integrity of the Gram-negative OM. PMID:26627837

Detecting gene subnetworks under selection in biological pathways.

PubMed

Gouy, Alexandre; Daub, Joséphine T; Excoffier, Laurent

2017-09-19

Advances in high throughput sequencing technologies have created a gap between data production and functional data analysis. Indeed, phenotypes result from interactions between numerous genes, but traditional methods treat loci independently, missing important knowledge brought by network-level emerging properties. Therefore, detecting selection acting on multiple genes affecting the evolution of complex traits remains challenging. In this context, gene network analysis provides a powerful framework to study the evolution of adaptive traits and facilitates the interpretation of genome-wide data. We developed a method to analyse gene networks that is suitable to evidence polygenic selection. The general idea is to search biological pathways for subnetworks of genes that directly interact with each other and that present unusual evolutionary features. Subnetwork search is a typical combinatorial optimization problem that we solve using a simulated annealing approach. We have applied our methodology to find signals of adaptation to high-altitude in human populations. We show that this adaptation has a clear polygenic basis and is influenced by many genetic components. Our approach, implemented in the R package signet, improves on gene-level classical tests for selection by identifying both new candidate genes and new biological processes involved in adaptation to altitude. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Large-scale rainfall diversity for ACTS

NASA Technical Reports Server (NTRS)

Lin, H. P.; Vogel, Wolfhard J.

1993-01-01

From the NOAA 15 minute precipitation file for the US, data were selected for a set of 23 stations spanning a 5 year period. The selection covers the spot beam locations for ACTS and the propagation experiment sites. There is a 2 percent probability of having any simultaneous rain at 3 or more stations, but this reduces to less than 0.001 percent at a rainfall rate of 40 mm/hr.

Signal transduction in a covalent post-assembly modification cascade

NASA Astrophysics Data System (ADS)

Pilgrim, Ben S.; Roberts, Derrick A.; Lohr, Thorsten G.; Ronson, Tanya K.; Nitschke, Jonathan R.

2017-12-01

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels-Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels-Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes.

Coupling between Buoyancy Forces and Electroconvective Instability near Ion-Selective Surfaces.

PubMed

Karatay, Elif; Andersen, Mathias Bækbo; Wessling, Matthias; Mani, Ali

2016-05-13

Recent investigations have revealed that ion transport from aqueous electrolytes to ion-selective surfaces is subject to electroconvective instability that stems from coupling of hydrodynamics with electrostatic forces. These systems inherently involve fluid density variation set by salinity gradients. However, the coupling between the buoyancy effects and electroconvective instability has not yet been investigated although a wide range of electrochemical systems are naturally prone to these interplaying effects. In this study we thoroughly examine the interplay of gravitational convection and chaotic electroconvection. Our results reveal that buoyant forces can significantly influence the transport rates, otherwise set by electroconvection, when the Rayleigh number Ra of the system exceeds a value Ra∼1000. We show that buoyancy forces can significantly alter the flow patterns in these systems. When the buoyancy acts in the stabilizing direction, it limits the extent of penetration of electroconvection, but without eliminating it. When the buoyancy destabilizes the flow, it alters the electroconvective patterns by introducing upward and downward fingers of respectively light and heavy fluids.

Optimized Target Residence Time: Type I1/2 Inhibitors for p38α MAP Kinase with Improved Binding Kinetics through Direct Interaction with the R-Spine.

PubMed

Wentsch, Heike K; Walter, Niklas M; Bührmann, Mike; Mayer-Wrangowski, Svenja; Rauh, Daniel; Zaman, Guido J R; Willemsen-Seegers, Nicole; Buijsman, Rogier C; Henning, Melanie; Dauch, Daniel; Zender, Lars; Laufer, Stefan

2017-05-02

Skepinone-L was recently reported to be a p38α MAP kinase inhibitor with high potency and excellent selectivity in vitro and in vivo. However, this class of compounds still act as fully ATP-competitive Type I binders which, furthermore, suffer from short residence times at the enzyme. We herein describe a further development with the first Type I1/2 binders for p38α MAP kinase. Type I1/2 inhibitors interfere with the R-spine, inducing a glycine flip and occupying both hydrophobic regions I and II. This design approach leads to prolonged target residence time, binding to both the active and inactive states of the kinase, excellent selectivity, excellent potency on the enzyme level, and low nanomolar activity in a human whole blood assay. This promising binding mode is proven by X-ray crystallography. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Calcium transport in vesicles energized by cytochrome oxidase

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

Rosier, Randy N.

1979-01-01

Experiments on the reconstitution of cytochrome oxidase into phospholipid vesicles were carried out using techniques of selectivity energizing the suspensions with ascorbate and cytochrome c or ascorbate, PMS, and internally trapped cytochrome c. It was found that the K + selective ionophore valinomycin stimulated the rate of respiration of cytochrome oxidase vesicles regardless of the direction of the K + flux across the vesicle membranes. The stimulation occurred in the presence of protonophoric uncouplers and in the complete absence of potassium or in detergent-lysed suspensions. Gramicidin had similar effects and it was determined that the ionophores acted by specific interactionmore » with cytochrome oxidase rather than by the previously assumed collapse of membrane potentials. When hydrophobic proteins and appropriate coupling factors were incorporated into the cytochrome oxidase, vesicles phosphorylation of ADP could be coupled to the oxidation reaction of cytochrome oxidase. Relatively low P:O, representing poor coupling of the system, were problematical and precluded measurements of protonmotive force. However the system was used to study ion translocation.« less

Design and Synthesis of Neuroprotective Methylthiazoles and Modification as NO-Chimeras for Neurodegenerative Therapy

PubMed Central

Qin, Zhihui; Luo, Jia; VandeVrede, Lawren; Tavassoli, Ehsan; Fa’, Mauro; Teich, Andrew; Arancio, Ottavio; Thatcher, Gregory R. J.

2012-01-01

Learning and memory deficits in Alzheimer’s disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described, which uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4-Methylthiazole (MZ) derivatives were synthesized, based upon a lead neuroprotective pharmacophore acting in part by GABAA receptor potentiation. MZ derivatives were assayed for protection of primary neurons against oxygen-glucose deprivation and excitotoxicity. Selected neuroprotective derivatives were incorporated into NO-chimera prodrugs, coined nomethiazoles. To provide proof of concept for the nomethiazole drug class, selected examples were assayed for: restoration of synaptic function in hippocampal slices from AD-transgenic mice; reversal of cognitive deficits; and, brain bioavailability of the prodrug and its neuroprotective MZ metabolite. Taken together the assay data suggest that these chimeric nomethiazoles may be of use in treatment of multiple components of neurodegenerative disorders, such as AD. PMID:22779770

Lanthanum hexaboride for solar energy applications.

PubMed

Sani, Elisa; Mercatelli, Luca; Meucci, Marco; Zoli, Luca; Sciti, Diletta

2017-04-06

We investigate the optical properties of LaB 6 - based materials, as possible candidates for solid absorbers in Concentrating Solar Power (CSP) systems. Bulk LaB 6 materials were thermally consolidated by hot pressing starting from commercial powders. To assess the solar absorbance and spectral selectivity properties, room-temperature hemispherical reflectance spectra were measured from the ultraviolet to the mid-infrared, considering different compositions, porosities and surface roughnesses. Thermal emittance at around 1100 K has been measured. Experimental results showed that LaB 6 can have a solar absorbance comparable to that of the most advanced solar absorber material in actual plants such as Silicon Carbide, with a higher spectral selectivity. Moreover, LaB 6 has also the appealing characteristics to be a thermionic material, so that it could act at the same time both as direct high-temperature solar absorber and as electron source, significantly reducing system complexity in future concentrating solar thermionic systems and bringing a real innovation in this field.

Flexible single-layer ionic organic-inorganic frameworks towards precise nano-size separation

NASA Astrophysics Data System (ADS)

Yue, Liang; Wang, Shan; Zhou, Ding; Zhang, Hao; Li, Bao; Wu, Lixin

2016-02-01

Consecutive two-dimensional frameworks comprised of molecular or cluster building blocks in large area represent ideal candidates for membranes sieving molecules and nano-objects, but challenges still remain in methodology and practical preparation. Here we exploit a new strategy to build soft single-layer ionic organic-inorganic frameworks via electrostatic interaction without preferential binding direction in water. Upon consideration of steric effect and additional interaction, polyanionic clusters as connection nodes and cationic pseudorotaxanes acting as bridging monomers connect with each other to form a single-layer ionic self-assembled framework with 1.4 nm layer thickness. Such soft supramolecular polymer frameworks possess uniform and adjustable ortho-tetragonal nanoporous structure in pore size of 3.4-4.1 nm and exhibit greatly convenient solution processability. The stable membranes maintaining uniform porous structure demonstrate precisely size-selective separation of semiconductor quantum dots within 0.1 nm of accuracy and may hold promise for practical applications in selective transport, molecular separation and dialysis systems.

A composite material based on nanoparticles of yttrium (III) oxide for the selective and sensitive electrochemical determination of acetaminophen.

PubMed

Baytak, Aysegul Kutluay; Teker, Tugce; Duzmen, Sehriban; Aslanoglu, Mehmet

2016-09-01

An electrochemical sensor was prepared by modifying a glassy carbon electrode (GCE) with a composite of yttrium (III) oxide nanoparticles (Y2O3NPs) and carbon nanotubes (CNTs) for the determination of acetaminophen (ACT). Compared with a bare GCE and CNTs/GCE, the Y2O3NPs/CNTs/GCE exhibited a well-defined redox couple for ACT and highly enhanced the current response. The separations in the anodic and cathodic peak potentials (ΔEp) for ACT were 552mV, 24mV and 10mV at ba4re GCE, CNTs/GCE and Y2O3NPs/CNTs/GCE, respectively. The observation of only 10mV of ΔEp for ACT at Y2O3NPs/CNTs/GCE was a clear indication of a great acceleration of the electrode process compared to bare GCE and GCE modified with CNTs. Also, l-ascorbic acid (l-AA) and l-tyrosine (l-TRY) did not interfere with the selective determination of ACT. Square wave voltammetry (SWV) was performed for the quantification of ACT. A linear plot was obtained for current responses versus the concentrations of ACT over the range from 1.0×10(-10) to 1.8×10(-8)M with a detection limit of 3.0×10(-11)M (based on 3Sb/m). The proposed composite material provided high electrocatalytic activity, improved voltammetric behavior, good selectivity and good reproducibility. The accurate quantification of ACT makes the proposed electrode of great interest for the public health. Copyright © 2016 Elsevier B.V. All rights reserved.

Recovery Act: Head Start Grantees Expand Services, but More Consistent Communication Could Improve Accountability and Decisions about Spending. Report to the Congress. GAO-11-166

ERIC Educational Resources Information Center

Ashby, Cornelia M.; Jones, Yvonne D.

2010-01-01

This report responds to two mandates for GAO under the American Recovery and Reinvestment Act of 2009 (Recovery Act). First, it is the latest report on the uses of and accountability for Recovery Act funds in selected states and localities. Second, it comments on recipients' reports of the jobs created and retained. The Recovery Act provided $2.1…

Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual dimorphism in Oryzias latipes.

PubMed

Katsumura, Takafumi; Oda, Shoji; Nakagome, Shigeki; Hanihara, Tsunehiko; Kataoka, Hiroshi; Mitani, Hiroshi; Kawamura, Shoji; Oota, Hiroki

2014-12-22

Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection. Interestingly, sexually selected traits show geographical variations within species despite strong directional selective pressures. This paradox has eluded many evolutionary biologists for some time, and several models have been proposed (e.g. 'indicator model' and 'trade-off model'). However, disentangling which of these theories explains empirical patterns remains difficult, because genetic polymorphisms that cause variation in sexual differences are still unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are associated with geographical differences in sexual dimorphism in the anal fin morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross experiments show that high- and low-activity CYP1B1 alleles enhanced and declined sex differences in anal fin shapes, respectively. Behavioural and phylogenetic analyses suggest maintenance of the high-activity allele by sexual selection, whereas the low-activity allele possibly has experienced positive selection due to by-product effects of CYP1B1 in inferred ancestral populations. The present data can elucidate evolutionary mechanisms behind genetic variations in sexual dimorphism and indicate trade-off interactions between two distinct mechanisms acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing enzymes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

The Sensitivity of the ACT to Instruction. Issues in College Readiness

ERIC Educational Resources Information Center

ACT, Inc., 2005

2005-01-01

The ACT is an educational achievement test that measures the typical content and skills learned from college preparatory curricula. Consequently, the ACT can be used not only to predict college success, but also to provide direct feedback to high school teachers about the effectiveness of their teaching. ACT results also assist teachers in…

30 CFR 843.25 - Energy Policy Act enforcement in States with approved State programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Energy Policy Act enforcement in States with... ENFORCEMENT § 843.25 Energy Policy Act enforcement in States with approved State programs. (a) State-by-State... whether: (1) Direct Federal enforcement of the Energy Policy Act and implementing Federal regulations will...

30 CFR 843.25 - Energy Policy Act enforcement in States with approved State programs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Energy Policy Act enforcement in States with... ENFORCEMENT § 843.25 Energy Policy Act enforcement in States with approved State programs. (a) State-by-State... whether: (1) Direct Federal enforcement of the Energy Policy Act and implementing Federal regulations will...

30 CFR 843.25 - Energy Policy Act enforcement in States with approved State programs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Energy Policy Act enforcement in States with... ENFORCEMENT § 843.25 Energy Policy Act enforcement in States with approved State programs. (a) State-by-State... whether: (1) Direct Federal enforcement of the Energy Policy Act and implementing Federal regulations will...

30 CFR 843.25 - Energy Policy Act enforcement in States with approved State programs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Energy Policy Act enforcement in States with... ENFORCEMENT § 843.25 Energy Policy Act enforcement in States with approved State programs. (a) State-by-State... whether: (1) Direct Federal enforcement of the Energy Policy Act and implementing Federal regulations will...

30 CFR 843.25 - Energy Policy Act enforcement in States with approved State programs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Energy Policy Act enforcement in States with... ENFORCEMENT § 843.25 Energy Policy Act enforcement in States with approved State programs. (a) State-by-State... whether: (1) Direct Federal enforcement of the Energy Policy Act and implementing Federal regulations will...

30 CFR 285.203 - With whom will MMS consult before issuance of a lease?

Code of Federal Regulations, 2010 CFR

2010-07-01

... include the Endangered Species Act (ESA), and the Magnuson-Stevens Fishery Conservation and Management Act... government, and any affected Indian tribe, as directed by subsections 8(p)(4) and (7) of the OCS Lands Act or...

21 CFR 17.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS... certain violations of the act that relate to dissemination of direct-to-consumer advertisements for...) Section 351(d)(2) of the Public Health Service Act (the PHS Act) authorizing civil money penalties for...

21 CFR 17.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS... certain violations of the act that relate to dissemination of direct-to-consumer advertisements for...) Section 351(d)(2) of the Public Health Service Act (the PHS Act) authorizing civil money penalties for...

21 CFR 17.1 - Scope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS... certain violations of the act that relate to dissemination of direct-to-consumer advertisements for...) Section 351(d)(2) of the Public Health Service Act (the PHS Act) authorizing civil money penalties for...

21 CFR 17.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS... certain violations of the act that relate to dissemination of direct-to-consumer advertisements for...) Section 351(d)(2) of the Public Health Service Act (the PHS Act) authorizing civil money penalties for...

77 FR 15590 - Privacy Act; Implementation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... Act; Implementation AGENCY: Defense Intelligence Agency, DoD. ACTION: Direct final rule with request for comments. SUMMARY: Defense Intelligence Agency (DIA) is proposing to update the DIA Privacy Act... nonsubstantive changes to the Defense Intelligence Agency (DIA) Privacy Program rules. These changes will allow...

77 FR 57016 - Privacy Act; Implementation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... Act; Implementation AGENCY: Defense Intelligence Agency, DoD. ACTION: Direct final rule with request for comments. SUMMARY: Defense Intelligence Agency (DIA) is updating the DIA Privacy Act Program by... final rule makes non-substantive changes to the Defense Intelligence Agency Program rules. These changes...

78 FR 42486 - Notice of New Recreation Fees; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

... New Recreation Fees; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY... Enhancement Act (Title VII, Pub. L. 108-447) directed the Secretary of Agriculture to publish a six month...

Rapid adaptation to mammalian sociality via sexually selected traits

PubMed Central

2013-01-01

Background Laboratory studies show that the components of sexual selection (e.g., mate choice and intrasexual competition) can profoundly affect the development and fitness of offspring. Less is known, however, about the total effects of sexual selection on offspring in normal social conditions. Complex social networks, such as dominance hierarchies, regulate the opportunity for mating success, and are often missing from laboratory studies. Social selection is an extended view of sexual selection that incorporates competition during sexual and nonsexual interactions, and predicts complex evolutionary dynamics. Whether social selection improves or constrains offspring fitness is controversial. Results To identify fitness consequences of social selection, wild-derived mice that had bred under laboratory conditions for eight generations were re-introduced to naturalistic competition in enclosures for three consecutive generations (promiscuous line). In parallel, a control lineage bred in cages under random mate assignment (monogamous line). A direct competition experiment using second-generation animals revealed that promiscuous line males had greater reproductive success than monogamous line males (particularly during extra-territorial matings), in spite of higher mortality and equivalent success in social dominance and sperm competition. There were no major female fitness effects (though promiscuous line females had fewer litters than monogamous line females). This result suggested that selection primarily acted upon a sexually attractive male phenotype in the promiscuous line, a hypothesis we confirmed in female odor and mating preference trials. Conclusions We present novel evidence for the strength of sexual selection under normal social conditions, and show rapid male adaptation driven largely by sexual trait expression, with tradeoffs in survivorship and female fecundity. Re-introducing wild-derived mice to competition quickly uncovers sexually selected phenotypes otherwise lost in normal colony breeding. PMID:23577674

ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase)

PubMed Central

Andrade, Erika C.; Musante, Veronica; Horiuchi, Atsuko; Greengard, Paul; Taylor, Jane R.

2017-01-01

ARPP-16 (cAMP-regulated phospho-protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A. Ser46 of ARPP-16 is phosphorylated to a high basal stoichiometry in striatum, suggestive of basal inhibition of PP2A in striatal neurons. In support of this hypothesis, conditional knock-out of ARPP-16 in CaMKIIα::cre/floxed ARPP-16/19 mice results in dephosphorylation of a subset of PP2A substrates including phospho-Thr75-DARPP-32, phospho-T308-Akt, and phospho-T202/Y204-ERK. Conditional knock-out of ARPP-16/19 is associated with increased motivation measured on a progressive ratio schedule of food reinforcement, yet an attenuated locomotor response to acute cocaine. Our previous studies have shown that ARPP-16 is phosphorylated at Ser88 by PKA. Activation of PKA in striatal slices leads to phosphorylation of Ser88, and this is accompanied by marked dephosphorylation of Ser46. Together, these studies suggest that phospho-Ser46-ARPP-16 acts to basally control PP2A in striatal medium spiny neurons but that dopamine acting via PKA inactivates ARPP-16 leading to selective potentiation of PP2A signaling. SIGNIFICANCE STATEMENT We describe a novel mechanism of signal transduction enriched in medium spiny neurons of striatum that likely mediates effects of the neurotransmitter dopamine acting on these cells. We find that the protein ARPP-16, which is highly expressed in striatal medium spiny neurons, acts as a selective inhibitor of certain forms of the serine/threonine protein phosphatase, PP2A, when phosphorylated by the kinase, MAST3. Under basal conditions, ARPP-16 is phosphorylated by MAST3 to a very high stoichiometry. However, the actions of MAST3 are antagonized by dopamine and cAMP-regulated signaling leading to disinhibition of ARPP-16 and increased PP2A action. PMID:28167675

ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase).

PubMed

Andrade, Erika C; Musante, Veronica; Horiuchi, Atsuko; Matsuzaki, Hideo; Brody, A Harrison; Wu, Terence; Greengard, Paul; Taylor, Jane R; Nairn, Angus C

2017-03-08

ARPP-16 (cAMP-regulated phospho-protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A. Ser46 of ARPP-16 is phosphorylated to a high basal stoichiometry in striatum, suggestive of basal inhibition of PP2A in striatal neurons. In support of this hypothesis, conditional knock-out of ARPP-16 in CaMKIIα::cre/floxed ARPP-16/19 mice results in dephosphorylation of a subset of PP2A substrates including phospho-Thr75-DARPP-32, phospho-T308-Akt, and phospho-T202/Y204-ERK. Conditional knock-out of ARPP-16/19 is associated with increased motivation measured on a progressive ratio schedule of food reinforcement, yet an attenuated locomotor response to acute cocaine. Our previous studies have shown that ARPP-16 is phosphorylated at Ser88 by PKA. Activation of PKA in striatal slices leads to phosphorylation of Ser88, and this is accompanied by marked dephosphorylation of Ser46. Together, these studies suggest that phospho-Ser46-ARPP-16 acts to basally control PP2A in striatal medium spiny neurons but that dopamine acting via PKA inactivates ARPP-16 leading to selective potentiation of PP2A signaling. SIGNIFICANCE STATEMENT We describe a novel mechanism of signal transduction enriched in medium spiny neurons of striatum that likely mediates effects of the neurotransmitter dopamine acting on these cells. We find that the protein ARPP-16, which is highly expressed in striatal medium spiny neurons, acts as a selective inhibitor of certain forms of the serine/threonine protein phosphatase, PP2A, when phosphorylated by the kinase, MAST3. Under basal conditions, ARPP-16 is phosphorylated by MAST3 to a very high stoichiometry. However, the actions of MAST3 are antagonized by dopamine and cAMP-regulated signaling leading to disinhibition of ARPP-16 and increased PP2A action. Copyright © 2017 the authors 0270-6474/17/372709-14$15.00/0.

Analysis of Corporate Average Fuel Economy (CAFE) Standards for Light Trucks and Increased Alternative Fuel Use

EIA Publications

2002-01-01

Sen. Frank Murkowski, the Ranking Minority Member of the Senate Committee on Energy and Natural Resources requested an analysis of selected portions of Senate Bill 1766 (S. 1766, the Energy Policy Act of 2002), House Resolution 4 (the Securing America's Future Energy Act of 2001) and Senate Bill 517 (S. 517, the Energy Policy Act of 2002). In response, the Energy Information Administration (EIA) has prepared a series of analyses showing the impacts of each of the selected provisions of the bills on energy supply, demand, and prices, macroeconomic variables where feasible, import dependence, and emissions.

32 CFR Appendix E to Part 516 - Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 3 2014-07-01 2014-07-01 false Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act E Appendix E to Part 516 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Pt...

32 CFR Appendix E to Part 516 - Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 3 2013-07-01 2013-07-01 false Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act E Appendix E to Part 516 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Pt...

32 CFR Appendix E to Part 516 - Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 3 2012-07-01 2009-07-01 true Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act E Appendix E to Part 516 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Pt...

32 CFR Appendix E to Part 516 - Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act E Appendix E to Part 516 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Pt...

32 CFR Appendix E to Part 516 - Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Department of Defense Directive 5505.5, Implementation of the Program Fraud Civil Remedies Act E Appendix E to Part 516 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Pt...

25 CFR 170.935 - How does a direct service tribe begin the alternative dispute resolution process?

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADR process, a direct service tribe must write to the BIA Regional Director or the Chief of BIA... (ADR) procedures in the Administrative Dispute Resolution Act of 1996, 5 U.S.C. 571-583 (ADR Act); and (2) Explain the factual and legal basis for the dispute. (b) ADR proceedings will be governed by...

75 FR 11189 - Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

...] Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C Infection in... hepatitis C (CHC) infection in patients with unmet medical need. This public hearing is being held to obtain.... Background A. CHC In the United States, hepatitis C virus infection causes 20 percent of all cases of acute...

A direct translaminar inhibitory circuit tunes cortical output

PubMed Central

Pluta, Scott; Naka, Alexander; Veit, Julia; Telian, Gregory; Yao, Lucille; Hakim, Richard; Taylor, David; Adesnik, Hillel

2015-01-01

Summary Anatomical and physiological experiments have outlined a blueprint for the feed-forward flow of activity in cortical circuits: signals are thought to propagate primarily from the middle cortical layer, L4, up to L2/3, and down to the major cortical output layer, L5. Pharmacological manipulations, however, have contested this model and suggested that L4 may not be critical for sensory responses of neurons in either superficial or deep layers. To address these conflicting models we reversibly manipulated L4 activity in awake, behaving mice using cell-type specific optogenetics. In contrast to both prevailing models, we show that activity in L4 directly suppresses L5, in part by activating deep, fast spiking inhibitory neurons. Our data suggest that the net impact of L4 activity is to sharpen the spatial representations of L5 neurons. Thus we establish a novel translaminar inhibitory circuit in the sensory cortex that acts to enhance the feature selectivity of cortical output. PMID:26414615

Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

PubMed

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.

Merging the "Morphology-Performance-Fitness" Paradigm and Life-History Theory in the Eagle Lake Garter Snake Research Project.

PubMed

Addis, Elizabeth A; Gangloff, Eric J; Palacios, Maria G; Carr, Katherine E; Bronikowski, Anne M

2017-08-01

The morphology-performance-fitness paradigm for testing selection on morphological traits has seen decades of successful application. At the same time, life-history approaches using matrix methods and perturbation studies have also allowed the direct estimate of selection acting on vital rates and the traits that comprise them. Both methodologies have been successfully applied to the garter snakes of the long-term Eagle Lake research project to reveal selection on morphology, such as color pattern, number of vertebrae, and gape size; and life-history traits such as birth size, growth rates, and juvenile survival. Here we conduct a reciprocal transplant study in a common laboratory environment to study selection on morphology and life-history. To place our results in the ecomorphology paradigm, we measure performance outcomes (feeding rates, growth, insulin-like growth factor 1 titers) of morphological variation (body size, condition) and their fitness consequences for juvenile survival-a trait that has large fitness sensitivities in these garter snake populations, and therefore is thought to be subject to strong selection. To better merge these two complementary theories, we end by discussing our findings in a nexus of morphology-performance-fitness-life history to highlight what these approaches, when combined, can reveal about selection in the wild. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Multiple-Line Inference of Selection on Quantitative Traits

PubMed Central

Riedel, Nico; Khatri, Bhavin S.; Lässig, Michael; Berg, Johannes

2015-01-01

Trait differences between species may be attributable to natural selection. However, quantifying the strength of evidence for selection acting on a particular trait is a difficult task. Here we develop a population genetics test for selection acting on a quantitative trait that is based on multiple-line crosses. We show that using multiple lines increases both the power and the scope of selection inferences. First, a test based on three or more lines detects selection with strongly increased statistical significance, and we show explicitly how the sensitivity of the test depends on the number of lines. Second, a multiple-line test can distinguish between different lineage-specific selection scenarios. Our analytical results are complemented by extensive numerical simulations. We then apply the multiple-line test to QTL data on floral character traits in plant species of the Mimulus genus and on photoperiodic traits in different maize strains, where we find a signature of lineage-specific selection not seen in two-line tests. PMID:26139839

7 CFR 57.100 - Specific exemptions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) INSPECTION OF EGGS (EGG PRODUCTS INSPECTION ACT) Regulations Governing the Inspection of Eggs Exemptions § 57.100 Specific... production directly to a household consumer exclusively for use by such consumer and members of his household...

7 CFR 57.100 - Specific exemptions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) INSPECTION OF EGGS (EGG PRODUCTS INSPECTION ACT) Regulations Governing the Inspection of Eggs Exemptions § 57.100 Specific... production directly to a household consumer exclusively for use by such consumer and members of his household...

7 CFR 57.100 - Specific exemptions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) INSPECTION OF EGGS (EGG PRODUCTS INSPECTION ACT) Regulations Governing the Inspection of Eggs Exemptions § 57.100 Specific... production directly to a household consumer exclusively for use by such consumer and members of his household...

7 CFR 57.100 - Specific exemptions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) INSPECTION OF EGGS (EGG PRODUCTS INSPECTION ACT) Regulations Governing the Inspection of Eggs Exemptions § 57.100 Specific... production directly to a household consumer exclusively for use by such consumer and members of his household...

10 CFR 52.10 - Attacks and destructive acts.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Attacks and destructive acts. 52.10 Section 52.10 Energy... protection against the effects of— (a) Attacks and destructive acts, including sabotage, directed against the... deployment of weapons incident to U.S. defense activities. ...

10 CFR 52.10 - Attacks and destructive acts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Attacks and destructive acts. 52.10 Section 52.10 Energy... protection against the effects of— (a) Attacks and destructive acts, including sabotage, directed against the... deployment of weapons incident to U.S. defense activities. ...

10 CFR 52.10 - Attacks and destructive acts.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Attacks and destructive acts. 52.10 Section 52.10 Energy... protection against the effects of— (a) Attacks and destructive acts, including sabotage, directed against the... deployment of weapons incident to U.S. defense activities. ...

10 CFR 52.10 - Attacks and destructive acts.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Attacks and destructive acts. 52.10 Section 52.10 Energy... protection against the effects of— (a) Attacks and destructive acts, including sabotage, directed against the... deployment of weapons incident to U.S. defense activities. ...

10 CFR 52.10 - Attacks and destructive acts.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Attacks and destructive acts. 52.10 Section 52.10 Energy... protection against the effects of— (a) Attacks and destructive acts, including sabotage, directed against the... deployment of weapons incident to U.S. defense activities. ...

75 FR 1333 - Notice of New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447) AGENCY: Forest... Recreation Enhancement Act (Title VIII, Pub. L. 108-447) directed the Secretary of Agriculture to publish a...

The inferior parietal lobule: where action becomes perception.

PubMed

Rizzolatti, Giacomo; Ferrari, Pier Francesco; Rozzi, Stefano; Fogassi, Leonardo

2006-01-01

The view defended in this article is that action and perception share the same neural substrate. To substantiate this view, the anatomical and functional organization of the inferior parietal lobule (IPL) is reviewed. In particular, it will be shown that many IPL neurons discharge selectively when the monkey executes a given motor act (e.g. grasping). Most interestingly, most of them fire only if the coded motor act is followed by a subsequent specific motor act (e.g. placing). Some of these action-constrained motor neurons have mirror properties and selectively discharge during the observation of motor acts when these are embedded in a given action (e.g. grasping for eating, but not grasping for placing). Thus, the activation of these IPL neurons allows the observer not only to recognize the observed motor act, but also to predict what will be the next motor act of the action, that is to understand the intentions of the action's agent. The finding that the same neurons that are active during the execution of specific motor acts also mediate the understanding of the 'what' and the 'why' of others' actions provides strong evidence for a common neural substrate for action and perception.

Stumpage price projections for selected Western species.

Treesearch

Richard W. Haynes; Kent P. Connaughton; Darius M. Adams

1980-01-01

The 1980 Resources Planning Act Timber Assessment and Program prepared in response to provisions of the Forest and Rangeland Renewable Resources Planning Act of 1974 (as amended by the National Forest Management Act of 1976) contains regional projections of average stumpage prices that are potentially useful in national forest planning. Their usefulness can be improved...

77 FR 517 - Notice of Lodging of Consent Decree Under the Clean Air Act

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-05

... given that on December 29, 2011, a proposed consent decree in United States, et al. v. Essroc Cement... statutory and regulatory requirements of the Clean Air Act (the ``Act'') at Essroc cement plants: the... X at five cement kilns. The proposed consent decree also requires testing a selective catalytic...

78 FR 32257 - Privacy Act of 1974; Report of a New Routine Use for Selected CMS Systems of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... systems of records to assist in preventing and detecting fraud, waste and abuse. The new routine use will... for the purpose of preventing and detecting fraud, waste and abuse, pursuant to section 1128C(a)(2) of the Social Security Act (``the Act''). At section 1128C(c) of the Act, a health plan is defined as a...

The evolution of trade-offs under directional and correlational selection.

PubMed

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.

Validating Standardized Testing: The Role of the SAT and ACT in Undergraduate Admissions. [Hearing before the California Legislature, Senate Select Committee on Higher Education Admissions and Outreach, Sacramento, California, February 5, 1998].

ERIC Educational Resources Information Center

California State Legislature, Sacramento. Senate Select Committee on Higher Education Admissions and Outreach.

This report contains testimony and materials presented at the California Senate Select Committee on Higher Education Admissions and Outreach hearing, February 1998, held to examine the role of the Scholastic Assessment Test (SAT) and the American College Test (ACT) in undergraduate admissions to the public universities of California. In her…

Mate choice, sexual selection, and endocrine-disrupting chemicals.

PubMed

Gore, Andrea C; Holley, Amanda M; Crews, David

2018-05-01

Humans have disproportionately affected the habitat and survival of species through environmental contamination. Important among these anthropogenic influences is the proliferation of organic chemicals, some of which perturb hormone systems, the latter referred to as endocrine-disrupting chemicals (EDCs). EDCs are widespread in the environment and affect all levels of reproduction, including development of reproductive organs, hormone release and regulation through the life cycle, the development of secondary sexual characteristics, and the maturation and maintenance of adult physiology and behavior. However, what is not well-known is how the confluence of EDC actions on the manifestation of morphological and behavioral sexual traits influences mate choice, a process that requires the reciprocal evaluation of and/or acceptance of a sexual partner. Moreover, the outcomes of EDC-induced perturbations are likely to influence sexual selection; yet this has rarely been directly tested. Here, we provide background on the development and manifestation of sexual traits, reproductive competence, and the neurobiology of sexual behavior, and evidence for their perturbation by EDCs. Selection acts on individuals, with the consequences manifest in populations, and we discuss the implications for EDC contamination of these processes, and the future of species. Copyright © 2017 Elsevier Inc. All rights reserved.

Island Rule, quantitative genetics and brain–body size evolution in Homo floresiensis

PubMed Central

2017-01-01

Colonization of islands often activate a complex chain of adaptive events that, over a relatively short evolutionary time, may drive strong shifts in body size, a pattern known as the Island Rule. It is arguably difficult to perform a direct analysis of the natural selection forces behind such a change in body size. Here, we used quantitative evolutionary genetic models, coupled with simulations and pattern-oriented modelling, to analyse the evolution of brain and body size in Homo floresiensis, a diminutive hominin species that appeared around 700 kya and survived up to relatively recent times (60–90 kya) on Flores Island, Indonesia. The hypothesis of neutral evolution was rejected in 97% of the simulations, and estimated selection gradients are within the range found in living natural populations. We showed that insularity may have triggered slightly different evolutionary trajectories for body and brain size, which means explaining the exceedingly small cranial volume of H. floresiensis requires additional selective forces acting on brain size alone. Our analyses also support previous conclusions that H. floresiensis may be most likely derived from an early Indonesian H. erectus, which is coherent with currently accepted biogeographical scenario for Homo expansion out of Africa. PMID:28637851

Island Rule, quantitative genetics and brain-body size evolution in Homo floresiensis.

PubMed

Diniz-Filho, José Alexandre Felizola; Raia, Pasquale

2017-06-28

Colonization of islands often activate a complex chain of adaptive events that, over a relatively short evolutionary time, may drive strong shifts in body size, a pattern known as the Island Rule. It is arguably difficult to perform a direct analysis of the natural selection forces behind such a change in body size. Here, we used quantitative evolutionary genetic models, coupled with simulations and pattern-oriented modelling, to analyse the evolution of brain and body size in Homo floresiensis , a diminutive hominin species that appeared around 700 kya and survived up to relatively recent times (60-90 kya) on Flores Island, Indonesia. The hypothesis of neutral evolution was rejected in 97% of the simulations, and estimated selection gradients are within the range found in living natural populations. We showed that insularity may have triggered slightly different evolutionary trajectories for body and brain size, which means explaining the exceedingly small cranial volume of H. floresiensis requires additional selective forces acting on brain size alone. Our analyses also support previous conclusions that H. floresiensis may be most likely derived from an early Indonesian H. erectus , which is coherent with currently accepted biogeographical scenario for Homo expansion out of Africa. © 2017 The Author(s).

Plant-parasite coevolution: bridging the gap between genetics and ecology.

PubMed

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.

Evidence of natural selection acting on a polymorphic hybrid incompatibility locus in Mimulus.

PubMed

Sweigart, Andrea L; Flagel, Lex E

2015-02-01

As a common cause of reproductive isolation in diverse taxa, hybrid incompatibilities are fundamentally important to speciation. A key question is which evolutionary forces drive the initial substitutions within species that lead to hybrid dysfunction. Previously, we discovered a simple genetic incompatibility that causes nearly complete male sterility and partial female sterility in hybrids between the two closely related yellow monkeyflower species Mimulus guttatus and M. nasutus. In this report, we fine map the two major incompatibility loci-hybrid male sterility 1 (hms1) and hybrid male sterility 2 (hms2)-to small nuclear genomic regions (each <70 kb) that include strong candidate genes. With this improved genetic resolution, we also investigate the evolutionary dynamics of hms1 in a natural population of M. guttatus known to be polymorphic at this locus. Using classical genetic crosses and population genomics, we show that a 320-kb region containing the hms1 incompatibility allele has risen to intermediate frequency in this population by strong natural selection. This finding provides direct evidence that natural selection within plant species can lead to hybrid dysfunction between species. Copyright © 2015 by the Genetics Society of America.

Identification of Direct Target Genes Using Joint Sequence and Expression Likelihood with Application to DAF-16

PubMed Central

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

Planning Ahead: Object-Directed Sequential Actions Decoded from Human Frontoparietal and Occipitotemporal Networks

PubMed Central

Gallivan, Jason P.; Johnsrude, Ingrid S.; Randall Flanagan, J.

2016-01-01

Object-manipulation tasks (e.g., drinking from a cup) typically involve sequencing together a series of distinct motor acts (e.g., reaching toward, grasping, lifting, and transporting the cup) in order to accomplish some overarching goal (e.g., quenching thirst). Although several studies in humans have investigated the neural mechanisms supporting the planning of visually guided movements directed toward objects (such as reaching or pointing), only a handful have examined how manipulatory sequences of actions—those that occur after an object has been grasped—are planned and represented in the brain. Here, using event-related functional MRI and pattern decoding methods, we investigated the neural basis of real-object manipulation using a delayed-movement task in which participants first prepared and then executed different object-directed action sequences that varied either in their complexity or final spatial goals. Consistent with previous reports of preparatory brain activity in non-human primates, we found that activity patterns in several frontoparietal areas reliably predicted entire action sequences in advance of movement. Notably, we found that similar sequence-related information could also be decoded from pre-movement signals in object- and body-selective occipitotemporal cortex (OTC). These findings suggest that both frontoparietal and occipitotemporal circuits are engaged in transforming object-related information into complex, goal-directed movements. PMID:25576538

Repeated divergent selection on pigmentation genes in a rapid finch radiation

PubMed Central

Campagna, Leonardo; Repenning, Márcio; Silveira, Luís Fábio; Fontana, Carla Suertegaray; Tubaro, Pablo L.; Lovette, Irby J.

2017-01-01

Instances of recent and rapid speciation are suitable for associating phenotypes with their causal genotypes, especially if gene flow homogenizes areas of the genome that are not under divergent selection. We study a rapid radiation of nine sympatric bird species known as capuchino seedeaters, which are differentiated in sexually selected characters of male plumage and song. We sequenced the genomes of a phenotypically diverse set of species to search for differentiated genomic regions. Capuchinos show differences in a small proportion of their genomes, yet selection has acted independently on the same targets in different members of this radiation. Many divergent regions contain genes involved in the melanogenesis pathway, with the strongest signal originating from putative regulatory regions. Selection has acted on these same genomic regions in different lineages, likely shaping the evolution of cis-regulatory elements, which control how more conserved genes are expressed and thereby generate diversity in classically sexually selected traits. PMID:28560331

Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia

PubMed Central

Vit, Jean-Philippe; Ohara, Peter T; Sundberg, Christopher; Rubi, Blanca; Maechler, Pierre; Liu, Chunyan; Puntel, Mariana; Lowenstein, Pedro; Castro, Maria; Jasmin, Luc

2009-01-01

Background Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animal model of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) gene into satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector with high tropisms for glial cells. We postulated that GABA produced from the expression of GAD would reduce pain behavior by acting on GABA receptors on neurons within the ganglion. Results Injection of adenoviral vectors (AdGAD65) directly into the trigeminal ganglion leads to sustained expression of the GAD65 isoform over the 4 weeks observation period. Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABA synthesis were mainly in SGCs. GABAA and GABAB receptors were both seen in sensory neurons, yet only GABAA receptors decorated the neuronal surface. GABA receptors were not found on SGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statistically significant decrease of pain behavior in the orofacial formalin test, a model of inflammatory pain. Rats injected with control virus (AdGFP or AdLacZ) had no reduction in their pain behavior. AdGAD65-dependent analgesia was blocked by bicuculline, a selective GABAA receptor antagonist, but not by CGP46381, a selective GABAB receptor antagonist. Conclusion Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks pain behavior by acting on GABAA receptors on neuronal perikarya. PMID:19656360

Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia.

PubMed

Vit, Jean-Philippe; Ohara, Peter T; Sundberg, Christopher; Rubi, Blanca; Maechler, Pierre; Liu, Chunyan; Puntel, Mariana; Lowenstein, Pedro; Castro, Maria; Jasmin, Luc

2009-08-05

Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animal model of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) gene into satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector with high tropisms for glial cells. We postulated that GABA produced from the expression of GAD would reduce pain behavior by acting on GABA receptors on neurons within the ganglion. Injection of adenoviral vectors (AdGAD65) directly into the trigeminal ganglion leads to sustained expression of the GAD65 isoform over the 4 weeks observation period. Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABA synthesis were mainly in SGCs. GABAA and GABAB receptors were both seen in sensory neurons, yet only GABAA receptors decorated the neuronal surface. GABA receptors were not found on SGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statistically significant decrease of pain behavior in the orofacial formalin test, a model of inflammatory pain. Rats injected with control virus (AdGFP or AdLacZ) had no reduction in their pain behavior. AdGAD65-dependent analgesia was blocked by bicuculline, a selective GABAA receptor antagonist, but not by CGP46381, a selective GABAB receptor antagonist. Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks pain behavior by acting on GABAA receptors on neuronal perikarya.

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2011-10-07

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Undocumented & Unafraid: The DREAM Act 5 and the Public Disclosure of Undocumented Status as a Political Act

ERIC Educational Resources Information Center

Galindo, Rene

2012-01-01

In 2010, the political advocacy of undocumented immigrant students in support of the DREAM Act took a new and decisive direction when the public disclosure of undocumented status as political act was adopted. This new political strategy included the first case of civil disobedience practiced by a group of undocumented immigrant students now known…

Broncho-Vaxom and spontaneous allergic autocytotoxicity (spACT) in bronchial asthma associated with food hypersensitivity.

PubMed

Podleski, W K

1986-01-01

Spontaneous allergic autocytotoxicity (spACT) of white blood cells (WBC) was assessed in six bronchial asthma patients and eighteen normal control individuals. The observed alterations of non-primed WBC membrane were revealed as an increased uptake of trypan blue exclusion dye, an indicator of death cells. The phenomenon of spACT might be associated with a lack of T suppressor cell intervention, increased refractoriness of WBC membrane leading to its increased permeability and enhanced releasability of chemical mediators of anaphylaxis, which probably bypasses IgE events. In six bronchial asthma patients, three were sensitive toward wheat, two had cow milk sensitivity, and one had corn sensitivity. When WBC of these patients were studied in the direct ACT assay, an additional augmentation of spACT effect by specific food antigens was observed. Surprisingly, Broncho-Vaxom (BX) did not inhibit or enhance spACT. However, BX has antagonistic activity toward direct ACT response in the dose-dependent concentration as previously reported. Our preliminary clinical experience leads us to believe that the spACT assay can serve as a useful clinical discriminator of potential responders versus non-responders to therapy with new agents, when WBC disintegration by autoinduction is involved.